Are convalescent plasma stocks collected during former COVID‐19 waves still effective against current SARS‐CoV‐2 variants?

Abstract

COVID-19 convalescent plasma (CCP) was among the few frontline therapies used to treat COVID-19. After large randomized controlled trials (RCTs) relying on late use in hospitalized patients and/or low antibody titres failed to meet their predefined primary endpoint, the infectious disease community reduced usage of CCP in favour of monoclonal antibodies. Consequently, there are CCP stocks at most transfusion centres worldwide, although scattered usage continues. Further, better designed RCTs are also being launched. The urgent question here is: should we use CCP units collected months before given the largely changed viral variant landscape? We review here in vitro evidence that discourages usage of such CCP units against Delta and other variants of concern. CCP collections should be continued in order to update the armamentarium of therapeutics against vaccine breakthrough infections or in unvaccinated patients and is especially relevant in next-generation RCTs.

How do I implement an outpatient program for the administration of convalescent plasma for COVID‐19?

“…Vaccination and a declining incidence of COVID‐19 allied with evidence of futility in late‐stage disease contributed to waning demand and collection ceased. Consequently, extant CCP inventories of CCP were poorly matched to later variants such as delta and omicron 19 . This underscores the need to maintain a minimum inventory of CCP and ongoing capability to recruit new donors, particularly those who have recovered from infection with a virus that is similar to that which has infected the intended recipient.…”

“…Consequently, extant CCP inventories of CCP were poorly matched to later variants such as delta and omicron. 19 This underscores the need to maintain a minimum inventory of CCP and ongoing capability to recruit new donors, particularly those who have recovered from infection with a virus that is similar to that which has infected the intended recipient. Temporal and geographic matching is ideal but is also logistically challenging.…”

Convalescent plasma in outpatients with COVID-19

“…Based on a systematic review of COVID-19 convalescent plasma RCTs, 8 on Dec 27, 2021, the US Food and Drug Administration expanded its emergency use authorisation for COVID-19 convalescent plasma for outpatients with immune deficiency. Although COVID-19 convalescent plasma collected during former COVID-19 waves is unlikely to be effective against omicron, 9 collection of convalescent plasma from vaccinated individuals currently represents a promising alternative with a very large pool of regular donors and very high and broad-spectrum neutralising antibody concentrations. 10 CONV-ERT teaches us that even well designed RCTs that test COVID-19 convalescent plasma in conditions where antibody therapies are expected to be effective can have negative results.…”

Neutralization profile of SARS‐CoV‐2 omicron BA.1 variant in high binding titer plasma

“…However, some early in vitro evidence suggests that HT-CCP collected during previous waves of COVID-19 may not be effective against Omicron. 3 In this retrospective study, we evaluated the neutralizing capacity (i.e., neutralizing antibody concentrations) against SARS-CoV-2 Omicron BA.1 variant in high binding antibody concentration plasma samples obtained from subjects with diverse exposure to SARS-CoV-2 through infection, vaccination, or both. The plasma samples were obtained from Vilnius University Hospital Santaros Klinikos Biobank (Vilnius, Lithuania).…”

“…The antigenic shift of SARS-CoV-2 may prompt blood banks to constantly update its HT-CCP collections as stocks obtained during previous waves of infection will unlikely have adequate neutralization potency. 2,3 However, the feasibility of continuously collecting and updating an inventory of HT-CCP on a large scale has never been formally assessed.…”