Subcutaneous REGEN-COV Antibody Combination to Prevent #Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2109682
… combination of the monoclonal antibodies #casirivimab and #imdevimab
Subcutaneous REGEN-COV Antibody Combination to Prevent #Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2109682
… combination of the monoclonal antibodies #casirivimab and #imdevimab
#Covid-19 Breakthrough Infections in Vaccinated Health Care Workers | NEJM
►https://www.nejm.org/doi/full/10.1056/NEJMoa2109072
La constatation importante est la corrélation avec le titre d’#anticorps neutralisant ; si c’est confirmé une troisième dose ne serait nécessaire* qu’en-dessous d’une valeur seuil qui resterait à définir.
(* d’autant plus nécessaire que 19% des infectés ont quand même eu des symptômes persistant)
Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks).
A Blood Marker for the Vaccinated but Vulnerable? | Global Health NOW
https://www.globalhealthnow.org/2021-07/blood-marker-vaccinated-vulnerable
Caveats: The pool of infections was small, and the difference in antibody levels between infected and non-infected participants was not statistically significant.
Household Transmission of #SARS-CoV-2 from Children and Adolescents | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMc2031915
(Étude prolongeant la suivante :
Coronavirus : des centaines d’enfants américains infectés en colonie de vacances
►https://seenthis.net/messages/870068)
Les #enfants sont bien contagieux
This retrospective study showed that the efficient transmission of SARS-CoV-2 from school-age children and adolescents to household members led to the hospitalization of adults with secondary cases of Covid-19. In households in which transmission occurred, half the household contacts were infected. The secondary attack rates in this study were probably underestimates because test results were reported by the patients themselves and testing was voluntary. In addition, a third of the index patients returned home from camp after the onset of symptoms, when they were presumably not as infectious as they were before and during the onset of symptoms,5 and two thirds adopted physical distancing because of a known exposure at camp; both of these factors probably reduced the transmission of SARS-CoV-2 in the household. When feasible, children and adolescents with a known exposure to SARS-CoV-2 or a diagnosis of #Covid-19 should remain at home and maintain physical distance from household members.
Eric Topol sur Twitter : “New NEJM: mRNA vaccine (@BioNTech_Group/Pfizer) holds up very well in lab studies for immune response against B.1. 526 (New York), B.1.429 (California), B.1.1.7(UK)+ E484K #variants 👍” / Twitter
▻https://twitter.com/EricTopol/status/1392585566324068358
BNT162b2-Elicited Neutralization against New SARS-CoV-2 Spike Variants | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMc2106083
Effectiveness of the BNT162b2 Covid-19 Vaccine against the B.1.1.7 and B.1.351 #Variants | NEJM
▻https://www.nejm.org/doi/10.1056/NEJMc2104974
Effectiveness was estimated to be 87.0% (95% CI, 81.8 to 90.7) against the B.1.1.7 variant and 72.1% (95% CI, 66.4 to 76.8) against the B.1.351 variant [...]
The BNT162b2 vaccine was effective against infection and disease in the population of Qatar, despite the B.1.1.7 and B.1.351 variants being predominant within the country; however, vaccine effectiveness against the B.1.351 variant was approximately 20 percentage points lower than the effectiveness (>90%) reported in the clinical trial1 and in real-world conditions [...] Nevertheless, the reduced protection against infection with the B.1.351 variant did not seem to translate into poor protection against the most severe forms of infection (i.e., those resulting in hospitalization or death), which was robust, at greater than 90%.
Vaccine Breakthrough Infections with #SARS-CoV-2 Variants | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2105000
In accordance with New York State regulations regarding eligibility, 417 employees who had received a second dose of either the BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously were tested between January 21 and March 17, 2021, and weekly testing continued thereafter.
Deux patientes ont développé une forme légère de la maladie après la deuxième dose de #vaccin, 19 jours pour la première et 36 pour la seconde, le séquençage objectivant des #variants dans les deux cas.
Par ailleurs la #charge_virale de la première patiente était particulièrement élevée.
[...] our observations underscore the importance of the ongoing race between immunization and the natural selection of potential viral escape #mutants.
Covid-19 : infections post-vaccinales dues à des variants – Réalités Biomédicales
►https://www.lemonde.fr/blog/realitesbiomedicales/2021/05/05/covid-19-infections-post-vaccinales-dues-a-des-variants
Aux États-Unis, le 26 avril 2021, le Centre de prévention et de contrôle des maladies (CDC) dénombrait 9245 cas d’infections post-vaccinales survenues parmi plus de 95 millions de personnes qui avaient été complètement vaccinées. Dans 45 % de cas, il s’agit de personnes de plus de 60 ans. Soixante-trois pour cent des cas d’infections post-vaccinales ont été rapportés chez des femmes.
Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2102214
L’inefficacité du #vaccin AstraZeneca contre les formes légères et modérées de #COVID-19 en rapport avec le #variant « sud-africain » de #SARS-CoV-2 semble se confirmer.
Il n’y a pas eu de formes graves dans les deux groupes (AZ versus placebo), probablement en rapport avec le fait que les sujets testés étaient peu nombreux et qu’ils avaient moins de 65 ans.
METHODS
We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×1010 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose.
RESULTS
Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], −49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups.
CONCLUSIONS
A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.
Although the mRNA Covid-19 vaccines have modest neutralizing antibody activity after the first dose, they produce a greater increase in neutralizing activity after the second dose than that produced by the ChAdOx1 nCoV-19 and heterologous Sputnik V (adenovirus-26 followed by adenovirus-5 vector) Covid-19 vaccines.5,6,9 Neutralizing activity of the two mRNA vaccines against the B.1.351 variant has also been observed to be lower [voir ▻https://seenthis.net/messages/903588], by a factor of 8.6 (mRNA-1273 vaccine [Moderna]) or 6.5 (BNT-162b2 vaccine [Pfizer]) on pseudovirus neutralization assay, than activity against the D614G virus, whereas no difference was evident against the N510Y.V1 (B.1.1.7)–like mutant.
Eric Topol sur Twitter : “Keep in mind that there were 2 vaccines tested in clinical trials in South Africa vs B.1.351 Novavax 60% efficacy J & J 64% efficacy Most (>90%) of that efficacy was related to ⬇️mild/moderate infections So results for Astra Zeneca vs B.1.351 differs from the other 2 vaccines” / Twitter
▻https://twitter.com/EricTopol/status/1371947190906544128
Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMc2101667
#Vaccination chez les #SARS-CoV-2 séropositifs.
The antibody titers of vaccinees with preexisting immunity were 10 to 45 times as high as those of vaccinees without preexisting immunity at the same time points after the first vaccine dose (e.g., 25 times as high at 13 to 16 days) and also exceeded the median antibody titers measured in participants without preexisting immunity after the second vaccine dose by more than a factor of 6. Although the antibody titers of the vaccinees without preexisting immunity increased by a factor of 3 after the second vaccine dose, no increase in antibody titers was observed in the Covid-19 survivors who received the second vaccine dose.
Early High-Titer #Plasma Therapy to Prevent Severe #COVID-19 in Older Adults | NEJM
▻https://www.nejm.org/doi/10.1056/NEJMoa2033700
Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.
METHODS
We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.
RESULTS
A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P=0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.
CONCLUSIONS
Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19. (Funded by the Bill and Melinda Gates Foundation and the Fundación INFANT Pandemic Fund; Dirección de Sangre y Medicina Transfusional del Ministerio de Salud number, PAEPCC19, Plataforma de Registro Informatizado de Investigaciones en Salud number, 1421, and ClinicalTrials.gov number, NCT04479163. opens in new tab.)
Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2034545
Les anticorps développés après une infection par le #sars-cov2 sont protecteurs.
BACKGROUND
The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear.
METHODS
We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time.
RESULTS
A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike–seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike–seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P=0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status.
CONCLUSIONS
The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.)
Complément :
Past SARS-CoV-2 Infection Mostly Protects Survivors | The Scientist Magazine®
►https://seenthis.net/messages/896532
Traitement du COVID-19 par du plasma de convalescents.
Convalescent #plasma in the management of moderate #covid-19 in adults in India : open label phase II multicentre randomised controlled trial (PLACID Trial) | The BMJ
▻https://www.bmj.com/content/371/bmj.m3939
Échec, mais
The presence and levels of neutralising antibodies were not measured a priori
Covid-19 : le plasma de patients guéris ne fait pas de miracles - Le Parisien
▻https://www.leparisien.fr/societe/covid-19-le-plasma-de-patients-gueris-ne-fait-pas-de-miracles-23-10-2020-
... le service de santé britannique National Health Service, qui mène le même type d’essai sur le plasma, a fait remarquer que l’essai indien a utilisé des dons de plasma contenant entre 6 et 10 fois moins d’anticorps que ceux collectés au Royaume-Uni. Ce qui pourrait signifier qu’à doses plus fortes, les bénéfices pourraient être supérieurs.
A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2031304
Taux d’anticorps vérifié avant perfusion.
Échec.
... studies with specific antibodies administered within 72 hours of Covid-19 diagnosis in patients with risk factors for severe disease are currently ongoing or planned.
Early High-Titer Plasma Therapy to Prevent Severe COVID-19 in Older Adults | NEJM
►https://seenthis.net/messages/895468
Étude randomisée en double aveugle qui a utilisé du sérum de convalescents à haute teneur en anticorps chez des sujets âgés (> ou égal à 75 ans ou 64-74 ans avec au moins un facteur de risque) atteints d’une forme légère de covid-19 dans les premières 72 heures de la maladie : plus efficace que le placebo pour prévenir l’évolution vers une forme sévère.
