SARS-COV-2 Infection, Vaccination, and Immune-Mediated Diseases: Results of a Single-Center Retrospective Study

Abstract

Objectives: The relationship between infections or vaccine antigens and exacerbations or new onset of immune-mediated diseases (IMDs) has long been known. In this observational study, conducted during the COVID-19 pandemic, we evaluated the onset of clinical and laboratory immune manifestations related to COVID-19 or SARS-CoV-2 vaccination.

Methods: Four groups of patients were evaluated: A) 584 COVID-19 inpatients hospitalized from March 2020 to June 2020 and from November 2020 to May 2021; B) 135 outpatients with previous SARS-CoV-2 infection, assessed within 6 months of recovery; C) outpatients with IMDs in remission and flared after SARS-COV-2 infection; D) outpatients with symptoms of probable immune-mediated origin after SARS-CoV-2 vaccination.

Results: In cohort A we observed n. 28 (4.8%) arthralgia/myalgia, n. 2 (0.3%) arthritis, n. 3 (0.5%) pericarditis, n. 1 (0.2%) myocarditis, n. 11 (1.9%) thrombocytopenia or pancytopenia, and in the follow up cohort B we identified 9 (6.7%) cases of newly diagnosed IMDs after the recovery from COVID-19. In all cases, serological alterations were not observed.In cohort C we observed n.5 flares of pre-existing IMD after SARS-COV2 infection, and in the cohort D n. 13 IMD temporally close with SARS-CoV-2 vaccination in 8 healthy subjects (with clinical classifiable IMD-like presentation) and in 5 patients affected by an anamnestic IMD. Also in these latter cases, except in 2 healthy subjects, there were not found serological alterations specific of a classifiable IMD.

Conclusions: This study suggests that the interplay between SARS-CoV-2 and the host may induce complex immune-mediated reactions, probably induced by the anti-spike antibodies, in healthy people and IMD patients without specific serological autoimmunity. Moreover, our data suggest that the anti-SARS-CoV-2 antibodies generated by the vaccination may cause in healthy subjects' clinical manifestations similar to well-definite IMDs. These findings support the hypothesis that SARS-Cov2 infection in COVID-19 induce an innate and adaptive immune response that may be both responsible of the symptoms correlated with the occurrence of the IMDs described in our study. And, in this context, the IMDs observed in healthy people in close temporal correlation with the vaccination suggest that the anti-Spike antibodies may play a key role in the induction of an abnormal and deregulated immune response.

Keywords: COVID-19; Immuno-Mediated Reactions; SARS-CoV2; autoimmunity; vaccine.

Figure 1

Schematic representation of the study and patients’ groups. In the flow chart are represented the composition of the patients’ cohorts/groups, inclusion/exclusion criteria in the study and brief presentations of the clinical outcomes. All the patients who suffered of IMDs symptoms after the vaccination had been vaccinated with two boost doses of the vaccines listed in the Table 6 . For more details, see the Materials and Methods section.

Figure 2

Dermatomyositis-like clinical presentation closely correlated with anti-SARS-2 vaccination. The figure shows a representative case of a dermatomyositis-like clinical presentation in a patient after SARS-COV2 vaccination.

Figure 3

Rheumatoid arthritis-like clinical presentation closely correlated with anti-SARS-2 vaccination. The figure shows a representative case of a rheumatoid arthritis-like clinical presentation in a patient after SARS-COV2 vaccination. Panel (A) From left to right: acute phase of the disease, a particular of the right hand, and clinical examination after 4 weeks of corticosteroid therapy. Panel (B) Ultrasound doppler examination of the 3rd metacarpal-phalangeal joint of the right hand (from left to right): Grayscale US, Joint capsule (arrow) of MCF III dilated by synovial proliferation (open arrow) grade III (gs) according to OMERACT criteria. Below are shown the surfaces of metacarpal bone (arrowhead) and proximal phalanx (open arrowhead); Power Doppler Same scan of Figure 1 with PD showing severly active synovitis (arrow) of grade III (pd) according to OMERACT criteria With PD signal becames evident an associated paratenonitis of third digit extensor tendons (open arrows).