covid-19

Sans me livrer à une vraie revue de la littérature scientifique, je repère surtout les publications qui me semblent dignes d’intérêt depuis le 18 mars 2021 (voir aussi les archives) dans le listing quotidien de Kamps et Hoffmann : https://covidreference.com/top10

Remarques en français en caractères bleus.

A noter que les mises à jour de cette page ne feront pas systématiquement l'objet d'un avis de publication par courriel comme les autres articles.

9 juillet 2021

Edara VV, Pinksy BA, Suthar MS, et al. Infection and Vaccine-Induced Neutralizing-Antibody Responses to the SARS-CoV-2 B.1.617 Variants. NEJM July 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2107799?query=featured_home

Moindre réponse par anticorps neutralisants contre les variants indiens Kappa et Delta. Ainsi, l'immunisation par infection oui par vaccination est moindre contre le Kappa (6,8 fois moins) que contre le Delta (2,9 fois moins). Toutefois, la majorité des sérums de convalescents (19 sur 24 pour le Kappa et 23 sur 24 pour le Delta) ainsi que la totalité du sérum des vaccinés montraient une activité neutralisante détectable.

Good news: protective immunity conferred by the mRNA vaccines is most likely retained against the B.1.617.1 and B.1.617.2 variants. Although the B.1.617.1 variant was 6.8 times (B.1.617.2 variant: 2.9 times) less susceptible to neutralization by serum from recovered or vaccinated persons, the majority of the convalescent serum samples (19/24) against B.1.617.1 (23/24 against B.1.617.2) and all serum samples from vaccinated persons still had detectable neutralizing activity.

Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the Advisory Committee on Immunization Practices — United States, June 2021. MMWR Morb Mortal Wkly Rep. ePub: 6 July 2021. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e2.htm?s_cid=mm7027e2_w

Myocardites après vaccin à ARNm : même chez les hommes jeunes, le rapport bénéfice-risque est en faveur de al vaccination. 

D'un coté, par million de vaccins ARNm  administrés avec deux doses à des hommes âgés de 12 à 29 ans, 11 000 cas de COVID-19, 560 hospitalisations, 138 admissions en soins intensifs et six décès dus à la COVID-19 pourraient être évités.

De l'autre, 39 à 47 cas attendus de myocardite après vaccination COVID-19.

The Committee concluded that the benefits of COVID-19 vaccination to individual persons and at the population level clearly outweighed the risks of myocarditis after vaccination. Even in young men: per million second doses of mRNA COVID-19 vaccine administered to males aged 12–29 years, 11,000 COVID-19 cases, 560 hospitalizations, 138 ICU admissions, and six deaths due to COVID-19 could be prevented, compared with 39–47 expected myocarditis cases after COVID-19 vaccination.

Patriquin CJ, Laroche V, Selby R, et al. Therapeutic Plasma Exchange in Vaccine-Induced Immune Thrombotic Thrombocytopenia. NEJM July 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2109465?query=featured_home

Trois cas de VITT réfractaires au Canada : deux guérisons après échange plasmatique.

Three cases from Canada, indicating that therapeutic plasma exchange may be effective for the treatment of refractory VITT. Two recovered despite their severe presentation.

8 juillet 2021

Golan Y, Prahl M, Cassidy A, et al. Evaluation of Messenger RNA From COVID-19 BTN162b2 and mRNA-1273 Vaccines in Human Milk. JAMA Pediatr July 6, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2781679?resultClick=1

Pas de présence d'ARNm provenant des vaccins Pfizer et Moderna dans 13 échantillons de lait de 7 femmes allaitantes.

Vaccine-associated mRNA was not detected in 13 milk samples collected 4 to 48 hours after vaccination from 7 breastfeeding individuals.

Melo AK, Milby KM, Caparroz AL, et al. Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis. PLOS ONE, June 29, 2021. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253894

Les marqueurs de l'orage cytokinique indiquent la sévérité de l'inflammation et sont un indice de pronostic mauvais : interleukine 6 et ferritinémie.

According to this review, elevated levels of interleukin-6 and hyperferritinemia should be considered red flags of systemic inflammation and poor prognosis in COVID-19.

7 juillet 2021

Seeßle J, Waterboer T, Hippchen T, et al. Persistent symptoms in adult patients one year after COVID-19: a prospective cohort study. Clinical Infectious Diseases July 5, 2021, ciab611, https://doi.org/10.1093/cid/ciab611

Long Covid : réduction des possibilités d'efforts physiques et fatigue pour plus de la moitié des patients. Les femmes présentent davantage de troubles cognitifs que les hommes. 

Is autoimmunity a cofactor in aetiology of long COVID? Of 96 patients who were included at 5 months after acute COVID-19 in this prospective, non-interventional study, only 23% were completely free of symptoms at 12 months. The most frequent symptoms were reduced exercise capacity (56%) and fatigue (53%). Females showed significantly more neurocognitive symptoms than males. ANA titres were ≥1:160 in 44% of patients at 12 months, and neurocognitive symptom frequency was significantly higher in the group with an ANA titre ≥1:160 compared to <1:160.

Lustig Y, Zuckerman N, Nemet I, et al. Neutralising capacity against Delta (B.1.617.2) and other variants of concern following Comirnaty (BNT162b2, BioNTech/Pfizer) vaccination in health care workers, Israel. Euro Surveill Jul 1, 2021;26(26):pii=2100557. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.26.2100557

Pfizer : capacité de neutralisation diminuée contre le delta en Israël mais réponse significative toutefois.

This study has used micro-neutralisation assays with sera obtained after BNT162b2 (BioNTech/Pfizer) vaccination in 36 healthcare workers. It is shown that, despite a somewhat reduced neutralisation capacity, mRNA vaccination induces a substantial antibody response also for the Delta VOC.

Sangli S, Virani A, Cheronis N, et al. Thrombosis With Thrombocytopenia After the Messenger RNA–1273 Vaccine. Annals Int Med, June 29, 2021. https://www.acpjournals.org/doi/10.7326/L21-0244

Thrombocytopénie induite par le vaccin chez un homme de 65 ans après Moderna. Ce cas indique que ce syndrome n'est pas exclusif aux vaccins à adénovirus.

A 65-year old man with vaccine-induced thrombosis with thrombocytopenia (VITT), developing a few days after administration of the mRNA-1273 vaccine from Moderna. Most of his clotting and other relevant work-up were consistent with the syndrome. This report complicates hypotheses that implicate adenoviral vectors as the sole cause of VITT or TTS.

6 juillet 2021

Leach DA, Mohr A, Giotis ES, et al. The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells. Nat Commun Jul 1, 2021, 12, 4068. https://www.nature.com/articles/s41467-021-24342-y

Espoir du côté d'un anti-androgène par protection des cellules pulmonaires ? Au moins chez la souris...

Treatment with the anti-androgen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lungs. Anti-androgens significantly reduced SARS-CoV-2 entry and infection in lung cells.

5 juillet 2021

Lindsley WG, Derk RC, Coyle JP, et al. Efficacy of Portable Air Cleaners and Masking for Reducing Indoor Exposure to Simulated Exhaled SARS-CoV-2 Aerosols — United States, 2021. MMWR Morb Mortal Wkly Rep. ePub: 2 July 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e1.htm?s_cid=mm7027e1_w

Efficacité partielle de purificateurs d'air, à compléter avec le masque pour réduire l'exposition de 90 %.

A simulated infected meeting participant who was exhaling aerosols was placed in a room with two simulated uninfected participants and a simulated uninfected speaker. Using two high efficiency particulate air (HEPA) cleaners close to the aerosol source reduced the aerosol exposure of the uninfected participants and speaker by up to 65%. A combination of HEPA air cleaners and universal masking reduced exposure by up to 90%.

Lemey P, Ruktanonchai N, Hong SL, et al. Untangling introductions and persistence in COVID-19 resurgence in Europe. Nature June 30, 2021. https://www.nature.com/articles/s41586-021-03754-2

En Europe, dans beaucoup de pays, c'est le nouveau variant qui prévaut depuis le 15 juin 2021.

The authors estimate that in many countries over half of the lineages circulating in late summer 2020 resulted from new variant introductions since June 15^th.

4 juillet 2021

Thompson MG, Burgess JL, Naleway AL, et al. Prevention and Attenuation of Covid-19 with the BNT162b2 and mRNA-1273 Vaccines. NEJM June 30, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107058?query=featured_home

Prévention et atténuation de la covid par vaccins à ARNm : confirmation d'efficacité chez des travailleurs de première ligne dont des soignants.

This prospective cohort study involving 3975 health care personnel, first responders, and other essential and frontline workers shows that mRNA vaccines attenuated the viral RNA load, risk of febrile symptoms, and duration of illness among those who had breakthrough infection despite vaccination.

Roman YM, Burela PA, Pasupuleti V, et al. Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clinical Infectious Diseases June 28, 2021, ciab591, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab591/6310839

Ivermectine : confirmation d'inefficacité.

In comparison to standard of care or placebo, ivermectin did not reduce all-cause mortality, length of stay or viral clearance in this review of 10 RCTs in COVID-19 patients with mostly mild disease. Ivermectin is not a viable option for treating COVID-19 patients.

3 juillet 2021

Lee SA, Park R, Yang JH. et al. Increased risk of acute kidney injury in coronavirus disease patients with renin–angiotensin–aldosterone-system blockade use: a systematic review and meta-analysis. Sci Rep Jun 30, 2021, 11, 13588. https://www.nature.com/articles/s41598-021-92323-8

Augmentation du risque d'atteinte rénale en cas de covid chez des personnes prenant des inhibiteurs de l’enzyme de conversion (IEC) ou des antagonistes des récepteurs AT1 (ARA). Le risque relatif est de 2,45 pour les IEC et de 2,32 pour les AT1. Toutefois, un lien de causalité ne peut pas être établi et donc les recommandations ne doivent pas être modifiées (maintien du blocage du SRA en ttemsp de apndémie)

This meta-analysis of published retrospective and prospective cohort studies observed that the exposure to RAAS blockade was associated with a higher risk of incident acute kidney injury in patients with laboratory-confirmed or clinically diagnosed COVID-19. Odds ratio were 2.45 for ACEI use and 2.32 for ARB use. However, a causal relationship cannot be ascribed to the RAAS blockade and practice changing recommendations cannot be made on the basis of these data.

2 juillet 2021

Hoffmann M, Hofmann-Winkler H, Krüger N, et al. SARS-CoV-2 variant B.1.617 is resistant to Bamlanivimab and evades antibodies induced by infection and vaccination. Cell Reports June 28, 2021. https://www.cell.com/cell-reports/fulltext/S2211-1247(21)00828-7

Le variant delta possède deux mutations dans le RBD qui interagissent avec le récepteur ACE2 et constitue la principale cible des anticorps neutralisants. La spike protein  du delta peut faciliter son entrée dans les cellules pulmonaires avec une efficacité légèrement augmentée et son entrée peut être bloquée par l'ACE2 soluble et le camostat. Le delta échappe aux anticorps induits par la vaccination et par l'infection mais moins que ne le fait le sud-africain.

The spike protein of B.1.617 (delta) harbors two mutations in the receptor-binding domain, which interacts with the ACE2 receptor and constitutes the main target of neutralizing antibodies. The B.1.617 spike protein can facilitate entry into lung cells with slightly increased efficiency and shows that entry can be blocked by soluble ACE2 and camostat. B.1.617 also evades antibodies induced by infection or vaccination, although less so than the B.1.351 variant.

Jung JH, Rha MS, Sa M, et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Commun June 30, 2021, 12, 4043. https://www.nature.com/articles/s41467-021-24377-1

Une immunité cellulaire présente dix mois après l'infection.

In the present study, it is demonstrated that SARS-CoV-2-specific memory T cell responses were maintained in COVID-19 convalescent patients 10 months post-infection regardless of disease severity. Notably, SARS-CoV-2-specific stem cell-like memory T (TSCM) cells were successfully developed, indicating that T cell memory may be long-lasting in COVID-19 convalescent patients.

Castro MC, Gurzenda S, Turra CM, et al. Reduction in life expectancy in Brazil after COVID-19. Nat Med June 29, 2021. https://www.nature.com/articles/s41591-021-01437-z

Espérance de vie à la naissance : réduite de 1,3 ans au Brésil, un niveau de mortalité jamais vu depuis 2014. L'espérance de vie au temps de la covid est équivalent à celui d'il y a 20 ans ou plus dans certains états.

The authors estimate a decline in 2020 life expectancy from birth of 1.3 years, a mortality level not seen since 2014. Life expectancy in the presence of COVID-19 was equivalent to levels observed in Brazil as far back as 20 or more years in some states.

1er juillet 2021

Kim HW, Jenista ER, Wendell DC, et al. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol June 29, 2021. https://jamanetwork.com/journals/jamacardiology/fullarticle/2781602?resultClick=1

7 patients présentent une myocardite post-vaccinale à ARNm dont 4 dans les 5 jours qui suivent l'injection entre le 1er février et le 30 avril 2021 : 3 hommes jeunes et une femme de 70 ans.

Texte complet : https://cloud.leviia.com/s/zqd2DYLJtBCYBQ3

In this study of 7 patients with acute myocarditis, 4 occurred within 5 days of COVID-19 vaccination between February 1 and April 30, 2021. Fortunately, the hospital courses of the 4 patients with myocarditis following COVID-19 vaccination were uneventful.

Montgomery J, Ryan M, Engler R, et al. Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. JAMA Cardiol, June 29, 2021; doi: https://jamanetwork.com/journals/jamacardiology/fullarticle/2781601?resultClick=1

23 hommes de 20 à 51 ans : douleurs thoraciques dans les 4 jours suivant un vaccin à ARNm. Huit présentent une IRM évocatrice de myocardite. Dans le même temps, plus de 2,8 millions de doses de ces vaccins ont été injectées. Pour 16 patients, la résolution des symptômes s'est réalisée en une semaine. Les sept autres font l'objet d'une surveillance à l'heure de la publication de ce texte dans le JAMA. On trouvera le texte complet en lien ici : 

https://cloud.leviia.com/s/nJoQkDBFJm9s23E

A total of 23 male patients (20-51 years) presented with acute onset of marked chest pain within 4 days after receipt of an mRNA COVID-19 vaccine. Eight patients had cMRI findings consistent with myocarditis. More than 2.8 million doses of mRNA COVID-19 vaccine were administered in this period.

Van Oekelen O, Gleason CR, Agte S, et al. Highly variable SARS-CoV-2 spike antibody responses to two doses of COVID-19 RNA vaccination in patients with multiple myeloma. Cancer Cell June 28, 2021. https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00336-6

Myélome : pas d'immunisation malgré humorale malgré deux doses de vaccin à ARNm.

Of note, 15.8% of myeloma patients (41/260) failed to develop any SARS-CoV-2 spike-binding IgG antibodies despite having received both doses of mRNA vaccines.

Lustig Y, Nemet I, Kliker L, et al. Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2. N Engl J Med June 24, 2021; 384:2453-2454.  https://www.nejm.org/doi/full/10.1056/NEJMc2104036?query=featured_home

Vaccination : activité neutralisante augmentée par une dose de Pfizer chez des personnes préalablement infectées par le SARS-CoV-2. Ceci contre les variants : anglais, sud-africain et brésilien.

In this study, one dose of the BNT162b2 vaccine increases neutralizing activity against the B.1.1.7, B.1.351, and P.1 variants in six persons previously infected with SARS-CoV-2. This highlights the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the variants tested.

Collier DA, Ferreira IA, Kotagiri P, et al. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature June 30, 2021. https://www.nature.com/articles/s41586-021-03739-1

Immunité humorale diminuée après 80 ans chez des vaccinés par Pfizer. Pas d'activité neutralisante pour le variant brésilien et le variant anglais après la première dose dans cette population.

This study analyzed immune responses following vaccination with the mRNA vaccine BNT162b22 in elderly participants and younger health care workers. Serum neutralization and binding IgG/IgA after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Of note, a greater proportion of individuals in the over 80 age group lost all neutralizing activity to P.1 and B.1.1.7 following the first dose compared to the wild type.

Harris RJ, Hall JA, Zaidi A, et al. Effect of Vaccination on Household Transmission of SARS-CoV-2 in England. NEJM June 23, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2107717?query=featured_home

Transmission domestique diminuée de 40 à 50 % chez des personnes vaccinées depuis au moins 21 jours avant d'être testées positives.

Overall, the likelihood of household transmission was approximately 40 to 50% lower in households of index patients who had been vaccinated 21 days or more before testing positive than in households of unvaccinated index patients; the findings were similar for the two vaccines from Pfizer/BioNTech and AstraZeneca.

Pawlowski C, Lenehan P, Puranik A, et al. FDA-authorized mRNA COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. Med June 28, 2021. https://www.cell.com/med/fulltext/S2666-6340(21)00238-5

Prévention de l'hospitalisation de 88,8% et 86% pour le Pfizer et le Moderna.

This retrospective analysis of 136,532 individuals in the Mayo Clinic health system shows comparable real-world vaccine effectiveness in preventing SARS-CoV-2 infection for BNT162b2 (BioNTech/Pfizer, 86.1%) and mRNA-1273 (Moderna, 93.3%). BNT162b2 and mRNA-1273 were 88.8% and 86.0% effective in preventing COVID-19 associated hospitalization.

30 juin 2021

Jalkanen P, Kolehmainen P, Häkkinen HK, et al. COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants. Nat Commun June 28, 2021, 12, 3991. https://www.nature.com/articles/s41467-021-24285-4

Vaccins à ARN chez des soignants en Finlande : moindre efficacité sur le variant sud-africain mais suffisante pour indiquer un certain degré de protection.

After the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) from Finland effectively neutralized the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant was five-fold reduced. However, 92% of the seronegative vaccinees had a neutralization titre of >20 for the B.1.351 variant indicating some protection.

29 juin 2021

Hall S. COVID vaccines and breastfeeding: what the data say. Nature NEWS June 23, 2021. https://www.nature.com/articles/d41586-021-01680-x

Etat de la science : les vaccins ne passent pas dans le lait maternel mais des anticorps y sont retrouvés, faisant naitre l'espoir d'un certain degré de protection des nourrissons.

Shannon Halls summarizes current knowledge. The vaccines do not pass through breastmilk, but antibodies do — providing hope that breastfed babies might have some level of protection. While reading this article, we have learnt a new word: “milk mysteries”.

28 juin 2021

Woolf SH, Masters RK, Aron LY. Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. BMJ June 24, 2021; 373 doi: https://doi.org/10.1136/bmj.n1343

Baisse de l'espérance de vie aux USA de 1,87 an entre 2018 et 2020, surtout aux dépens des Noirs et des Hispaniques. Chez les Noirs, retour à l'espérance de vie de 1998. Autres pays à haut revenu global : perte de 0,22 ans.

