Convalescent plasma for preventing critical illness in COVID-19: A phase 2 trial and immune profile

Abstract

Rationale: The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an unprecedented event requiring rapid adaptation to changing clinical circumstances. Convalescent immune plasma (CIP) is a promising treatment that can be mobilized rapidly in a pandemic setting. Objectives: We tested whether administration of SARS-CoV-2 CIP at hospital admission could reduce the rate of ICU transfer or 28 day mortality. Methods: In a single-arm phase II study, patients >18 years-old with respiratory symptoms documented with COVID-19 infection who were admitted to a non-ICU bed were administered two units of CIP within 72 hours of admission. Detection of respiratory tract SARS-CoV-2 by polymerase chain reaction and circulating anti-SARS-CoV-2 antibody titers were measured before and at time points after CIP transfusion. Measurements and Main Results: Twenty-nine patients were transfused CIP and forty-eight contemporaneous controls were identified with comparable baseline characteristics. Levels of anti-SARS-CoV-2 IgG, IgM, and IgA anti-spike, anti-receptor-binding domain, and anti-nucleocapsid significantly increased from baseline to post-transfusion for all proteins tested. In patients transfused with CIP, the rate of ICU transfer was 13.8% compared to 27.1% for controls with a hazard ratio 0.506 (95% CI 0.165-1.554), and 28-day mortality was 6.9% compared to 10.4% for controls, hazard ratio 0.640 (95% CI 0.124-3.298). Conclusions: Transfusion of high-titer CIP to patients early after admission with COVID-19 respiratory disease was associated with reduced ICU transfer and 28-day mortality but was not statistically significant. Follow up randomized trials may inform the use of CIP for COVID-19 or future coronavirus pandemics.

Lessons learned from the use of convalescent plasma for the treatment of COVID-19 and specific considerations for immunocompromised patients

“…There were 13 RCTs, of which four were categorized as Oxford LoE 2 [25,26,28,33], seven were downgraded to Oxford LoE 3 [21][22][23][29][30][31][32], and two to Oxford LoE 4 [24,27]. Of the remaining papers, eight were prospective controlled clinical trials, of which three were categorized as Oxford LoE 3 [34,35,50], four as Oxford LoE 4 [46,48,53,55], and one as Oxford LoE 5 [37]. Of the 16 matched case-control series, 14 were categorized as Oxford LoE 4 [20, 36, 38-41, 43, 44, 47, 49, 51, 52, 54, 56] and two as Oxford LoE 5 [42,45].…”

“…The impact of CovCP on the clinical status of patients with COVID-19 was also difficult to assess because the parameters evaluated in the studies with available results were inconsistent (Table 3). In some studies, no statistically significant improvements in clinical outcomes were observed [21,22,26,28,29,31,33,37,39,40,42,44,46,49,52,53]. In contrast, other studies showed benefits of CovCP in terms of disease progression [23,25,27], mitigation of hypoxia [30], World Health Organization (WHO) severity score [32], respiratory parameters [24,54], rate and time to clinical improvement [20,34], need for intubation [50], extubation rate [35], recovery time from critical illness [55], rate of MV and vasopressor support [51], rate of transfer to MV [41], and clinical status [38] in the overall study population or specific subgroups of patients with COVID-19.…”

“…In 25 of 37 articles identified during screening 1, mortality rates were significantly lower [20, 29, 34, 40, 41, 43, 47-49, 54, 55] or tended to be lower [25,27,30,32,35,37,38,42,44,[50][51][52][53]56] in all patients or specific subpopulations of patients with COVID-19 who received CovCP compared with control patients (Table 3). In other studies, no positive impact of CovCP infusions on mortality rates was detected [21-24, 26, 28, 31, 33, 36, 39, 45, 46].…”

The protective immunity induced by SARS-CoV-2 infection and vaccination: a critical appraisal

“…Moreover, convalescent plasma [185,186] and monoclonal neutralizing antibodies [187,188] have relatively limited effects on COVID-19 evolution. Finally, neutralizing antibodies comprise a heterogeneous array of antibodies of different isotypes, affinities, kinetics, functionality, and specificities [104,105,184,189,190] making it unrealistic to assign a single effect to them.…”