key: cord-0883919-y0gn62w4
authors: Franchini, Massimo; Glingani, Claudia; Bellani, Angela; Cicorella, Nicola; Amadini, Alessandro; Donno, Giuseppe De; Casari, Salvatore
title: Early and persistent viral clearance in COVID-19 patients treated with convalescent plasma
date: 2021-04-20
journal: Transfus Clin Biol
DOI: 10.1016/j.tracli.2021.04.003
sha: c97650a4844f36961c210e05b835419f3702b7cd
doc_id: 883919
cord_uid: y0gn62w4

nan

potential beneficial effects of convalescent plasma (CP) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are ongoing or have been published [1] . Although mostly inconclusive, recent evidence does suggest that CP is clinically effective when administered early (within 72 hours of hospital admission), with a high titer of anti-SARS-CoV-2 neutralizing antibodies (> 1:160 as determined using the plaque reduction neutralization test) and in COVID-19 patients with an inadequate antibody virus response, such as elderly subjects and immunocompromised patients [2, 3] .

The initial rate, timing and temporal duration of the viral clearance in COVID-19 patients receiving CP are poorly understood, mostly because of the lack of studies with an adequate follow-up. With the aim of elucidating these issues, we followed 54 consecutive patients with severe COVID-19 treated with CP for compassionate use between April 1 and April 30, 2020. Their demographic, clinical and treatment characteristics are summarized in Table 1 . Overall, 81 CP units, each of 300 mL, were transfused to the 54 COVID-19 patients (median: 1 CP unit per patient, range 1-3 units). The median neutralizing anti-SARS-CoV-2 antibody titer per CP unit was 1:160 (range 1:80-1:640, measured using the standard plaque reduction neutralizing test). The molecular test for SARS-CoV-2 became negative in 85.2% of patients already 72 hours after CP infusion and by day 7, all patients resulted negative. The viral clearance persisted at the end of follow-up (median: 9 months).

In conclusion, the results of this study document the short-and long-term SARS-CoV-2 suppression by CP therapy. While the high efficacy of passive immune therapy in rapidly eradicating SARS-CoV-2 is in accordance with previously published data [4] , the sustained virus eradication by CP infusion is reported here for the first time. The latter finding enables us to make some important considerations regarding the possibility that in vivo CP transfusion could induce mutations in receptor binding and N-terminal domains able to escape from CP neutralizing antibodies, as suggested by in vitro studies [5] . In fact, it is somewhat unlikely that this phenomenon could happen in a clinical setting considering the very early suppression of the virus by CP. In other words, findings in experimental studies do not always translate into real-life clinical evidence. 

Severe COVID-19 respiratory distress was defined as follows: >30 breaths/minute, oxygen saturation <93% in room air, PAO2/FIO2 <200. 1 Anti-SARS-CoV-2 IgG antibodies were measured using a chemiluminescent immunoassay (LIAISON SARS-CoV-2 IgG, DiaSorin, Vercelli, Italy).

Convalescent plasma or hyperimmune immunoglobulin for people with COVID-19: a living systematic review

Fundación INFANT-COVID-19 Group. Early high-titer plasma therapy to prevent severe Covid-19 in older adults

Convalescent plasma antibody levels and the risk of death from COVID-19

Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial

Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants