Spike-specific circulating T follicular helper cell and cross-neutralizing antibody responses in recovered COVID-19 individuals

Coronavirus Disease 2019 (COVID-19), an emerging disease caused by infection with SARS-CoV-21-3, has spread worldwide and caused 21.2 million infections and 0.76 million deaths (as of August 15, 2020)4. Symptoms of COVID-19 are varied and can be asymptomatic, mild, moderate, and severe5,6. In the early phase of SARS-CoV-2 infection, T and B cell counts are dramatically decreased7,8; however, IgM9-12 and IgG13-15 are detectable within 14 days after symptom onset. In COVID-19 convalescents, spike-specific neutralizing antibodies (nAbs) are variable3,16,17. To date, no specific drug or vaccine is available for COVID-19. Clinical trials have shown that patients benefit from the treatments with convalescent serum18,19. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in the COVID-19 convalescents are largely unknown. Here we show that the majority of COVID-19 convalescents maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus and that some of the antibodies cross-neutralized SARS-CoV, MERS-CoV, or both pseudotyped viruses. Convalescents who experienced severe COVID-19 disease showed higher nAb titers, a faster increase of lymphocyte counts, and a higher frequency of CXCR3+ T follicular help (Tfh) cells than did non-severe convalescents. Circulating Tfh cells were spike-specific and functional, and the frequencies of CXCR3+ Tfh cells were positively associated with nAb titers in recovered COVID-19 individuals. No subjects had detectable autoantibodies. These findings provide insights into nAb responses in COVID-19 convalescents and facilitate the treatment and vaccine development for SARS-CoV-2 infection.