Between 2018 and 2020, life expectancy in the US decreased by 1.87 years (to 76.87 years), 8.5 times the average decrease in peer countries (0.22 years). Losses were more pronounced among the Hispanic and non-Hispanic Black populations. Life expectancy in Black men reached its lowest level since 1998.

Choe PG, Kang CK, Kim KH, et al. Persistence of Neutralizing Antibody Response up to One Year after Asymptomatic or Symptomatic SARS-CoV-2 infection. The Journal of Infectious Diseases June 24, 2021, jiab339, https://doi.org/10.1093/infdis/jiab339

Chez 16 patients dont 7 asymptomatiques, présence d'anticorps neutralisants jusqu'à 1 an après l'infection.

Of 16 patients (7 asymptomatic), all showed neutralizing antibody response up to 1 year after infection.

Ginther DK, Zambrana C. Association of Mask Mandates and COVID-19 Case Rates, Hospitalizations, and Deaths in Kansas. JAMA Netw Open June 23, 2021; 4(6):e2114514. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781283?resultClick=1

Efficacité du masque : mais faut-il encore la démontrer ?

At the start of the mask mandate, COVID-19 case rates in mask counties were 3 times higher than in no-mask counties (15 versus 5 cases per 100,000). These trends reversed, and by October 26, 2020, cases were 2.1 times higher in no-mask counties (44 versus 21 cases per 100,000). Similar results were found for hospitalizations and deaths.

27 juin 2021

Renaud M, Thibault C, LeNormand F, et al. Clinical Outcomes for Patients With Anosmia 1 Year After COVID-19 Diagnosis. JAMA Netw Open June 24, 2021;4(6):e2115352. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781319?resultClick=1

A 8 mois, l'anosmie n'est pas retrouvée chez 49 de 51 patients. Deux demeurent hyposmiques à 1 an.

At 8 months, objective olfactory assessment confirmed full recovery in 49 of 51 patients (96%). Two patients remained hyposmic at 1 year. Findings suggest that an additional 10% gain in recovery can be expected at 12 months, compared to studies with 6 months of follow-up.

Bliddal S, Banasik K, Pedersen OB, et al. Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients. Sci Rep June 23, 2021, 11, 13153. https://www.nature.com/articles/s41598-021-92045-x

Covid long : fatigue, troubles mnésiques et de la concentration chez 36% de 198 patients symptomatiques dans un suivi de plus de 4 semaines. Facteurs de risque : le genre féminin (44 % vs  24% chez les hommes) et l'IMC.

Among non-hospitalized PCR-confirmed COVID-19 patients, one third were asymptomatic while one third of symptomatic participants had persistent symptoms illustrating the heterogeneity of disease presentation. The most common persistent symptoms were fatigue and memory and concentration difficulties, reported by 36% of 198 symptomatic participants with follow-up > 4 weeks. Risk factors for persistent symptoms included female sex (women 44% vs. men 24%) and BMI.

Pratt J, Lester E, Parker R. Could SARS-CoV-2 cause tauopathy? Lancet Neurology, July, 2021. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00168-X/fulltext

Suivi à long terme pour éventuelle tauopathie après covid.

James Pratt, Evan Lester and Roy Parker believe that follow-up studies of neurological dysfunction in survivors of COVID-19 should be done, particularly in people who showed acute or subacute neurological symptoms. Such studies should continue for at least a decade and focus on young individuals in order to reduce the proportion of participants who develop tauopathies due to age.

Blomberg B, Mohn KG, Brokstad KA, et al. Long COVID in a prospective cohort of home-isolated patients. Nat Med June 22, 2021. https://www.nature.com/articles/s41591-021-01433-3

Long covid en Norvège. Parmi 61 jeunes de 16 à 32 ans, 32 ont des symptômes à 6 mois : perte du goût ou de l'odorat dans 28% des cas, fatigue pour 21 %, dyspnée pour 13 %, concentration mentale altérée pour 13% et problèmes de mémoire dans 11% des cas.

In this study from Norway, 32/61 of home-isolated young adults aged 16–30 years had symptoms at 6 months, including loss of taste and/or smell (28%), fatigue (21%), dyspnea (13%), impaired concentration (13%) and memory problems (11%).

Bugembe DL, Phan MV, Ssewanyana I, et al. Emergence and spread of a SARS-CoV-2 lineage A variant (A.23.1) with altered spike protein in Uganda. Nat Microbiol June 23, 2021. https://www.nature.com/articles/s41564-021-00933-9

Ouganda : un nouveau variant préoccupant ?

A new variant of concern? The authors describe the emergence and spread of a SARS-CoV-2 variant of the A lineage (A.23.1) with multiple protein changes throughout the viral genome. A.23.1 shares many features found in the lineage B VOCs, including alteration of key spike protein regions, especially the ACE 2 binding region, the furin cleavage site and the 613/614 change.

McEwen AE, Cohen S, Bryson-Cahn C, et al. Variants of concern are overrepresented among post-vaccination breakthrough infections of SARS-CoV-2 in Washington State. Clinical Infectious Diseases June 24, 2021, ciab581, https://doi.org/10.1093/cid/ciab581

Deux variants californiens et un anglais : les trois variants sont davantage susceptibles d'apparaitre chez des personnes vaccinées.

Across 20 vaccine breakthrough cases detected, all 20 were due to variants of concern (VOC) and had a low median Ct of 20.2 (IQR=17.1-23.3). Variants B.1.427, B.1.429, and B.1.1.7 were 3.38-fold, 1.51-fold, and 1.29-fold more common in breakthrough cases compared to controls.

26 juin 2021

Larson KF, Ammirati E, Adler ED, et al. Myocarditis after BNT162b2 and mRNA-1273 Vaccination. Circulation 16 Jun 2021. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055913

Huit patients hospitalisés pour myocardite 2 à 4 jours après vaccin à ARNm. Tous des hommes en bonne santé entre 21 et 56 ans. Troponine toujours élevée.

Eight patients hospitalized with chest pain who were diagnosed with myocarditis by laboratory and cardiac magnetic resonance imaging within 2-4 days of receiving either the BNT162b2 or mRNA-1273 vaccine. All were otherwise healthy males between the ages of 21 and 56. Troponin values were elevated in all individuals.

Rosner CM, Genovese L, Tehrani BN, et al. Myocarditis Temporally Associated with COVID-19 Vaccination. Circulation 16 Jun 2021. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055891

Myocardite après vaccin : 7 cas, tous des hommes blancs de moins de 40 ans, tous avec douleur thoracique de 3 à 7 jours après vaccination, témoin biologique présent : troponine I. Evolution favorable.

Seven patients hospitalized for acute myocarditis-like illness following COVID-19 vaccination. All were white males < 40 years of age. All patients presented 3-7 days post vaccination with acute onset chest pain and biochemical evidence of myocardial injury, by cardiac troponin I. The clinical course was favorable.

Shemer A, Pras E, Einan-Lifshitz A, et al. Association of COVID-19 Vaccination and Facial Nerve Palsy – A Case-Control Study. JAMA Otolaryngol Head Neck Surg June 24, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2781367?resultClick=1

Seulement 37 patients vs contrôles. Mais pas de lien établi entre Pfizer et paralysie faciale.

In this case-control study of 37 patients with acute-onset facial nerve palsy and a matched control group, no increased risk of facial nerve palsy was observed after vaccination with the Pfizer-BioNTech BNT162b2 COVID-19 vaccine.

Mazzola A, Todesco E, Drouin S, et al. Poor Antibody Response after Two Doses of SARS-CoV-2 vaccine in Transplant Recipients. Clinical Infectious Diseases June 24, 2021, ciab580, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab580/6309017

Faible efficacité du Pfizer chez des receveurs d'organe solide. Meilleure réponse avec trois doses. Voir publication suivante.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients.

Kamar N, Abravanel F, Marion O, et al. Three Doses of an mRNA Covid-19 Vaccine in Solid-Organ Transplant Recipients. N Engl J Med Jun 23, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2108861
Is a third jab the solution? Among the 59 solid organ transplant recipients who had been seronegative before the third dose of the BioNTech vaccine, 26 (44%) were seropositive 4 weeks after the third dose.

Yu J, Tostanoski LH, Mercado NB, et al. Protective efficacy of Ad26.COV2.S against SARS-CoV-2 B.1.351 in macaques. Nature June 23, 2021. https://www.nature.com/articles/s41586-021-03732-8

Publication favorable au Janssen, réputé efficace sur le variant sud-africain. L'explication pourrait venir d'une réponse croisée entre immunité humorale et cellulaire contre les varaints préoccupants chez... les macaques

This study may provide an explanation of why the Johnson & Johnson vaccine worked well in South Africa. In rhesus macaques, Ad26.COV2.S induced cross-reactive antibody and T cell responses against SARS-CoV-2 variants of concern, including the B.1.351 variant.

25 juin 2021

Shroti M, Krutikov M, Palmer T, et al. Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): a prospective cohort study. Lancet Inf Dis June 23, 2021. https://doi.org/10.1016/S1473-3099(21)00289-9

10 412 résidents de soins de longue durée en Angleterre : diminution à 0,44 des infections à PCR positives à J28 - J34 de la première injection d'AstraZeneca ou de Pfizer et à 0,38 à J35 - J48.

Among 10,412 care home residents aged 65 years and older, adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0.44 (95% CI 0.24–0.81) at 28–34 days and 0.38 (0.19–0.77) at 35–48 days. Similar effect sizes were seen for ChAdOx1 and BNT162b2 vaccines at 35–48 days.

Hyams C, Marlow R, Maseko Z. Effectiveness of BNT162b2 and ChAdOx1 nCoV-19 COVID-19 vaccination at preventing hospitalisations in people aged at least 80 years: a test-negative, case-control study. Lancet Inf Dis June 23, 2021. https://doi.org/10.1016/S1473-3099(21)00330-3

Prévention des hospitalisations chez les plus de 80 ans : une dose d'AstraZeneca ou de Pfizer diminue le risque de 80,4%.

Same direction. One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years. The adjusted vaccine effectiveness was 80.4% (95% CI 36.4–94.5).

24 juin 2021

Lepak AJ, Taylor LN, Stone CA, et al. Association of Changes in Seasonal Respiratory Virus Activity and Ambulatory Antibiotic Prescriptions With the COVID-19 Pandemic. JAMA Intern Med June 21, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781312

Moindre détection des virus respiratoires habituels dans le Wisconsin en période de covid-19 et diminution de 79% de la prescripton d'antibiotiques.

This study from Wisconsin, US demonstrated a marked decrease in respiratory virus detection, with a concomitant 79% decline in ambulatory antibiotic prescribing rates for respiratory tract infections, during the COVID-19 pandemic.

Duffy E, Thomas M, Hills T, Ritchie S. The impacts of New Zealand’s COVID-19 epidemic response on community antibiotic use and hospitalisation for pneumonia, peritonsillar abscess and rheumatic fever. Lancet Regional Health July 01, 2021. https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(21)00071-7/fulltext

Moindre prescription d'antibiotiques, en Nouvelle-Zélande aussi.

Same findings from New Zealand. Antibiotic dispensing rates fell by 36%, suggesting that countries with high rates of antibiotic use could significantly reduce their use without an increase in morbidity.

Steenblock C, Richter S, Berger I. et al. Viral infiltration of pancreatic islets in patients with COVID-19. Nat Commun June 21, 2021, 12, 3534. https://www.nature.com/articles/s41467-021-23886-3

Infiltration virale du pancréas retrouvée à l'autopsie sans physiopathologie complétemtn descriptible.

Using human islets and autopsy tissue from patients that died of COVID-19, this study provides clear proof that beta cells are permissive to infection with SARS-CoV-2. The mechanism of virus entry is not completely clear at this point as ACE2 is only expressed in beta cells in a subset of patients. Therefore, other receptors/factors may be involved in facilitating uptake of SARS-CoV-2 into beta-cells. SARS-CoV-2 may induce a local inflammation and may be associated with necroptotic cell death in islets, but the current study cannot answer in detail the mechanism that may lead to islet impairment and metabolic dysregulation.

Matheney M, Maleque N, Channell N, et al. Severe Exacerbations of Systemic Capillary Leak Syndrome After COVID-19 Vaccination: A Case Series. Ann Int Med June 15, 2021. https://doi.org/10.7326/L21-0250

Trois cas de syndrome d'hyperperméabilité capillaire après AstraZeneca, Pfizer et Moderna. Les auteurs recommandent l'utilisation d'immunoglobulines intraveineuses.

Three patients who had severe flares of SCLS immediately after receiving standard doses of the COVID-19 vaccines (AstraZeneca, BioNTech and Moderna). The authors recommend that patients with a diagnosis or suspected diagnosis of SCLS should receive IVIG prophylaxis before vaccination.

Bøhler AD, Strøm ME, Sandvig KU et al. Acute macular neuroretinopathy following COVID-19 vaccination. Eye June 21, 2021. https://www.nature.com/articles/s41433-021-01610-1

Un cas de rétinopathie maculaire après AstraZeneca.

A patient who developed an acute paracentral scotoma after having received the AstraZeneca vaccine: the signs and symptoms were consistent with acute macular neuroretinopathy (AMN).

Kwon S, Joshi AD, Lo CH. et al. Association of social distancing and face mask use with risk of COVID-19. Nat Commun Jun 21, 2021, 12, 3737. https://www.nature.com/articles/s41467-021-24115-7

Diminution du risque de transmission : 31% avec la distanciation, 62% avec le masque, même chez des personnes avec mauvaise distanciation sociale.

Individuals living in communities with the greatest social distancing had a 31% lower risk of predicted COVID-19 compared with those living in communities with poor social distancing. Self-reported ‘always’ use of face mask was associated with a 62% reduced risk of predicted COVID-19 even among individuals living in a community with poor social distancing.

23 juin 2021

Whaley CM, Cantor J, Pera M, et al. Assessing the Association Between Social Gatherings and COVID-19 Risk Using Birthdays. JAMA Intern Med June 21, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2781306?resultClick=1

Anniversaires à domicile aux USA : 8,6 de diagnostics supplémentaires pour 10 000 personnes si anniversaire dans les quinze jours qui précédent.

Yes, there is an association between household birthdays, which likely correspond to informal social gatherings, and COVID-19. Among the 2.9 million households in the study, in the top 10% of counties in COVID-19 prevalence, households with a birthday in the 2 weeks prior had 8.6 more diagnoses per 10,000 individuals compared with households without a birthday in the 2 weeks prior. The relative increase was 31% of county-level prevalence and was even larger in magnitude in households that had a recent child’s (vs adult’s) birthday.

Kentish-Barnes N, Cohen-Solal Z, Morin L, et al. Lived Experiences of Family Members of Patients With Severe COVID-19 Who Died in Intensive Care Units in France. JAMA Netw Open June 21, 2021; 4(6):e2113355. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781115?resultClick=1

France : confirmation de l'importance prioritaire de la présence de la famille en soins intensifs. 

This study reports how bereaved family members’ experiences of care, death, and mourning were disrupted during the first wave of the COVID-19 pandemic, both during hospitalization in the ICU and after the patient’s death. The main finding is “what family-centered research has taught us in the last 20 years: the presence of family members in ICUs should remain a priority”.

22 juin 2021

Braunstein SL, Slutsker JS, Lazar R, et al. Epidemiology of reported HIV and other sexually transmitted infections during the COVID-19 pandemic, New York City. J Inf Dis Jun 16, 2021, jiab319, https://doi.org/10.1093/infdis/jiab319.

MST et confinement dans la ville de New York : des effets positifs qui doivent interroger els sociologues.

During NYC lockdown, the volume of positive HIV/STI tests, and diagnoses of HIV, chlamydia, gonorrhea, and syphilis declined substantially, reaching a nadir in April before rebounding.

21 juin 2021

De Paula Eduardo F, Corrêa L, Heller D, et al. Salivary SARS-CoV-2 load reduction with mouthwash use: a randomized pilot clinical trial. Heliyon June 17, 2021. https://doi.org/10.1016/j.heliyon.2021.e07346

Des lavages de bouche à l'étude pour diminuer la charge virale salivaire.

Mouthwash with cetylpyridinium chloride + Zinc and chlorhexidine gluconate resulted in significant reductions of the SARS-CoV-2 viral load in saliva up to 60 mins after rinsing, while hydrogen peroxide mouthwash resulted in a significant reduction up to 30 mins after rinsing.

Son BF, Murray N, Friedman K, et al. Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes. NEJM June 16, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2102605?query=featured_home

Syndrome inflammatoire multisystémique chez l'enfant : diminution des atteintes cardiaques avec un traitement  initial associant immunoglobulines IV et corticoïdes.

This may be the case here. Surveillance data on 518 inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 US hospitals. In the propensity-score–matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%).

20 juin 2021

Hunter RF, Garcia L, de Sa TH et al. Effect of COVID-19 response policies on walking behavior in US cities. Nat Commun 12 June 15, 2021, 3652. https://www.nature.com/articles/s41467-021-23937-9

L'analyse des podomètres de nos smartphones : réduction de la marche "utilitaire" dans les métropoles aux USA à la faveur de la covid-19.

Analyzing mobility data from mobile devices and area-level data to study the walking patterns of 1.62 million anonymous users in 10 metropolitan areas in the US, this study reveals dramatic declines in walking, particularly utilitarian walking, while recreational walking has recovered and even surpassed pre-pandemic levels.

Bi Q, Lessler J, Eckerle I, et al. Insights into household transmission of SARS-CoV-2 from a population-based serological survey. Nat Commun June 15, 2021, 12, 3643. https://doi.org/10.1038/s41467-021-23733-5

Suisse : la transmission domestique trois fois plus fréquente que la transmission à l'extérieur lors de la première vague chez des personnes de plus de 5 ans d'âge.

This was a cross-sectional, household-based population serosurvey of 4534 people ≥ 5 years from 2267 households enrolled April-June 2020 in Geneva, Switzerland. The risk of infection from exposure to a single infected household member aged ≥ 5 years (17.3%, 13.7-21.7) was more than three-times that of extra-household exposures over the first pandemic wave (5.1%, 4.5-5.8). Young children had a lower risk of infection from household members.

Campbell F, Archer B, Laurenson-Schafer H, et al. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021. Eurosurveillance June 2021; 26(24):pii=2100509. https://doi.org/10.2807/1560-7917.ES.2021.26.24.2100509

C'est le variant indien qui pose problème par ses capacités de diffusion. Il devrait supplanter tous les autres.

This analysis of the effective reproduction number and global spread of SARS-CoV-2 variants with data available by 3 June 2021 suggest that B.1.617.2 is expected to rapidly out-compete other variants and become the dominant circulating lineage over the coming months.

19 juin 2021

Liu C, Ginn HM, Dehnirattisai W, et al. Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell June 16, 2021. https://doi.org/10.1016/j.cell.2021.06.020

Mieux vaut ne pas avoir été infecté par le variant brésilien pour être protégé du variant indien.

