Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells.

Neutrophil extracellular traps (NETs) can capture and kill viruses, such as influenza viruses, human immunodeficiency virus (HIV), and respiratory syncytial virus (RSV), thus contributing to host defense. Contrary to our expectation, we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2, as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model. The histone H3 or H4 selectively binds to subunit 2 of the spike (S) protein, as shown by a biochemical binding assay, surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids. Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein. Moreover, histones enhance cell-cell fusion. Finally, treatment with an inhibitor of NETosis, histone H3 or H4, or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model. These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS.

Acute kidney injury (AKI) is a common complication among patients with the novel coronavirus (COVID-19). COVID-19 along with AKI usually resulted in a poor prognosis for those affected. Remdesivir is a novel antiviral drug that was urgently approved for the treatment of COVID-19. In the current study, safety data of remdesivir were limited. We gathered information on COVID-19 cases in patients with adverse events that were reported to the U.S. Food and Drug Administration (US FDA) Adverse Event Reporting System (FAERS) database. We employed the reporting odds ratio (ROR) method to perform disproportionality analysis. Finally, we identified 12,869 COVID-19 cases. A total of 3,991 of these cases reported remdesivir as a primary suspected drug, while 8,878 cases were treated with other drugs. More AKI events occurred in cases of male patients and those above the age of 65 years. We detected a significant association between remdesivir and AKI: ROR = 2.81, 95% CI (2.48, 3.18). The association was stronger after the propensity score matching ROR = 3.85, 95% CI (3.11, 4.78). The mean time to AKI event onset was 4.91 ± 7.25 days in COVID-19 cases with remdesivir therapy. The fatality proportion was 36.45% in AKI cases with remdesivir treatment. This pharmacovigilance study identified a significant association between AKI events and remdesivir treatment in COVID-19 patients by mining FAERS real-world big data. Although causality was not confirmed, the association between remdesivir and AKI should not be ignored, especially in the older, male COVID-19 inpatients.

Update on treatment and preventive interventions against COVID-19: an overview of potential pharmacological agents and vaccines.

The outbreak of coronavirus disease 2019 (COVID-19) triggered by the new member of the coronaviridae family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented challenge for global health. In addition to mild to moderate clinical manifestations such as fever, cough, and fatigue, severe cases often developed lethal complications including acute respiratory distress syndrome (ARDS) and acute lung injury. Given the alarming rate of infection and increasing trend of mortality, the development of underlying therapeutic and preventive treatment, as well as the verification of its effectiveness, are the top priorities. Current research mainly referred to and evaluated the application of the empirical treatment based on two precedents, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), including antiviral drugs targeting different stages of virus replication, immunotherapy modulating the overactivated inflammation response, and other therapies such as herbal medicine and mesenchymal stem cells. Besides, the ongoing development of inventing prophylactic interventions such as various vaccines by companies and institutions worldwide is crucial to decline morbidity and mortality. This review mainly focused on promising candidates for the treatment of COVID-19 and collected recently updated evidence relevant to its feasibility in clinical practice in the near future.

Literature Analysis of the Efficacy of Arbidol in Virus Infectious Diseases

Arbidol (ARB) is a broad-spectrum antiviral drug. However, its effects on virus infectious diseases remain unclear. We aimed to evaluate the efficacy of ARB in infectious virus diseases. We searched up to March 2020 in MEDLINE (Ovid SP), EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), for studies investigating ARB in virus infectious diseases. Descriptive analysis was made on the main results of the eligible articles that meet the inclusion criteria. Fifty-two studies were included finally, which involving influenza virus, respiratory syncytial virus (RSV), severe acute respiratory syndrome-coronaviruses (SARS-CoV), middle east respiratory syndrome-coronaviruses (MERS-CoV), hepatitis c virus (HCV), herpes simplex virus (HSV), severe acute respiratory syndromes-coronaviruses-2 (SARS-CoV-2), chikungunya virus (CHIKV), hantaan virus (HTNV), zika virus (ZIKV), coxsackievirus, lassa virus(LASV), Ebola virus (EBOV) and adenovirus (ADV). ARB is effective in the above viruses. Two studies showed that ARB was effective in SARS-CoV-2. In vivo and in vitro studies showed ARB had the capability of inhibiting SARS-CoV, MERS-CoV, HCV, HSV, ZIKV, CV, HTNV, ZIKV, CHIKV, LASV, EBOV, and ADV. Conclusion Clinical studies are still needed to confirm the efficacy of ARB in novel coronavirus pneumonia (COVID-19).

Hydroxychloroquine Treatment may Benefit Nucleic Acid Testing of SARS-CoV-2 Turning Negative in Critically ill COVID-19 Patients: Report of 3 Cases

Since the outbreak of coronavirus disease 2019(COVID-19), hundreds of thousands of people have been infected. After fighting with the virus for two months, the epidemic in China is well controlled. However, many countries are still struggling with the coronavirus. Effective anti-viral drugs are important to reverse the patient's condition, especially for critically ill patients. We report 3 cases of using hydroxychloroquine in the treatment of critically ill COVID-19 patients. Results show that hydroxychloroquine treatment may benefit nucleic acid testing, turning negative in these patients.