Kinetics of SARS-CoV-2 antibody responses pre-COVID-19 and post-COVID-19 convalescent plasma transfusion in patients with severe respiratory failure: an observational case–control study

Abstract

AimsWhile the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes.MethodsPatients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively.ResultsPrior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls.ConclusionsCCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.

Kinetics of Nucleocapsid, Spike and Neutralizing Antibodies, and Viral Load in Patients with Severe COVID-19 Treated with Convalescent Plasma

“…Regarding the comparison of immune response between CP recipients and non-CPtreated patients, Klein et al showed similar Spike-RBD kinetics between a cohort of 34 CP recipients compared to a matched control group; however, in this study, CP was given at a median of 11 days from symptom onset. Delayed intervention might explain the null effect on CP kinetics [33]. Similarly, the PlasmAr study showed increased antibody levels only on day 2 following CP infusion compared to controls, whereas no differences were observed at the subsequent time points evaluated [9].…”

Pharmacokinetics of high-titer anti–SARS-CoV-2 human convalescent plasma in high-risk children

“…Randomized controlled trials to evaluate COVID-19 convalescent plasma for prophylaxis and early treatment in adults are currently underway ( 13 , 14 ). Studies evaluating antibody kinetics of convalescent plasma have been conducted in infected individuals who developed endogenous anti–SARS-CoV-2 antibodies ( 15 ). However, antibody kinetics in SARS-CoV-2–exposed individuals or those early in disease and without endogenous antibody production, where antibody therapies are most useful ( 11 ), have not been well characterized.…”

Early administration of COVID‐19 convalescent plasma with high titer antibody content by live viral neutralization assay is associated with modest clinical efficacy

“…In contrast, the PennCCP2 trial (US) 44 found a benefit in the primary clinical endpoint of disease severity and 28-day mortality, and a double-blind RCT study by O'Donnell et al, (US and Brazil) 45 found CCP was not associated with significant improvement in day 28 clinical status, but was associated with significantly improved survival. Observational studies [46][47][48][49][50][51][52][53][54] have reported mixed findings, but generally suggest that efficacy is more likely with high titer CCP in earlier and less severe disease, [46][47][48][49][50][51][52][53] or when used in those with impaired immunity. [55][56][57] Interpretation of RCT data, including those in recent metaanalyses, 58,59 is made challenging for multiple reasons: 1) the use of either untitered plasma or plasma qualified by serologic testing alone,…”

“…In contrast, the PennCCP2 trial (US) 44 found a benefit in the primary clinical endpoint of disease severity and 28‐day mortality, and a double‐blind RCT study by O'Donnell et al, (US and Brazil) 45 found CCP was not associated with significant improvement in day 28 clinical status, but was associated with significantly improved survival. Observational studies 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 have reported mixed findings, but generally suggest that efficacy is more likely with high titer CCP in earlier and less severe disease, 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 or when used in those with impaired immunity. 55 , 56 , 57 …”