RESUMO
BackgroundA fraction of COVID-19 patients develops severe disease requiring hospitalization, while the majority, including high-risk individuals, experience mild symptoms. Severe disease has been associated with higher levels of antibodies and inflammatory cytokines, but the association has often resulted from comparison of patients with diverse demographics and comorbidity status. This study examined patients with defined demographic risk factors for severe COVID-19 who developed mild vs. severe COVID-19. MethodsThis study evaluated hospitalized vs. ambulatory COVID-19 patients in the James J. Peters VA Medical Center, Bronx, NY. This cohort presented demographic risk factors for severe COVID-19: median age of 63, >80% male, >85% black and/or Hispanic. Sera were collected four to 243 days after symptom onset and evaluated for binding and functional antibodies as well as 48 cytokines/chemokines. FindingsAmbulatory and hospitalized patients showed no difference in SARS-CoV-2-specific antibody levels and functions. However, a strong correlation between anti-S2 antibody levels and the other antibody parameters was observed in hospitalized but not in ambulatory cases. Cytokine/chemokine levels also revealed differences, with notably higher IL-27 levels in hospitalized patients. Hence, among the older, mostly male patients studied here, SARS-CoV-2-specific antibody levels and functions did not distinguish hospitalized and ambulatory cases but a discordance in S2-specific antibody responses was noted in ambulatory patients, and elevated levels of specific cytokines were maintained in convalescent sera of hospitalized cases. InterpretationThe data indicate that antibodies against the relatively conserved S2 spike subunit and immunoregulatory cytokines such as IL-27 are potential immune determinants of COVID-19. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies demonstrated that high levels of SARS-CoV-2 spike binding antibodies and neutralizing antibodies were associated with COVID-19 disease severity. However, the comparisons were often made without considering demographics and comorbidities. Correlation was similarly shown between severe disease and marked elevation of several plasma cytokines but again, most analyses of cytokine responses to COVID-19 were conducted by comparison of patient cohorts with diverse demographic characteristics and risk factors. Added value of this studyWe evaluated here a comprehensive profile of SARS-CoV-2-specific antibodies (total Ig, isotypes/subtypes, Fab- and Fc-mediated functions) and a panel of 48 cytokines and chemokines in serum samples from a cohort of SARS-CoV-2-infected patients with demographic risk factors for severe COVID-19: 81% were male, 79% were >50 years old (median of 63), and 85% belonged to US minority groups (black and/or Hispanic). Comparison of hospitalized vs. ambulatory patients within this cohort revealed two features that differed between severe vs. mild COVID-19 cases: a discordant Ab response to the S2 subunit of the viral spike protein in the mild cases and an elevated response of specific cytokines and chemokines, notably IL-27, in the severe cases. Implications of all the available evidenceData from the study identified key immunologic markers for severe vs. mild COVID-19 that provide a path forward for investigations of their roles in minimizing or augmenting disease severity.
RESUMO
Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.
