Post-COVID-19 syndrome and humoral response association after 1 year in vaccinated and unvaccinated patients

Abstract

Objectives: This study aimed to describe the impact of vaccination and the role of humoral responses on post-COVID-19 syndrome 1 year after the onset of SARS coronavirus type 2 (CoV-2).

Methods: This prospective study was conducted through interviews to investigate post-COVID-19 syndrome 6 and 12 months after disease onset in all adult in- and outpatients with COVID-19 at Udine Hospital (March-May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain (RBD) SARS-CoV-2 IgG) and/or natural infection (non-RBD-SARS-CoV-2 IgG) were also assessed.

Results: A total of 479 patients (52.6% female; mean age: 53 years) were interviewed 13.5 months (standard deviation: 0.6 months) after acute infection. Post-COVID-19 syndrome was observed in 47.2% of patients (n = 226) after 1 year. There were no significant differences in the worsening of post-COVID-19 symptoms (22.7% vs. 15.8%; p = 0.209) among vaccinated (n = 132) and unvaccinated (n = 347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR: 1.35; 95% CI, 1.11-1.64; p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long haulers than in patients without symptoms (22 kAU/L (interquartile range, 9.7-37.2 kAU/L) vs. 14.1 kAU/L (interquartile range, 5.4-31.3 kAU/L); p = 0.009) after 1 year. In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs. 0.9-2500 U/mL; OR: 1.36; 95% CI, 0.62-3.00; p = 0.441), and RBD SARS-CoV-2 IgG titres were similar in long haulers as in patients without symptoms (50% values > 2500 U/mL vs. 55.6% values > 2500 U/mL; p = 0.451).

Discussion: The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms more than 1 year after acute infection. The persistence of high serological titre response induced by natural infection, but not vaccination, may play a role in long-haul COVID-19.

Keywords: COVID-19 vaccination; Hybrid immunity; Long COVID-19; Natural immunity; Post–COVID-19; SARS-CoV-2 antibodies; SARS-CoV-2 serology; SARS-CoV-2 vaccination; Unvaccinated; Vaccinated.

Graphical abstract

Fig. 1

Flow diagram of in- and out- COVID-19 patients included in the post-COVID-19 syndrome study at 6-12 months and serological follow-up up to May 2021. Legend: CORMOR 3-4 study. ^∗ Non-RBD SARS-CoV-2 IgG antibodies (iFlash) concentrations were measured at the serological follow-up visits each month (±15 days) after symptom onset during the first four months, and every month up to 12 months (±15 days), from March 2020 to May 2021. Among the 479 patients, only 275 were evaluated at 12 months. ^§ RBD SARS-CoV-2 IgG antibodies (Roche) at 12 months after the onset of symptom (±60 days). Patients were categorized as vaccinated or hybrid immunity if they had received the vaccine at least two weeks before the interview. COVID-19, Coronavirus Disease 2019; RBD, receptor binding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Fig. 2

Acute– and post–COVID-19 related symptoms at 6 and 12 months. ^∗ p refers to post–COVID-19 symptoms at 6 and 12 months. COVID-19, Coronavirus Disease 2019; URTI, upper respiratory tract infection.

Fig. 3

Serological evolution against SARS-CoV-2 measured with non-RBD SARS-CoV-2 IgG in patients with or without post–COVID-19 syndrome at 12 months. COVID-19, Coronavirus Disease 2019; RBD, receptor binding domain; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.