The ability of monoclonal antibodies, convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2 is reduced when compared with ancestral Wuhan strains but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2 suggesting that individuals previously infected by these variants may be more susceptible to re-infection by B.1.617.2.

18 juin 2021

Gupta K, O’Brian WJ, Bellino P, et al. Incidence of SARS-CoV-2 Infection in Health Care Workers After a Single Dose of mRNA-1273 Vaccine. JAMA Netw Open June 16, 2021;4(6):e2116416. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2781173?resultClick=1

Efficacité du Moderna dès la première dose chez des soignants : 95% du jour 15 au jour 42.

This study demonstrated an association between receipt of the mRNA-1273 vaccine and a reduction in SARS-CoV-2 infection in HCWs beginning 8 days after dose 1. Vaccine clinical effectiveness was 50.3% for the entire 42-day period of follow-up, 77.5% for days 8 through 42, and 95.0% for days 15 through 42.

Samarakoon U, Alvarez-Arango S, Blumenthal KG. Delayed Large Local Reactions to mRNA Covid-19 Vaccines in Blacks, Indigenous Persons, and People of Color. NEJM June 9, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2108620?query=featured_home

Réactions locales étendues apparaissant de manière retardée, à 8 jours en moyenne (plus ou moins 2 jours) après vaccin à ARNm

Photos of eight large local reactions are shown. The mean time from vaccination until the onset of the reaction was 8 ± 2 days (range, 4 to 14).

Une fake news stérile : la vaccination à ARNm ne modifie pas la composition du sperme chez 45 volontaires.

Source :

Gonzalez DC, Nassau DE, Khodamoradi K, et al. Sperm Parameters Before and After COVID-19 mRNA Vaccination. JAMA. Published online June 17, 2021. doi:10.1001/jama.2021.9976

17 juin 2021

Nyberg TR, Twohig KA, Harris RJ, et al. Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis. BMJ 2021 June 15, 2021; 373. https://www.bmj.com/content/373/bmj.n1412

Admission en hôpital après variant anglais : tout-de-même une fois et demi plus fréquente qu'avec la souche initiale.

This retrospective analysis identified through community testing in England indicated that the risk of hospital admission within 14 days after a positive test was 1.52 (1.47 to 1.57) times higher for patients infected with the B.1.1.7 variant compared with those infected with wild-type variants, after adjustment for age, sex, deprivation, ethnicity, region, and week of diagnosis.

Xin H, Wong JY, Murphy C, et al. The incubation period distribution of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis. Clin Inf Dis June 12, ciab501, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab501/6297425

Une période moyenne d'incubation un peu plus longue que prévue initialement : 6,3 jours (de 1.8 à 11.9 jours).

Mean, median and 95th percentile for incubation period are 6.3 days (range: 1.8 to 11.9 days), 5.4 days (range: 2.0 to 17.9 days) and 13.1 days (range: 3.2 to 17.8 days), respectively.

16 juin 2021

Kustin T, Harel N, Finkel U, et al. Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals. Nat Med June 14, 2021. https://www.nature.com/articles/s41591-021-01413-7

Le vaccin à ARNm BNT162b2 (Pfizer) est très efficace contre le SRAS-CoV-2. Cependant, il existe une crainte que les variants préoccupants (VOC : variants of concern) puissent échapper à la protection vaccinale, en raison des preuves d'une neutralisation réduite des VOC B.1.1.7 (anglais) et B.1.351 (sud-africain) par les sérums vaccinaux dans les analyses de laboratoire. Nous avons effectué une étude de cohorte appariée pour examiner la distribution des VOC dans les infections de vaccinés par ARNm BNT162b2 aux Clalit Health Services (Israël) en utilisant le séquençage génomique viral, et avons émis l'hypothèse que si l'efficacité du vaccin contre un VOC est réduite, sa proportion parmi les cas incidents serait plus élevée que chez les témoins non vaccinés. En analysant 813 séquences de génome viral à partir d'écouvillons nasopharyngés, nous avons montré que les vaccinés testés positifs au moins 7 jours après la deuxième dose étaient infectés de manière disproportionnée par le B.1.351 par rapport aux témoins. Ceux qui ont été testés positifs entre 2 semaines après la première dose et 6 jours après la deuxième dose ont été infectés de manière disproportionnée par le B.1.1.7. Ces résultats suggèrent une efficacité réduite du vaccin contre les deux VOC dans des fenêtres de temps particulières. Nos résultats soulignent l'importance de suivre rigoureusement les variants viraux et d'augmenter le nombre des vaccinations pour empêcher la propagation des VOC.

Analyzing 813 viral genome sequences, the authors showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7.

Bauer A, Schreinlechner M Sappler N, et al. Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial. Lancet Resp Med June 11, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00214-9/fulltext

Une étude qui plaiderait pour une interruption des IEC lors d'une Covid-19 mais une  méthodologie contestée (voir citation suivante).

In this open label RCT (ACEI-COVID) performed at 35 centers in Austria and Germany, 204 patients (median age 75 years) were randomly assigned to discontinue or continue RAS inhibitors. Of note, discontinuation had no significant effect on the maximum severity of COVID-19 but led to a faster and better recovery. At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥ 1) or were dead (p = 0·017).

Kerneis M, Montalescot G. RAS inhibition and COVID-19: more questions than answers? Lancet Resp Med June 11, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00233-2/fulltext

Comment on ACEI-COVID. See title. Mathieu Kerneis and Gilles Montalescot argue that the study should be interpreted with great caution, considering that it derives from secondary analyses of a study that did not meet its primary endpoint.

15 juin 2021

Vaughn VM, Yost M, Abshire C, et al. Trends in Venous Thromboembolism Anticoagulation in Patients Hospitalized With COVID-19. JAMA Netw Open June 11, 2021;4(6):e2111788. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780927?resultClick=1

Chez 1351 patients hospitalisés pour Covid-19 aux USA, l'anticoagulation à doses prophylactiques a réduit la mortalité à 60 jours.

In this cohort study of 1351 patients hospitalized with COVID-19 in which 1127 patients received anti-coagulation, prophylactic anti-coagulation remained associated with lower mortality at 60 days.

Receiving any dose of anticoagulation (vs no anticoagulation) was associated with lower in-hospital mortality (only prophylactic dose: aHR, 0.36; 95% CI, 0.26-0.52; any treatment dose: aHR, 0.38; 95% CI, 0.25-0.58). However, only the prophylactic dose of anticoagulation remained associated with lower mortality at 60 days (prophylactic dose: aHR, 0.71; 95% CI, 0.51-0.90; treatment dose: aHR, 0.92; 95% CI, 0.63-1.35).

14 juin 2021

Vitamine D et covid grave : des facteurs génétiques

Després JP. Severe COVID-19 outcomes — the role of physical activity. Nature Reviews Endocrinology 10 June 2021. https://www.nature.com/articles/s41574-021-00521-1

Covid graves : pas seulement l'obésité mais aussi les comportements sédentaires et le manque d'activité physique. Il est vrai que ceux-ci vont souvent avec celle-là.

It’s not only obesity: according to this nice review, current sedentary behaviors and lack of physical activity are also contributing to morbidity and mortality associated with COVID-19.

13 juin 2021

Simpson CR, Shi T, Vasileiou E et al. First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland. Nat Med June 9, 2021. https://www.nature.com/articles/s41591-021-01408-4

Entre le 8 décembre 2020 et le 14 avril 2021, 1,71 million de personnes en Écosse ont été vaccinées avec le vaccin AstraZeneca et 0,82 million de personnes ont été vaccinées avec le vaccin Pfizer. La première dose de vaccin AstraZeneca s'est avérée être associée à une légère augmentation des risques de thrombocytopénie induite par le vaccin, avec des preuves suggérant un risque accru d'événements thromboemboliques et hémorragiques artériels. Il n'y avait pas de risque global accru de ces événements indésirables chez les personnes recevant le vaccin Pfizer.

Between 8 December 2020 and 14 April 2021, 1.71 million people from Scotland were vaccinated with the ChAdOx1 vaccine, and 0.82 million people were vaccinated with the BNT162b2 vaccine. First dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. There was no overall increased risk in these adverse events in individuals receiving BNT162b2.

Bourguignon A, Arnold DM, Warkentin TE, et al. Adjunct Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia. NEJM June 9, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2107051?query=featured_home

Cofirmation du rôle bénéfique des immunoglobulines en cas de thrombocytopénie thrombotique induite par le vaccin AstraZeneca.

Three older patients with vaccine-induced immune thrombotic thrombocytopenia (VITT), occurring after the AstraZenec vaccine. Of note, all had one or more arterial thrombotic events. After the initiation of high-dose intravenous immune globulin treatment, reduced antibody-induced platelet activation in serum was seen in all three patients.

Liu J, Liu Y, Xia H, et al. BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants. Nature June 10, 2021. https://www.nature.com/articles/s41586-021-03693-y

Action du Pfizer jugée satisfaisante sur tous les variants bien que moindre sur le B.1.617.1 indien.

Good news. A total of 20 human sera, drawn 2 or 4 weeks after two doses of BNT162b2, neutralized engineered SARS-CoV-2 with different spike proteins of the delta variants (from India). B.1.617.1 was the least neutralized, probably due to the presence of both L452R and E484Q substitutions at the receptor binding site. Nevertheless, all variants were neutralized by all tested sera at titers ≥ 40

Milman O, Yelin I, Aharony N et al. Community-level evidence for SARS-CoV-2 vaccine protection of unvaccinated individuals. Nat Med June 10, 2021. https://doi.org/10.1038/s41591-021-01407-5

Protection croisée en Israël : pour chaque 20% de personnes vaccinées, diminution de moitié des tests positifs chez les non vaccinés.

Vaccination provides cross-protection to unvaccinated individuals in the community: this groundbreaking study from Israel shows that on average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold.

12 juin 2021

Payne AB, Gilari Z, Godfred-Cato S, et al. Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2. JAMA Netw Open June 10, 2021;4(6):e2116420. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780861?resultClick=1

Incidence du syndrome inflammatoire multisystémique chez les enfants aux USA : 5,1 pour un millon et par mois alors que 316 par million d'infections au SARS-CoV-2 chez les personnes de moins de 21 ans.

MIS-C incidence was 5.1 persons per 1,000,000 person-months and 316 persons per 1,000,000 SARS-CoV-2 infections in persons younger than 21 years.

Discepolo V, Catzola A, Pierri L, et al. Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic. JAMA Netw Open June 10, 2021;4(6):e2111369. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780866?resultClick=1

Lésions des orteils évocatrices d'engelures chez l'adolescent : penser à la Covid.

This case series of 17 adolescents found that chilblain-like lesions of the toes emerged during the COVID-19 pandemic in otherwise healthy adolescents without signs of SARS-CoV-2 infection or other inflammatory, autoimmune, or thrombophilic phenomena.

11 juin 2021

Razani N, Malekinejad M, Rutherford GW. Clarification regarding Outdoor Transmission of SARS-CoV-2 and Other Respiratory Viruses, a Systematic Review. J Inf Dis June 4, 2021, jiab298, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab298/6291889

Encore une confirmation. La contamination en extérieur pourrait être de moins de 10% des cas, peut-être moindre que 1% des cas pour la plupart des études.

Update of a previous paper, supporting the initial conclusion that the risk of SARS-CoV-2 transmission is much lower outdoors than indoors. The proportion of infections happening outdoors is likely much lower than 10%, and most studies suggest that it is likely less than 1%.

Kompaniyets L, Agathus NT, Nelson JM, et al. Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children. JAMA Netw Open June 7, 2021;4(6):e2111182. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780706?resultClick=1

Covid sévère chez l'enfant : des comorbidités dont le diabète de type 1, des pathologies cardiaques et l'obèsité.

This cross-sectional study on 43,465 patients with COVID-19 aged 18 years or younger found a higher risk of severe illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes (strongest risk factor with an adjusted risk ratio of 2.38), cardiac and circulatory congenital anomalies, and obesity.

10 juin 2021

Christie A, Henley SJ, Mattocks L, et al. Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021. MMWR Morb Mortal Wkly Rep. ePub: 8 June 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e2.htm?s_cid=mm7023e2_w

Vaccination aux USA : déclin de la mortalité de la Covid-19 depuis le mi-décembre 2020. Entre les deux semaines avant vaccination et la période de deux semaines fin avril, l'amélioration de la situation a été plus importante chez les personnes âgées car davantage vaccinées que chez les jeunes moins protégés.

The ratio for COVID-19 deaths began to decline in mid-December while rate ratios for COVID-19 incidence, ED visits, and hospital admissions began to decline in late December to mid-January. Comparing the 2-week pre-vaccination period with 2 weeks in late April, declines were significantly greater among older adults, who had higher vaccination coverage, than among younger adults, who had lower coverage.

9 juin 2021

Chodick G, Tene K, Patalon T, et al. Assessment of Effectiveness of 1 Dose of BNT162b2 Vaccine for SARS-CoV-2 Infection 13 to 24 Days After Immunization. JAMA Netw Open June 7, 2021; 4(6):e2115985. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780700?resultClick=1

Réduction de 54% environ des infections symptomatiques après une dose Pfizer au bout de 13 à 24 jours en Israël.

In this study of 503,875 individuals from Israel who received 1 dose of the BNT162b2 vaccine, the first dose was associated with an approximately 54% reduction in the risk of symptomatic SARS-CoV-2 infections at 13 to 24 days after immunization compared to 1 to 12 days after vaccination.

8 juin 2021

Havers FP, Whitaker M, Self JL, et al. Hospitalization of Adolescents Aged 12–17 Years with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1, 2020–April 24, 2021. MMWR Morb Mortal Wkly Rep. ePub: 4 June 2021 https://www.cdc.gov/mmwr/volumes/70/wr/mm7023e1.htm?s_cid=mm7023e1_w

Adolescents (12 à 17 ans) aux USA : 204 hospitalisés au premier trimestre de 2021, 31,4% admis en soins intensifs, 4,9% nécessitant une ventilation mécanique, aucun décès.

Among 204 adolescents who were likely hospitalized primarily for COVID-19 during January 1–March 31, 2021, 31.4% were admitted to an intensive care unit (ICU), and 4.9% required invasive mechanical ventilation; there were no associated deaths.

Vanker A, McGeer A, O’Byrne G, et al. Adverse Outcomes Associated with SARS-CoV-2 variant B.1.351 Infection in Vaccinated Residents of a Long Term Care Home, Ontario, Canada. Clin Inf Dis, June 6, 2021, ciab523, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab523/6294072

Episode de variant sud-africain dans un établissement de soins de longue durée au Canada. Sur les neuf résidents vaccinés avec le Pfizer, quatre ont développé une hypoxémie. Trois sont décédés.

Another outbreak of B.1.351 (south Africa) in a long term care home (LTCH) in Canada. Of the 9 residents (vaccinated with B162.B2 from BionTech/Pfizer) and infected with B.1.351, 4 developed hypoxemia. Of these, 3 (including both hospitalized patients) died.

De Giorgi V, West KA, Henning AN, et al. Naturally acquired SARS-CoV-2 immunity persists for up to 11 months following infection. J Inf Dis, June 5, 2021, jiab295,  https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab295/6293992

Parmi 228 personnes, 116 ayant présenté la Covid-219 ; chez ces dernières, 91,4% montraient des niveaux détectables d'IgG jusqu'à 11 mois après guérison, 63 % considérés comme neutralisants. 

Of the 116 donors presenting for repeat timepoints, 91.4% of donors had detectable IgG levels up to 11 months post-symptom recovery, while 63% had detectable neutralizing titers. Of note, 25% of donors had neutralizing levels that dropped to an undetectable titer over time.

Sender R, Bar-On YM, Gleizer S, et al. The total number and mass of SARS-CoV-2 virions. PNAS June 3, 2021. https://www.pnas.org/content/118/25/e2024815118

Un poids plume qui pèse lourd : le SARS-CoV-2.

All SARS-CoV-2 virions currently in all human hosts have a mass of between 100 g and 10 kg. Although each infected person carries an estimated 1 billion to 100 billion virions during peak infection, their total mass is no more than 0.1 mg.

7 juin 2021

Goyal A, Reeves DB, Thakkar N, et al. Slight reduction in SARS-CoV-2 exposure viral load due to masking results in a significant reduction in transmission with widespread implementation. Sci Rep 11, 11838 (2021). https://doi.org/10.1038/s41598-021-91338-5

S'il en étati besoisn, encore une étude en faveur de l'efficacité des masques.

This modeling study shows that the use of masks by both a potential transmitter and exposed person substantially reduces the probability of successful transmission, even if masks only lower exposure viral load by ~ 50%. The model also predicts that moderately efficacious masks will lower exposure viral load tenfold among people who get infected despite masking, potentially limiting infection severity.

6 juin 2021

Lash RR, Moonan PK, Byers BL, et al. COVID-19 Case Investigation and Contact Tracing in the US, 2020. JAMA Netw Open June 3, 2021. 2021;4(6):e2115850. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780568?resultClick=1

Bien joli de vouloir contacter et tracer les cas contacts aux USA en 2020. Encore fallait-il que l'on pût joindre les cas contacts en question et que leurs noms fussent connus. Ce ne fut pas le cas deux fois sur trois.

In this cross-sectional study of US local COVID-19 surveillance data, contact tracing had suboptimal impact on SARS-CoV-2 transmission, largely because two of three cases were either not reached for interview or named no contacts when interviewed.

Tardif JC, Bouabdallaoui N, L’Allier PL, et al. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Resp Med May 27, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00222-8/fulltext

Colchicine et Covid-19 : peut-être des résultats encourageants mais loin d'être confirmés. Sans oublier les effets secondaires. Trop tôt pour conclure et surtout initier cette thérapeutique.

In this large RCT enrolling high-risk patients from six countries (Brazil, Canada, Greece, South Africa, Spain, and the USA) who were not under immediate consideration for hospital admission, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Among 4,159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4.6%) of 2,075 patients in the colchicine group and 126 (6,0%) of 2,084 patients in the placebo group (odds ratio 0.75, 0.57–0.99; p=0.042). Diarrhoea was reported by 14% of patients in the colchicine group and 7% in the placebo group. But do the authors trust their own data? They conclude that “replication in other studies… is recommended”.

5 juin 2021

Hag-Ali M, Al Shamsi AS, Boeijen L et al. The detection dogs test is more sensitive than real-time PCR in screening for SARS-CoV-2. Commun Biol June 3, 2021, 4, 686. https://www.nature.com/articles/s42003-021-02232-9

Notre ami le chien meilleur que le RT-PCR à l'aéroport ?  La valeur prédictive positive (VPP) est de 52 %, la valeur prédictive négative (VPN) est de... 99,8%.

La VPP indique la probabilité que la maladie soit réellement présente lorsque le résultat du test est positif.

La valeur VPN est la probabilité que la condition ne soit pas présente lorsque le test est négatif.

