COVID-19, caused by SARS-CoV-2, is the most consequential pandemic of this century. Since the outbreak in late 2019, animal models have been playing crucial roles in aiding the rapid development of vaccines/drugs for prevention and therapy, as well as understanding the pathogenesis of SARS-CoV-2 infection and immune responses of hosts. However, the current animal models have some deficits and there is an urgent need for novel models to evaluate the virulence of variants of concerns (VOC), antibody-dependent enhancement (ADE), and various comorbidities of COVID-19. This review summarizes the clinical features of COVID-19 in different populations, and the characteristics of the major animal models of SARS-CoV-2, including those naturally susceptible animals, such as non-human primates, Syrian hamster, ferret, minks, poultry, livestock, and mouse models sensitized by genetically modified, AAV/adenoviral transduced, mouse-adapted strain of SARS-CoV-2, and by engraftment of human tissues or cells. Since understanding the host receptors and proteases is essential for designing advanced genetically modified animal models, successful studies on receptors and proteases are also reviewed. Several improved alternatives for future mouse models are proposed, including the reselection of alternative receptor genes or multiple gene combinations, the use of transgenic or knock-in method, and different strains for establishing the next generation of genetically modified mice. 

/pdf/animal-models-for-covid-19-advances-gaps-and-perspectives-1ddv5yhc.pdf

Animal models for COVID-19: advances, gaps and perspectives

While many early clinical guidelines during the pandemic were based on previous experience with acute respiratory distress syndrome, the landscape has evolved since then. Today, we have a wealth of high-quality studies that support evidence-based recommendations to address these complex issues. This document, the result of a collaborative effort between four leading scientiﬁc societies (SEDAR, SEMES, SEMICYUC, SEPAR), draws on the experience of 25 experts in the ﬁeld to synthesize knowledge to address pertinent clinical questions and reﬁne the approach to patient care in the face of the challenges posed by severe COVID-19 infection.

Multidisciplinary Consensus on the Management of Non-Invasive Respiratory Support in the COVID-19 Patient.

Objective: Pulmonary complications could badly affect the recovery of neurological function and neurological prognosis of neurological critically ill patients. This study evaluated the effect of high-flow nasal cannula (HFNC) therapy on decreasing pulmonary complications in neurologically critically ill patients. Patients and Methods: The patients admitted to the intensive care unit (ICU) with serious neurological disease and receiving oxygen therapy were retrospectively reviewed (Ethical No. IRB2021-YX-001). Patients were divided into the HFNC group and the conventional oxygen therapy (COT) group. We analyzed the data within these two groups, including patients’ baseline data, short-term outcomes of respiratory complications, general outcomes including hospital stay, ICU stay and mortality, and neurological functions. To analyze the relevant factors, we performed multivariable logistic regression analysis. Results: A total of 283 patients met the criteria, including 164 cases in the HFNC group and 119 cases in the COT group. The HFNC group had remarkably less mechanical ventilation requirement with lower phlegm viscosity. Even more, ICU stay and total hospital stay were significantly shortened in the HNFC group. Conclusion: HFNC decreased pulmonary complications in neurologically critically ill patients and improved recovery of neurological function and neurological prognosis.

/pdf/high-flow-nasal-cannula-decreased-pulmonary-complications-in-24sc72ex.pdf

High Flow Nasal Cannula Decreased Pulmonary Complications in Neurologically Critically Ill Patients

Introduction/Background Coronavirus disease 2019 (COVID-19) has high transmissibility and mortality rates. High-flow nasal cannula therapy (HFNC) might reduce the need for orotracheal intubation, easing the burden on the health system caused by COVID-19. The objective of the present study was to examine the effectiveness of HFNC in adult patients hospitalized with COVID-19. Specifically, the present study explores the effects of HFNC on rates of mortality, intubation and intensive care units (ICU) length of stay. The present study also seeks to define predictors of success and failure of HFNC. Methods A systematic literature search was conducted in the PubMed, EMBASE and SCOPUS databases, and the study was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Study quality was assessed using the National Heart, Lung, and Blood Institute’s Study Quality Assessment Tools. Results The search identified 1,476 unique titles; 95 articles received full-text reviews and 40 studies were included in this review. HFNC was associated with a reduction in the rate of orotracheal intubation, notably when compared to conventional oxygen therapy. Studies reported inconsistency in whether HFNC reduced ICU length of stay or mortality rates. Among the predictors of HFNC failure/success, a ratio of oxygen saturation index of approximately 5 or more was associated with HFNC success. Conclusion In adult patients hospitalized with COVID-19, HFNC may prove effective in reducing the rate of orotracheal intubation. The ratio of the oxygen saturation index was the parameter most examined as a predictor of HFNC success. Low-level research designs, inherent study weaknesses and inconsistent findings made it impossible to conclude whether HFNC reduces ICU length of stay or mortality. Future studies should employ higher level research designs.

Effectiveness of high-flow nasal cannula therapy on clinical outcomes in adults with COVID-19: A systematic review

High-Flow Nasal Cannula

Coronavirus disease-2019 (COVID-19) has rapidly spread worldwide and causes high mortality of elderly patients. High-flow nasal cannula therapy (HFNC) is an oxygen delivery method for severely ill patients. We retrospectively analyzed the course of illness and outcomes in 110 elderly COVID-19 patients (≥65 years) treated with HFNC from 6 hospitals. 38 patients received HFNC (200 mmHg < PaO2/FiO2 ≤ 300 mmHg, early HFNC group), and 72 patients received HFNC (100 mmHg < PaO2/FiO2 ≤ 200 mmHg, late HFNC group). There were no significant differences of sequential organ failure assessment (SOFA) scores and APECH II scores between early and late HFNC group on admission. Compared with the late HFNC group, patients in the early HFNC group had a lower likelihood of developing severe acute respiratory distress syndrome (ARDS), longer time from illness onset to severe ARDS and shorter duration of viral shedding after illness onset, as well as shorter lengths of ICU and hospital stay. 24 patients died during hospitalization, of whom 22 deaths (30.6%) were in the late HFNC group and 2 (5.3%) in the early HFNC group. The present study suggested that the outcomes were better in severely ill elderly patients with COVID-19 receiving early compared to late HFNC.

/pdf/course-of-illness-and-outcomes-in-older-covid-19-patients-5cqwbiln86.pdf

Course of illness and outcomes in older COVID-19 patients treated with HFNC: a retrospective analysis.

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Course of illness and outcomes in older COVID-19 patients treated with HFNC: a retrospective analysis.