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Background COVID-19 can induce a hyperinflammatory state, which might lead to poor clinical outcomes. We aimed to assess whether patients with a systemic rheumatic disease might be at increased risk for hyperinflammation and respiratory failure from COVID-19. Methods We did a retrospective, comparative cohort study of patients aged 18 years or older admitted to hospital with PCR-confirmed COVID-19 at Mass General Brigham (Boston, USA). We identified patients by a search of electronic health records and matched patients with a systemic rheumatic disease 1:5 to comparators. We compared individual laboratory results by case status and extracted laboratory results and COVID-19 outcomes for each participant. We calculated the COVID-19-associated hyperinflammation score (cHIS), a composite of six domains (a score of ≥2 indicating hyperinflammation) and used logistic regression to estimate odds ratios (ORs) for COVID-19 outcomes by hyperinflammation and case status. Findings We identified 57 patients with a systemic rheumatic disease and 232 matched comparators who were admitted to hospital with COVID-19 between Jan 30 and July 7, 2020; 38 (67%) patients with a rheumatic disease were female compared with 158 (68%) matched comparators. Patients with a systemic rheumatic disease had higher peak median neutrophil-to-lymphocyte ratio (9·6 [IQR 6·4–22·2] vs 7·8 [4·5–16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297–528] vs 345 U/L [254–479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9–2·0] vs 1·0 mg/dL [0·8–1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15–61] vs 23 mg/dL [13–37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4–275·3] vs 116·3 mg/L [58·8–225·9]; p=0·11) was not significantly different. Patients with a systemic rheumatic disease had higher peak median cHIS than comparators (3 [1–5] vs 2 [1–4]; p=0·013). All patients with a peak cHIS of 2 or more had higher odds of admission to intensive care (OR 3·45 [95% CI 1·98–5·99]), mechanical ventilation (66·20 [8·98–487·80]), and in-hospital mortality (16·37 [4·75–56·38]) than patients with a peak cHIS of less than 2. In adjusted analyses, patients with a rheumatic disease had higher odds of admission to intensive care (2·08 [1·09–3·96]) and mechanical ventilation (2·60 [1·32–5·12]) than comparators, but not in-hospital mortality (1.78 [0·79–4·02]). Among patients who were discharged from hospital, risk of rehospitalisation (1·08 [0·37–3·16]) and mortality within 60 days (1·20 [0·58–2·47]) was similar in patients and comparators. Interpretation Patients with a systemic rheumatic disease who were admitted to hospital for COVID-19 had increased risk for hyperinflammation, kidney injury, admission to intensive care, and mechanic...

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Purpose of review The current review summarizes the current evidence on inhalants other than personal cigarette smoking and risk for developing rheumatoid arthritis (RA). Recent findings Personal cigarette smoking has been implicated as an environmental risk factor for seropositive RA, perhaps by inducing autoimmunity at pulmonary mucosa. Since many patients with RA are nonsmokers, other inhalants are being investigated as potential RA risk factors. Recent case–control and cohort studies have investigated passive cigarette smoking, air pollution, inhalant-related occupations, silica, pesticides, household environment, and allergic inhalants as inhalant exposures for RA risk. Inhalant-related occupations and silica inhalants have the most consistent evidence for associations with increased RA risk. However, most studies relied on retrospective designs and had limited ability to adjust for personal cigarette smoking or investigate associations among nonsmokers. Summary Several inhalants other than personal cigarette smoking may be associated with increased risk for developing RA. These results support the hypothesis that inhalants, pulmonary mucosal inflammation, and RA pathogenesis may be linked. Future studies are needed to firmly establish the independence of these findings from personal cigarette smoking and to determine the specific inhalants and biologic mechanisms related to RA pathogenesis.

Objective Patients with immune‐mediated diseases treated with anti‐CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID‐19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown. Methods We identified patients with immune‐mediated diseases who received anti‐CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction–confirmed COVID‐19 between January 31, 2020, and January 31, 2021. General population comparators with COVID‐19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti‐CD20 monoclonal antibodies versus comparators were estimated by using Cox regression. Results We identified 114 cases patients COVID‐19 who had received anti‐CD20 monoclonal antibodies for immune‐mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID‐19 (mean age 54 years, 70% female). Patients treated with anti‐CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03‐4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62‐1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36‐1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti‐CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID‐19 diagnosis were excluded. Conclusion Patients who received anti‐CD20 monoclonal antibodies for immune‐mediated diseases prior to COVID‐19 had higher mortality following COVID‐19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti‐CD20 monoclonal antibodies during the ongoing pandemic.