Can we use dogs at the airports to identify COVID-19 patients? Upon training explosives detection dogs on sniffing COVID-19 odor in patients’ sweat, those dogs were able to successfully screen out 3249 individuals who tested negative for the SARS-CoV-2, from a cohort of 3290 individuals. The positive predictive value of dog detection was 52% (probability that identified individuals do truly have the disease). The negative predictive value was 99.8%. Almost better than PCR testing.

Cohen MS, Nirula A, Mulligan MJ, et al. Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial. JAMA June 3, 2021. https://jamanetwork.com/journals/jama/fullarticle/2780870?resultClick=1

Un anticorps monoclonal neutralisant, le bamlanivimab est efficace en réduisant l'incidence des cas légers ou graves chez 966 résidents et soignants d'établissements pour personnes âgées aux USA. Etude randomisée en double insu de phase 3, toutefois réalisée avant l'apparition des variants.

Paper of the day. Bamlanivimab (BAM), a neutralizing monoclonal antibody, is effective in reducing the incidence of mild or worse COVID-19 in residents and participants at high risk of severe COVID-19. This large phase 3 RCT included 966 participants who were residents and staff at US skilled nursing facilities with at least one confirmed SARS-CoV-2 index case. The incidence of COVID-19 infection among those treated with a single infusion of BAM was 8.5% vs 15.2% with placebo, with an odds ratio of 0.43 (95% CI, 0.28-0.68, beautiful Figure below!). Moreover, participants who received BAM and acquired SARS-CoV-2 had lower baseline viral loads and shorter time to viral clearance. However, one limitation is that the study was conducted prior to the occurrence of SARS-CoV-2 variants that may have reduced susceptibility to BAM.

Time From Infusion to Development of Mild or Worse COVID-19 With Bamlanivimab vs Placebo Among Resident and Staff Participants

4 juin 2021

Takuva S, Takalani A, Garrett N, et al. Thromboembolic Events in the South African Ad26.COV2.S Vaccine Study. NEJM 3, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2107920?query=featured_home

MTE après Janssen : rares et surtout chez des personnes avec facteurs de risque en Afrique du Sud.

esseInterim safety data from the first 288,368 participants who were vaccinated with Ad26.COV2.S (Johnson & Johnson) in the Sisonke study — an open-label, Phase IIIb implementation study. The rate of adverse events with vaccination is low, and thromboembolic events occur mainly in persons with risk factors for thromboembolism.

3 juin 2021

Patel MD, Rosenstrom E, Ivy JS, et al. Association of Simulated COVID-19 Vaccination and Nonpharmaceutical Interventions With Infections, Hospitalizations, and Mortality. JAMA Netw Open June 1, 2021;4(6):e2110782. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780539

Vaccins moins efficaces et mesures non médicamenteuses : meilleure attitude que vaccination plus efficace sans mesures non médicamenteuses.

Interesting finding: compared with more efficacious vaccines with lower population coverage, as NPIs are removed, higher vaccination coverage with less efficacious vaccines can contribute to a larger reduction in risk of SARS-CoV-2 infection.

Vogel G, Couzin-Frankel J. Israel reports link between rare cases of heart inflammation and COVID-19 vaccination in young men. Nature NEWS June 1, 2021. https://www.sciencemag.org/news/2021/06/israel-reports-link-between-rare-cases-heart-inflammation-and-covid-19-vaccination

Israël : un sur 3000 à un sur 6000 jeunes hommes de 16 à 24 ans ont présenté une myocardite après Pfizer. La plupart des cas étaient légers et se sont amendés en quelques semaines. Une forte production d'anticorps pourrait être responsable de ces rares cas.

Brief summary of current knowledge: in Israel, between one in 3000 and one in 6000 men ages 16 to 24 who received the BioNTech vaccine developed myocarditis. Most cases were mild and resolved within a few weeks. It is speculated that very high antibody levels generated in young people may also, in rare cases, lead to a sort of immune overreaction that inflames the heart.

2 juin 2021

Arnold DT, Milne A, Samms E, et al. Symptoms After COVID-19 Vaccination in Patients With Persistent Symptoms After Acute Infection: A Case Series. Ann Int Med, 25 May 2021. https://www.acpjournals.org/doi/10.7326/M21-1976

36 patients avec Covid long souffrant d'au moins un symptôme 8 mois après l'épisode aigu. Sont vaccinés par Pfizer ou AstraZeneca. Légère amélioration et pas de diminution de la qualité de vie ou aggravation des symptômes. 

In total, 36 patients who reported at least 1 persistent symptom 8 months after acute infection were vaccinated with Astra Zeneca or the BionTech vaccine. There was some improvement and no decrease in quality of life or worsening of symptoms.

1er juin 2021

Massarweh A, Eliakim-Raz N, Stemmer A, et al. Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer.  JAMA Oncol May 28, 2021. https://jamanetwork.com/journals/jamaoncology/fullarticle/2780584?resultClick=1

Moindre immunisation après Pfizer si cancer plus chimiothérapie plus immunothérapie.

In this cohort study of 102 patients with cancer from Israel who were receiving active treatment and 78 healthy controls, 92 patients with cancer (90%) and 100% of the controls were seropositive after the BNT162b2 vaccine (BioNTech/Pfizer). The median IgG titer in the patients with cancer was significantly lower than that in the controls. In a multivariate analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy.

Yazaki S, Yoshida T, Kolima Y, et al. Difference in SARS-CoV-2 Antibody Status Between Patients With Cancer and Health Care Workers During the COVID-19 Pandemic in Japan. JAMA Oncol 28, 2021. https://jamanetwork.com/journals/jamaoncology/fullarticle/2780583?resultClick=1

Comparaison entre 500 patients cancéreux et 1190 soignants. Les anticorps anti-S et anti-N sont diminués en cas de cancer sauf chez les patients recevant une immunothérapie par inhibiteurs de point de contrôle. 

In this cross-sectional study including 500 patients with cancer and 1190 HCWs, the seroprevalence was similar, but the levels of IgG antibodies against nucleocapsid and spike protein were significantly lower in patients than in HCWs. Interestingly, N-IgG and S-IgG levels were significantly higher in patients who received immune checkpoint inhibitors than in those who did not.

31 mai 2021

Loenenbach A, Markus I, Lehfeld AS, et al. SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021. Euro Surveill. 2021;26(21):pii=2100433. https://doi.org/10.2807/1560-7917.ES.2021.26.21.2100433

Variant anglais en Allemagne : les enfants de 1 à 6 ans aussi, peut-être autant que les adultes.

This analysis of three simultaneously occurring outbreaks in childcare facilities (a total of 47 infections), suggests that both susceptibility and infectiousness of children aged between 1 to 6 years are substantially higher compared to the pre-B.1.1.7 period, and may be converging with those among adults.

García-García D, Vigo MI, Fonfría ES, et al. Retrospective methodology to estimate daily infections from deaths (REMEDID) in COVID-19: the Spain case study. Sci Rep 11, 11274 (2021). https://www.nature.com/articles/s41598-021-90051-7

Sous-estimation très importante du nombre de cas d'infections à SARS-CoV-2 en Espagne lors de la première vague.

During the first wave, infection numbers were largely underestimated in Spain. The authors propose a retrospective methodology to estimate daily infections from daily deaths because deaths are usually more accurately documented. They estimate that probable daily infections during the first wave were between 35 and 42 times higher than those officially documented on 14 March, when the national government decreed a national lockdown and still 9 times more than those documented by the updated version of the official data.

30 mai 2021

Myocardite après Pfizer

Un cas chez un homme de 39 ans

Adverse reactions to vaccines are usually insignificant, but there have been reports of myopericarditis after vaccination.¹ Recently, several cases have been published of myopericarditis associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.^2, 3

We describe the case of a 39-year-old male physician, with a past medical history of asthma, autoimmune hypothyroidism, chronic atrophic gastritis, an isolated episode of atrial fibrillation, and recurrent spontaneous pneumothorax with left apical lobectomy. In recent months, he had undergone several PCR and serology screening tests for SARS-CoV-2 infection, all of which were negative. The patient gave informed consent for the write-up and publication of this clinical case.

Lien : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075838/

Frenck RW, Klein NP, Kitchin N, et al. Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. NEJM May 27, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2107456?query=featured_home

Profil favorable du Pfizer chez 1131 adolescents entre 12 et 15 ans.

In 1,131 adolescents (12-to-15-year-old), the BNT162b2 vaccine had a favorable safety profile. The immune response was noninferior to that observed in another cohort of 16-to-25-year-old young adults.

Schulz C, Wylezich C, Wernike K, Gründl M, Dangel A, Baechlein C, et al. Prolonged SARS-CoV-2 RNA shedding from therapy cat after cluster outbreak in retirement home. Emerg Inf Dis May 26, 2021 https://wwwnc.cdc.gov/eid/article/27/7/20-4670_article

Faut-il tester le chat de l'EHPAD ?

Although an infected and asymptomatic therapy cat in a nursing home in Germany showed prolonged shedding of SARS-CoV-2 RNA up to day 21 after the first detection, genome sequencing found no further role of the cat in human infections on site.

Bodilsen J, Nielsen PB, Søgaard M. Hospital admission and mortality rates for non-covid diseases in Denmark during covid-19 pandemic: nationwide population based cohort study. BMJ 25 May 2021, 373. https://www.bmj.com/content/373/bmj.n1135

Malades non-covid-19 au Danemark : hospitalisations diminuées de 30% et de 22 % lors des deux confinements nationaux en comparaison avec les années précédentes. Hausse de la mortalité chez les patients hospitalisés avec des pathologies respiratoires, des cancers, des pneumonies et des infections.

Hospital admissions for all major non-COVID-19 disease groups were 30% and 22% lower during the two national lockdowns compared to previous years. Additionally, mortality rates were higher overall and for patients admitted to hospital with conditions such as respiratory diseases, cancer, pneumonia, and sepsis.

29 mai 2021

Leidi A, Koegler F, Dumont R, et al. Risk of reinfection after seroconversion to SARS-CoV-2: A population-based propensity-score matched cohort study. Clin Inf Dis 27 May 2021, ciab495, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab495/6287116

Séropositif à la Covid : 94% de diminution du nombre des tests positifs.

Among 8344 serosurvey participants from Geneva, Switzerland, 498 seropositive individuals were selected and matched with 996 seronegative controls. After a mean follow up of 35 weeks, there was a 94% (95% CI: 86% to 98%, P < 0.001) reduction in the hazard of having a positive SARS-CoV-2 test in seropositive people.

Daniels CJ, Rajpal S, Greenshields JT, et al. Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection. JAMA Cardiol May 27, 2021. https://jamanetwork.com/journals/jamacardiology/fullarticle/2780548?resultClick=1

Myocardites après Covid-19 : plutôt une IRM ?

In this study of aggregate data from 13 Big Ten universities, 1597 athletes who tested positive by PCR underwent comprehensive cardiac evaluation including ECG, echocardiogram, troponin, and CMR imaging. Of these, 2.3% had either clinical or subclinical myocarditis that restricted them from training and competitive play. The authors believe that the role of CMR imaging in routine screening for athletes’ safe return to play should be explored further.

28 mai 2021

Salzman MB, Huang C-W, O’Brien CM, Castillo RD. Multisystem inflammatory syndrome after SARS-CoV-2 infection and COVID-19 vaccination. Emerg Infect Dis May 26, 2021. https://wwwnc.cdc.gov/eid/article/27/7/21-0594_article

Trois cas de syndrome inflammatoire multisystémique chez des adultes de 18, 20 et 40 ans après vaccination par Pfizer précédée dans deux cas d'une Covid-19. Voir aussi : https://wwwnc.cdc.gov/eid/article/27/7/21-0594-t1

Three patients from California are described, who experienced multisystem inflammatory syndrome (MIS) after immunization and severe acute respiratory syndrome coronavirus 2 infection.

27 mai 2021

CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep. ePub: 25 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7021e3.htm?s_cid=mm7021e3_w

Covid-19 malgré la vaccination, données américaines. On sait que les USA ont massivement vacciné avec des vaccins à ARNm. Sur 101 millions de personnes vaccinées au 30 avril 2021, un total de 10 262 infections à SARS-CoV2 s'est tout-de-même produit ; 6446 (63%) sont des femmes, 995 (10%) des patients ont été hospitalisés et 160 (2%) sont morts. Les virus ont été séquencés dans 555 (5%) cas dont 356 (64%) étaient des variants préoccupants. Parmi ces derniers, le variant anglais (199 ; 56%), les variants californiens (88 ; 25%) et (28 ; 8%), le variant brésilien (28 ; 8%) et le sud-africain (13 ; 4%).

As of April 30, 2021, approximately 101 million persons in the US had been fully vaccinated against COVID-19. A total of 10,262 SARS-CoV-2 vaccine breakthrough infections had been reported, among them 6446 (63%) in females. In total, 995 (10%) patients were known to be hospitalized, and 160 (2%) patients died. Sequence data were available from 555 (5%) reported cases, 356 (64%) of which were identified as SARS-CoV-2 variants of concern, including B.1.1.7 (199; 56%), B.1.429 (88; 25%), B.1.427 (28; 8%), P.1 (28; 8%), and B.1.351 (13; 4%).

26 mai 2021

Selon l'OMS, 115 000 soignants ont trouvé la mort dans le monde depuis le début de la pandémie :

Vayne C, Rollin J, Gruel Y, et al. PF4 Immunoassays in Vaccine-Induced Thrombotic Thrombocytopenia. NEJM May 19. 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2106383?query=featured_coronavirus

Diagnostic des troubles de la coagulation induits pas le vaccin : non-validité des tests rapides de détection des PF4.

It is important to use the right assay in patients with suspected VITT. Rapid immunoassays should be avoided in the detection of PF4-specific antibodies.

Mariette X, Hermine O, Tharaux PL, et al. Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19A Follow-up of the CORIMUNO-TOCI-1 Randomized Clinical Trial. JAMA Network May 24, 2021. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2780021?resultClick=1

Tocilizumab : encore des résultats encourageants sur la mortalité (étude française).

Post hoc analysis of a French RCT, including hospitalized patients who were receiving oxygen but did not require high-flow or mechanical ventilation. Results were stratified by CRP. In patients with CRP levels greater than 15.0 mg/dL, the percentage of patients who received ventilation or those who died was 18% and 57% in the tocilizumab and usual care groups, respectively. Day-90 mortality was 9% and 35% in the tocilizumab and usual care groups, respectively.

25 mai 2021

Hodgson D, Flasche S, Jit M, et al. The potential for vaccination-induced herd immunity against the SARS-CoV-2 B.1.1.7 variant. Euro Surveill May 20, 2021. 26(20):pii=2100428. https://doi.org/10.2807/1560-7917.ES.2021.26.20.2100428

Avec un modèle reposant sur le seul variant anglais, il faudrait, en l'absence d'intervention non-médicamenteuse, une efficacité vaccinale ≥ 80% (tels les vaccins à ARNm)  et vacciner toute la population, y compris les enfants.

This brilliant modeling study suggests that if highly transmissible variants become dominant in areas with low seroprevalence, control of infection by vaccination, in the absence of non-pharmaceutical interventions, may only be achievable with a vaccine effectiveness against infectiousness of ≥ 80% – as suggested by early data for mRNA vaccines – extended to the full population, including children.

24 mai 2021

Formeister EJ, Chien W, Agrawal Y, et al. Preliminary Analysis of Association Between COVID-19 Vaccination and Sudden Hearing Loss Using US Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System Data. JAMA Otolaryngology–Head & Neck Surgery, May 20, 2021. https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2780288?resultClick=1

Pas d'association entre perte de l'audition et vaccins à ARNm.

No association exists between mRNA vaccines and sudden hearing loss.

Le Vu, S., Jones, G., Anna, F. et al. Prevalence of SARS-CoV-2 antibodies in France: results from nationwide serological surveillance. Nat Commun May 21, 12, 3025. https://www.nature.com/articles/s41467-021-23233-6

Mortalité de près de 10% des patients de 80 ans et plus en mai 2020 en France.

The first wave in France. Testing 11,000 residual specimens for anti-SARS-CoV-2 IgG and neutralizing antibodies, the authors found nationwide seroprevalence of 0.41% mid-March, 4.14% mid-April and 4.93% mid-May 2020. The authors infer that as of 17 May 2020, only 1 in 24 cumulative infections was reported as a confirmed case. Overall infection fatality rate (IFR) was estimated at 0.84% and increased exponentially with age, peaking in those ≥ 80 years old at 9.70%.

Sans me livrer à une vraie revue de la littérature scientifique, je repère surtout les publications qui me semblent dignes d’intérêt depuis le 18 mars 2021 dans le listing quotidien de Kamps et Hoffmann : https://covidreference.com/top10

Remarques en français en caractères bleus.

A noter que les mises à jour de cette page ne feront pas systématiquement l'objet d'un avis de publication par courriel comme les autres articles.

23 mai 2021

Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ May 19, 2021; 373. doi: https://doi.org/10.1136/bmj.n1098

Environ 14 % de séquelles cliniques nécessitant des soins médicaux après la phase aiguë.

This retrospective study, conducted in a large administrative database, evaluated the excess risk of developing a wide range of clinical sequelae after the acute phase of SARS-CoV-2 infection in commercially insured adults aged 18-65. Around 14% developed at least one new type of clinical sequelae that required medical care after the acute phase of SARS-CoV-2 infection, which was 4.95% higher than the 2020 comparator group and 1.65% higher than individuals diagnosed as having viral lower respiratory tract illness. The risk for incident sequelae increased with age, pre-existing conditions, and admission to hospital for COVID-19, and in adults aged ≤ 50 and those with no pre-existing conditions or not admitted to hospital, the risk for some clinical sequelae was still elevated.

22 mai 2021

Chu DKW, Gu H, Chang LDJ, Cheuk SSY, Gurung S, Krishnan P, et al. SARS-CoV-2 superspread in fitness center, Hong Kong, China, March 2021. Emerg Infect Dis. 2021 Aug [date cited]. https://doi.org/10.3201/eid2708.210833

Fitness : à savoir avant d'abandonner le masque

An asymptomatic 27-year-old male fitness trainer with a positive PCR. About 300 visitors were tested and 101 cases were confirmed (7 staff members and 94 customers). Mask wearing during exercise was not compulsory by law at the time of this outbreak.

Cheng Y, Ma N, Witt C, et al. Face masks effectively limit the probability of SARS-CoV-2 transmission. Science 20 May 2021. https://science.sciencemag.org/content/early/2021/05/19/science.abg6296

A savoir aussi avant d'abandonner le masque.

When people see images of millions of respiratory particles exhaled by talking or coughing, they may be afraid that simple masks cannot really protect them. This modeling study explains why wearing simple masks can indeed keep the number of inhaled viruses low. However, unfavorable conditions and the large variability of viral loads may lead to a virus-rich regime in certain indoor environments. In such environments, high efficiency masks and further protective measures like efficient ventilation should be used. The non-linear dependence of mask efficacy on airborne virus concentration also highlights the importance of combining masks with other preventive measures.

