Contribution of endogenous and exogenous antibodies to clearance of SARS-CoV-2 during convalescent plasma therapy (preprint)

Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The ability of antibody-based therapies, including convalescent plasma, to affect established disease remains to be elucidated. Only few monoclonal therapies and only when used at a very early stage of infection have shown efficacy. Here, we conducted a proof-of-principle study of convalescent plasma therapy in a phase I trial in 30 COVID-19 patients including immunocompromised individuals hospitalized early after onset of symptoms. A comprehensive longitudinal monitoring of the virologic, serologic, and disease status of recipients in conjunction with detailed post-hoc seroprofiling of transfused convalescent plasma, allowed deciphering of parameters on which plasma therapy efficacy depends. Plasma therapy was safe and had a significant effect on viral clearance depending on neutralizing and spike SARS-CoV-2 antibody levels in the supplied convalescent plasma. Endogenous immunity had strong effects on virus control. Lack of endogenous neutralizing activity at baseline was associated with a higher risk of systemic viremia. The onset of endogenous neutralization had a noticeable effect on viral clearance but, importantly, even after adjusting for their endogenous neutralization status recipients benefitted from therapy with high neutralizing antibody containing plasma. In summary, our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia in the early stages of infection and provide directions for improved efficacy evaluation of current and future SARS-CoV-2 therapies beyond antibody-based interventions. Incorporating an assessment of the endogenous immune response and its dynamic interplay with viral production is critical for determining therapeutic effects. One Sentence SummaryThis study demonstrates the impact of exogenous antibody therapy by convalescent plasma containing high neutralizing titers on the rapid clearance of viremia in the early stages of SARS-CoV-2 infection.

Multifactorial SARS-CoV-2 seroprofiling dissects interdependencies with human coronaviruses and predicts neutralization activity (preprint)

Definition of SARS-CoV-2 antibody responses is essential to verify protective immunity following infection and vaccination. Here, we devised a versatile serological test, named ABCORA, that is based on a multifactorial analysis of SARS-CoV-2 and circulating human coronavirus (HCoV) antibody responses. Utilizing empirical tailored cut-offs and computational approaches based on training and validation cohorts comprising pre-pandemic (N=825) and SARS-CoV-2 infected plasma donors (N=389), we defined several analysis strategies that allow a highly accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity. Intriguingly, HCoV reactivity was significantly higher in SARS-CoV-2 negative donors. Amongst SARS-CoV-2 infected individuals, elevated SARS-CoV-2 responses were linked to higher HCoV activity suggesting that pre-existing HCoV immunity may confer protection against SARS-CoV-2 acquisition and promote development of SARS-CoV-2 specific antibody responses. Deciphering interdependencies between SARS-CoV-2 and HCoV immunity should be enforced as understanding their impact on infection may allow soliciting cross-protective activities for broader coronavirus prevention.