he global pandemic of novel coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide. 1 As of April 5, 2020, there have been more than 1.2 million reported cases and 69 000 deaths in more than 200 countries. This novel Betacoronavirus is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV); based on its genetic proximity, it likely originated from bat-derived coronaviruses with spread via an unknown intermediate mammal host to humans. 1 The viral genome of SARS-CoV-2 was rapidly sequenced to enable diagnostic testing, epidemiologic tracking, and development of preventive and therapeutic strategies.Currently, there is no evidence from randomized clinical trials (RCTs) that any potential therapy improves outcomes in patients with either suspected or confirmed COVID-19. There are no clinical trial data supporting any prophylactic therapy. More than 300 active clinical treatment trials are underway. This narrative review summarizes current evidence regarding major proposed treatments, repurposed or experimental, for COVID-19 and provides a summary of current clinical experience and treatment guidance for this novel epidemic coronavirus. MethodsA literature review was performed using PubMed to identify relevant English-language articles published through March 25, 2020. Search terms included coronavirus, severe acute respiratory syndrome coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS-CoV, and COVID-19 in combination with treatment and pharmacology. The search resulted in 1315 total articles. Due to the lack of RCTs, the authors also included case reports, case series, and review articles. The authors independently reviewed the titles and abstracts for inclusion. Additional relevant articles were identified from the review of citations referenced. Active clinical trials were identified using the disease search term coronavirus infection on ClinicalTrials.gov and the index of studies of novel coronavirus pneumonia in the Chinese Clinical Trial Registry. 2 SARS-CoV-2: Virology and Drug Targets SARS-CoV-2, a single-stranded RNA-enveloped virus, targets cells through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Following IMPORTANCE The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection.OBSERVATIONS No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The mo...

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Purpose Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. Methods This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72–96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. Results Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57–1.40). There were no significant differences in secondary outcomes or complications. Conclusions In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06684-3.

BackgroundNRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.MethodsIn the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48. Bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry (DXA) scan at baseline and week 48, and bone turnover markers (BTM) assessed at weeks 0, 16 and 48.ResultsUsing an intention-to-treat analysis, 62.5% of RAL subjects and 83.7% of TDF/FTC subjects were responders (VL<48 copies/mL) at week 48 (p = 0.045; chi-square test). The proportions of patients achieving VL<200 copies/mL were similar: 72.5% and 86.0% (p = 0.175). Premature treatment discontinuation was the main cause for failure. No treatment-emergent resistance was observed. Changes from baseline in RAL vs. TDF/FTC for CD4+ (+199 vs. +216 cells/µL, p = 0.63), total cholesterol/HDL (−0.25 vs. −0.71 mg/dL (p = 0.270), and eGFR (−4.4 vs. −7.9 ml/min, p = 0.44) were comparable between groups. Changes in subtotal BMD to week 48 were: +9.2 with RAL vs. −7 g/cm2 with TDF/FTC (p = 0.002). Mean CTX changes were +0.04 vs. +0.24 ng/mL (p = 0.001), and mean P1NP changes were +3.59 vs. +30.09 ng/mL (p = 0.023). BTM changes at week 16 predicted change in BMD by week 48 (R = −0.394, p = 0.003 for CTX; and R = −0.477, p<0.001 for P1NP).ConclusionThe NRTI-sparing regimen RAL+DRV/r did not achieve similar week 48 virologic efficacy compared with TDF/FTC+DRV/r, but was better with regard to markers of bone health.Trial RegistrationClinicalTrials.gov NCT 00677300

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