Islam N, Shkolnikov VM, Acosta RJ, et al. Excess deaths associated with covid-19 pandemic in 2020: age and sex disaggregated time series analysis in 29 high income countries. BMJ May 19, 2021; 373. https://www.bmj.com/content/373/bmj.n1137

Il ne fait pas bon être une homme, au moins sous l'aspect de la surmortalité en 2020 :

In this international comparative study of excess deaths in relation to the COVID-19 pandemic in 29 high income countries, all countries had excess deaths in 2020, except New Zealand, Norway, and Denmark. The highest excess deaths were in the US, Italy, England and Wales, Spain, and Poland. Accounting for difference in age, the excess death rates were much higher in men than women in almost all countries.

21 mai 2021

Wang EY, Mao T, Klein J, et al. Diverse Functional Autoantibodies in Patients with COVID-19. Nature May 19, 2021. https://www.nature.com/articles/s41586-021-03631-y

Covid-19 : maladie auto-immune ?

Is it just all dysregulated humoral immunity? This important paper revealed an expansive autoantibody landscape in COVID-19 and identified distinct autoantibodies that exerted striking immunological and clinical outcomes. COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. These autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition.

White EM, Yang X, Blackman C, et al. Incident SARS-CoV-2 Infection among mRNA-Vaccinated and Unvaccinated Nursing Home Residents. NEJM May 19, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104849?query=featured_coronavirus

Encore une confirmation de l'efficacité des ARNm chez des personnes âgées en établissement.

This large study on 18,242 residents shows real-world effectiveness of the mRNA vaccines in reducing the incidence of asymptomatic and symptomatic SARS-CoV-2 infections in a vulnerable nursing home population.

Meister TL, Fortmann J, Todt D, et al. Comparable environmental stability and disinfection profiles of the currently circulating SARS-CoV-2 variants of concern B.1.1.7 and B.1.351. J Inf Dis 2021, May 16, 2021.  https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab260/6276396

Désinfection des surfaces : pas de différence entre les variants anglais et sud-africain.

Treatment with heat, soap and ethanol revealed similar inactivation profiles indicative of a comparable susceptibility towards disinfection. Surface stability was comparable on steel, silver, copper and face masks.

Li Y, Tong CH, Bare LA, et al. Assessment of the Association of Vitamin D Level With SARS-CoV-2 Seropositivity Among Working-Age Adults. JAMA Netw Open May 19,2021;4(5):e2111634. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779952?resultClick=1

Corrélation entre le niveau de vitamine D et la séropositivité au SARS-CoV-2 : reste à démontrer.

Have you ever heard about the strong correlation between per capita cheese consumption and the number of people who died by becoming tangled in their bedsheets (r=0.95!)? Between the divorce rate in Maine and the per capita consumption of margarine (r=0.99!)? Then please consult this website: http://www.tylervigen.com/spurious-correlations. Vitamin D and COVID-19 seem to be another nice example. In this large study on 18,148 employees and spouses, SARS-CoV-2–seropositive individuals did have lower vitamin D levels than seronegative individuals. However, low vitamin D levels were not independently associated with the risk of seropositivity. Vitamin D deficiency and insufficiency were more common in individuals who had a BMI greater than or equal to 30. And in people who did not have a college degree, or who were younger. Who were current smokers, hypertensive, or Asian, Black, Hispanic, American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander race/ethnicity. (Bottom line: Correlation does not imply causation)

20 mai 2021

Prince SE, Chen H, Tong H, et al. Assessing the effect of beard hair lengths on face masks used as personal protective equipment during the COVID-19 pandemic. J Expo Sci Environ Epidemiol May 18, 2021. https://www.nature.com/articles/s41370-021-00337-1

Passer de la barbe au bouc comme votre serviteur ou bien respecter au maximum une longueur de poils de 10 mm avec les FFP2.

Where is your shaving kit? In bearded men, KF94 and KN95 masks lost up to 40% of their fitted filtration efficiency (FFE). Although N95 respirators showed considerable variability among bearded men, they had the highest FFE for beard lengths of maximum 10 mm.

Garrido-Pontnou M, Navarro A, Camacho J, et al. Diffuse trophoblast damage is the hallmark of SARS-CoV-2-associated fetal demise. Mod Pathol May 18, 2021. https://www.nature.com/articles/s41379-021-00827-5

SARS-CoV-2 délétère aussi pour le placenta.

SARS-CoV-2-positive placentas show a particular lesion characterized by trophoblast necrosis and intervillous space collapse. It can be seen as tiny foci in the less affected cases or as massively extensive lesions in the more severe ones.

19 mai 2021

Suivre la pandémie (Johns Hopkins):

Bian H, Zheng ZH, Wei D, et al. Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial. Sig Transduct Target Ther May 17, 2021, 6, 194.

Un nouvel anticorps monoclonal efficace contre la Covid ? Le meplazumab.

CD147 serves as a novel receptor for SARS-CoV-2 infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection. This small pilot study on 19 COVID-19 patients suggests that meplazumab could accelerate the recovery of patients from pneumonia with a favorable safety profile.

18 mai 2021

Pilishvili T, Fleming-Dutra KE, Farrar JL, et al. Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel — 33 U.S. Sites, January–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 14 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7020e2.htm?s_cid=mm7020e2_w

USA : vaccins à ARNm efficaces à 82 % lors de la première dose pour éviter les symptômes de la Covid chez les soignants mais à 94 % après la deuxième injection.

This large US multisite test-negative design vaccine effectiveness study among HCP found a single dose of Pfizer-BioNTech or Moderna vaccines to be 82% effective against symptomatic COVID-19 and 2 doses to be 94% effective.

Chodick G, Tene L, Rotem RS, et al. The effectiveness of the TWO-DOSE BNT162b2 vaccine: analysis of real-world data. Clinical Infectious Diseases May 17, 2021, ciab438, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab438/6276888

Pfizer en Israël : sur 1 100 000 personnes vaccinées, 94 % après la deuxième dose. Incidence de la Covid post-vaccinale dans la figure 1 ci-dessous.

Real life data from Israel. Incidence rate of a SARS-CoV-2 infection between 7 to 27 days after the second dose (the protection period) was compared to days 1 to 7 after the first dose, where no protection by the vaccine is assumed (the reference period). In 1.1 million vaccinated persons, vaccine effectiveness in preventing infection was 90% and 94% against COVID-19. Look at the beautiful Figure 1.

Spencer AJ, McKay PF, Belij-Rammerstorfer S. et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat commun May 17, 2021. 12, 2893. https://www.nature.com/articles/s41467-021-23173-1

Alterner une dose ARNm et une autre AstraZeneca ou vice versa : une meilleure immunité cellulaire, au moins chez la souris. Essais en cours chez l'homme.

Switching vaccines (first dose vs second) may induce strong immune responses. In mice, antibody responses were high with two-dose heterologous vaccination (first shot with mRNA, second with AstraZeneca, or vice versa) regimens. Neutralizing titers were at least comparable or higher than the titers measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen was dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens. Several trials in humans are underway (https://comcovstudy.org.uk/home).

Bailly B, Guilpain L, Bouiller K, et al. BNT162b2 mRNA vaccination did not prevent an outbreak of SARS COV-2 variant 501Y.V2 in an elderly nursing home but reduced transmission and disease severity. Clinical Infectious Diseases, 16 May 2021. ciab446, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab446/6276392

France, Jura : variant sud-africain en cluster. Protection nulle chez les non-vaccinés, à 50 % chez les vaccinés par Pfizer.

An outbreak of SARS-CoV-2 1.351 (the South African variant) in a nursing home in Jura, in eastern France. 5/5 non-vaccinated residents versus 13/26 of those vaccinated with BNT162b2 were infected. Two of 13 vaccinated versus 4 of 5 non-vaccinated residents presented severe disease.

17 mai 2021

Wu K, Choi A, Koch M, et al. Preliminary Analysis of Safety and Immunogenicity of a SARS-CoV-2 Variant Vaccine Booster. doi: https://doi.org/10.1101/2021.05.05.21256716

Pas encore revu par les pairs : Moderna efficace sur le variant sud-africain ?

Not yet peer reviewed, but important, good news. In total, 40 people who had already been fully vaccinated with mRNA-1273, received a third shot 6 months later. A booster dose of mRNA-1273.351, Moderna’s variant-matched vaccine, achieved higher neutralizing antibody titers against the B.1.351 variant (the “immune escape” variant from South Africa) than a booster dose of mRNA-1273. However, the best news is that the titers were high enough to kill B.1.351 even in those who received the conventional vaccine.

Alkharaan H, Bayati S, Hellström C, et al. Persisting Salivary IgG against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys. J Inf Dis May 12, 2021, jiab256, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab256/6274637

Vers un test d'anticorps salivaires ?

Unlike SARS-CoV-2 salivary IgA that appeared short-lived, the specific IgG in saliva appeared stable even after mild COVID-19 as noted for blood serology. This non-invasive saliva-based antibody test may serve as a complementary alternative to conventional blood serology.

Holmdahl I, Kahn R, Hay JA, et al. Estimation of Transmission of COVID-19 in Simulated Nursing Homes With Frequent Testing and Immunity-Based Staffing. JAMA Netw Open May 14, 2021, 4(5):e2110071. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779870

Et un test antigénique chaque jour en EHPAD !

Frequent and rapid testing! This decision analytical modeling study has evaluated COVID-19 transmission in nursing homes associated with contact-targeted interventions and testing. The testing strategy associated with the greatest estimated reduction in infections was daily antigen testing, indicating that faster results should be prioritized over higher sensitivity.

16 mai 2021

Decaro N, Vaccari G, Lorusso A, Lorusso E, De Sabato L, Patterson EI, et al. Possible human-to-dog transmission of SARS-CoV-2, Italy, 2020. Emerg Infect Dis May 12, 2021. https://doi.org/10.3201/eid2707.204959

Le caniche, aussi !

Pet story, volume one: A female poodle, who was 1.5 years of age, lived with 4 family members in Bitonto, Italy. All five became infected. Full-length genome sequencing showed that the canine and human viruses were identical, suggesting human-to-animal transmission.

Colitti B, Bertolotti L, Mannelli A, et al. Cross-sectional serosurvey of companion animals housed with SARS-CoV-2–infected owners, Italy. Emerg Infect Dis May 11, 2021. 2021 Jul [date cited]. https://doi.org/10.3201/eid2707.203314

Il ne manquait plus que le chat.

Pet story, volume two: Among animals living with SARS-CoV-2–infected owners, 20.4% (11/54) of cats and 3.2% (3/93) of dogs were seropositive. A 13-year-old female cat was hospitalized for a brachial cephalic thrombosis and a 3-year-old male cat was hospitalized for interstitial pneumonia.

RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet May 14, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00897-7/fulltext

Plasma de convalescent : inefficace

No, it’s not a matter of titres, antibodies, timing, endpoints etc: convalescent plasma (CP) has NO clinical benefit. In RECOVERY, the by far largest study to date on patients hospitalized with COVID-19, high-titre CP did not improve survival: 1399 (24%) of 5795 patients died in the CP group and 1408 (24%) of 5763 patients died in the usual care group. Of note, there were no differences in other prespecified clinical outcomes and the results were consistent across subgroups of age, sex, ethnicity, duration of symptoms before randomization, level of respiratory support received at randomisation, and use of corticosteroids. Time to face the reality.

15 mai 2021

Yang Q, Saldi TK, Gonzales PK, et al. Just 2% of SARS-CoV-2−positive individuals carry 90% of the virus circulating in communities. PNAS May 11, 2021.  118 (21) e2104547118; https://doi.org/10.1073/pnas.2104547118

Vade retro Satanas. 2% des individus sont susceptibles de contaminer autrui : "super-porteurs" et "super-contamineurs".

The vast majority of circulating virions in communities are found within the bodies of a small number of individuals. Testing more than 72,500 saliva samples by PCR from individuals who reported no symptoms on the day of collection, 1405 positive cases were identified. Regardless of symptomatic status, ∼ 50% of individuals who test positive for SARS-CoV-2 seem to be in non-infectious phases of the disease, with low viral loads in a range from which live virus has rarely been isolated. At any given time, only 2% of individuals carry 90% of the virions circulating within communities, serving as viral “super-carriers” and possibly also super-spreaders.

Yao L, Wang GL, Shen Y, et al. Persistence of Antibody and Cellular Immune Responses in COVID-19 patients over Nine Months after Infection. J Inf Dis May 12, 2021, jiab255, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab255/6274562

Immunité humorale et cellulaire plus de neuf mois après infection.

Of 59 COVID-19 patients, approximately 90% of patients had detectable IgG antibodies against spike and nucleocapsid proteins and neutralizing antibodies against pseudovirus, whereas ~ 60% of patients had detectable IgG antibodies against receptor binding domain and surrogate virus-neutralizing antibodies. Specific IgG + memory B cell and IFN-γ secreting T cell responses were detectable in over 70% of patients.

Carr J, Wright AK, Leelarathna L, et al. Impact of COVID-19 on diagnoses, monitoring, and mortality in people with type 2 diabetes in the UK. Lancet Diab Endocrin May 11, 2021. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00116-9/fulltext

Diabètes de type 2 : réduction du nombre des diagnostics comme effet collatéral de la Covid-19.

In April 2020, the rate reduction of new diagnoses of type 2 diabetes in primary care practices in England was 0.70 when compared with 10-year historical trends. Older individuals (65 years and older), men, and people from deprived areas had the greatest reductions in diagnosis rates.

14 mai 2021

Bernal JL, Andrews N, Gower C, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ May 13, 2021; 373. https://www.bmj.com/content/373/bmj.n1088

Efficacité un mois après la première injection de Pfizer et d'AstraZeneca en Angleterre chez des personnes de 70 ans et plus.

13 mai 2021

Chou SH, Beghi E, Helbok R, et al. Global Incidence of Neurological Manifestations Among Patients Hospitalized With COVID-19—A Report for the GCS-NeuroCOVID Consortium and the ENERGY Consortium. JAMA Netw Open May 11, 2021. 4(5):e2112131. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779759?resultClick=1

Covid-19,  les signes et syndromes neurologiques les plus fréquents : encéphalopathie aiguë (49%), coma (17%), accident vasculaire cérébral (6%) alors que méningites et encéphalites sont rares (0,5%).

The largest study of neurological manifestations in patients hospitalized with COVID-19. This cohort included 3055 patients with COVID-19 at 28 centers, representing 13 countries and 4 continents. The most prevalent neurological signs and/or syndromes were acute encephalopathy (49%), coma (17%), and stroke (6%), while meningitis and/or encephalitis were rare (0.5%). Neurological symptoms were associated with premature mortality.

Bertuzzi AF, Ciccarelli M, Marrari A, et al. Impact of active cancer on COVID-19 survival: a matched-analysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy. Br J Cancer May 11, 2021). https://www.nature.com/articles/s41416-021-01396-9

Covid et cancer non stabilisé: 1,9 fois plus de décès.

Propensity score matching showed a 1.9 × risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-related bias.

11 mai 2021

Panda AK, Pati A, Padhi S, et al. Granulin rs5848 (C>T) polymorphism is associated with SARS-CoV-2 infection and mortality. J Inf Dis 5 May 2021, jiab237, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab237/6265298

Inégalité génétique : un facteur contribuant à éclairer les inégalités incomprises de gravité de l'infection à SARS-CoV-2 ?

A common genetic polymorphism in the granulin gene (C>T, rs5848) has been reported to be associated with altered mRNA and protein levels. This preliminary data indicates that the C allele of the progranulin rs5848 polymorphism predisposes to SARS-CoV-2 infection susceptibility and mortality.

9 mai 2021

Angel Y, Spitzer A, Henig O, et al. Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers. JAMA May 6, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779853

Tel-Aviv, Pfizer : 6710 soignants, 757 non vaccinés. Covid-19 chez 8 vaccinés et 38 chez les autres. Nombre comparable d'infections asymptomatiques à SARS-CoV-2 : 19 et 17.

Among 6710 health care workers in Tel Aviv, 757 (11.3%) were not vaccinated. Symptomatic SARS-CoV-2 infection occurred in 8 fully vaccinated and 38 unvaccinated health care workers (adjusted IRR, 0.03). The corresponding numbers for asymptomatic SARS-CoV-2 infections were 19 and 17, respectively (adjusted IRR, 0.14). Results were qualitatively unchanged by the propensity score sensitivity analysis.

Pottegård A, Lund LC, Karlstad Ø, et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ May 5, 2021; 373. https://www.bmj.com/content/373/bmj.n1114

Après AstraZeneca, sur 281 264 personnes au Danemark et en Norvège, 11 MTE classiques supplémentaires et 2,5 thromboses des sinus veineux encéphaliques.

Among 281,264 people who received ChAdOx1-S, 11 and 2.5 excess events per 100,000 vaccinations were seen for venous thromboembolic events and cerebral venous thrombosis, respectively.

Drake TM, Fairfield CJ, Pius R, et al. Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study. Lancet Rheumatology May 07, 2021. https://doi.org/10.1016/S2665-9913(21)00104-1

AINS : pas de relation avec une mortalité ou une susceptibilité accrue au SARS-CoV-2

Do you remember the rumors surrounding ibuprofen use during the first wave? Forget it. Among 78,674 patients across 255 health-care facilities in England, Scotland, and Wales, NSAID use was not associated with higher mortality or increased severity of COVID-19.

8 mai 2021

Borchering RK, Viboud C, Howerton E, et al. Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios — United States, April–September 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 May 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7019e3.htm?s_cid=mm7019e3_w#suggestedcitation

Déclin net du nombre de Covid-19 prévu pour juillet 2021 si vaccination et mesures non pharmacologiques sont associées aux USA

Data from six models indicate that with high vaccination coverage and moderate non-pharmaceutical intervention (NPI) adherence, hospitalizations and deaths will likely remain low nationally, with a sharp decline in cases projected by July 2021. Lower NPI adherence could lead to substantial increases in severe COVID-19 outcomes, even with improved vaccination coverage.

7 mai 2021

Abu-Raddad LJ, Chemaitelly H, Butt AA. Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 Variants. NEJM May 5, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104974?query=featured_home

Au Qatar, efficacité du Pfizer à 97% sur les formes sévères, critiques et mortelels, les variants britannique et sud-africain étant prédominants.

Following a mass immunization campaign with BNT162b2 in Quatar, as of March 31, 2021, a total of 385,853 persons had received at least one vaccine dose and 265,410 had completed the two doses. The estimated effectiveness against any documented infection with the B.1.1.7 variant was 89.5% at 14 or more days after the second dose. The effectiveness against any documented infection with the B.1.351 variant was 75.0%. Of note, effectiveness against severe, critical, or fatal disease (with the B.1.1.7 and B.1.351 variants being predominant within Qatar) was very high, at 97%.

