Treatment of severe COVID-19 with convalescent plasma in Bronx, NYC

Abstract

Convalescent plasma with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) antibodies (CCP) may hold promise as a treatment for coronavirus disease 2019 (COVID-19). We compared the mortality and clinical outcome of patients with COVID-19 who received 200 mL of CCP with a spike protein IgG titer ≥ 1:2430 (median 1:47,385) within 72 hours of admission with propensity score-matched controls cared for at a medical center in the Bronx, between April 13 and May 4, 2020. Matching criteria for controls were age, sex, body mass index, race, ethnicity, comorbidities, week of admission, oxygen requirement, D-dimer, lymphocyte counts, corticosteroid use, and anticoagulation use. There was no difference in mortality or oxygenation between CCP recipients and controls at day 28. When stratified by age, compared with matched controls, CCP recipients less than 65 years had 4-fold lower risk of mortality and 4-fold lower risk of deterioration in oxygenation or mortality at day 28. For CCP recipients, pretransfusion spike protein IgG, IgM, and IgA titers were associated with mortality at day 28 in univariate analyses. No adverse effects of CCP were observed. Our results suggest CCP may be beneficial for hospitalized patients less than 65 years, but data from controlled trials are needed to validate this finding and establish the effect of aging on CCP efficacy.

Keywords: COVID-19; Immunoglobulins; Infectious disease.

Figure 1. Enrollment of study patients and distribution of study cohorts.

Study baseline was defined as time of CCP transfusion for CCP recipients and admission day 2 for non-CCP recipients. COVID-19, coronavirus disease 2019; CCP, COVID-19 convalescent plasma; EAP, expanded access protocol; LAR, legally authorized representative; MMC, Montefiore Medical Center; NC, nasal cannula.

Figure 2. Kaplan-Meier plots of the probability of survival from time of transfusion to day 28 in CCP recipients (n = 73) versus matched controls (n = 73).

(A) All age groups. (B) Age < 65 years. (C) Age ≥ 65 years. The P value of a log-rank test is shown for each plot.

Figure 3. Day 28 outcomes for CCP recipients (n = 73) versus matched controls (n = 73) presented by OR and 95% confidence intervals using a logistic regression model.

(A) All age groups (n = 73 cases vs. 73 controls). (B) Age < 65 years (n = 34 vs. 34). (C) Age ≥ 65 years (n = 39 vs. 39).

Figure 4. SARS-CoV-2 spike protein IgG titers determined by ELISA at baseline (day –1) and 1, 3, and 7 days after transfusion in CCP recipients.

(A) Age < 65 years. (B) Age ≥ 65 years. (C) Alive at day 28. (D) Died by day 28. (E) Not intubated on day of transfusion. (F) Intubated on day of transfusion. Correlation between baseline spike protein IgG titer and (G) D-dimer and (H) cycle threshold (Ct) value from initial nasopharyngeal SARS-CoV-2 RT-PCR in CCP recipients. The median titers and IQRs are shown on the y axis for each time point shown on the x axis (A–F). The x axis shows days relative to CCP transfusion (A–F). Open circles show patients who died by day 28 (G and H). r, Spearman’s correlation coefficient; D, day; Ct value, cycle threshold value.