Antibody response and intra‐host viral evolution after plasma therapy in COVID‐19 patients pre‐exposed or not to B‐cell‐depleting agents

Abstract

Summary Administration of plasma therapy may contribute to viral control and survival of COVID‐19 patients receiving B‐cell‐depleting agents that impair humoral immunity. However, little is known on the impact of anti‐CD20 pre‐exposition on the kinetics of SARS‐CoV‐2‐specific antibodies. Here, we evaluated the relationship between anti‐spike immunoglobulin G (IgG) kinetics and the clinical status or intra‐host viral evolution after plasma therapy in 36 eligible hospitalized COVID‐19 patients, pre‐exposed or not to B‐cell‐depleting treatments. The majority of anti‐CD20 pre‐exposed patients (14/17) showed progressive declines of anti‐spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B‐cell‐depleting agents ( p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification ( p = 0.0267) and SARS‐CoV‐2 viral loads ( p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response ( p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA‐vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow‐up in the management of COVID‐19 patients with B‐cell lymphopenia.

Understanding the parameters guiding the best practice for treating B‐cell‐depleted patients with COVID‐19 convalescent plasma therapy

“…Patients were classified according to whether they had Vax-CCP treatment once or twice (Figure 1B) and presented various Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages, depending on the predominant circulating strain(s) at the time of diagnosis (Figure 1C). Our data indicate that seven out nine patients were able to clear the virus within the same time-range (<35 days, Figure 1D,E) as reported for patients with endogenous anti-SARS-CoV-2 responses, 6 among them two had received two serial transfusions. Hence, our tailored approach is consistent with the relative low number of refractory cases (six of 36) previously observed 6 and enables sparing Vax-CCP resources of high anti-SARS-CoV-2 titres, which heavily rely on the continuous collection of donor plasma.…”

“…Our data indicate that seven out nine patients were able to clear the virus within the same time-range (<35 days, Figure 1D,E) as reported for patients with endogenous anti-SARS-CoV-2 responses, 6 among them two had received two serial transfusions. Hence, our tailored approach is consistent with the relative low number of refractory cases (six of 36) previously observed 6 and enables sparing Vax-CCP resources of high anti-SARS-CoV-2 titres, which heavily rely on the continuous collection of donor plasma.…”

“… 5 From March to July 2021, we treated 19 immunosuppressed patients with plasma collected from COVID‐naive two‐dose mRNA‐vaccinated donors, under a compassionate use protocol, according to the Swiss regulation rules. 6 No relevant difference was observed between patients receiving CCP ( n = 17) versus vaccinated plasma (VP, n = 19), indicating that VP therapy is safe and effective in patients with B‐cell lymphopenia. In the meantime, CCP donors are increasingly getting vaccinated, and three‐dose VP donors are being boosted by a breakthrough infection (defined as ‘hybrid plasma’, Vax‐CCP or CP/VP).…”

“…Understanding which parameter(s) may be predictive of complete viral clearance would likely help adjusting Vax‐CCP treatment. As such, the question of whether basal viral load is typically higher in B‐cell‐depleted patients than in B‐cell‐undepleted ones and thus represents a red‐flag could alas not be addressed in the dataset initially reported, 6 as both cohorts differed substantially in terms of the underlying viral variant (pre‐alpha vs. alpha predominance respectively). Still, we recently observed that patients transfused twice with Vax‐CCP had higher levels of initial SARS‐CoV‐2 viral loads than those receiving only one‐time plasma (Figure 1D ).…”

Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019

“…It is biologically plausible that IC individuals who fail to produce an appropriate antibody response to COVID-19 and/or SARS-CoV-2 vaccination are likely to benefit from the SARS-CoV-2 antibodies provided by CCP. Established high risk groups that would qualify for CCP based on this definition include—but are not limited to—organ transplant recipients, patients with auto-immune diseases treated by B-cell depleting agents, and patients with cancer diagnoses, especially those with B-cell deficiency or depletion that may be primary (eg, due to malignancy) or acquired (eg, due to treatment with B-cell depleting agents such as Rituximab) [ 27 , 28 ]. Practically, these patients are likely to have a minimal or absent response to SARS-CoV-2 vaccination.…”