Haas EJ, Angulo FJ, McLaughlin JM, et al. Impact and effectiveness of mRNA BNT162b2 vaccine against SARS-CoV-2 infections and COVID-19 cases, hospitalisations, and deaths following a nationwide vaccination campaign in Israel: an observational study using national surveillance data. The Lancet May 05, 2021. DOI:https://doi.org/10.1016/S0140-6736(21)00947-8

Pfizer et variant anglais présent à 95 % en Israël : efficacité confirmée à 98 % des formes sévères et critiques, toutes souches confondues.

By April 3, 2021, 4.7 Million people aged 16 years and older were fully vaccinated with two doses of BNT162b2 in Israel. Vaccine effectiveness at 7 days or longer after the second dose were 95% against SARS-CoV-2 infection, 97% against symptomatic COVID-19, 97% against hospitalization, and 98% against severe or critical disease. In all age groups, as vaccine coverage increased, the incidence of SARS-CoV-2 outcomes declined. Estimated prevalence of the B.1.1.7 variant was 95%.

6 mai 2021

Au moins deux, peut-être trois injections vaccinales pour certains vaccins dans la perspective des mutants.

5 mai 2021

Fabiani M, Ramigni M, Gobbetto V, et al. Effectiveness of the Comirnaty (BNT162b2, BioNTech/Pfizer) vaccine in preventing SARS-CoV-2 infection among healthcare workers, Treviso province, Veneto region, Italy, 27 December 2020 to 24 March 2021. Eurosurveillance May 3, 2021. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.17.2100420

Pfizer chez des soignants : efficacité démontrée

In this study on 6,423 HCW from northern Italy, vaccine effectiveness (VE) was high. VE in preventing symptomatic infections during the time intervals 1–14 days and 15–28 days from administration of the first dose were 40% (95% CI: 9–60) and 86% (95% CI: 33–97), respectively.

Diao B, Wang C, Wang R, et al. Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection. Nat Commun May 4, 2021, 12, 2506. https://doi.org/10.1038/s41467-021-22781-1

Le rein aussi !

SARS-CoV-2 virus can directly infect human renal cells. Both viral NP and S protein antigens were found in the kidneys from 6 COVID-19 autopsies, accumulating in ACE2+ kidney tubules.

4 mai 2021

Issakhov A, Zhandaulet Y, Omarova P et al. A numerical assessment of social distancing of preventing airborne transmission of COVID-19 during different breathing and coughing processes. Sci Rep May 3, 2021, 11, 9412. https://www.nature.com/articles/s41598-021-88645-2

Tousseurs et éternueurs : s'en tenir à 5 mètres plutôt qu'à 2.

Paper of the day. This study looked at the transport of droplets or particles generated by the respiratory system in a room during various scenarios. Results: Social distance of 2 m is sufficient for simple breathing for all cases (without ventilation and with ventilation). However, when coughing or sneezing, this distance is clearly not enough and it needs at least 5 m social distance in order not to get into the zone of exposure to these particles.

Solforosi L, Kuipers H, Jongeneelen M, et al. Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP. J Exp Med April 28 2021. https://rupress.org/jem/article/218/7/e20202756/212032/Immunogenicity-and-efficacy-of-one-and-two-doses?searchresult=1

Bon, je ne suis pas un macaque rhésus mais j'eus préféré me contenter de la seule injection que j'ai reçue. Nota : ENSEMBLE 2 est interrompue en France à la date où ces lignes sont écrites.

In rhesus macaques, spike protein–specific immune responses were better with two-doses of the Ad26.COV2.S vaccine. In humans, a two-dose regimen is currently evaluated in a Phase 3 study (ENSEMBLE 2).

Tan AX, Hinman JA, Magidf HS, et al. Association Between Income Inequality and County-Level COVID-19 Cases and Deaths in the US. JAMA Netw Open. May 3, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779417?resultClick=1

Quand on vous dit qu'il vaut mieux être riche que pauvre...

This ecological cohort study found that there was a positive correlation between Gini coefficients (a measure of unequal income distribution) and county-level COVID-19 cases and deaths during the study period. Of note, the association varied over time and was strongest in the summer months of 2020.

Danemark renonce à utiliser le vaccin Johnson & Johnson, une première en Europe : https://www.francetvinfo.fr/sante/maladie/coronavirus/covid-19-le-danemark-renonce-a-utiliser-le-vaccin-johnson-johnson-une-premiere-en-europe_4609847.html#xtor=CS2-765-[share]-

3 mai 2021

Hause AM, Gee J, Johnson T, et al. Anxiety-Related Adverse Event Clusters After Janssen COVID-19 Vaccination — Five U.S. Mass Vaccination Sites, April 2021. MMWR Morb Mortal Wkly Rep. ePub: 30 April 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e3.htm?s_cid=mm7018e3_w#suggestedcitation

Syncopes liées à l'anxiété après injection de Janssen : bien plus fréquentes qu'après la vaccination contre la grippe saisonnière. Garder les vaccinés au moins 15 minutes.

Anxiety-related events, including fainting, can occur immediately after vaccination with any vaccine and might be caused by anxiety about receiving an injection. The stress of an ongoing pandemic might increase anxiety: Reports of syncope (fainting) are approximately 164 times more common after the Janssen COVID-19 vaccination (8.2 per 100,000) than after influenza vaccination (0.05 per 100,000).

What are the implications for public health practice?

Vaccine providers should be aware of anxiety-related events after vaccination and observe all COVID-19 vaccine recipients for any adverse reactions for at least 15 minutes after vaccine administration.

Thell R, Zimmermann J, Szell M, et al. Standard blood laboratory values as a clinical support tool to distinguish between SARS-CoV-2 positive and negative patients. Sci Rep 11, 9365 (2021). https://doi.org/10.1038/s41598-021-88844-x

Des témoins sériques communs de l'infection par SARS-CoV-2 ? Leucopénie, éosinopénie et élévation de l'hémoglobine en seraient-ils les témoins ? Encore trop tôt pour une utilisation clinique.

In this large study from Vienna, Austria, leukopenia, eosinopenia, elevated erythrocytes, hemoglobin and ferritin were detected to be among the best standard laboratory parameters to distinguish between COVID-19-positive and -negative patients.

Our findings suggest that especially leukopenia, eosinopenia, and elevated hemoglobin are helpful to distinguish between COVID-19 positive and negative tested patients.

2 mai 2021

Bartoszko JJ, Siemieniuk RA, Kum E, et al. Prophylaxis against covid-19: living systematic review and network meta-analysis. BMJ April 26, 2021; 373. https://www.bmj.com/content/373/bmj.n949

Décidément, on n'en finit pas d'achever l'HCQ qui devrait être abandonnée depuis longtemps. Quant à l'ivermectine, son bénéfice est "hautement incertain".

Bottom line of this review, including 9 RCTs: HCQ is not protective and probably increases adverse effects. Any effect of ivermectin is “highly uncertain”.

Reynolds CJ, Pade C, Gibbons JM, et al. Prior SARS-CoV-2 infection rescues B and T cell responses to variants after first vaccine dose. Science 30 Apr 2021: eabh1282. https://science.sciencemag.org/content/early/2021/04/29/science.abh1282

Immunité cellulaire et humorale : mieux vaut avoir eu la Covid-19 avant la vaccination par le Pfizer pour faire face aux variants anglais et sud-africain.

T and B cell responses after first dose vaccination with the Pfizer/BioNTech vaccine BNT162b2 were followed longitudinally in healthcare workers (HCW), with (n=23) or without (n=23) prior SARS-CoV-2 infection. After one dose, individuals with prior infection showed enhanced T cell immunity, antibody secreting memory B cell response to spike and neutralizing antibodies effective against B.1.1.7 and B.1.351.

See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA April 30, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779731?resultClick=1

Douze thromboses des sinus veineux cérébraux aux USA avec Janssen entre le 2 mars et le 21 avril 2021 : que des femmes, ayant moins de 60 ans, avec début de la symptomatologie entre le sixième et le quinzième jour après la vaccination.

 Twelve US cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia following vaccination with Ad26.COV2.S, the COVID-19 vaccine produced by Janssen/Johnson & Johnson. All were women, younger than 60 years, and had symptom onset ranging from 6 to 15 days after vaccination requiring hospitalization.

1er mai 2021

Norman M, Navér L, Söderling J, et al. Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes. JAMA April 29, 2021. https://jamanetwork.com/journals/jama/fullarticle/2779586?resultClick=1

2323 mères positives pour le SARS-CoV-2 en Suède : davantage de problèmes respiratoires à la naissance. Doute sur une mortinatalité plus élevée.

Among 88,159 infants in Sweden, 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. Maternal infection was associated with higher risk of any neonatal respiratory disorder (2.8% vs 2.0%; odds ratio, 1.42, 95% CI: 1.50-3.84). Neonatal mortality was also slightly higher but this was not statistically significant (0.30% vs 0.12%; odds ratio, 2.55, 95% CI: 0.99-6.57).

RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet May 01, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00676-0/fulltext

Tocilizumab : un espoir ?

Paper of the day: The RECOVERY results do support the use of tocilizumab (TCZ)! Overall, 621 (31%) of the 2022 patients allocated to TCZ and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0.85; 95% CI: 0.76–0.94; p = 0.0028). TCZ patients were more likely to be discharged from hospital within 28 days (57% vs 50%). Benefits were consistent across all patient groups studied, including those receiving invasive mechanical ventilation, non-invasive respiratory support, or no respiratory support other than simple oxygen. The benefits were also clearly seen among those also receiving steroids. Of note, the RECOVERY trial contains around four times as much information as all previous trials combined.

Smadja DM, Yue QY, Chocron R, Sanchez O, Lillo-Le Louet A. Vaccination against COVID-19: insight from arterial and venous thrombosis occurrence using data from VigiBase. Eur Respir J. 2021 Apr 16:2100956. doi: 10.1183/13993003.00956-2021. Epub ahead of print. PMID: 33863748; PMCID: PMC8051185.

La pubication et la table 1 de Smadja et al. qui interroge :

30 avril 2021

Allaitement et vaccination anti-Covid : position favorable des sociétés scientifiques italiennes et attitude polonaise  mais position d'expectative pour d'autres sources (voir une référence sous la référence polonaise)

Gao M, Piernas C, Astbury NM, et al. Associations between body-mass index and COVID-19 severity in 6·9 million people in England: a prospective, community-based, cohort study. Lancet Diab Endoc April 28, 2021. https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00089-9/fulltext

Obésité : encore plus dangereuse chez les moins de 40 ans et chez les personnes à la peau noire.

At a BMI of more than 23 kg/m², there was a linear increase in risk of severe COVID-19 leading to admission to hospital and death, and a linear increase in admission to an ICU across the whole BMI range, which was not attributable to excess risks of related diseases. The relative risk due to increasing BMI was particularly notable people younger than 40 years and of Black ethnicity.

Tenforde MW, Olson SM, Self WH. Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged ≥65 Years — United States, January–March 2021. MMWR April 28. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w

Première dose de Pfizer ou de Moderna : pas efficace sur l'évitement des hospitalisations avant 14 jours

In a multi-state network of US hospitals during January–March 2021, receipt of Pfizer/BioNTech or Moderna COVID-19 vaccines was 94% effective against COVID-19 hospitalization among fully vaccinated adults and 64% effective among partially vaccinated adults aged ≥ 65 years. There was no significant effect for receiving the first dose of a 2-dose COVID-19 vaccine series within 14 days prior to illness onset.

Oliu-Barton M, Pradelski BS, Aghion OP, et al. SARS-CoV-2 elimination, not mitigation, creates best outcomes for health, the economy, and civil liberties. April 28, 2021. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00978-8/fulltext

Eliminer le virus plutôt que "vivre avec"

See title. “Living with the virus“ is not a good idea. And will not work. Important comment, good arguments. Evidence suggests that countries that opt for rapid action to eliminate SARS-CoV-2—with the strong back-up of their inhabitants—also better protect their economies and minimize restrictions on civil liberties compared to those that strive for mitigation.

The analysis by Smadja et al in the present issue of the Journal (1) provides new, potentially relevant insights into the field of vaccine-related thrombosis. In a global pharmacovigilance database including a 15 times larger vaccinated population than that reviewed by the EMA and focusing on three rather than one particular vaccine, rare reports of thrombotic complications now also appear in relation to the mRNA-based Pfizer-BioNtech and Moderna vaccines. If these results are confirmed and elaborated by thorough laboratory testing, as were the few cases described above, they may trigger investigation of further mediators of this aberrant immune response, searching beyond the adenoviral sequence or other components of the particular ChAdOx1 nCoV-19 (AstraZeneca) and, possibly, the Ad26.COV2.S (Johnson & Johnson/Janssen) adenoviral vector vaccine.

Thromboses : les vaccins à ARN messager aussi ? Une suspicion forte à prouver.

Konstantinides S. Thrombotic complications of vaccination against SARS-CoV-2: what pharmacovigilance reports tell us - and what they don't. Eur Respir J. 2021 Apr 22:2101111. doi: 10.1183/13993003.01111-2021. Epub ahead of print. PMID: 33888525; PMCID: PMC8061197.

Référence :

Fausses-couches et vaccinations anti-Covid-19 : fake news ? Pas davantage, peut-être moins. Voir tableau ci-dessous :

Miscarriage = fausse couche

Référence :

29 avril 2021

Monin L, Laing AG, Muñoz-Ruiz M, et al. Safety and immunogenicity of one versus two doses of the COVID-19 vaccine BNT162b2 for patients with cancer: interim analysis of a prospective observational study. Lancet Inf Dis April 27, 2021. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00213-8/fulltext

Pfizer avec la première dose chez les cancéreux : mieux vaut compter sur la deuxième dose 

Better not wait too long with the second shot in cancer patients? In this prospective observational study of 151 patients with solid and hematological cancers, one 30 μg dose of the BNT162b2 vaccine yielded poor efficacy, as measured by seroconversion rates, viral neutralization capacity, and T cell responses, at 3 weeks and 5 weeks following the first inoculum. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose.

MacNeil JR, Su JR, Broder KR, et al. Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021. MMWR Morb Mortal Wkly Rep. ePub: 27 April 2021. DOI: https://www.cdc.gov/mmwr/volumes/70/wr/mm7017e4.htm?s_cid=mm7017e4_w

Janssen : au 23 avril 2021, 15 cas rapportés aux USA de thromboses veineuses du sinus caverneux, aucun chez les hommes.

On April 23, the Advisory Committee on Immunization Practices concluded that the benefits of resuming Janssen’s vaccination in persons aged ≥ 18 years outweigh the risks. Up to now, there are 15 cases of cerebral venous sinus thrombosis (CVST), mostly among women aged 18−49 years. Two occurred among women aged ≥ 50 years; no cases post-authorization were reported among men. Reporting rates were 7.0 cases per million doses administered to women aged 18−49 years and 0.9 per million to women aged ≥ 50 years.

Resende PC, Bezerra JF, Vasconcelos RHT, Arantes I, Appolinario L, Mendonça AC, et al. Severe acute respiratory syndrome coronavirus 2 P.2 lineage associated with reinfection case, Brazil, June–October 2020. Emerg Infect Dis April 21, 2021 Jul [date cited] https://wwwnc.cdc.gov/eid/article/27/7/21-0401_article

Brésil : un cas sévère de réinfection à 116 jours de distance

Case report of a 37-year-old healthcare worker from the northeastern region of Brazil who experienced two clinical episodes, 116 days apart. The two infections were caused by the most prevalent lineage in Brazil, B.1.1.33, and the emerging lineage P.2.

Pour Drosten, pas de preuve d'une dangerosité accrue per se par le variant indien :

28 avril 2021

Amorim MR, Souza WM, Barros ACG Jr, Toledo-Teixeira DA, Bispo-dos-Santos K, Simeoni CL, et al. Respiratory viral shedding in healthcare workers reinfected with SARS-CoV-2, Brazil, 2020. Emerg Infect Dis. 2021 June [date cited]. https://doi.org/10.3201/eid2706.210558

Brésil : quatre soignants deux fois infectés, deux fois potentiellement contaminants.

Four cases of SARS-CoV-2 reinfection among HCWs. In each HCW, shedding of infectious viral particles was observed during both infection episodes.

Gonzalo EM, Martinez PP, Mahmud AS, et al. Socioeconomic status determines COVID-19 incidence and related mortality in Santiago, Chile. Science 27 Apr 2021: eabg5298. DOI: https://science.sciencemag.org/content/early/2021/04/26/science.abg5298

Chili : le saviez-vous, il vaut mieux être riche que pauvre...

Data from the capital of Chile, a highly segregated city: People living in municipalities with low socioeconomic status did not reduce their mobility during lockdowns as much as those in more affluent municipalities. Both test positivity rates and testing delays were much higher. There was a strong association between socioeconomic status and mortality, measured either by COVID-19 attributed deaths or excess deaths. Finally, infection fatality rates in young people were (1.7-3.1 fold) higher in low-income municipalities.

Huang L, Yuen TT, Ye Z et al. Berbamine inhibits SARS-CoV-2 infection by compromising TRPMLs-mediated endolysosomal trafficking of ACE2. Sig Transduct Target Ther 6, 168 April 24, 2021. https://www.nature.com/articles/s41392-021-00584-6

Espoir du côté d'un inhibiteur calcique, la berbamine.

Berbamine compromises the endolysosomal trafficking of ACE2 via inhibition of TRPMLs, and this leads to an increase in the secretion of ACE2 via exosomes and a concomitant decrease in the levels of ACE2 at the cell surface, thereby preventing SARS-CoV-2 from entering the host cells. Before ordering (and drinking) barberry tea, however, let’s wait for clinical data.

Reis G, Moreira Silva EA, Medeiros Silva DC, et al. Effect of Early Treatment With Hydroxychloroquine or Lopinavir and Ritonavir on Risk of Hospitalization Among Patients With COVID-19The TOGETHER Randomized Clinical Trial. JAMA Netw Open April 22, 2021;4(4):e216468. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044?resultClick=1

Brésil : reflop !

In this large trial from Brazil, rates of COVID-19–associated hospitalization in 685 patients treated with hydroxychloroquine or lopinavir-ritonavir were not significantly different compared with those who received placebo. The trial was stopped after the interim analysis for futility.

Derington CG, Cohen JB, Mohanty AF, et al. Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans. PLOS April 23, 2021 https://doi.org/10.1371/journal.pone.0248080

USA, personnes âgées : les sartans préférables aux IEC ?

