Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

Egloff, Shanna A Arnold; Junglen, Angela; Restivo, Joseph S.A.; Wongskhaluang, Marjorie; Martin, Casey; Doshi, Pratik; Schlauch, Daniel; Fromell, Gregg; Sears, Lindsay E.; Correll, Mick; Burris, Howard A.; LeMaistre, Charles F.

doi:10.1172/jci151788

Cited by 39 publications

(39 citation statements)

References 37 publications

(45 reference statements)

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“…If so, the beneficial effect observed on less severely ill patients could be indeed inexistent. While that is a certain possibility, a large body of evidence points to a beneficial effect of early plasma on non-intubated patients with COVID-19 pneumonia 9 16–28. We did not measure antibody levels in all patients.…”

Section: Discussionmentioning

confidence: 95%

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia

González

Regairaz

Salazar

et al. 2022

Journal of Investigative Medicine

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This is a multicenter cohort study including consecutive, hospitalized patients ≥18 years, with moderate to severe COVID-19, carried out to evaluate the relationship between the timing of convalescent plasma administration and 28-day mortality. Data were prospectively collected between May 14, 2020 and October 31, 2020. Patients were grouped according to the timing of administration of convalescent plasma as <3 days, between 3 and 7 days, and >7 days. The main outcome variable was 28-day mortality. Independent predictors of mortality were identified by logistic regression. Of 4719 patients receiving convalescent plasma, 3036 (64.3%) were in the general ward, 1171 (24.8%) in the intensive care unit (ICU), and 512 (10.8%) in the ICU on mechanical ventilation. Convalescent plasma was administered to 3113 (66%) patients within the first 3 days of hospital admission, to 1380 (29.2%) between 3 and 7 days, and to 226 after 7 days; 28-day mortality was, respectively, 18.1%, 30.4% and 38.9% (p<0.001). In the regression model, convalescent plasma administration within the first 3 days of admission was associated with reduced 28-day mortality, compared with the administration after 7 days (OR 0.40, 95% CI 0.30 to 0.53). Early convalescent plasma administration was associated to a significant decreased mortality in patients in the general ward (OR 0.45, 95% CI 0.29 to 0.69) and in the ICU (OR 0.35, 95% CI 0.19 to 0.64), but not in those requiring mechanical ventilation (OR 0.52, 95% CI 0.27 to 1.01). In conclusion, this study suggests that early administration of convalescent plasma to patients with COVID-19 pneumonia is critical to obtain therapeutic benefit.

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Section: Discussionmentioning

confidence: 95%

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia

González

Regairaz

Salazar

et al. 2022

Journal of Investigative Medicine

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“…Convalescent plasma or sera transfusion has been highlighted as a promising therapy in fighting newly emerged viral infections. Indeed, transfusion of convalescent plasma harvested from recovered COVID-19 patients is reported to be beneficial in treating critically ill patients with SARS-CoV-2 infection (32)(33)(34)(35). Given the neutralization resistance of SARS-CoV-2 VOCs to convalescent sera collected from individuals infected with WT SARS-CoV-2 infection in early 2020, transfusion of these convalescent sera might not be suitable in treating COVID-19 patients infected with SARS-CoV-2 VOCs.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody

Yue

Yang

et al. 2021

Front. Immunol.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). Though vaccines and neutralizing monoclonal antibodies (mAbs) have been developed to fight COVID-19 in the past year, one major concern is the emergence of SARS-CoV-2 variants of concern (VOCs). Indeed, SARS-CoV-2 VOCs such as B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and B.1.617.1 (India) now dominate the pandemic. Herein, we found that binding activity and neutralizing capacity of sera collected from convalescent patients in early 2020 for SARS-CoV-2 VOCs, but not non-VOC variants, were severely blunted. Furthermore, we observed evasion of SARS-CoV-2 VOCs from a VH3-30 mAb 32D4, which was proved to exhibit highly potential neutralization against wild-type (WT) SARS-CoV-2. Thus, these results indicated that SARS-CoV-2 VOCs might be able to spread in convalescent patients and even harbor resistance to medical countermeasures. New interventions against these SARS-CoV-2 VOCs are urgently needed.

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“…Depending on the statistical model, the RR for 30-day mortality in high-titer CCP compared to low-titer CCP recipients ranged from 0.64 – 0.67, with an upper 95% confidence bound of 0.91 (8). Similarly, the large retrospective PSM study from HCA reported a 0.2% decreased risk of mortality for every 1 unit of S/Co serology level (28).…”

Section: Resultsmentioning

confidence: 94%

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

Focosi¹,

Franchini

Pirofski

et al. 2021

Preprint

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Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light into mechanisms of action, safety and efficacy of convalescent plasma using modern evidence-based medicine approaches. Studies ranging from observational case series to randomized controlled trials (RCT) have reported highly variable efficacy results for COVID-19 CP (CCP), resulting in more doubt than certainty. Reasons for CCP success and failure may be hidden in study details, which are usually difficult to explain to physicians and the public but provide fertile ground for designing next-generation studies. In this paper we analyzed variables associated with efficacy such as clinical settings, disease severity, CCP SARS-CoV-2 antibody levels and function, dose, timing of administration (variously defined as time from onset of symptoms, molecular diagnosis, diagnosis of pneumonia, or hospitalization, or by serostatus), outcomes (defined as hospitalization, requirement for ventilation, clinical improvement or mortality), CCP provenance and time for collection, and criteria for efficacy. Focusing only on the results from the 23 available RCT we noted that these were more likely to show signals of efficacy, including reductions in mortality, if the plasma neutralizing titer was ≥ 160 and the time to randomization was ≤ 9 days, consistent with passive antibody therapy efficacy requiring dosing with sufficient antibody. The fact that most studies revealed signals of efficacy despite variability in CCP and its use suggest robust therapeutic effects that become apparent despite the data noise.

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Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19

Cited by 39 publications

References 37 publications

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia

Timing of convalescent plasma administration and 28-day mortality in COVID-19 pneumonia

Sensitivity of SARS-CoV-2 Variants to Neutralization by Convalescent Sera and a VH3-30 Monoclonal Antibody

COVID-19 convalescent plasma and randomized clinical trials: explaining conflicting outcomes and finding signals of efficacy

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