ABSTRACT
Background: RA has been associated with poor COVID-19 outcomes, but few studies have investigated outcomes in RA features such as interstitial lung disease. Objectives: To assess COVID-19 outcomes in patients with RA overall, and those with and without ILD, compared to general population comparators. Methods: A multicenter, retrospective cohort study was conducted at Mayo Clinic (19 hospitals and affiliated outpatient centers in 4 states) and Mass General Brigham (14 hospitals and affiliated outpatient centers in New England). Consecutive patients with RA meeting ACR/EULAR criteria and a positive COVID-19 test from March 1, 2020 through June 6, 2021 were matched 1:5 on age, sex, race, and COVID-19 test date with general population comparators without RA. RA features assessed included: RA-ILD per Bongartz criteria [1], duration, rheumatoid factor (RF), cyclic citrullinated peptide antibody (CCP), bone erosions, and treatments. The primary outcome was a composite of hospitalization or death following COVID-19 diagnosis. We used multivariable Cox regression to investigate the association of RA, and features such as ILD, with COVID-19 outcomes compared to matched comparators. Results: We analyzed 582 patients with RA and 2892 comparators without RA, all with COVID-19. Mean age was 62 years, 51% were female, and 79% were White. Mean RA duration was 11 years, 67% were seropositive (52% RF+ and 54% CCP+), 27% had bone erosions, 28% were on steroids, and 79% were on DMARDs. 50/582 (9%) patients with RA had ILD. The COVID-19 hospitalization or death rate for RA patients was higher than comparators (3.0 per 1,000 days [95% CI 2.5-3.6] vs. 1.9 per 1,000 days [95% CI 1.7-2.1], respectively). Overall, RA patients had a 53% higher risk of hospitalization or death than comparators after adjustment (95% CI 1.20-1.94). Among those with RA-ILD, the hospitalization or death rate was signifcantly higher than comparators (10.9 [95% CI 6.7-15.2] vs. 2.5 per 1,000 days [1.8-3.2], respectively). RA-ILD was associated with nearly 3-fold higher risk for hospitalization or death than comparators (multivariable HR 2.84 [95% CI 1.64-4.91], Table 1). There was a signifcant interaction between RA/comparator status and presence/absence of ILD for risk of severe COVID-19 (p<0.001, Figure 1). The elevated risk for severe COVID-19 was similar for RA subgroups defned by serostatus or bone erosions. Conclusion: We confrmed that RA was associated with severe COVID-19 outcomes compared to the general population. We found evidence that ILD may be an effect modifer for the relationship between RA and severe COVID-19 outcomes, but RA subgroups defned by serostatus and bone erosions had similarly elevated risk. These fndings suggest that ILD or its treatment may be a major contributor to severe COVID-19 outcomes in RA.
ABSTRACT
Background: Systemic autoimmune rheumatic disease (SARD) patients may be at risk for disease fare and prolonged symptom duration after COVID-19, perhaps related to DMARD disruption and immune activation. Objectives: To describe DMARD disruption and identify differences in SARD activity among patients with and without prolonged COVID-19 symptom duration. Methods: We identifed all SARD patients with confrmed COVID-19 at the Mass General Brigham healthcare system in Boston, USA;prospective recruitment is ongoing. Surveys were used to collect demographics, clinical characteristics, DMARD disruption, COVID-19 course, and SARD disease activity before and after COVID-19. The survey included validated instruments measuring disease activity, pain, fatigue, functional status, and respiratory quality of life. Prolonged symptom duration was defned as COVID-19 symptoms lasting ≥28 days. We compared differences in patient-reported measures between those with and without prolonged symptoms. Results: We analyzed survey responses from 174 COVID-19 survivors with SARDs (mean age 52±16 years, 81% female, 80% White). The most common SARDs were RA (40%) and SLE (14%). Fifty-one percent of the 127 respondents on any DMARD reported a disruption to their regimen at COVID-19 onset (Figure 1). Among individual DMARDs, 56-77% were reported to have any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD fare after COVID-19 was reported by 41% of respondents (Table 1). Patient global assessment of SARD activity was worse after COVID-19 (mean 7.6±2.3 before vs. 6.6±2.9 after COVID-19, p<0.001). Prolonged symptom duration was reported by 45% of participants. Those with prolonged symptoms had a higher initial COVID-19 symptom count (median 7 vs. 4, p<0.001) and were more likely to be hospitalized for COVID-19 (28% vs. 17%, p=0.001). Respondents experiencing prolonged symptom duration had higher disease activity on RAPID3 (p=0.007) as well as more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. Conclusion: DMARD disruption, SARD fare, and prolonged symptoms were common in this prospective study of COVID-19 survivors with SARDs. Those with prolonged COVID-19 symptom duration, defned as ≥28 days, had higher SARD activity, more pain, and more fatigue compared to those without prolonged symptoms. These fndings suggest that post-acute sequelae of COVID-19 may have a large impact on underlying SARD activity and quality of life.
ABSTRACT
Background: COVID-19 can induce a hyperinflammatory state resulting in cytokine storm, which can lead to poor outcomes. Patients with systemic rheumatic diseases may be at increased risk for respiratory failure with COVID-19. Therefore, we investigated the relationship between rheumatic disease, hyperinflammation, and clinical outcomes among hospitalized COVID-19 patients. Objectives: To compare laboratory values, hyperinflammation, and clinical outcomes of hospitalized COVID-19 rheumatic patients and matched comparators. Methods: We performed a comparative cohort study of patients with polymerase chain reaction (PCR)-confirmed COVID-19 requiring hospitalization between 3/1/20-7/7/20 at a large health care system. We compared each systemic rheumatic disease case to up to 5 matched (by age, sex, and date of +SARS-CoV-2 PCR) comparators without systemic rheumatic disease. We extracted laboratory values from their hospitalization to compare peaks/troughs of individual laboratory results by case status and derived the COVID-19-associated hyperinflammation score (cHIS), a composite of 6 laboratory domains (0-6, ≥2 indicating hyperinflammation), as previously developed1. We used multivariable logistic regression to estimate ORs for COVID-19 outcomes by hyperinflammation and case status. Results: We identified 57 hospitalized rheumatic disease cases (mean age 67 years, 67% female) and 232 matched comparators hospitalized with PCR-confirmed COVID-19. Among cases, 26 (46%) had rheumatoid arthritis and 14 (25%) had systemic lupus erythematosus. Most cases (34, 60%) had active rheumatic disease. At baseline, 15 (27%) of cases were treated with biologic DMARDs, and 32 (56%) were using glucocorticoids. We analyzed 39,900 total laboratory results (median 85 per patient). Cases had higher peak neutrophil-to-lymphocyte ratio (9.6 vs 7.8, p=0.02), LDH (421 vs 345 U/L, p=0.04), creatinine (1.2 vs 1.0 mg/dL, p=0.01), and BUN (31 vs 23 mg/dL, p=0.03) than comparators but similar peak CRP (149 vs 116 mg/L, p=0.11, Figure 1). Cases had higher peak median cHIS (3 vs 2, p=0.01). Peak cHIS ≥2 had higher odds of intensive care unit (ICU) admission (OR 3.45, 95%CI 1.98-5.99), mechanical ventilation (OR 66.0, 95%CI 9.0-487.8), and mortality (OR 16.4, 95%CI 4.8-56.4) compared to cHIS <2 (Table 1). Cases had increased risk of ICU admission (OR 2.0, 95%CI 1.1-3.7) and mechanical ventilation (OR 2.7, 95%CI 1.4-5.2) than comparators Conclusion: Patients with systemic rheumatic disease hospitalized for COVID-19 had higher risk for hyperinflammation, kidney injury, and mechanical ventilation than non-rheumatic comparators. We validated the cHIS in our cohort, which was strongly associated with poor COVID-19 outcomes. These findings highlight that hospitalized patients with rheumatic diseases may be vulnerable to poor COVID-19 outcomes.