One of the first observational study to show a protective association among outpatients between current users of an ARB compared to ACEI on COVID-19-related outcomes. In this retrospective cohort study of 4,969 Veterans with treated hypertension (and without compelling indications), current users of an ARB in the outpatient cohort had a 9% lower relative risk of all-cause hospitalization or mortality and 16% lower relative risk of ICU admission compared to ACEI users

27 avril 2021

Bastard P, Orlova E, Sozaeva L, et al. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J Exp Med April 23m, 2021, 218 (7): e20210554. https://rupress.org/jem/article/218/7/e20210554/212019/Preexisting-autoantibodies-to-type-I-IFNs-underlie?searchresult=1

Un facteur génétique de gravité découvert

Patients with biallelic loss-of-function variants of the autoimmune regulator suffer from autoimmune polyendocrine syndrome type-1 (APS-1). They produce a broad range of autoantibodies, including circulating auto-Abs neutralizing most type I interferons. In this small cohort of 22 APS-1 patients with COVID-19 from seven countries, aged between 8 and 48 years, 19 (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an ICU, 11 (50%) who required mechanical ventilation, and four (18%) who died.

Somekh I, Boker KL, Shohat T, et al. Comparison of COVID-19 Incidence Rates Before and After School Reopening in Israel. JAMA Netw Open April 26, 2021. 2021; 4(4):e217105. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778940?resultClick=1

"Innocence" des enfants de 0 à 9 ans ?

This study suggests that children aged 0 to 9 years did not have substantial rates of SARS-CoV-2 infection during school attendance periods, and it may be assumed that they did not have a substantial role in COVID-19 spread either during this period. Therefore, resuming school for this age group when lockdown was relaxed appears to have been safe for them.

26 avril 2021

Mallapaty S. India’s massive COVID surge puzzles scientists. Nature NEWS, April 21, 2021. https://www.nature.com/articles/d41586-021-01059-y

Variant indien: plus agressif ou nouvelle flambée épidémique liée au mode de vie ?

The virus is spreading faster than ever before in the country despite previous high infection rates in megacities, which should have conferred some protection. Smriti Mallapaty summarizes the current knowledge. It remains unclear whether the surge is due to the new variant B.1.617 or due a fully open society where people were mixing and moving and travelling. Or both.

Brief summary on B.1.617: https://www.sciencemediacentre.org/expert-reaction-to-cases-of-variant-b-1-617-the-indian-variant-being-investigated-in-the-uk/

25 avril 2021

Moghadas SM, Fitzpatrick MC, Shoukat A, et al. Simulated Identification of Silent COVID-19 Infections Among Children and Estimated Future Infection Rates With Vaccination. JAMA Netw Open April 23, 2021; 4(4):e217097. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779052?resultClick=1

Serons-nous efficaces avec le seule vaccination des adultes sans des mesures spécifiques pour les enfants ?

In this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. Without these measures, vaccination of adults is unlikely to contain the outbreaks in the near term.

Shimabukuro TT, Kim SY, Myers TR. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. NEJM April 22, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2104983?query=featured_home

Pour l'instant, rien à signaler en termes d'EI chez les femmes enceintes avec les vaccins à ARNm. L'étude porte toutefois seulement sur 35 000 femmes. De plus, on peut bien sûr s'interroger sur d'éventuels effets à long terme.

Data on more than 35000 pregnant women, receiving mRNA vaccines (BioNTech or Moderna), indicate no safety signals. However, as this was a participant-reported surveillance system, more data is needed.

Vasileiou E, Simpson CR, Shi T, et al. Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study. Lancet April 23, 2021. https://www.thelancet.com/action/showPdf?pii=S0140-6736%2821%2900677-2

Pfizer et AstraZeneca : efficacité comparable chez les plus de 80 ans en Ecosse.

Paper of the day. Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated in Scotland. The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85–94) for reduced COVID-19 hospital admission at 28–34 days post-vaccination. Vaccine effect for the ChAdOx1 vaccine was 88% (95% CI 75–94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72–89).

Tu TM, Seet CY, Koh JS, et al. Acute Ischemic Stroke During the Convalescent Phase of Asymptomatic COVID-2019 Infection in Men. JAMA Netw Open April 22 2021;4(4):e217498. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779040?resultClick=1

Singapour : 18 hommes de 50 ans ou moins de 50 ans : AVC ischémique en période de convalescence (médiane 54,5 jours)

This case series from Singapure describes 18 adults 50 years or younger who presented with AIS in the convalescent period of COVID-19 infection. The median (range) time from a positive serological test result to AIS was 54.5 (0-130) days. The findings suggest an increased risk of AIS for these patients even months after a serological diagnosis.

24 avril 2021

Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequalae of COVID-19. Nature April 22, 2021. https://www.nature.com/articles/s41586-021-03553-9

La Covid longue, au delà de 30 jours après le début des symptômes : mortalité augmentée, recours accru aux services de soins, plus grande incidence de symptômes pulmonaires et extrapulmonaires.

This incredible work, the largest post-acute COVID-19 study to date, has included 73,435 non-hospitalized and 13,654 hospitalized patients with COVID-19, 4,990,835 controls, and 13,997 patients hospitalized with seasonal influenza. The results suggest that beyond the first 30 days of illness, people with COVID-19 are at higher risk of death, health care resource utilization, and exhibit a broad array of incident pulmonary and extrapulmonary clinical manifestations.

Villar J, Ariff S, Gunier RB. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection. JAMA Pediatr April 22, 2021. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2779182?resultClick=1

Grossesses et Covid : mortalité accrue, davantage de prééclampsie et d'éclampsie ainsi que d'HELLP syndrome.

This prospective, multinational study compared 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19. The risk of maternal mortality was 1.6%, ie, 22 times higher in the group of women with COVID-19 diagnosis. Of note, these deaths were concentrated in institutions from less developed regions. Data also indicate an association between COVID-19 and higher rates of preeclampsia/eclampsia/HELLP syndrome.

23 avril 2021

Sadoff J, Gray G, Vandebosch A, et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. NEJM Apr 22, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2101544?query=featured_home

Etude de phase III avec le Janssen incluant  19 630 participants négatifs au SARS-CoV-2 qui reçoivent l'Ad26.COV2.S et 19 691 qui reçoivent un placebo :  une différence quantitative a été observée pour les événements thromboemboliques veineux, 11 dans le groupe vaccin contre 3 dans le groupe placebo. La plupart de ces participants avaient des conditions médicales sous-jacentes et des facteurs prédisposants qui auraient pu contribuer à ces événements. D’autres différences ont également été observés en ce qui concerne les convulsions survenues chez 4 participants du groupe vaccin contre 1 dans le groupe placebo et les acouphènes : 6 vs 0. Ces événements seront surveillés dans le cadre de la post-commercialisation.

Trois décès ont été signalés dans le groupe vaccin et 16 dans le groupe placebo, qui ont tous été considérés comme n'étant pas liés à l'essai clinique.  Aucun décès lié à Covid-19 n'a été signalé dans le groupe vaccin, tandis que 5 décès liés à la Covid-19 ont été signalés dans le groupe placebo. Une thrombose du sinus transverse avec hémorragie cérébrale et un cas de syndrome de Guillain-Barré ont été observés des personnes vaccinées.

Le variant sud-africain demeure sensible à cette vaccination. Vingt-huit jours après l'injection, l'efficacité est estimée à 82% pour les formes qualifiées de sévères et critiques de la covid-19.

Paper of the day. In this large Phase III study, Johnson & Johnson’s Ad26.COV2.S vaccine protected 67% (66%) against moderate to severe/critical COVID-19 with onset at least 14 (28) days after administration. Vaccine efficacy was higher against severe/critical disease (85% for onset at ≥ 28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 82% against severe/critical COVID-19 with onset at least 28 days after administration.

22 avril 2021

Goepfert PA, Fu B, Chabanon AL, et al. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1–2, dose-ranging study. Lancet Inf Dis April 19, 2021. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00147-X/fulltext

Optimisation nécessaire pour la formulation antigénique du vaccin candidat de Sanofi. Voir aussi lien ci-dessous.

Recombinant protein vaccines offer the advantages of fewer potential safety concerns and lower production costs than other traditional (eg, attenuated or inactivated) vaccines. However, they often require the use of an adjuvant to enhance the magnitude and quality of the immune response. In this first-in-human evaluation, CoV2 preS dTM (a stabilized pre-fusion spike protein vaccine produced in a baculovirus expression system) had suboptimal immunogenicity and greater than expected reactogenicity, requiring optimization of the antigen formulation.

Munitz A, Yechezkel M, Dickstein Y. BNT162b2 Vaccination Effectively Prevents the Rapid Rise of SARS-CoV-2 Variant B.1.1.7 in high risk populations in Israel. Cell Rep Med April 17, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00080-X

Je n'ai rien contre les anglais mais quand leur variant est bloqué par la vaccination en Israël chez les personnes âgées, cela me fait plaisir. ☺

Good news. Although B.1.1.7 is 45% more transmissible than the wild type strain, becoming the dominant lineage in Israel within a few weeks, focused RT-PCR testing and prioritized vaccination programs can prevent the spread of the B.1.1.7 variant in the elderly.

21 avril 2021

Rossman H, Shilo S, Meir T, et al. COVID-19 dynamics after a national immunization program in Israel. Nat Med April 19, 2021. https://www.nature.com/articles/s41591-021-01337-2

En Israël, un peu plus de 2 mois après le lancement de la campagne de vaccination, le 24 février 2021, 85% des individus de plus de 60 ans sont déjà vaccinés avec deux doses. On relève une baisse d'environ 77% des cas de COVID-19, de 45% du pourcentage de tests positifs et de 68% des hospitalisations par rapport aux valeurs de pic. La diminution la plus importante et la plus précoce des cas de COVID-19 et des hospitalisations a été observée chez les personnes de plus de 60 ans, suivies par les groupes d'âge plus jeunes, selon l'ordre de priorité de la vaccination. Ce schéma n'a pas été observé lors du confinement précédent ; il était plus prononcé dans les villes vaccinées précocement.

By no doubt the paper of the day, analyzing the early effect of the national vaccination campaign in Israel on the pandemic dynamics. A little over 2 months after the initiation of the campaign, with 85% of individuals older than 60 years already vaccinated with two doses (24 February 2021), there was an approximately 77% drop in cases, a 45% drop in positive test percentage, and a 68% drop in hospitalizations compared to peak values. Larger and earlier decrease in COVID-19 cases and hospitalization was observed in individuals older than 60 years, followed by younger age groups, by the order of vaccination prioritization. This pattern was not observed in the previous lockdown and was more pronounced in early-vaccinated cities.

Taylor PC, Adams AC, Hufford MM, et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol April 17, 2021. https://doi.org/10.1038/s41577-021-00542-x

Anticorps monoclonaux : des indications à préciser

Excellent review. Early clinical trial data is encouraging, but many unanswered questions set a pressing research agenda. Which at-risk individuals would benefit most from prophylactic neutralizing mAbs? What is the duration of protection? Is there any potential impact of mAb therapy on subsequent vaccination? It will also be important to determine the optimum timing for administration of neutralizing mAbs on the basis of viral load, serology and other potential clinical factors.

20 avril 2021

Di Domenico L, Sabbatini CE, Pullano G, et al. Impact of January 2021 curfew measures on SARS-CoV-2 B.1.1.7 circulation in France. Euro Surveill. 2021;26(15):pii=2100272. https://doi.org/10.2807/1560-7917.ES.2021.26.15.2100272

Oui, nous ne sommes pas "sortis de l'auberge".

Curfew alone is not enough. The authors estimate that curfew measures allowed hospitalizations to plateau by decreasing transmission of the historical strains while B.1.1.7 continued to grow. Without progressively strengthened social distancing, a rapid surge of hospitalizations is expected, despite the foreseen increase in vaccination rhythm.

19 avril 2021

Blain H, Tuaillon E, Gamon L, et al. Spike Antibody Levels of Nursing Home Residents With or Without Prior COVID-19 3 Weeks After a Single BNT162b2 Vaccine Dose. JAMA April 15, 2021. https://jamanetwork.com/journals/jama/fullarticle/2778926?resultClick=1

Une confirmation : un seule injection de Pfizer après Covid suffit à rendre les résidents constamment séropositifs au SARS-CoV-2

One shot may be enough in people with previous COVID-19. What had already been described in HCW (https://jamanetwork.com/journals/jama/fullarticle/2777171?resultClick=1) may also be true for nursing home residents: all 36 residents (100%) with prior COVID-19 were seropositive for S protein IgG after one mRNA vaccine dose vs only 29 of 60 residents (49.2%) without prior COVID-19.

Braun KM, Moreno GK, Buys A, et al. Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact. Clinical Infectious Diseases April 15, 2021, ciab281. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab281/6226897?searchresult=1

Les travailleurs de la santé ne se contaminent que peu souvent par leurs patients 

Katarina Braun and colleagues from Madison, Wisconsin, US investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. Strikingly, only 4/95 of HCP infections could be traced back to a patient source.

18 avril 2021

Scully M, Sing D, Lown R, et al. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19. NEJM April 16, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2105385

Le mécanisme TIH-like toujours suspecté

The next case series of 23 patients from London who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). All patients had d-dimer levels at presentation that were much higher than would be expected in patients with acute venous thromboembolism.

Alshukairi AN, Zhao J, Al-Mozaini MA, Wang Y, Dada A, Baharoon SA, et al. Longevity of Middle East respiratory syndrome coronavirus antibody responses in humans, Saudi Arabia. Emerg Infect Dis April 14, 2021. https://wwwnc.cdc.gov/eid/article/27/5/20-4056_article

Six ans d'immunité, au moins d'anticorps neutralisants six ans après MERS, surtout si le MERS était modéré à sévère.

Learning from MERS? Antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia, MERS-CoV–specific neutralizing antibodies were detected for 6 years postinfection. Positive neutralizing antibodies were found in 21/31 survivors who had mild disease, 12/12 who had moderate disease, and 5/6 survivors who had severe disease.

Sickbert-Bennett EE, Samet JM, Prince SE, et al. Fitted Filtration Efficiency of Double Masking During the COVID-19 Pandemic. JAMA Intern Med. 2021; https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2778913

L'efficacité maximale de filtration : un masque en tissu sur un masque FFP2

This study compared the fitted filtration efficiency (FFE) of commonly available masks worn singly, doubled, or in combinations. Wearing a medical procedure mask underneath a cloth mask provided the best improvement to FFE of all the combinations evaluated.

17 avril 2021

Alrubayyi A, Peppa D. Seeing SARS-CoV-2 variants through the eyes of T cells. Nat Rev Immunol April 14, 2021. https://www.nature.com/articles/s41577-021-00551-w

L'immunité cellulaire serait moins sensible aux mutations que l'immunité humorale (anticorps)

Best paper title of the day. It’s time to look at the T cells. They will do their job, irrespective as to what variant is present. The authors discuss a pre-print indicating a negligible impact of the SARS-CoV-2 variant mutations on global CD4+ and CD8+ T cell responses in COVID-19 convalescent donors and COVID-19 mRNA vaccine recipients. It’s not all about antibodies. Hopefully.

16 avril 2021

Faria NR, Mellan TA, Whittaker C, et al. Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science  14 Apr 2021: eabh2644. https://science.sciencemag.org/content/early/2021/04/13/science.abh2644

Sacré brésilien 1,7 à 2,4 fois plus transmissible

The second wave of infection in Manaus was associated with the emergence and rapid spread of lineage P.1. that occurred mid-November 2020 and had acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. P.1 may be 1.7–2.4-fold more transmissible, and previous (non-P.1) infection provides 54–79% of the protection against infection with P.1 that it provides against non-P.1 lineages.

Anichini G, Terrosi C Gandolfo C, et al. SARS-CoV-2 Antibody Response in Persons with Past Natural Infection. NEJM April 14, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2103825?query=featured_coronavirus

Mieux vaudrait deux injections de vaccin plutôt qu'une après covid

This study indicates a significantly lower neutralizing antibody titer after administration of a second dose of vaccine in previously uninfected patients than the titer after only a single dose of vaccine in previously infected participants.

15 avril 2021

Betton M, Livrozet M, Planas D, et al. Sera neutralizing activities against SARS-CoV-2 and multiple variants six month after hospitalization for COVID-19. Clinical Infectious Diseases 14 April 2020, ciab308, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab308/6225251?searchresult=1

Moindre durée de l'immunité après variant sud-africain

This prospective study analyzed sera of 107 patients hospitalized with COVID-19 at 3 and 6 months post-infection. Decrease of IgG rates and serological assays becoming negative did not imply loss of neutralizing capacity. Sera collected at 6 months showed efficient neutralizing effects against the D614G, B.1.1.7 and P.1 variants but a significantly weaker activity against the B.1.351 variant.

Suryamohan K, Diwanji D, Seshagiri S. Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Communications Biology 4 , 1–11, 12 April 2021. https://www.nature.com/articles/s42003-021-02030-3

Un facteur de susceptibilité différente d'origine génétique : le polymorphisme de l'ACE2

ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting interaction. The authors analyzed over 290,000 samples from public genomic datasets and identified several ACE2 protein-altering variants. Some experiments indicate that ACE2 variants can modulate susceptibility to SARS-CoV-2.

Pirkis J, John A, Shin S, et al. Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries. Lancet Psychiatry April 13, 2021. https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00091-2/fulltext

Hausse des suicides en pays à moyens et hauts revenus ? Pas démontré.

Was there an early effect of the COVID-19 pandemic on suicide rates around the world? Probably not. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period.

Caessens Am Keita-Perse O, Berthier F, et al. Self-Illusion and Medical Expertise in the Era of COVID-19. Open Forum Infectious Diseases, Volume 8, Issue 4, 13 April 2021, ofab058, https://academic.oup.com/ofid/article/8/4/ofab058/6224992?searchresult=1

Etre sûr de sa compétence n'assure pas de l'être vraiment.

This was a survey among 2487 participants (from Monaco, May/June 2020) looking at public perception of one’s knowledge regarding COVID-19. Results confirm the concept of “over average syndrome”. In other words: a high level of self-confidence contrasted with low performance on the test. Level of medical literacy obviously altered quality of response. Physicians had the best ratings but other health care professionals (nurses, etc) did not perform well.

14 avril 2021

Nayagam JS, Jeyaraj R, Mitchell T, et al. Persistent cholestasis in survivors of SARS-CoV-2. J Infection April 03, 2021. DOI: https://doi.org/10.1016/j.jinf.2021.03.029

Le foie aussi !

A considerable proportion of patients with SARS-CoV-2 infection do not normalize their liver blood tests during follow-up, particularly those with highly elevated GGT. Of 397 patients who survived to 60 days, 216 had abnormal liver blood tests. Repeat blood tests at day 60 were performed in 43 of these patients, and a persistent abnormality in liver blood tests was detected in 24/43 patients (55.8%), predominantly in a cholestatic pattern: 3/38 (7.9%) AST abnormal; 12/43 (27.9%) ALP abnormal; and 23/43 (53.5%) GGT abnormal.

