Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals

Abstract

Seroconversion appeared early after COVID-19 onset, and convalescent sera therapy benefit some critical patients. However, neutralizing antibody (nAb) in convalescents is largely unknown. We found that 97.01% (65/67) of COVID-19 convalescents maintained IgG antibodies with high binding and avidity to SARS-CoV-2 spike subunits S1 and S2, and 95.52% (64/67) had neutralization activity against SARS-CoV-2 pesudovirus, one month after discharge (median ID50, 2.75; IQR, 2.34-3.08). Some sera exhibited cross-neutralization against SARS-CoV (76.12%), MERS-CoV (17.91%), or both (10.45%). Interestingly, individuals recovered from severe disease (severe group) had nAbs with binding and neutralization titers higher than non-severe group. Severe group appeared a rapid increase of lymphocytes and a high proportion of circulating CXCR3+ Tfh cells. Interestingly, the later were spike-specific and positively correlated with SARS-CoV-2 nAb titers. All subjects had no autoimmunity. Our findings provide novel insights into nAb responses in COVID-19 convalescents and facilitate treatment and vaccine development for SARS-CoV-2 infection.

Antibody response to SARS-CoV-2 infection in humans: a systematic review

“…Neutralising antibody responses correlated with disease severity in all studies in which this association was tested. 7,43,49,66,76,85,87,[96][97][98] Importantly, the few studies that investigated asymptomatic cases found those individuals were considerably less likely to develop detectable serum neutralising antibody responses than cases with symptoms. With regard to age and sex, evidence was mixed and a limitation across all papers was a lack of statistical adjustment for severity.…”

“…Most studies, including all those considered high quality, suggested that neutralisation ability broadly correlated with total virus-specific IgG. 29,49,67,74,87,[99][100][101] Specifically, high quality studies found that neutralisation ability correlated positively with anti-S IgG 49,72,87,99 or anti-RBD IgG. 72,74,87,102 There was more limited evidence for correlation with anti-RBD IgM, including one high quality study, 51,84 and IgA.…”

“…There is limited evidence on the cross-reactivity of antibodies specific to other coronaviruses. 49,51,94,[119][120][121] Using a variety of assays, several in-vitro studies explored both crossreactive antibody-binding responses and cross-neutralisation between SARS-CoV-2 and seasonal coronaviruses, MERS-CoV and SARS-CoV-1. Cross-reactive antibody-binding responses appear to be highest between SARS-CoV-1 and SARS-CoV-2, however crossneutralisation is rare and where reported is weak.…”

“…159 Antibody titre • Ten studies reported a higher titre of neutralising antibodies in more clinically severe cases. 7,43,49,66,85,87,[95][96][97][98]…”

“…N/A • Five studies reported neutralising antibody response was positively correlated with male sex, 66,68,87,96 although it is unclear how this is related to disease severity. 49…”