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.