Impact of Hydroxychloroquine Used as DMARD on SARS CoV-2 Tests and COVID-19 Evolution (preprint)

Objectives: Data remain scarce on the impact of long-term hydroxychloroquine (HCQ) treatment on infection with SARS CoV-2. Our aim was to analyse the data of COVID-19 patients with inflammatory rheumatic and musculoskeletal diseases (iRMD-COVID-19 patients), and to compare those receiving HCQ as disease-modifying anti-rheumatic drug (DMARD) with those not receiving the drug.Methods: From the French iRMD-COVID-19 cohort, data on COVID-19 in patients receiving HCQ were compared to those of patients not receiving HCQ at the time of infection. Matching criteria were age, gender, comorbidities, immunosuppressive treatment and use of nasopharyngeal PCR test.Results: Among the 871 patients, 71 treated with HCQ prior to COVID-19 were matched with and compared to 191 controls. There was no significant difference between cases and controls in terms of nasopharyngeal PCR-positive rate (85% vs 81%; absolute standardized difference = 6.0%), clinical symptoms, rate of hospitalization (33.8% vs 27.7%; OR=1.75 (0.86-3.56); p=0.12), rate of severe form (admission to intensive care unit/death) (11.3% vs 9.4%; OR=1.94 (0.69-5.41); p=0.21).Conclusions: In a cohort of patients with iRMD, treatment with HCQ as DMARD did not modify either the SARS-CoV-2 nasopharyngeal PCR-positive rate or the clinical presentation and did not reduce the occurrence of severe forms of SARS CoV-2 infection, compared to patients not receiving HCQ.Trial Registration: ClinicalTrials.gov (NCT04353609).Funding Statement: This study was not supported by research funding, but FAI2R is funded by the French Ministry of Social Affairs and Health (ministère des solidarités et de la santé).Declaration of Interests: The authors have no competing interests.Ethics Approval Statement: Under French law, ethics committee approval was not required. The study was performed in compliance with MR-004, received permission from Lille University Hospital, and was declared to the Commission Nationale de l’Informatique et des Libertés (reference DEC20-107).

Interleukin-6 blockade for severe COVID-19 (preprint)

In the context of COVID-19 pandemic and growing tensions worldwide regarding healthcare facilities, there is an urgent need for effective treatments likely to reduce the crunch of ICU beds. Following the assumption by Mehta and colleagues who exhorted physicians to screen patients with severe COVID-19 for hyperinflammation and investigate immunomodulatory drugs in this setting, we relate our short-term - yet promising - experience regarding IL6 blockade with tocilizumab in 30 selected patients of less than 80 years of age, >5 days of prior disease duration, severe (i.e. requiring strictly over 6L/min of oxygen therapy) rapidly deteriorating (i.e. increase by more than 3L/min of oxygen flow within the previous 12 hours) COVID-19-related pneumonia. By comparison with a control group of patients (matched for age, gender and disease severity using the inverse probability of treatment weighted methodology) that did not receive tocilizumab. We demonstrate that, in highly selected patients, IL6 blockade could curb the "cytokine storm", prevent ICU admission and the requirement for mechanical ventilation. Notwithstanding the shortcomings of this retrospective small sample-size study, we believe that these preliminary findings support the fostering of research efforts in the fight against COVID-19-induced inflammation, especially before patients require admission to the ICU.

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial (preprint)

Background Treatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. Methods We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen [≥] 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. Results This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. Interpretation These results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.