Efficacy and safety of convalescent plasma to treat hospitalised COVID-19 patients with or without underlying immunodeficiency: a randomized clinical trial (preprint)

Background: Efficacy of COVID-19 convalescent plasma (CCP) in COVID-19 pneumonia is uncertain. Early transfusion of high antibody titre CCP may be beneficial, especially in case of underlying immunosuppression. Methods: The CORIPLASM study was a multicentric, open-label, Bayesian randomised clinical trial evaluating the efficacy of CCP in patients with moderate COVID-19 pneumonia, including patients with underlying immunosuppression. Patients hospitalised with COVID-19 for less than 9 days were assigned to receive 2 plasma units/day over 2 days (CCP) or usual care (UC) alone. Primary outcomes were the proportion of patients with a WHO-Clinical Progression Score (CPS) >= 6 on the 10-point scale on day 4 and survival without ventilation or additional immunomodulatory treatment by day 14. Main analysis was conducted on the whole population and a planned subgroup analysis was performed according to immunosuppression status. Findings: A total of 120 patients were recruited between April 16, 2020, and April 21, 2021, and assigned to CCP (n=60) or UC (n=60) with a 28 day-follow-up. The median time from symptoms onset to randomisation (days) was 7.0 [interquartile range (IQR) 5.0-9.0] and 7.0 [IQR 4.0-8.5] in CCP and UC, respectively. Thirteen (22%) patients with CCP had a WHO-CPS >= 6 at day 4 versus 8 (13%) with UC, adjusted odds ratio (aOR) 1.88 [95% confidence interval (CI), 0.71 to 5.24]. By d14, 19 (31.6%) patients with CCP and 20 (33.3%) patients with UC had ventilation, additional immunomodulatory treatment or had died. Cumulative incidence of death was 3 (5%) with CCP and 8 (13%) with UC at d14 (aHR 0.40 [95%CI 0.10 -1.53]), and 7 (12%) with CCP and 12 (20%) with UC at day 28 (aHR 0.51 [95% CI 0.20-1.32]). Subgroup analysis indicated that CCP might be associated with a lower mortality in patients with underlying immunosuppression (HR 0.37 [95% CI 0.14-0.97]). Serious adverse events were noted in 30 (50%) and 26 (43%) patients with CCP or UC, respectively. Interpretation: CCP treatment did not improve early outcomes in patients with mild-to-moderate form COVID-19 pneumonia but was associated with reduced mortality in the subgroup of immunosuppressed patients. Trial registration: clinicaltrials.gov Identifier: NCT04345991

Immunogenicity and Safety of Beta Adjuvanted Recombinant Booster Vaccine (preprint)

Background. Variant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response. Methods. In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a [≥] 10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15. Findings. The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor [≥]10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines. Interpretation. Heterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants.

Hospital Admissions for Acute Myocardial Infarction Before and After Lockdown According to Regional Prevalence of COVID-19 and Patient Profile (preprint)

Aim: to evaluate the impact of a nationwide lockdown in France on acute myocardial infarction (AMI) admissions, by patient characteristics and regional prevalence of the pandemic. Methods and Results: We collected data from 21 centres participating in the on-going FRENCHIE registry (NCT04050956), which collects data from all patients admitted for STEMI or NSTEMI within 48 hours of symptom onset. We compared weekly admissions in the 4 weeks preceding and the 4 weeks following institution of the lockdown. We observed a brutal 30% decrease in AMI admissions (24% for STEMI and 36% for NSTEMI, P=0.14) following institution of the lockdown, with similar trends according to gender (30% decrease in both men and women), risk factors, and regional prevalence of COVID-19. The decrease was numerically greater in patients aged 80 years or more (44% vs 27%, P=0.10). Patient characteristics, including time to hospital admission in STEMI patients, did not differ between the 2 periods. In-hospital mortality was numerically higher following institution of the lockdown (5.2% vs 3.4%, P=0.12), with similar trends for STEMI and NSTEMI. Conclusion: A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19. Health authorities should be aware of these findings, in order to adapt their message in case of a second wave of the pandemic or future major epidemics.Funding Statement: The FRENCHIE registry is supported by Recherche Hospitalo-universitaire en santé (RHU) iVasc within the programme "Investissements d'avenir", and sponsored by Assistance Publique – Hôpitaux de Paris (Délégation à la Recherche Clinique et à l'Innovation).Declaration of Interests: YC reports research Grants to the Institution or Consulting/Lecture Fees from : Novartis , Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Coste reports having received fees from Amgen, AstraZeneca, Bayer and Servier, outside the submitted work G. Lemesle reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BristolMyers Squibb, MSD, Novartis, Pfizer, Sanofi-Aventis, Servier, and The Medicine Co, outside the submitted work. FS reports personal fees from Amgen, Astra Zeneca, Bayer, BMS, MSD, Pfizer, and Sanofi, outside the submitted work D. Angoulvant reports receiving consulting and lecture fees from AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, Sanofi, Amgen, Novartis, Novo-Nordisk, Servier and MSD, outside the submitted work C. Bouleti reports receiving consulting and lecture fees from Novartis and AstraZeneca, outside the submitted work. G. Cayla has received research grants/consultant fees/lectures fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Pfizer, Sanofi-Aventis, outside the submitted work. P. Goube reports receiving consulting and lecture fees from AMGEN, SANOFI, BMS, ABBOT, outside the submitted work. T. Lhermusier has received research grants/consultant fees/lectures fees from AstraZeneca, Boston scientifics and Abbott, outside the submitted work A. Saib reports lectures fees from Novartis, outside the submitted work JG Dillinger reports receiving consulting and lecture fees from AstraZeneca, Bayer, BoehringerIngelheim, Bristol-Myers Squibb/Pfizer, Sanofi, and Daiichi-Sankyo and grants from Bayer, BristolMyers Squibb/Pfizer and Biosensors, outside the submitted work. F. Boccara reports research grants from Amgen; lecture fees from Janssen, Gilead, ViiV Healthcare, Amgen, Sanofi, MSD, and Servier outside the submitted work. And personal consultant or lecture fees from Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Intercept, MSD, Novartis, Pfizer, Sanofi, and Servier, outside the submitted work. T. Simon reports grants from Astrazeneca, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Sanofi, and personal fees for board membership and/or consultancy and/or lectures from AstraZeneca, BMS, Sanofi, and Novartis, outside the submitted work. N. Danchin has received research grants, or speaking and consulting fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli-Lilly, Intercept, MSD, Novartis, Novo-Nordisk, Pfizer, Sanofi, Servier, outside the submitted work. The other authors have nothing to report.Ethics Approval Statement: FRENCHIE has been approved by the Comité de Protection des Personnes and by the French data regulatory authority (Commission Nationale de l'Informatique et des Libertés).