Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021–June 2022

Abstract

Background: We assessed the association between antibody concentration within 5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021 to June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95% CI:690 to 981) among COVID-19 case-patients versus 1,189 BAU/mL (95% CI:1,050 to 1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

Antibody response to symptomatic infection with SARS-CoV-2 Omicron variant viruses, December 2021—June 2022

“…Against pre-Omicron variants, virus neutralization titers and IgG antibody concentrations were associated with protection; however, antibody binding and neutralization activity was lower against Omicron variants [2,8,18]. In addition, anti-N bAb seropositivity cut-off values were based on mean fluorescence intensity using serum standards rather than blood spots [10,13]. All case patients included in this study had mild illness; baseline antibody levels and immune responses may differ among patients with severe or prolonged SARS-CoV-2 infection [19].…”

“…Between December 2021 and June 2022, respiratory swabs and acute-phase dried blood spots on filter paper were obtained <5 days after symptom onset from ambulatory patients with respiratory illness enrolled in the US Influenza Vaccine Effectiveness Network, as previously described [9,10]. Patients who tested positive for SARS-CoV-2 by nucleic acid amplification in respiratory specimens were scheduled for convalescent-phase blood sample collection at 21-56 days after enrollment.…”

“…Eluted specimens were diluted 1:300 and individual specimen median fluorescence intensity (MFI) ratios were calculated compared to antigen-specific human IgG calibrator serum. MFI units were standardized to binding antibody units per mL (BAU/mL) against World Health Organization (WHO) international standards [10,13].…”

Antibody Response to Symptomatic Infection With SARS‐CoV‐2 Omicron Variant Viruses, December 2021–June 2022

“…Using DBS specimens collected during acute illness from patients with laboratory‐confirmed COVID‐19 and non‐COVID‐19 illnesses, we previously showed that anti‐N antibody seropositivity modified COVID‐19 mRNA vaccine effectiveness against symptomatic SARS‐CoV‐2 infection with SARS‐CoV‐2 Delta and Omicron variants [12]. Among acutely ill patients, higher levels of binding antibodies against ancestral S protein reduced the odds of testing positive for SARS‐CoV‐2 Delta and Omicron variants [13]. Here, we assessed humoral immune response to SARS‐CoV‐2 infection comparing acute‐ and convalescent‐phase IgG antibody levels against N and ancestral S RBD antigens among case patients infected during Omicron variant–predominant periods from December 2021 through June 2022.…”

“…Respiratory swabs and acute‐phase DBS were obtained < 5 days after symptom onset from ambulatory patients with respiratory illness enrolled in the US Influenza Vaccine Effectiveness Network [12, 13]. Previous analysis demonstrated no increase in mean anti‐N antibody concentration from DBS collected < 5 days after symptom onset among SARS‐CoV‐2‐infected patients [13].…”