Antibody response and risk of reinfection over 2 years among the patients with first wave of COVID-19

Maddalena Peghin; Maria De Martino; Alvisa Palese; Stefania Chiappinotto; Federico Fonda; Valentina Gerussi; Assunta Sartor; Francesco Curcio; Paolo Antonio Grossi; Miriam Isola; Carlo Tascini

doi:10.1016/j.cmi.2023.12.017

Antibody response and risk of reinfection over 2 years among the patients with first wave of COVID-19

Clin Microbiol Infect. 2024 Apr;30(4):522-530. doi: 10.1016/j.cmi.2023.12.017. Epub 2023 Dec 22.

Affiliations

¹ Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria-ASST-Sette Laghi, Varese, Italy.
² Division of Medical Statistics, Department of Medicine, University of Udine, Udine, Italy. Electronic address: maria.demartino@uniud.it.
³ Department of Medicine, University of Udine, Udine, Italy.
⁴ Infectious Diseases Division, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Udine, Italy.
⁵ Institute of Clinical Pathology, Department of Laboratory Medicine, University of Udine, ASUFC, Udine, Italy.
⁶ Division of Medical Statistics, Department of Medicine, University of Udine, Udine, Italy.

PMID: 38141821
DOI: 10.1016/j.cmi.2023.12.017

Abstract

Objectives: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients.

Methods: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response.

Results: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014).

Discussion: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.

Keywords: COVID-19; Longitudinal study; Reinfection; SARS-CoV-2 IgG; SARS-CoV-2 IgM; SARS-CoV-2 antibodies; SARS-CoV-2 serology.

MeSH terms

Antibodies, Viral
Antibody Formation
COVID-19* / epidemiology
Child, Preschool
Humans
Immunoglobulin G
Immunoglobulin M
Longitudinal Studies
Male
Prospective Studies
Reinfection / epidemiology
SARS-CoV-2

Substances

Antibodies, Viral
Immunoglobulin G
Immunoglobulin M

Supplementary concepts

SARS-CoV-2 variants