Summary Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non‐SARS‐CoV2 infection supported the use of these agents in the present SARS‐CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection ( n = 6), acute chikungunya infection ( n = 1), acute dengue virus infection ( n = 2), chronic HCV ( n = 2), and as preventive measures for influenza infection ( n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non‐SARS‐CoV2 viral infections do not support these agents' use for the SARS‐CoV2 outbreak.

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Background Determining how prior immune checkpoint inhibitor (ICI) therapy influences outcomes in cancer patients presenting with COVID‐19 is essential for patient management but must account for confounding variables. Methods We performed a systematic review and meta‐analysis of studies reporting adjusted effects of ICIs on survival, severe events, or hospitalisation in cancer patients with COVID‐19 based on variables including age, gender, diabetes mellitus, hypertension (HTN), chronic obstructive pulmonary disease, and other comorbidities. When adjusted effects were unavailable, unadjusted data were analysed. Results Of 42 observational studies (38 retrospective), 7 reported adjusted outcomes for ICIs and 2 provided sufficient individual patient data to calculate adjusted outcomes. In eight studies, adjusted outcomes were based on ≤7 variables. Over all studies, only one included >100 ICI patients while 26 included <10. ICIs did not alter the odds ratio (95%CI) (OR) of death significantly (random effects model), across adjusted ( n = 8) [1.31 (0.58–2.95) p = 0.46; I 2 = 42%, p = 0.10], unadjusted ( n = 30) [1.06 (0.85–1.32) p = 0.58; I 2 = 0%, p = 0.76] or combined [1.09 (0.88;1.36) p = 0.41; I 2 = 0%, p = 0.5)] studies. Similarly, ICIs did not alter severe events significantly across adjusted ( n = 5) [1.20 (0.30–4.74) p = 0.73; I 2 = 52%, p = 0.08], unadjusted ( n = 19) [(1.23 (0.87–1.75) p = 0.23; I 2 = 16%, p = 0.26] or combined [1.26 (0.90–1.77) p = 0.16; I 2 = 25%, p = 0.14] studies. Two studies provided adjusted hospitalisation data and when combined with 13 unadjusted studies, ICIs did not alter hospitalisation significantly [1.19 (0.85–1.68) p = 029; I 2 = 5%, p = 0.40]. Results of sensitivity analyses examining ICI effects based on 5 variables were inconclusive. Certainty of evidence was very low. Conclusions Across studies with adjusted and unadjusted results, ICIs did not alter outcomes significantly. But studies with comprehensive adjusted outcome data controlling for confounding variables are necessary to determine whether ICIs impact COVID‐19 outcomes in cancer patients.

Background Extensive animal investigation informed clinical practice regarding the harmful effects of high fractional inspired oxygen concentrations (FiO2s > 0.60). Since questions persist whether lower but still supraphysiologic FiO2 ≤ 0.60 and > 0.21 (FiO2 ≤ 0.60/ > 0.21) are also harmful with inflammatory lung injury in patients, we performed a systematic review examining this question in animal models. Methods Studies retrieved from systematic literature searches of three databases, that compared the effects of exposure to FiO2 ≤ 0.60/ > 0.21 vs. FiO2 = 0.21 for ≥ 24 h in adult in vivo animal models including an inflammatory challenge or not were analyzed. Survival, body weight and/or lung injury measures were included in meta-analysis if reported in ≥ 3 studies. Results More than 600 retrieved reports investigated only FiO2s > 0.60 and were not analyzed. Ten studies with an inflammatory challenge (6 infectious and 4 noninfectious) and 14 studies without, investigated FiO2s ≤ 0.60/ > 0.21 and were analyzed separately. In seven studies with an inflammatory challenge, compared to FiO2 = 0.21, FiO2 ≤ 0.60/ > 0.21 had consistent effects across animal types on the overall odds ratio of survival (95%CI) that was on the side of harm but not significant [0.68 (0.38,1.23), p = 0.21; I2 = 0%, p = 0.57]. However, oxygen exposure times were only 1d in 4 studies and 2–4d in another. In a trend approaching significance, FiO2 ≤ 0.60/ > 0.21 with an inflammatory challenge consistently increased the standardized mean difference (95%CI) (SMD) in lung weights [0.47 (− 0.07,1.00), p = 0.09; I2 = 0%, p = 0.50; n = 4 studies] but had inconsistent effects on lung lavage protein concentrations (n = 3), lung pathology scores (n = 4) and/or arterial oxygenation (n = 4) (I2 ≥ 43%, p ≤ 0.17). Studies without an inflammatory challenge had consistent effects on lung lavage protein concentration (n = 3) SMDs on the side of being increased that was not significant [0.43 (− 0.23,1.09), p = 0.20; I2 = 0%, p = 0.40] but had inconsistent effects on body and lung weights (n = 6 and 8 studies, respectively) (I2 ≥ 71%, p < 0.01). Quality of evidence for studies was weak. Interpretation Limited animal studies have investigated FiO2 ≤ 0.60/ > 0.21 with clinically relevant models and endpoints but suggest even these lower FiO2s may be injurious. Given the influence animal studies examining FiO2 > 0.60 have had on clinical practice, additional ones investigating FiO2 ≤ 0.60/ > 0.21 appear warranted, particularly in pneumonia models.

Background In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab—a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody—has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking. Case presentation We present a multinational case series of 18 PWH with COVID-19 who were treated with IL-6ri’s during the period from April to June 2020. Four patients received tocilizumab, six sarilumab, and eight received an undocumented IL-6ri. Of the 18 patients in the series, 4 (22%) had CD4 counts < 200 cells/mm3; 14 (82%) had a suppressed HIV viral load. Eight patients (44%), all admitted to ICU, were treated for secondary infection; 5 had a confirmed organism. Of the four patients with CD4 counts < 200 cells/mm3, three were treated for secondary infection, with 2 confirmed organisms. Overall outcomes were poor—12 patients (67%) were admitted to the ICU, 11 (61%) required mechanical ventilation, and 7 (39%) died. Conclusions In this case series of hospitalized PWH with COVID-19 and given IL-6ri prior to the common use of corticosteroids, there are reports of secondary or co-infection in severely ill patients. Comprehensive studies in PWH, particularly with CD4 counts < 200 cells, are warranted to assess infectious and other outcomes after IL-6ri use, particularly in the context of co-administered corticosteroids.