COVID-19 presentation and outcomes in patients with inflammatory rheumatic and musculoskeletal diseases receiving IL6-receptor antagonists prior to SARS-CoV-2 infection.

Objective: COVID-19 outcome may be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases (RMD) receiving immunosuppressive therapy. We aimed to investigate whether RMD patients on anti-IL6 therapy prior to SARS-CoV-2 infection have less severe disease and better outcomes of COVID-19. Methods: We conducted a retrospective national, multicentre cohort study using data from the French RMD COVID-19 cohort. We compared the severity and outcome of highly suspected or confirmed COVID-19 infection in RMD patients previously treated with tocilizumab or sarilumab (anti-IL6 group) with patients who did not receive anti-IL6 therapy (no anti-IL6 group). Results: Data were collected for 1883 patients with mean age of 55.2 years [SD 16.7] and 1256 (66.7%) female. Two hundred ten (11.1%) developed severe COVID-19 and 115 (6.4%) died. After adjusting for potential confounding factors, severe COVID-19 was less frequent in the anti-IL6 group compared with the no anti-IL6 group (aOR for moderate vs. mild severity, 0.23 [95% CI, 0.10 to 0.54], p ≤ 0.01 and aOR for severe vs. mild, 0.29 [95% CI, 0.10 to 0.81], p ≤ 0.01). No significant differences were found for the evolution of COVID-19 between the anti-IL6 group and the no anti-IL6 group (aOR for recovery with sequelae vs recovery without sequelae, 0.78 [95% CI, 0.41 to 1.48] and aOR for death vs recovery without sequelae, 0.29 [95% CI, 0.07 to 1.30]). Conclusion: RMD patients receiving anti-IL6 therapy prior to SARS-CoV-2 infection have less severe forms of COVID-19. No difference was observed in COVID-19 evolution, i.e., sequelae or death, between the groups.

Outcome of COVID-19 in patients with rheumatic and inflammatory diseases treated with mycophenolic acid: data from the French RMD COVID-19 cohort.

BACKGROUND: Patients with inflammatory rheumatic and musculoskeletal diseases (iRMD) receiving mycophenolic acid (MPA) may have a less favourable outcome from COVID-19 infection. Our aim was to investigate whether MPA treatment is associated with severe infection and/or death. METHODS: IRMD patients with and without MPA treatment with highly suspected/confirmed COVID-19 were included in this observational multicentre study. The primary outcome was death rate from COVID-19 with secondary objectives to determine the severity of infection and length of hospital stay. Outcome comparisons were made using regression models with and without adjustment on prespecified confounding factors. ORs, sub-HR (sHR) and 95% CIs were calculated using patients not treated with MPA as a reference group. RESULTS: Of the 1977 patients, 1928 were not treated with MPA (393 were MPA eligible), and 49 patients were treated with MPA. MPA-treated patients had more severe disease, longer hospital stays and higher death rate from COVID-19 than non-MPA patients (OR 8.02 (95% CI 3.35 to 19.20), p<0.001; sHR 0.57 (95% CI 0.33 to 0.98), p=0.040; OR 11.58 (95% CI 4.10 to 32.69), p<0.001). In adjusted analyses, however, no outcome was independently associated with MPA treatment. Death rate, severity and length of hospital stay of MPA-treated patients were not significantly different from those of not treated but MPA-eligible patients. CONCLUSION: MPA therapy is not associated with a more severe COVID-19 infection. However, due to increased vulnerability of developing a severe form of COVID-19, careful consideration should be taken with iRMD patients likely to be treated with MPA. TRIAL REGISTRATION NUMBER: NCT04353609.

COVID-19 outcomes in giant cell arteritis and polymyalgia rheumatica versus rheumatoid arthritis: A national, multicenter, cohort study.