13 avril 2021

Haffner MR, Le HV, Saiz Jr AM, et al. Postoperative In-Hospital Morbidity and Mortality of Patients With COVID-19 Infection Compared With Patients Without COVID-19 Infection. JAMA Netw Open April 12, 2021;4(4):e215697. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2778455?resultClick=1

Post-opératoire : deux fois plus de décès si Covid.

A total of 5470 surgical patients with positive COVID-19 test results were matched with 5470 surgical patients with negative COVID-19 test results during the same study period. COVID-19 infection was an independent risk factor for increased perioperative mortality but not complications. Specifically, the overall mortality rate was more than double in the cohort with COVID-19 (14.8% vs 7.1%).

Park M, Pawliuk C, Nguyen T, et al. Determining the communicable period of SARS-CoV-2: A rapid review of the literature, March to September 2020. Euro Surveill. 2021;26(14):pii=2001506. https://doi.org/10.2807/1560-7917.ES.2021.26.14.2001506

Une médiane à 9 jours mais jusqu'à 21 jours

After reviewing 160 studies, the authors conclude (not surprisingly) significant heterogeneity in reported data. The median duration after symptom onset that virus was successfully isolated was 9 days (IQR: 2.25; range: 2–21), while the corresponding median value for longest duration until viral clearance by RT-PCR was 26 days (IQR: 16.8; range: 8–63).

12 avril 2021

Sunday evening: Cold, heavy rain. Curfew. Exponential growth of infections. ICUs on the limit, vaccines are still in shortage. Politicians quarrel over lockdown rules. Everyone tired. Johnson & Johnson’s vaccine may bear the same clotting risk as Astra Zeneca’s Vaxzevria®: https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-6-9-april-2021

Johnson & Johnson : anaphlaxie et thromboembolie observées de prés dans les essais cliniques avant la phase IV et à son décours.

Depressed? Well, here are some good news.

Shen X, Tang H, Pajon R, et al. Neutralization of SARS-CoV-2 Variants B.1.429 and B.1.351. NEJM April 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2103740?query=featured_home

Sacré africain du sud : même pas peur.

Vaccine-elicited neutralizing antibodies are likely to remain effective against the B.1.429 variant (“California”). The modestly lower value in neutralization titers was similar to B.1.1.7, using serum from recipients of the mRNA-1273 (Moderna) and NVX-CoV2373 (Novavax). The magnitude of resistance seen with the B.1.351 variant is of greater concern. However, this is good news, because immune escape seems to be limited in most variants.

Ramakrishnan S, Nicolau Jr DV, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Resp Med April 09, 2021. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltext

Un corticoïde inhalé efficace ?

In this open-label, phase 2 RCT in 146 adults with mild COVID-19 symptoms, early administration of inhaled budesonide within 7 days reduced the likelihood of needing urgent medical care (1% vs 14%) and reduced time to recovery after early COVID-19. The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. According to the authors, their findings “require urgent validation and dissemination”. However, this encouraging early data is good news and the differences in the endpoints are impressive. Inhaled budesonide is a simple, safe, well studied, inexpensive, and widely available treatment. A game changer – if confirmed by a phase 3 RCT.

11 avril 2021

Greinacher A, Thiele T, Warkentin TE, et al. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. NEJM April 9, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2104840?query=featured_home

Vers une confirmation du mécanisme TIH-like

A case series of 11 patients (9 women) from Germany and Austria in whom thrombosis or thrombocytopenia developed after vaccination with ChAdOx1 nCov-19. All had moderate-to-severe thrombocytopenia and thrombotic complications at unusual sites beginning 5-16 days after first vaccination. All had platelet-activating antibodies directed against platelet factor 4 (PF4)–heparin.

Schultz NH, Sørvoll ICH, Michelsen AE, et al. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. NEJM April 9, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2104882?query=featured_home

Idem publication ci-dessus de Greinacher et al.

Another five patients (four women) from Norway. Same findings.

10 avril 2021

Havervall S, Rosell A, Phillipson M, et al. Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers. JAMA April 7, 2021, https://jamanetwork.com/journals/jama/fullarticle/2778528?resultClick=1

Covid long chez des travailleurs de la santé séropositifs ou non au SARS-CoV-2 (voir image ci-dessous)

Probably one of the best longitudinal studies on long COVID-19 to date, comparing 323 seropositive (with mild disease) vs 1072 seronegative HCW. At 8 months, 15% vs 3% (at 2 months: 26% vs 9%) reported at least one moderate to severe symptom. Symptoms disrupted work, social, and home life.

Van Praet JT, Vandecasteele S, de Roo A, et al. Humoral and cellular immunogenicity of the BNT162b2 mRNA Covid-19 Vaccine in nursing home residents. Clin Inf Dis, ciab300, April 7, 2021. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab300/6213866?searchresult=1

Des résultats peu surprenants si l'on en juge par la seule immunosénescence. Toutefois à confirmer. 

Four weeks after the first dose, the humoral and cellular immunogenicity of the BNT162b2 mRNA vaccine (BioNTech/Pfizer) was suboptimal in COVID-19-naïve nursing home residents in comparison to COVID-19-naïve healthcare workers.

Moyo-Gwete T, Madzivhandila M, Makhado Z, et al. Cross-Reactive Neutralizing Antibody Responses Elicited by SARS-CoV-2 501Y.V2 (B.1.351). NEJM April 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104192?query=featured_home

De la conception de vaccins efficaces sur les mutants.

Infection with B.1.351 (South Africa) elicits robust neutralizing antibody responses against P.1 (Brazil) and the original variants, which indicates high levels of cross-reactivity. Vaccines built on the spike protein of B.1.351 may be promising candidates for the elicitation of cross-reactive responses.

Lustig Y, Nemet I, Kliker L, et al. Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2. NEJM April 7, 2021. https://www.nejm.org/doi/full/10.1056/NEJMc2104036?query=featured_home

De quoi rassurer celles et ceux qui ont été vaccinés par le Pfizer

In six HCW who had been infected with the original virus, one shot of BNT162b2 (BioNTech/Pfizer) induced robust neutralizing antibody responses against all variants of concern, including B.1.351 from South Africa.

9 avril 2021

Doria-Rose N, Suthar MS, Makowski M, et al. Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19. N Engl J Med. 2021 Apr 6. PubMed: https://pubmed.gov/33822494. https://www.nejm.org/doi/10.1056/NEJMc2103916

Immunité supérieure à 6 mois après deuxième injection de Moderna.

In 33 healthy adult participants in an ongoing Phase I trial, antibodies that were elicited by mRNA-1273 (Moderna) persisted through 6 months after the second dose, as detected by three distinct serologic assays.

Westhölter D, Taube C. SARS-CoV-2 outbreak in a long-term care facility after vaccination with BNT162b2. Clin Inf Dis April 7, 2021, ciab299. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab299/6213878?searchresult=1

Cluster et décès en établissement allemand après vaccination par Pfizer. Comme attendu, aucune protection un et quatre jours après la première injection.

What a disaster. In early January 2021, 73/76 (96%) residents and about 90% of the employees in an elderly care home in North-Rhine Westfalia, Germany, received a first dose of BNT162b2 (BioNTech/Pfizer). SARS-CoV-2 rapid antigen tests were all negative among residents and participating employees the day before. However, a member of the mobile vaccination team as well as an employee reported respiratory symptoms one and four days after vaccination respectively and tested positive for SARS-CoV-2 by PCR. Overall case fatality rate was 9/26 (35%).

7 avril 2021

Hippich M, Sifft P, Zapardiel-Gonzalo J, et al. A Public Health Antibody Screening Indicates a Marked Increase of SARS-CoV-2 Exposure Rate in Children during the Second Wave. Med April 02, 2021. https://www.cell.com/med/fulltext/S2666-6340(21)00121-5

Deuxième vague, enfants et Bavière.

In this large monitoring study from Bavaria, Germany, antibody frequencies in 2021 were eight-fold higher than those observed at the end of the first wave and remained three- to four-fold higher than the cumulative reported PCR positive frequencies in both pre-school and school children. Among the 413 PCR-positive children who completed questionnaires regarding symptoms, no symptoms were reported in 68% of antibody-positive pre-school children and in 52% of school children.

6 avril 2021

Hosp JA, Dressing A, Blazhenets G, et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain April 3, 2021, awab009, https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab009/6209743?searchresult=1

Covid-19 et troubles cognitifs avec atteinte frontopariétale

Cognitive deficits are present in many COVID-19 patients requiring in-patient treatment. Of 15 patients undergoing extended neuropsychological testing, only two patients performed entirely normally. Orientation and language abilities were in the range of healthy subjects, while memory and executive items were most severely affected, making general deterioration unlikely. There was no decline in general attention or speed of processing. This specific pattern can hardly be explained by non-specific factors like fatigue. It also differs from cognitive impairment post-sepsis. Many patients displayed frontoparietal cognitive dysfunctions and 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism.

5 avril 2021

Woolf SH, Chapman DA, Sabo RT. Excess Deaths From COVID-19 and Other Causes in the US, March 1, 2020, to January 2, 2021. JAMA April 2, 2021. https://jamanetwork.com/journals/jama/fullarticle/2778361?resultClick=1

Une simple "grippette" :

Between March 1, 2020, and January 2, 2021, the US experienced 2,801,439 deaths, 22.9% more than expected, representing 522,368 excess deaths. The 22.9% increase in all-cause mortality reported here far exceeds annual increases observed in recent years (≤ 2.5%). Deaths attributed to COVID-19 accounted for 72.4% of US excess deaths.

The SARS-CoV-2 variant with lineage B.1.351 clusters investigation team. Linked transmission chains of imported SARS-CoV-2 variant B.1.351 across mainland France, January 2021. Euro Surveill 2021;26(13):pii=2100333. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.13.2100333

C'est gentil de ne pas répondre aux questions ! 

Two cases had travelled in mid-December 2020 with a group to Mozambique where they participated in a religious gathering and returned with the B.1.351 variant. A joint team of epidemiologists, public health workers and clinical and virological specialists co-operated across France to urgently investigate and initiate control measures. A total of 36 cases were analyzed. Believe it or not: “Another challenge was that some members of the clusters did not agree to answer questions”.

4 avril 2021

Cobey S, Larremore DB, Grad YH. et al. Concerns about SARS-CoV-2 evolution should not hold back efforts to expand vaccination. Nat Rev Immunol April 2, 2021. https://www.nature.com/articles/s41577-021-00544-9

La pression vaccinale compensée par son efficacité ?

Marc Lipsitch and colleagues argue that as long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation.

Malhotra HS, Gupta P, Prabhu V. COVID-19 vaccination-associated myelitis. QJM 31 March 2021, hcab069, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab069/6206408?searchresult=1

Un nouvel effet adverse de l'AstraZeneca ?

A rare case of myelitis, seen with the ChAdOX1 nCoV-19 vaccine. On the 8th post-vaccination day, this 38 yr old man presented with abnormal sensations in both lower limbs.

2 avril 2021

Etude américaine sur les facteurs de risque d'infection, d'hospitalisation et de décès dans les établissements américains pour personnes âgées :

Surlignage et mise en exergue en rouge par l'auteur de ce blog :

RESULTS Among 482 323 long-stay residents included, the mean (SD) age was 82.7 (9.2) years, with 326 861 (67.8%) women, and 383 838 residents (79.6%) identifying as White. Among 137 119 residents (28.4%) diagnosed with SARS-CoV-2 during follow up, 29 204 residents (21.3%) were hospitalized, and 26 384 residents (19.2%) died within 30 days. Nursing homes explained 37.2% of the variation in risk of infection, while county explained 23.4%.

Risk of infection increased with increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) (eg, BMI>45 vs BMI 18.5-25: adjusted hazard ratio [aHR], 1.19; 95% CI, 1.15-1.24) but varied little by other resident characteristics.

Risk of hospitalization after SARS-CoV-2 increased with increasing BMI (eg, BMI>45 vs BMI 18.5-25: aHR, 1.40; 95% CI, 1.28-1.52); male sex (aHR, 1.32; 95% CI, 1.29-1.35); Black (aHR, 1.28; 95% CI, 1.24-1.32), Hispanic (aHR, 1.20; 95% CI, 1.15-1.26), or Asian (aHR, 1.46; 95% CI, 1.36-1.57) race/ethnicity; impaired functional status (eg, severely impaired vs not impaired: aHR, 1.15; 95% CI, 1.10-1.22); and increasing comorbidities, such as renal disease (aHR, 1.21; 95% CI, 1.18-1.24) and diabetes (aHR, 1.16; 95% CI, 1.13-1.18).

Risk of mortality increased with age (eg, age >90 years vs 65-70 years: aHR, 2.55; 95% CI, 2.44-2.67), impaired cognition (eg, severely impaired vs not impaired: aHR, 1.79; 95% CI, 1.71-1.86), and functional impairment (eg, severely impaired vs not impaired: aHR, 1.94; 1.83-2.05).

Source : https://www.geriatrie-albi.com/mehta_2021.pdf

Jentsch PC, Anand M, Bauch CT. Prioritising COVID-19 vaccination in changing social and epidemiological landscapes: a mathematical modelling study. Lancet Inf Dis March 31, 2021. https://www.thelancet.com/action/showPdf?pii=S1473-3099%2821%2900057-8

The oldest-first strategy is not always the best option. This modelling study shows that in populations in which SARS-CoV-2 seropositivity is high, a contact-based strategy allocating vaccines according to the relative role played by different age groups in transmission may be more effective that targeting vulnerable groups.

Dejnirattisai W, Zhou D, Supasa P, et al. Antibody evasion by the P.1 strain of SARS-CoV-2. Cell March 30, 2021. https://www.cell.com/cell/fulltext/S0092-8674(21)00428-1

All new strains (P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK) have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, conferring similar increased affinity for ACE2. Surprisingly, P.1 was significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain impact neutralization.

Neutralization of P.1 and other variants by vaccine serum. (C) Pfizer vaccine, serum taken 7-17 days following the second dose (n = 25). (D) AstraZenca vaccine, serum taken 14 or 28 days following the second dose (n = 25).

Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations: P.1 from Brazil, B.1.351 from South Africa and B.1.1.7 from the UK (12, 10 and 9 changes in the spike respectively). All have mutations in the ACE2 binding site with P.1 and B.1.351 having a virtually identical triplet: E484K, K417N/T and N501Y, which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine induced antibody responses than B.1.351 suggesting that changes outside the RBD impact neutralisation. Monoclonal antibody 222 neutralises all three variants despite interacting with two of the ACE2 binding site mutations, we explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.

Ayoubkhani D, Khunti K, Nafilyan V, et al. Post-covid syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ 2021;372: n693. 31 March 2021. https://www.bmj.com/content/372/bmj.n693

Le "Covid long"

47,780 hospitalized patients (mean age 65) discharged alive by 31 August 2020 were exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics. Over a mean follow-up of 140 days, nearly a third were readmitted and more than 1 in 10 died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group. Rates of multi-organ dysfunction after discharge were raised compared to the matched control group, suggesting extrapulmonary pathophysiology. As shown in the Figure, diabetes and major adverse cardiovascular event were particularly common.

1er avril 2021

Jagannathan P, Andrews JR, Bonilla H, et al. Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nat Commun March 30, 2021, 12, 1967. https://www.nature.com/articles/s41467-021-22177-1

Next disappointment: in this well-conducted, placebo-controlled RCT, a single dose of subcutaneous peg-interferon lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in out-patients with uncomplicated COVID-19.

aplan–Meier analyses of the primary and key secondary outcomes in the intention-to-treat population.

31 mars 2021

Pfizer et Moderna chez les professionnels de santé :

Thompson MG, Burgess JL, Naleway AL, et al. Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep. ePub: 29 March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7013e3.htm

In this prospective cohort of 3950 health care personnel, first responders, and other essential and frontline workers who completed weekly SARS-CoV-2 testing for 13 consecutive weeks, mRNA vaccine effectiveness of full immunization (≥ 14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status; vaccine effectiveness of partial immunization (≥ 14 days after first dose but before second dose) was 80%.

30 mars 2021

By C. Hoffmann & B. S. Kamps
Copy-editor: Rob Camp

One year ago, we published the first edition of COVID Reference. It was a document on the fulminant accumulation of clinical knowledge about an emergent infectious disease in the previous three months. At that time, treatment strategies were tentative, the unutterable hydroxychloroquine was still en vogue, the multisystem inflammatory syndrome in children (MIS–C) as yet unheard of, and nobody knew about Long COVID or variants.

Since then, we have come a long way. An ultra-connected and worldwide cooperating science community has discovered – sometimes to their own surprise – how much they can achieve in a short time. Today, 15 months into the pandemic, more than 300 million people have been vaccinated. The development of these ultra-potent SARS-CoV-2 vaccines will be remembered as a milestone in medicine. They have opened new horizons and set a new benchmark for future pandemics.

29 mars 2021

Kupferschmidt K, Vogel G. A rare clotting disorder may cloud the world’s hopes for AstraZeneca’s COVID-19 vaccine. Science 2021, published 27 March. Full text: https://www.sciencemag.org/news/2021/03/rare-clotting-disorder-may-cloud-worlds-hopes-astrazenecas-covid-19-vaccine

https://gth-online.org/wp-content/uploads/2021/03/GTH_Stellungnahme_AstraZeneca_engl._3_22_2021.pdf

La physiopathologie des syndromes associant thromboses et hémorragies après vaccination AstraZeneca laisse penser que l'héparine et des immunoglobulines intraveineuses pourraient être utiles dans des conditions précises. Voir ci-dessus la publication de Kupferschmidt et celle d'Oldenburg et al. ci-dessous.

VIPIT – vaccine-induced prothrombotic immune thrombocytopenia – is a preliminary explanation for the unusual strokes and clotting disorders recorded in at least 30 recipients of the AstraZeneca vaccine. A summary.

Now, a group of researchers led by German clotting specialist Andreas Greinacher of the University of Greifswald says the highly unusual combination of symptoms—widespread blood clots and a low platelet count, sometimes with bleeding—resembles a rare side effect of the blood thinner heparin called heparin-induced thrombocytopenia (HIT).

In the event of side effects that persist or recur > 3 days after vaccination (e.g., dizziness; headache; visual disturbances; nausea / vomiting; shortness of breath; acute pain in chest, abdomen, or extremities), further medical diagnostics should be carried out to clarify a thrombosis. 

Source :

https://gth-online.org/wp-content/uploads/2021/03/GTH_Stellungnahme_AstraZeneca_engl._3_22_2021.pdf

Moschovis PP, Yonker LM, Shah J, et al. Aerosol transmission of SARS-CoV-2 by children and adults during the COVID-19 pandemic. Pediatric Pulmonology 2021. Full text: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ppul.25330

The authors outline the major methods of transmission of SARS-CoV-2 focusing on aerosol transmission and reviewing the principles of aerosol science and discussing their implications for mitigating the spread of SARS-CoV-2.

Cliquer sur l'image pour l'agrandir :

28 mars 2021