SARS-CoV-2 Spike and Nucleocapsid Antibody Response in Vaccinated Croatian Healthcare Workers and Infected Hospitalized Patients: A Single Center Cohort Study

Abstract

Studies assessing the dynamics and duration of antibody responses following SARS-CoV-2 infection or vaccination are an invaluable tool for vaccination schedule planning, assessment of risk groups and management of pandemics. In this study, we developed and employed ELISA assays to analyze the humoral responses to Nucleocapsid and Spike proteins in vaccinated health-care workers (HCW) and critically ill COVID-19 patients. Sera of more than 1000 HCWs and critically ill patients from the Clinical Hospital Center Rijeka were tested across a one-year period, encompassing the spread of major SARS-CoV-2 variants of concern (VOCs). We observed 97% of seroconversion in HCW cohort as well as sustained anti-Spike antibody response in vaccinees for more than 6 months. In contrast, the infection-induced anti-Nucleocapsid response was waning significantly in a six-month period. Furthermore, a substantial decrease in vaccinees’ anti-Spike antibodies binding to Spike protein of Omicron VOC was also observed. Critically ill COVID-19 patients had higher levels of anti-Spike and anti-Nucleocapsid antibodies compared to HCWs. No significant differences in anti-Spike and anti-Nucleocapsid antibody levels between the critically ill COVID-19 patients that were on non-invasive oxygen supplementation and those on invasive ventilation support were observed. However, stronger anti-Spike, but not anti-Nucleocapsid, antibody response correlated with a better disease outcome in the cohort of patients on invasive ventilation support. Altogether, our results contribute to the growing pool of data on humoral responses to SARS-CoV-2 infection and vaccination.

Predictors of SARS-CoV-2 anti-Spike IgG antibody levels following two COVID-19 vaccine doses among children and adults in the Canadian CHILD Cohort

“…We did not detect any sex differences, contrasting with other studies that found higher SARS-CoV-2 anti-spike IgG antibody levels in females compared to males 20,21,24,25 . However, similar to our findings, Brlić P. et al reported no significant gender-related differences in post-vaccination antibody levels among a cohort of 1072 healthcare workers in Croatia 26 . The lack of consistency regarding the association of biological sex and COVID-19 vaccine-induced humoral responses warrants further evaluation.…”

Development of an Affordable ELISA Targeting the SARS-CoV-2 Nucleocapsid and Its Application to Samples from the Ongoing COVID-19 Epidemic in Ghana

“…The antibody concentration levels increased over time for both groups. Even though there is not much literature comparing symptomatic and asymptomatic patients, higher anti-nucleocapsid was detected in critically ill patients with COVID-19 as compared with non-critically ill [31]. In another study in the Netherlands [32], higher anti-nucleocapsid antibodies were detected in moderate or severe cases while undetectable in asymptomatic patients.…”

Multisystem Inflammatory Syndrome in Children (MIS-C), Possibly Due to COVID-19 mRNA Vaccination

“…This is supported by high levels of SARS-CoV-2 spike protein IgG antibodies, consistent with vaccine immunization versus slightly positive IgG anti-nucleocapsid antibodies, possibly due to an early prior infection, even though no known exposure was available to inform the timing of the infection. Although anti-nucleocapsid antibodies are indicative of past or recent SARS-CoV-2 infection, anti-spike protein antibodies can be induced either by SARS-CoV-2 infection or COVID-19 vaccination [ 16 , 17 ]. In our case, the vaccination was only three weeks before, and, moreover, the level of anti-nucleocapsid antibodies was slightly positive, but dropped after a week.…”