Objective: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. Methods: We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. Results: We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. Conclusions: Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic.

Objective. To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking.Methods. We analyzed the Nurses' Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of 1) maternal smoking during pregnancy (in utero exposure), 2) childhood parental smoking, and 3) years lived with smokers since age 18. Incident RA and serostatus were determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early-life factors and time-updated adulthood factors including personal smoking.Results. Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during a median of 27.7 years of follow-up. Maternal smoking during pregnancy was associated with RA after adjustment for confounders, with a hazard ratio (HR) of 1.25 (95% confidence interval [95% CI] 1.03-1.52), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjustment for confounders ). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03-2.98]) after controlling for adulthood personal smoking, and the association was accentuated among ever smokers ). There was no significant association of adulthood passive smoking with RA (HR 1.30 for ≥20 years of living with a smoker versus none [95% CI 0.97-1.74]).Conclusion. We found a potential direct influence of childhood parental smoking on adult-onset incident seropositive RA even after controlling for adulthood personal smoking.

Objective. To identify predictors of rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) treatment for cancer.Methods. We performed a case-control study to predict the occurrence of rheumatic irAEs in cancer patients who initiated ICI treatment at Mass General Brigham and the Dana-Farber Cancer Institute between 2011 and 2020. We screened for the presence of rheumatic irAEs by reviewing the medical records of patients evaluated by rheumatologists or those prescribed nonglucocorticoid immunomodulatory drugs after the time of ICI initiation (baseline). Review of medical records confirmed the presence of rheumatic irAEs and the indications necessitating immunomodulatory drug treatment. Controls were defined as patients who did not experience rheumatic irAEs, did not have preexisting rheumatic disease, did not have a clinical evaluation by a rheumatologist after ICI treatment, did not receive an immunomodulatory drug after ICI, did not receive systemic glucocorticoids after ICI, and survived at least 6 months after the initial ICI treatment. We used logistic regression to estimate the odds ratios (ORs) (with 95% confidence intervals [95% CIs]) for the risk of a rheumatic irAE in the presence of various baseline predictors.Results. A total of 8,028 ICI recipients were identified (mean age 65.5 years, 43.1% female, 31.8% with lung cancer). After ICI initiation, 404 patients (5.0%) were evaluated by rheumatologists, and 475 patients (5.9%) received an immunomodulatory drug to treat any irAEs. There were 226 confirmed rheumatic irAE cases (2.8%) and 118 de novo inflammatory arthritis cases (1.5%). Rheumatic diseases (either preexisting rheumatic diseases or rheumatic irAEs) were a common indication for immunomodulatory drug use (27.9%). Baseline predictors of rheumatic irAEs included melanoma ) and genitourinary (GU) cancer ), both relative to patients with lung cancer; combination ICI treatment ), relative to patients receiving programmed death 1 inhibitor monotherapy; autoimmune disease (OR 2.04 [95% CI 1.45-2.85]) and recent glucocorticoid use (OR 2.13 [95% CI 1.51-2.98]), relative to patients not receiving a glucocorticoid, compared to the 2,312 controls without rheumatic irAEs. Predictors of de novo inflammatory arthritis were similar to those of rheumatic irAEs.Conclusion. We identified novel predictors of rheumatic irAE development in cancer patients, including baseline presence of melanoma, baseline presence of GU tract cancer, preexisting autoimmune disease, receiving or having received combination ICI treatment, and receiving or having received glucocorticoids. The proportion of cancer patients experiencing rheumatic irAEs may be even higher than was reported in the present study, since we used stringent criteria to identify cases of rheumatic irAEs. Our findings could be used to identify cancer patients at risk of developing rheumatic irAEs and de novo inflammatory arthritis and may help further elucidate the pathogenesis of rheumatic irAEs in patients with cancer who ar...