Blood plasma treatment has limited effect for sickest COVID-19 patients | Imperial News | Imperial…
▻https://seenthis.net/messages/904487
Étude REMAP-CAP : Le plasma de convalescents n’est pas efficace dans les formes critiques.
RECOVERY trial closes recruitment to convalescent plasma treatment for patients hospitalised with COVID-19 — RECOVERY Trial
▻https://seenthis.net/messages/904490
Échec du plasma de patients guéris chez les malades hospitalisés
Une méta-analyse pessimiste quant à l’efficacité du plasma de convalescents dans le traitement du…
▻https://seenthis.net/messages/904494
Monoclonal Antibody Trial Halted for Safety Concern | Brief19
▻https://brief19.com/2020/10/13/monoclonal-antibody-trial-halted-for-safety-concern
This news casts doubt as to the wisdom and safety of the approach used by President Trump’s medical team.
Définitivement arrêté pour cause d’inefficacité; concernait des malades hospitalisés uniquement.
Lilly Statement Regarding NIH’s ACTIV-3 Clinical Trial | Eli Lilly and Company
▻https://www.lilly.com/news/stories/statement-activ3-clinical-trial-nih-covid19
A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2033130
Rapid Decay of #Anti–SARS-CoV-2 Antibodies in Persons with Mild #Covid-19 | NEJM
▻https://www.nejm.org/doi/10.1056/NEJMc2025179
COVID-19 : L’#immunité ne dure que 3 mois | santé log
▻https://www.santelog.com/actualites/covid-19-limmunite-ne-dure-que-3-mois
Encore une fois, un titre et une interprétation qui supposent que l’immunité ne repose que sur les seuls #anticorps (#immunité_humorale).
Sur 80 participants volontaires post-COVID-19, les chercheurs ont suivi l’immunité de 20 femmes et 14 hommes rétablis de formes bégnines de la maladie. Des tests d’anticorps ont été réalisés en moyenne tous les 36 jours après les premiers symptômes de l’infection. L’analyse aboutit à ce déclin très rapide du taux d’anticorps, sur quelques semaines.
Si le rôle protecteur des anticorps contre le SRAS-CoV-2 reste à évaluer, ces anticorps sont généralement un corrélat de l’immunité antivirale, et les niveaux d’anticorps anti-domaine de liaison correspondent à l’activité plasmatique contre le virus. Dans cette étude, la désintégration précoce des anticorps est exponentielle (voir visuel ci-contre) et plus rapide que dans le cas du coronavirus SARS-CoV-1 (SRAS). Enfin, il est difficile d’extrapoler au-delà de la période d’observation d’environ 90 jours mais il est probable que la désintégration des anticorps ralentit ensuite.
#Hydroxychloroquine with or without #Azithromycin in Mild-to-Moderate Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2019014?query=C19&cid=DM95777_NEJM_Registered_Users_and_InActive&bid=234
Étude brésilienne, 504 patients,
CONCLUSIONS
Among patients hospitalized with mild-to-moderate #Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.
#HCQ
A Randomized Trial of #Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2016638?query=featured_home
Étude randomisée en double aveugle : des sujets asymptomatiques ont reçu de l’HCQ ou un placebo dans les 4 jours après exposition (à « risque élevé » ou « modéré ») à des malades du COVID-19 : pas de différence statistiquement significative entre les deux groupes quant à une contamination (développement de symptômes ou PCR positif).
Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.
RESULTS
We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
CONCLUSIONS
After high-risk or moderate-risk exposure to #Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.
#HCQ
Study : Hydroxychloroquine doesn’t prevent Covid-19 infection if exposed
▻https://www.statnews.com/2020/06/03/hydroxychloroquine-does-not-prevent-covid-19-infection-in-people-who-have-
Even though the study used the gold standard methodology of conducting clinical research, outside researchers saw significant limitations. The study was conducted in an unusual way: over the internet, without patients being seen by study doctors.
Wrong but Useful — What #Covid-19 Epidemiologic Models Can and Cannot Tell Us | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMp2016822?source=nejmfacebook&medium=organic-social
Compassionate Use of #Remdesivir for Patients with Severe Covid-19 | NEJM
▻https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)
Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 | NEJM
►https://www.nejm.org/doi/full/10.1056/NEJMc2004973
SARS-CoV-2 was more stable on plastic and stainless steel than on copper and cardboard, and viable virus was detected up to 72 hours after application to these surfaces
Résumé : c’est une bestiole très collante : après 3 jours on en trouve encore des traces sur du plastique, de l’acier, du cuivre et du carton. (L’article n’indique pas au bout de combien de temps ce n’est plus contagieux, ne lui faites pas dire ce qu’il ne dit pas.)