# Cross-reactivity IgG, viral load, severity and vaccination outcome as an approach for understanding humoral immune response against SARS-CoV-2

## TL;DR

This study explores how IgG antibodies, viral load, disease severity, and vaccination affect immune responses to SARS-CoV-2 in Mexican populations.

## Contribution

The study introduces a method to evaluate humoral immune responses by analyzing cross-reactivity, viral load, severity, and vaccination outcomes.

## Key findings

- Higher cross seropositivity was observed in pre-pandemic sera against SARS-CoV-2 proteins.
- Viral load in pediatric patients varied based on sex and comorbidities.
- Vaccine boosters increased IgG antibody reactivity in vaccinated individuals.

## Abstract

Serological evaluation plays a crucial role in understanding cross-reactivity, the prevalence of infection, immune response in COVID-19 disease, asymptomatic infections, and vaccine effectiveness.

Recombinant spike (rS) and Nucleocapsid (rN) proteins from SARS-CoV-2 were used to determine IgG antibodies (Abs) in serum samples obtained from Mexican adults and paediatrics before and during the pandemic by enzyme-linked immunosorbent assay.

Human sera from 2003 to 2016 showed higher levels of cross seropositivity (54.5‒75%) against rS and rN. In serum samples from adult patients with COVID-19, the reactivity intensity (RI) depended on the severity of the disease, whereas in convalescent paediatric patients with COVID-19, SARS-CoV-2 viral load depended on sex and comorbidities. Regarding vaccine effectiveness monitoring, an increased RI of anti-rS IgG was observed in people vaccinated against COVID-19 who had a natural infection with SARS-CoV-2. During the vaccination scheme, an increase in IgG Abs level was observed with the second dose, whereas a decrease was observed after six months of vaccination. Vaccine boosters increased RI in either homologous/heterologous administration of mRNA and non-replicating viral vector vaccines.

Epidemiological outbreaks and the circulation of non-SARS-CoV-2 coronaviruses may contribute to the primary causes of the observed cross-reactions in antibodies. Furthermore, factors such as viral load and disease severity in infected patients, prior illnesses, the dosage of vaccine and booster shots, and the type of vaccine used in COVID-19-vaccinated individuals may also influence the increase in IgG antibodies. Assessing the antibody-based humoral immune response in serum samples collected before and during an outbreak or pandemic could aid in comprehending emerging and re-emerging diseases and developing effective preventive strategies.

Not applicable.

The online version contains supplementary material available at 10.1186/s12879-025-12038-3.