SARS-CoV-2 Anti-Spike IgG Antibody and ACE2 Receptor Binding Inhibition Levels among Breakthrough Stage Veteran Patients.

SARS-CoV-2 mRNA vaccines have been critical to curbing pandemic COVID-19; however, a major shortcoming has been the inability to assess levels of protection after vaccination. This study assessed serologic status of breakthrough infections in vaccinated patients at a Veterans Administration medical center from June through December 2021 during a SARS-CoV-2 delta variant wave. Breakthrough occurred mostly beyond 150 days after two-dose vaccination with a mean of 239 days. Anti-SARS-CoV-2 spike (S) IgG levels were low at 0 to 2 days postsymptoms but increased in subjects presenting thereafter. Population measurements of anti-S IgG and angiotensin converting enzyme-2 receptor (ACE2-R) binding inhibition among uninfected, vaccinated patients suggested immune decay occurred after 150 days with 62% having anti-S IgG levels at or below 1,000 AU comparable with breakthrough patients at 0 to 2 days postsymptom onset. In contrast, vaccination after resolved infection conferred robust enduring anti-S IgG levels (5,000 to >50,000 AU) with >90% ACE2-R binding inhibition. However, monoclonal antibody (MAb)-treated patients did not benefit from their prior infection suggesting impaired establishment of B cell memory. Analysis of boosted patients confirmed the benefit of a third vaccine dose with most having anti-S IgG levels above 5,000 AU with >90% ACE2-R binding inhibition, but a subset had levels <5,000 AU. Anti-S IgG levels >5,000 AU were associated with >90% ACE2-R binding inhibition and no documented breakthrough infections, whereas levels falling below 5,000 AU and approaching 1,000 AU were associated with breakthrough infections. Thus, quantitative antibody measurements may provide a means to guide vaccination intervals for the individual. IMPORTANCE Currently, clinicians have no guidance for the serologic assessment of SARS-Cov-2 postvaccination status regarding protection and risk of infection. Vaccination and boosters are administered blindly without evaluation of need or outcome at the individual level. The recent development of automated quantitative assays for anti-SARS-CoV-2 spike protein IgG antibodies permits accurate measurement of humoral immunity in standardized units. Clinical studies, such as reported here, will help establish protective antibody levels allowing identification and targeted management of poor vaccine responders and vaccinated subjects undergoing immune decay.

Effect of monoclonal antibody therapy on the endogenous SARS-CoV-2 antibody response.

Monoclonal antibody treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been widely implemented. Effects of treatment on the endogenous primary humoral response to the virus are unknown. A retrospective cohort study performed at a Veterans Health Administration medical center compared serologic responses of treated and untreated COVID-19 patients at high risk for severe outcomes. Three anti-viral spike protein IgG monoclonal treatments were used during the study period, 1) bamlanivimab, 2) casirivimab with imdevimab, and 3) bamlanivimab with etesevimab. Data were analyzed at acute (0-9 days), seroconversion (10-19 days), and maximum antibody (20-39 days) stages. SARS-Cov-2 infection induced a dynamic primary humoral response with anti-spike IgM and anti-nucleocapsid IgG seroconversion occurring after 9 days with maximum serologic indices achieved by 20-39 days. All monoclonal antibody treatments suppressed the endogenous anti-spike IgM response by 85-90% with minor effect on the anti-nucleocapsid response. Thus, passive immunization therapy may cause immunologic interference.

Vaccine breakthrough infections in veterans hospitalized with coronavirus infectious disease-2019: A case series.

BACKGROUND: While Severe Acute Respiratory Syndrome Coronavirus-2 vaccine breakthrough infections are expected, reporting on breakthrough infections requiring hospitalization remains limited. This observational case series report reviewed 10 individuals hospitalized with vaccine breakthrough infections to identify patient risk factors and serologic responses upon admission. METHODS: Electronic medical records of BNT162b2 (Pfizer-BioNTech) or mRNA-1732 (Moderna) vaccinated patients admitted to Veterans Affairs Ann Arbor Healthcare System with newly diagnosed Coronavirus Infectious Disease 2019 (COVID-19) between March 15, 2021 and April 15, 2021 were reviewed. Patient variables, COVID-19 lab testing including anti-S IgM, anti-N IgG antibodies, and hospital course were recorded. Based on lab testing, infections were defined as acute infection or resolving/resolved infection. RESULTS: Of the 10 patients admitted with breakthrough infections, all were >70 years of age with multiple comorbidities. Mean time between second vaccine dose and COVID-19 diagnosis was 49 days. In the 7 individuals with acute infection, none had observed serologic response to mRNA vaccination, 5 developed severe disease, and 1 died. Three individuals had anti-N IgG antibodies and a high polymerase chain reaction cycle threshold value, suggesting resolving/resolved infection. CONCLUSIONS: Given the variability of vaccine breakthrough infections requiring hospitalization, serologic testing may impart clarity on timing of infection and disease prognosis. Individuals at risk of diminished response to vaccines and severe COVID-19 may also benefit from selective serologic testing after vaccination to guide risk mitigation strategies in a post-pandemic environment.