Fever, Diarrhea, and Severe Disease Correlate with High Persistent Antibody Levels against SARS-CoV-2

Abstract

Lasting immunity will be critical for overcoming the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, factors that drive the development of high titers of anti-SARS-CoV-2 antibodies and how long those antibodies persist remain unclear. Our objective was to comprehensively evaluate anti-SARS-CoV-2 antibodies in a clinically diverse COVID-19 convalescent cohort at defined time points to determine if anti-SARS-CoV-2 antibodies persist and to identify clinical and demographic factors that correlate with high titers. Using a novel multiplex assay to quantify IgG against four SARS-CoV-2 antigens, a receptor binding domain-angiotensin converting enzyme 2 inhibition assay, and a SARS-CoV-2 neutralization assay, we found that 98% of COVID-19 convalescent subjects had anti-SARS-CoV-2 antibodies five weeks after symptom resolution (n=113). Further, antibody levels did not decline three months after symptom resolution (n=79). As expected, greater disease severity, older age, male sex, obesity, and higher Charlson Comorbidity Index score correlated with increased anti-SARS-CoV-2 antibody levels. We demonstrated for the first time that COVID-19 symptoms, namely fever, abdominal pain, diarrhea and low appetite, correlated consistently with higher anti-SARS-CoV-2 antibody levels. Our results provide new insights into the development and persistence of anti-SARS-CoV-2 antibodies.

COVID-19 Convalescent Plasma Donor Characteristics: Correlation with Blood Group, Age, Gender, Symptoms and their Association with SARS CoV-2 Antibody Levels: A Bi-centric Study from India

“…Many studies have reported that titers of neutralizing antibodies are associated with disease severity [39][40][41] [42]. Our results on multiple linear regression indicated that a collective significant effect exists between the symptoms and antibody levels.…”

Clinical predictors of SARS‐CoV‐2 neutralizing antibody titers in COVID‐19 convalescents: Implications for convalescent plasma donor recruitment

“…A single study found no relation between nAb and symptom duration (1‐7 vs 8‐14 vs 15‐28 days) 18 . Similarly, a single study found no correlation between nAb and higher Charlson Comorbidity Index score 14 …”

“…Single studies reported a low lymphocyte count 15 or AB/B blood groups as additional proxies: 16 These parameters, albeit not strictly clinical, are widely available for patients discharged from hospitals. One study found that GI symptoms did not predict nAb titer, 17 while another showed that abdominal pain, diarrhea, and low appetite correlated consistently with higher nAb levels 14 . A single study found no relation between nAb and symptom duration (1‐7 vs 8‐14 vs 15‐28 days) 18 .…”

“…Most studies agreed that higher age, male sex, higher BMI, and disease severity (especially hospitalization) are the main predictors for high PRNT titers. Other clinical factors such as fever during acute illness or days since diagnosis (or recovery) instead show correlations only in a minority of studies 14 . Single studies reported a low lymphocyte count 15 or AB/B blood groups as additional proxies: 16 These parameters, albeit not strictly clinical, are widely available for patients discharged from hospitals.…”

“…In most studies several patients (ranging from 2% in ICU to 25% in non‐hospitalized patients 14,15,24,25 to 40% in healthcare workers) 26 show no nAb at all as assessed by the VNT. Lee et al reported that S‐specific antibodies are capable of engaging dimeric FcγRIIa and FcγRIIIa decay linearly over time.…”