Relationship Between New-Onset IRDs and COVID-19 Vaccination and Infection 

New-onset clinical manifestations of inflammatory rheumatic diseases (IRDs) may be associated with COVID-19 vaccination or SARS-CoV-2 infection, though causality cannot be assumed and a coincidental association cannot be ruled out, according to results of an observational cohort study published in RMD Open.

Exposure to COVID-19 vaccines may elicit an autoimmune response and suspicious onset of IRDs have been documented in close temporal association with SARS-CoV-2 infection. Investigators assessed the occurrence of new-onset IRDs closely following SARS-CoV-2 infection or COVID-19 vaccination and compared clinical manifestations between both groups.

Data were provided by the COVID-19 and autoimmune systemic diseases collaborative research group in Italy. The group submitted information on consecutive occurrences of IRD within their practice from November 2021 through October 2022. Onset of all IRDs occurred within 4 weeks of COVID-19 vaccine administration or SARS-CoV-2 infection.

The postvaccine cohort included 145 consecutive patients (mean age, 58±16 years; 66.2% women) and the postinfection cohort included 122 consecutive patients (mean age, 54±17 years; 69.7% women).

Four patients in the postinfection cohort experienced asymptomatic infection, 104 experienced mild disease, and 14 experienced severe disease.

In the postvaccine cohort, most IRDs (45.8%) occurred following the booster dose (third dose), 35.4% following the second dose, and 16% following the first dose. History of asymptomatic or mildly symptomatic COVID-19 was reported by 10.3% of patients, prior to receiving the vaccine dose associated with the onset of an IRD. Mean time to IRD diagnosis was 13.9±8.5 days postvaccine and 14.5±7.8 days postinfection.

More patients in the postvaccine cohort vs the postinfection cohort reported developing polymyalgia rheumatica (PMR) (33.1% vs 21.3%; P =.032), while fewer patients reported developing inflammatory joint diseases (IJDs) (37.2% vs 52.5%; P =.013).

Patients with PMR (about 70%) or IJDs (about 30%) achieved a drop in baseline disease activity scores with first-line therapy. Among all patients with PMR, those in the postinfection group had a shorter duration of follow-up compared with the postvaccine group (mean, 8±5 vs 14±13 weeks, respectively).

No differences were noted between the postvaccine and postinfection cohorts in percentage of patients diagnosed with vasculitis (9.0% vs 6.6%; P =.467) or with connective tissue diseases (CTDs) (20.7% vs 19.7%; P =.837). Prevalence of acrosyndrome was the only CTD to reach statistical significance, occurring more frequently among the postinfection group (20.8%) vs postvaccine group (3.3%; P =.02).

The investigators noted their study is limited by its observational nature. Additionally, they caution against forming patho-physiological conclusions based on this data, as temporal associations do not equate to causality. Finally, though this study reported similar numbers of IRDs among both the postinfection and postvaccine cohorts, the “denominator of the overall population” remains unknown and no epidemiological conclusions should be drawn.

The investigators stated, “Our article reports the largest cohort published to date of new-onset IRD following SARS-CoV-2 infection or COVID-19 vaccines. Although causality cannot be ascertained, the spectrum of possible clinical manifestations is broad and includes IJD, PMR, CTD and vasculitis.”

“[I]t is highly plausible that the risk conferred by SARS-CoV-2 infection is higher and thus the usefulness and safety of vaccines, in our opinion, are not to be questioned,” they concluded.