Revue de bibliographie quotidienne Covid-19 (archives du 18 mars au 23 mai 2021)
Publié par Bernard Pradines
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.
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.
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.
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.
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.
SARS-CoV-2-positive placentas show a particular lesion characterized by trophoblast necrosis and intervillous space collapse. It can be seen as tinyfociin the less affected cases or as massively extensive lesions in the more severe ones.
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 thein vitroSARS-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.
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.
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, orvice 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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
Paper of the day:The RECOVERY resultsdo supportthe 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 :
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)
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.
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.
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.
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 :
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.
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.
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, 2021https://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
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%).
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).
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.
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.
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.
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.
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.
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.
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.
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%).
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.
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.
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.
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”.
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.
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).
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.
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%.
One year ago, we published thefirst 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 stillen 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.
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.
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.
On 26 March, the French National Medicine Safety Agency (Agence nationale pour la sécurité du médicament et des produits de Santé –ANSM) declared that there is a risk of atypical thrombosis associated with the AstraZeneca vaccine. The Agency reports 9 cases of big vein thromboses that are atypical by their location (mostly cerebral, but also digestive) and associated with thrombocytopenia and coagulation disorders. With some 1,430,000 injections of the AstraZeneca vaccine as of 18 March 2021, this is one case per 158,000 injections. These cases occurred within a median time of 8.5 days after vaccination in persons without particular risk factors (7 patients under 55 years of age, 2 more than 55 years). Between 12 and 18 March, two deaths were reported, including that of a medical student who died several days after being vaccinated. In the coming months of relative vaccine abundance, the AstraZeneca vaccine does not have a good star.
McEllistrem MC, Clancy CJ, Buehrle DJ, et al.Single dose of a mRNA SARS-CoV-2 vaccine is associated with lower nasopharyngeal viral load among nursing home residents with asymptomatic COVID-19. Clin Infect Dis 2021, published 26 March. Full text:https://doi.org/10.1093/cid/ciab263
In nursing home residents with asymptomatic COVID-19 diagnosed through twice-weekly surveillance testing, single dose BNT162b2 vaccination (Pfizer-BioNTech) was associated with -2.4 mean log10lower nasopharyngeal viral load than that detected in absence of vaccination (p = 0.004).
27 mars 2021
Lefrancq N, Paireau J, Hozé N, et al.Evolution of outcomes for patients hospitalised during the first 9 months of the SARS-CoV-2 pandemic in France: A retrospective national surveillance data analysis.Lancet Regional Health, March 2021. Full-text:https://doi.org/10.1016/j.lanepe.2021.100087
Better get COVID-19 between waves when hospital capacities are not stretched to the limit. The authors find that both the probability of death and the probability of entering ICU were significantly correlated with COVID-19 ICU occupancy.
The preprint we presented on10 Februarynow published inScience. The study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.
Janssen : apparemment efficace à 85% pour éviter les formes graves liées au variant sud-africain501Y.V2
Source : Abdool Karim SS, de Oliveira T.New SARS-CoV-2 Variants — Clinical, Public Health, and Vaccine Implications.N Engl J Med 2021, published 24 March. Full text:https://doi.org/10.1056/NEJMc2100362
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25 mars 2021
Edara VV, Norwood C, Floyd K, et al.Infection and vaccine-induced antibody binding and neutralization of the B.1.351 SARS-CoV-2 variant.Cell Host Microbe 2021, published 20 March. Full text:https://doi.org/10.1016/j.chom.2021.03.009
Despite reduced antibody titers against the B.1.351 variant (first detected in South Africa), sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351. The authors conclude that protective humoral immunity may be retained against this variant.
The authors show that entry of all variants into human cells is susceptible to blockade by the entry inhibitors soluble ACE2, Camostat, EK-1 and EK-1-C4. In contrast, entry of B.1.351 and P.1 was partially (casirivimab) or fully (bamlanivimab) resistant to monoclonal antibodies. Moreover, entry of these variants was less efficiently inhibited by plasma from convalescent COVID-19 patients and sera from individuals vaccinated with the Pfizer-BioNTech vaccine.
Predictive models of immune protection are useful to identify immune correlates of protection to assist in the future deployment of vaccines. Here, the authors modelled the relationship betweenin vitroneutralisation levels and observed protection from SARS-CoV-2 infection using data from seven current vaccines as well as convalescent cohorts. They report that neutralisation level is highly predictive of immune protection. Attention: this is a pre-print, so don’t take the data for granted. However, in the future, with vaccines abundantly available, we will use figures such as Figure 1 to decide whether to prefer product A over product B.
Almost no flu this year. This 2020/21 influenza season is exceptional since the creation of the Global Influenza Surveillance and Response System (GISRS) network in 1952. Positivity was 0.1% (33/25,606) this season compared to an average positivity of 38% (14,966/39,407) between week 40 year X and week 8 the following year. Yes, this was statistically significant.
The future? An intranasally-administered chimpanzee adenovirus-vectored vaccine encoding a pre-fusion stabilized spike (S) protein (ChAd-SARS-CoV-2-S) worked well in macaques. A single intranasal dose induced neutralizing antibodies and T cell responses and limited or prevented infection in the upper and lower respiratory tract after a SARS-CoV-2 challenge.
Evidence grows that B.1.1.7 is more dangerous. In this data drawn from the OpenSAFELY electronic health records secure research platform (covering 40% of England’s population registered with a general practitioner), there was a consistently higher (about two thirds) absolute risk of death by 28 days after a SARS-CoV-2-positive test in all groups stratified by age, sex and presence of co-morbidities
19 mars 2021
Jevalikar G, Mithal A, Singh A, et al.Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19.Sci Rep 11, 6258 (2021).https://www.nature.com/articles/s41598-021-85809-y
Oh, again, no effect of vitamin D. In this prospective observational study on 404 patients, serum 25-OHD levels at admission did not correlate with inflammatory markers, clinical outcomes, or mortality in hospitalized COVID-19 patients. Treatment of vitamin D deficiency with cholecalciferol did not make any difference to the outcomes.
No protection from mild-to-moderate COVID-19 with AstraZeneca in this large RCT on young (median age 30 years), HIV-negative patients in South Africa. Infections were seen in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% CI, −49.9 to 59.8). Main caveat: as there were no cases of hospitalization in the study, it remains unclear whether ChAdOx1 nCov-19 may protect against severe infection with the B.1.351 variant.