Neutralizing antibody responses to SARS-CoV-2 in symptomatic COVID-19 is persistent and critical for survival

Abstract

Understanding how antibody responses to SARS-CoV-2 evolve during infection may provide important insight into therapeutic approaches and vaccination for COVID-19. Here we profile the antibody responses of 162 COVID-19 symptomatic patients in the COVID-BioB cohort followed longitudinally for up to eight months from symptom onset to find SARS-CoV-2 neutralization, as well as antibodies either recognizing SARS-CoV-2 spike antigens and nucleoprotein, or specific for S2 antigen of seasonal beta-coronaviruses and hemagglutinin of the H1N1 flu virus. The presence of neutralizing antibodies within the first weeks from symptoms onset correlates with time to a negative swab result (p = 0.002), while the lack of neutralizing capacity correlates with an increased risk of a fatal outcome (p = 0.008). Neutralizing antibody titers progressively drop after 5–8 weeks but are still detectable up to 8 months in the majority of recovered patients regardless of age or co-morbidities, with IgG to spike antigens providing the best correlate of neutralization. Antibody responses to seasonal coronaviruses are temporarily boosted, and parallel those to SARS-CoV-2 without dampening the specific response or worsening disease progression. Our results thus suggest compromised immune responses to the SARS-CoV-2 spike to be a major trait of COVID-19 patients with critical conditions, and thereby inform on the planning of COVID-19 patient care and therapy prioritization.

Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination

“…Many other reports have also shown strong correlations between disease severity and antibody responses [10][11][12][13][14][15]. Thus, a strong inflammatory response to viral infection inducing severe disease generally results in a robust immune response to COVID-19 while a strong antibody response is not expected following asymptomatic SARS-CoV-2 infection.…”

“…A similar study also determined that a high proportion of asymptomatic patients did not develop neutralizing antibodies, or lost them quickly [28]. Many investigations involve severely ill or hospitalized individuals and not a majority of asymptomatic people [10][11][12][13][14]. In these studies, failure to detect an antibody response is rare [10,16].…”

“…Many studies have assessed patients of varying disease severity and have found that antibody titers and capacity for neutralization are closely associated with disease severity [10][11][12][13][14]. In terms of the duration of the antibody response, most studies followed patients for a number of weeks to months [10][11][12][13]15]. Fewer studies followed the same participants for longer periods, and some have extended findings to the development of memory B cell populations up to eight months after infection [16,17].…”

“…Few studies broadly tested volunteers with highly sensitive tests and repeatedly sampled the same people. Furthermore, most assays utilize surrogate or pseudovirus neutralization assays that approximate the neutralization capacity of serum for SARS-CoV-2 [12,13,17]. The intent of this study was to determine the extent of antibody detection in the general population and to assess their duration and capacity to neutralize SARS-CoV-2.…”

Pediatric SARS-CoV-2 seroprevalence during mitigation procedures in Southwestern Pennsylvania

“…Published reports suggest that SARS-CoV-2 IgG antibodies are detectable 7-14 days from positive nasopharyngeal PCR; thus, blood samples collection began approximately two weeks after the peak of the first wave of cases of COVID-19 in Allegheny county [ 14 , 17 , 18 ]. PA DOH relaxed SWPA mitigation standards on May 15, 2020, thus, samples from April 27-May 19 were analyzed to reflect the red phase.…”