SARS-CoV-2 vaccination influence in the development of long-COVID clinical phenotypes

Abstract

Although SARS-CoV-2 vaccination reduces hospitalization and mortality, its long-term impact on Long-COVID remains to be elucidated. The aim of the study was to evaluate the different development of Long-COVID clinical phenotypes according to the vaccination status of patients. Clinical and demographic characteristics were assessed for each patient, while Long-COVID symptoms were self-reported and later stratified into distinct clinical phenotypes. Vaccination was significantly associated with the avoidance of hospitalization, less invasive respiratory support, and less alterations of cardiopulmonary functions, as well as reduced lasting lung parenchymal damage. However, no association between vaccination status and the development of at least one Long-COVID symptom was found. Nevertheless, clinical phenotypes were differently associated with vaccination status, as neuropsychiatric were more frequent in unvaccinated patients and cardiorespiratory symptoms were reported mostly in vaccinated patients. Different progression of disease could be at play in the different development of specific Long-COVID clinical phenotypes, as shown by the different serological responses between unvaccinated and vaccinated patients. A higher anti-Spike (S) antibody titre was protective for vaccinated patients, while it was detrimental for unvaccinated patients. A better understanding of the mechanism underlying the development of Long-COVID symptoms might be reached by standardized methodologies and symptom classification.

Keywords: COVID-19; PASC; anti-S antibodies; mRNA vaccine; post-COVID-19 syndrome.

Figure 1.

Study population Long-COVID visit (A) Long-COVID symptoms reported during the examination were distributed into distinct clinical phenotypes (B) Clinical-radiological diagnosis of pulmonary functions was performed through the combination of spirometry, 6-minute walking test (6MWT) and the use of chest CT (Computed Tomography) attributing to each CT scan a severity scores (CTSS); (C) Cardiology visit and assessment of each patient’s presence of cardiovascular risk factors, cardiovascular comorbidities, and any recent-onset symptoms compatible with long-COVID diagnosis; (D) Evaluation of SARS-CoV-2-specific total anti-Spike (anti-S) IgG antibodies using chemiluminescence immunoassay (CLIA).

Figure 2.

(A) Long-COVID symptoms in unvaccinated and vaccinated patients, stratified for vaccine doses. The percentages of patients with and without Long-COVID symptoms are reported in blue/red and grey, respectively (B) Frequency of unvaccinated (red) and vaccinated (blue) patients self-reported cluster of symptoms during Long-COVID evaluation. Patients who did not report any symptoms are indicated by the color grey. *: 0.05 < p < 0.01.

Figure 3.

(A) Association between hospitalization and development of Long-COVID symptoms in vaccinated and unvaccinated patients (B) Hospitalization and self-reported cluster of symptoms in vaccinated and unvaccinated patients.

Figure 4.

(A) Anti-Spike (S) IgG antibody titer measured in fully vaccinated, partially vaccinated and unvaccinated patients (B) Different serological response based on hospitalization status during acute phase of COVID-19 of vaccinated and unvaccinated patients (C) Anti-S IgG antibody titer variations in differently treated patients of the unvaccinated group during acute phase of COVID-19 (D) Correlation between serological response of vaccinated and unvaccinated patients and development of Long-COVID symptoms. Ns: p>0.05; *: 0.05 < p < 0.01; **: 0.01 < p < 0.001; ***: 0.001 < p < 0.0001; ****: p > 0.0001; Vax: Vaccinated.