OBJECTIVES: To determine whether giant cell arteritis and polymyalgia rheumatica (GCA/PMR) represent independent risk factors for worse outcomes in COVID-19. METHODS: Observational, national, French, multicenter cohort (NCT04353609) comprising patients aged ≥18 years with confirmed diagnoses of either GCA, PMR or rheumatoid arthritis (RA) having presented COVID-19; those under rituximab were excluded. Primary endpoint was COVID-19 severity in GCA/PMR patients as compared to RA. We also aimed to describe the evolution of GCA/PMR patients following COVID-19. Multinomial logistic regression models were performed, with and without adjustment on pre-specified confounding factors (i.e., age, sex, body mass index, arterial hypertension, diabetes and cardiovascular disease). Unadjusted and adjusted multinomial odds-ratio (OR/aOR) and their 95% confidence intervals (CIs) were calculated as effect size using RA as reference group. RESULTS: Between April 15, 2020, and August 20, 2021, 674 patients [45 (6.6%) GCA, 47 (7.0%) PMR, 582 (86.4%) RA; 62.8 years, 73.2% female] were included. Compared to RA patients, those with GCA/PMR were older and more frequently presented hypertension, diabetes and cardiovascular disease. Severe COVID-19 and death occurred in 24 (26.1%) and 16 (17.8%) patients with GCA/PMR, respectively. Unadjusted analyses revealed higher odds of severe COVID-19 [OR = 3.32 (95% CI 1.89-5.83; p < 0.001)] and death [OR = 3.20 (95%CI 1.67-6.13; p < 0.001)] for GCA/PMR compared to RA. After model adjustment, these odds were attenuated. CONCLUSION: Patients with GCA/PMR were more likely to have severe COVID-19 and higher mortality compared to those with RA. This worse prognosis is mostly due to well known risk factors for the general population rather than vasculitis per se.

Vascular skin manifestations in patients with severe COVID-19 in intensive care units: a monocentric prospective study.

Various skin manifestations have been reported during the coronavirus disease 2019 (COVID-19) pandemic. Among these are acral vascular skin lesions in non-severe patients, but few studies have focused specifically on patients with severe COVID-19 admitted to the intensive care unit (ICU) We aimed to assess the frequency of acral vascular skin manifestations (AVSM) in patients admitted to the ICU based on systematic dermatological examination We conducted a clinical, observational and prospective study in the ICU of Lille University Hospital (France). All adult patients with RT-PCR-confirmed severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) infection were included on May 5th and 6th, 2020 A total of 39 patients with severe COVID-19 were examined (34 males and five females; median age: 61 [55-59]). We observed AVSM in 11/39 patients (28%) including five with acral necrotic lesions, three with haemorrhagic blisters, one with acral livedoid rash, and one with erosive distal lesions. Chilblain or chilblain-like lesions were not seen, unlike ambulatory or non-severe patients described in the literature. There was no difference regarding the median length of stay in the ICU, initial symptoms of COVID-19 or baseline characteristics, except for a lower BMI in patients with AVSM. All patients had biological coagulation abnormalities (e.g. higher levels of fibrinogen or D-dimers), but there was no difference between patients with and without AVSM AVSM are infrequent and heterogenous and seem to be non-specific to patients with severe SARS-CoV-2, and possibly unrelated to COVID-19. The pathophysiology of AVSM described during the COVID-19 pandemic is not fully elucidated.

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.

BACKGROUND: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. METHODS: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. FINDINGS: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53). INTERPRETATION: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. FUNDING: None.

National early warning score to predict intensive care unit transfer and mortality in COVID-19 in a French cohort.

BACKGROUND: No risk stratification tool has been validated in hospitalised patients with coronavirus disease 2019 (COVID-19), despite a high rate of intensive care requirement and in-hospital mortality. We aimed to determine whether the National Early Warning Score (NEWS) at admission can accurately predict in-hospital mortality and ICU transfer. METHODS: This was a retrospective cohort study from January 24 to April 16, 2020, at Lille University Hospital. All consecutive adult patients with laboratory-confirmed COVID-19 who were initially admitted to non-ICU wards were included. The primary outcome was a composite criterion consisting of ICU transfer or in-hospital mortality. We evaluated the prognostic performance of NEWS by calculating the area under (AUC) the receiver operating characteristic curve, the optimal threshold value of NEWS, and its association with the primary outcome. RESULTS: Of the 202 COVID-19 patients, the median age was 65 (interquartile range 52-78), 38.6% were women and 136 had at least one comorbidity. The median NEWS was 4 (2-6). A total of 65 patients were transferred to the ICU or died in the hospital. Compared with patients with favourable outcome, these patients were significantly older, had more comorbidities and higher NEWS. The AUC for NEWS was 0.68 (0.60-0.77) and the best cutoff value was 6. Adjusted odds ratio for NEWS ≥ 6 as an independent predictor was 3.78 (1.94-7.09). CONCLUSIONS: In hospitalised COVID-19 patients, NEWS was an independent predictor of ICU transfer and in-hospital death. In daily practice, NEWS ≥ 6 at admission may help to identify patients who are at risk to deteriorate.