Human endogenous retrovirus K in the respiratory tract is associated with COVID-19 physiopathology (preprint)

Critically ill COVID-19 patients under invasive mechanical ventilation (IMV) are at greatly increased risk of death compared to the general population. While some drivers of COVID-19 disease progression, such as inflammation and hypercoagulability, have been identified, they do not completely explain the mortality of critically ill COVID-19 patients, making a search for overlooked factors necessary. A recent study examined the virome of tracheal aspirates from 25 COVID-19 patients under IMV. These samples were compared to tracheal aspirates from non-COVID patients and nasopharyngeal swabs from individuals with mild COVID-19. Critically ill COVID-19 patients had elevated expression of human endogenous retrovirus K (HERV-K), and elevated HERV-K expression in tracheal aspirate and plasma was associated with early mortality in those same patients. Among deceased patients, HERV-K expression was associated with IL-17-related inflammation, monocyte activation, and increased consumption of clotting factors. A subsequent in vitro experiment found that exposure to SARS-CoV-2 increased HERV-K expression in human primary monocytes from healthy donors. This preliminary study only included 25 individuals but implicates HERV-K in the physiopathology of COVID-19 and suggests that HERV-K could be used as a biomarker of disease severity in COVID-19 patients. 

Human endogenous retrovirus K activation in the lower respiratory tract of severe COVID-19 patients associates with early mortality (preprint)

Critically ill 2019 coronavirus disease patients (COVID-19) under invasive mechanical ventilation (IMV) are 10- to 40-times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation and coagulopathy, the mechanisms involved in progression to severity are poorly understood. By analyzing the virome from tracheal aspirates (TA) of 25 COVID-19 patients under IMV, we found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes compared to nasopharyngeal swabs from mild cases and TA from non-COVID patients. Proteomic analysis and RT-PCR confirmed the presence of HERV-K in these patients. Moreover, increased HERV-K expression was triggered in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days) in the intensive care unit. Increased HERV-K expression in deceased patients associated with IL-17-related inflammation, monocyte activation and higher consumption of clotting/fibrinolysis factors. Our data implicate the levels of HERV-K transcripts in the outcome of critical COVID-19 patients under invasive mechanical ventilation.

Characteristics and Outcomes of 4,942 Critically Ill Adult Patients with COVID-19 in Brazil (preprint)

Background: The spread of COVID-19 increased the stress of health systems globally, obligating adjustments to improve the management of severe cases. What are the impacts of preparedness measures on the outcomes of the COVID-19 critically ill patients? Our study aimed to analyze the clinical characteristics, resource use, and risk factors associated with 30-day in-hospital mortality of critically ill adult patients with COVID-19 requiring ICU admission in a network of Brazilian hospitals.Methods: A multicenter cohort of COVID-19-confirmed patients requiring ICU admission at 42 Brazilian hospitals between February 27th and June 27th, 2020. The primary outcome was 30-day in-hospital mortality. We evaluated the association of clinical characteristics, ICU resource use, and risk factors using a random-effects multivariable cox regression model, in which the hospital was the random intercept. Secondary outcomes were the length-of-stay, ICU, and in-hospital mortality, and the use of mechanical ventilation during hospitalization.Findings: From 4,942 patients, 713 (14·4%) died 30 days after the ICU admission. The median age was 56 (IQR: [43,72]) years, 38% of patients were over 60 years-old, and 41% were women. Being older than 70 years (70-79, Hazard Ratio [95%CI]: 1·95[1·3-2·93]; ≥ 80, 3·96[2·66-5·89]), frail (MFI≥3, 1·65 [1·26-2·15]) and requiring, early or late, invasive Mechanical Ventilation (<=48h, 5·42 [4·14-7·10]; >48h, 3·26 [2·46-4·32]) were independently associated with 30-day mortality. In 1,400 ventilated patients, 30-day mortality was 44·4% (622/1,400), the median duration of mechanical ventilation was ten days (IQR [6,16]), and ICU length of stay was 17 days (IQR [10,26]). Those who died within 30 days were more often older than 80 years (≥80: 37% vs. 14%) and previously frail (35% vs. 19%) compared to the survivors.Interpretation: In this large cohort, critically ill COVID-19 patients showed reasonable survival rates, including those requiring mechanical ventilation. Factors associated with worse outcome were age, frailty, and early need for invasive ventilation. Adequate preparedness, early hospitalization, and no shortage of critical care resources were probably key to achieve such results.Funding: The National Council for Scientific and Technological Development (CNPq); the Coordination for the Improvement of Higher Education Personnel (CAPES); the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ); the Pontifical Catholic University of Rio de Janeiro and the D’Or Institute for Research and Education.Declaration of Interests: Dr. Soares and Dr. Salluh are founders and equity shareholders of Epimed Solutions®, which commercializes the Epimed Monitor System®, a cloud-based software for ICU management and benchmarking. The other authors declare that they have no conflict of interest.Ethics Approval Statement: Local Ethics Committee and the Brazilian National Ethics Committee (CAAE: 17079119.7.0000.5249) approved the study without the need for informed consent.

Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study (preprint)

Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU. In this study, patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls. Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. Results: There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls. Conclusion: tocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease