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The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA. Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols. Electronic supplementary material The online version of this article (10.1007/s40121-020-00303-8) contains supplementary material, which is available to authorized users.

Background The emergence of SARS-CoV-2/2019 novel coronavirus (COVID19) has created a global pandemic with no approved treatments or vaccines. Repurposing existing drugs and rapidly launching clinical trials present the greatest near-term opportunities for mitigating COVID19s impact. Many treatments have already been administered to COVID19 patients but have not been systematically evaluated. We performed a systematic literature review to identify and assess all treatments reported to be administered to COVID19 patients. Methods We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID19 patients published between Dec 1, 2019 and Mar 27, 2020. All studies reporting treatments were included. Data for each paper were manually extracted by two independent extractors. Outcomes included the duration from drug administration to clinically-meaningful response (complete symptom resolution or hospital discharge). Data were analysed descriptively. Results We identified 2,706 articles from single patient case reports to single-centre interventional studies. Of these, 155 studies met inclusion criteria, comprising 9,152 patients from 14 different countries. The cohort was 45.4% female and 98.3% hospitalised, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a response time of 11.7 (1.09) days. Discussion A large number of treatments have been administered to the first 9,152 reported cases of COVID19. Further work is needed to prioritise drugs for investigation in well-controlled clinical trials and treatment protocols. Funding None.

Mitophagy is a selective mode of autophagy in which mitochondria are specifically targeted for degradation at the autophagolysosome. Mitophagy is activated by stresses such as hypoxia, nutrient deprivation, DNA damage, inflammation and mitochondrial membrane depolarization and plays a role in maintaining mitochondrial integrity and function. Defects in mitophagy lead to mitochondrial dysfunction that can affect metabolic reprogramming in response to stress, alter cell fate determination and differentiation, which in turn affects disease incidence and etiology, including cancer. Here, we discuss how different mitophagy adaptors and modulators, including Parkin, BNIP3, BNIP3L, p62/SQSTM1 and OPTN, are regulated in response to physiological stresses and deregulated in cancers. Additionally, we explore how these different mitophagy control pathways coordinate with each other. Finally, we review new developments in understanding how mitophagy affects stemness, cell fate determination, inflammation and DNA damage responses that are relevant to understanding the role of mitophagy in cancer.

Background Despite advances in rapid organism identification, clinicians must make empiric antibiotic decisions prior to knowing the causative organism. Though many risk factors and patient characteristics have been studied and incorporated into predictive clinical decision support tools for empiric antibiotic prescription, little evidence exists on the relative importance of these factors in clinician judgment. The purpose of this study was to establish how providers evaluate patient and clinical risk factors when making empiric antimicrobial decisions. Methods An anonymous survey tool was distributed in February 2019 to medical providers who routinely prescribe antibiotics in 4 acute care hospitals throughout the University of Pennsylvania Health System. Providers were asked to rank the importance of 12 clinical factors using a 5-point scale from not important at all (1) to extremely important (5) in 3 unique clinical scenarios: uncomplicated cystitis, septic shock of unknown etiology, and uncomplicated pneumonia. Results Response rate was 30% (217/732). The importance of each factor varied among different clinical scenarios except for prior antibiotic exposure, local resistance patterns, drug-drug interactions, and treatment guidelines. However, the absolute difference varied by the factor and clinical scenario. Presence of indwelling catheter(s) had the largest absolute variation (median difference of 2 between septic shock and pneumonia, P < 0.001), and it was one of the top 5 most important factors for septic shock, but the least important factor for pneumonia. Conclusion The importance of clinicians place on clinical factors varies in different clinical scenarios. A better understanding of clinical decision-making in empiric antibiotic prescribing has the potential to guide stewardship efforts and clinical decision support. Disclosures All authors: No reported disclosures.