Hyperinflammation and clinical outcomes for patients with systemic rheumatic diseases hospitalized for COVID-19: A comparative cohort study

Hsu, T.; D'Silva, K.; Serling-Boyd, N.; Wang, J.; Mueller, A.; Fu, X.; Prisco, L.; Martin, L.; Vanni, K.; Zaccardelli, A.; Cook, C.; Choi, H.; Zhang, Y.; Gravallese, E.; Wallace, Z.; Sparks, J.

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.