Age, Immunosuppressive Treatment Linked to Severe COVID-19 Breakthrough Infections in IIMs

Severe COVID-19 breakthrough infections were found among patients with idiopathic inflammatory myopathies (IIMs), with age and immunosuppressive treatment correlated with the risk for such infections, according to study findings published in Rheumatology.

Breakthrough COVID-19 infections suggest vaccine immunity may wane over time, though these infections are generally less severe than prevaccination cases. However, patients with autoimmune rheumatic diseases — especially individuals with IIMs — face heightened risks for severe outcomes from breakthrough infections, highlighting the need for further research on disease characteristics and the impact of booster vaccinations and advanced COVID-19 treatments.

To this aim, researchers examined data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study and reported on the prevalence, features, and risk factors associated with COVID-19 breakthrough infections among individuals with IIMs.

In 2022, the COVAD study group (157 collaborators across 106 countries) distributed an e-survey to collect data on COVID-19 infections, complications, and vaccination history. The current analysis included a convenience sample of adult patients with IIMs, autoimmune rheumatic and nonrheumatic diseases (AIRDs and nrAIDs), and healthy controls who had received at least 2 doses of the COVID-19 vaccine and were compared in terms of severity clinical features.

Breakthrough COVID-19 infections were defined as those occurring at least 14 days after completing 2 vaccine doses. Patients who required hospitalization, admission to the intensive care or high-dependency units, supplemental oxygen, or treatment with antivirals or monoclonal antibodies were considered to have severe breakthrough infections. 

A total of 9449 survey respondents (median age, 44 years; 77.4% women; 54.7% White) who had received at least 2 doses of the COVID-19 vaccine were included in the final analysis.

Breakthrough COVID-19 infections were reported among 1447 respondents (15.3%), with 12.9% of cases occurring among individuals with IIMs. Comorbidities such as mental health disorders (28.5%), hypertension (16.5%), and dyslipidemia (12.1%) were common among individuals experiencing these infections.

Breakthrough infections typically occurred a median of 117 days after receiving the second COVID-19 vaccine dose, with no significant differences observed among the various groups.

Age was identified as a protective factor against breakthrough infections (hazard ratio [HR], 0.98; 95% CI, 0.97-0.99), while treatment with hydroxychloroquine (HR, 1.81; 95% CI, 1.24-2.64) and sulfasalazine (HR, 3.79; 95% CI, 1.69-8.42) were identified as factors associated with an increased risk for COVID-19 breakthrough infections.

Additionally, the use of glucocorticoids was identified as a risk factor associated with severe breakthrough infections (HR, 3.61; 95% CI, 1.09-11.8). Non-White ethnicity was identified as an additional risk factor for hospitalization among patients with IIMs (HR, 2.61; 95% CI, 1.03-6.59).

Variations in the symptoms and severity of breakthrough COVID-19 infections differed between patients with IIMs, other autoimmune conditions, and healthy controls. Notably, the time taken for symptoms to resolve was longer among patients with IIMs (median, 12 days) and AIRDs (median, 11 days) compared against those with nrAIDs (median, 8 days) and healthy controls (median, 7 days; P <.001).

Symptoms such as cough were more prevalent among patients with IIMs (67.6%), while arthralgia (40.6%), headache (46.8%), and chest pain (15.5%) were more common among those with AIRDs. Furthermore, patients with IIMs had higher rates of supplemental oxygen therapy (6.0%), intensive care unit admission (2.2%), advanced treatment (34.1%), and all-cause hospitalization (7.7%) compared with other groups (P <.001).

Breakthrough infections varied among patients with different vaccine doses, occurring in 24.4% of patients after 2 doses, 11.2% after 3 doses, and 10.8% after 4 doses among individuals with IIMs (P <.001 among the groups; P <.001 between 2 and 3 doses; P =.861 between 3 and 4 doses). However, the severity of these infections did not differ significantly among patients with IIMs who had received 2, 3, or 4 doses.

A second breakthrough infection was reported among 2.9% of respondents, with consistent characteristics across groups. Among patients with IIMs, symptom resolution took longer (median, 15 days; P =.006) and the rate of treatment with antivirals or monoclonal antibodies was higher (42.1%; P =.002) compared with the other groups.

Study limitations included the inability to confirm the validity of COVID-19 infections with proper testing and potential recall bias in the self-reported data.

“Patients with IIMs required more supplemental oxygen therapy, intensive care unit admission, advanced treatment with antiviral or monoclonal antibodies, and had more all-cause [hospitalization] than their counterparts. Therefore, they can be considered a vulnerable subgroup for severe [breakthrough infections],” study authors concluded. Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.