Endothelial activation and dysfunction in COVID-19:from basic mechanisms to potential therapeutic approaches

On 12 March 2020,the outbreak of coronavirus disease 2019(COVID-19)was declared a pandemic by the World Health Organization.As of 4 August 2020,more than 18 million confirmed infections had been reported globally.Most patients have mild symptoms,but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients.Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation.Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier,promoting pro-coagulative state,inducing endothelial inflammation,and even mediating leukocyte infiltration.This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.

MicroRNA-628-5p Facilitates Enterovirus 71 Infection by Suppressing TRAF3 Signaling

To date,EV71 infection still poses a great challenge to the health of infants and young children.1 Much established evidence suggests that EV71 infection depends on a wide variety of host factors,including cell surface receptors for EV71 entry,innate immune response,miRNAs,and lncRNAs.2,3 It is thought that diverse signaling pathways are required for EV71 to escape the host immune response.4 Innate immunity serves as the first line of defense against pathogens.Tumor necrosis factor receptor-associated factor(TRAF)proteins are essential components of signaling pathways activated by Toll-like receptor(TLR)or RIG-I-like receptor(RLR)family members.TRAF3 is widely expressed by many cell types,including all nucleated immune cells,in which it plays many roles in the regulation of immune functions.5 TRAF3 plays a significant role in regulating the functions of B and T lymphocytes.TRAF3 is a highly versatile regulator that positively controls type I interferon and cytokine production through interferon regulatory factors(IRFs)and nuclear factor-κB(NF-κB).6 A recent study indicated that EV71-induced ubiquitin-specific protease 19(USP19)negatively regulates type I IFN signaling by targeting TRAF3.

The incubation period of COVID-19: a global meta-analysis of 53 studies and a Chinese observation study of 11 545 patients

Background:The incubation period is a crucial index of epidemiology in understanding the spread of the emerging Coronavirus disease 2019(COVID-19).In this study,we aimed to describe the incubation period of COVID-19 globally and in the mainland of China.Methods:The searched studies were published from December 1,2019 to May 26,2021 in CNKI,Wanfang,PubMed,and Embase databases.A random-efect model was used to pool the mean incubation period.Meta-regression was used to explore the sources of heterogeneity.Meanwhile,we collected 11545 patients in the mainland of China outside Hubei from January 19,2020 to September 21,2020.The incubation period ftted with the Log-normal model by the coarseDataTools package.Results:A total of 3235 articles were searched,53 of which were included in the meta-analysis.The pooled mean incubation period of COVID-19 was 6.0 days(95%confdence interval[CI]5.6–6.5)globally,6.5 days(95%CI 6.1–6.9)in the mainland of China,and 4.6 days(95%CI 4.1–5.1)outside the mainland of China(P=0.006).The incubation period varied with age(P=0.005).Meanwhile,in 11545 patients,the mean incubation period was 7.1 days(95%CI 7.0–7.2),which was similar to the fnding in our meta-analysis.Conclusions:For COVID-19,the mean incubation period was 6.0 days globally but near 7.0 days in the mainland of China,which will help identify the time of infection and make disease control decisions.Furthermore,attention should also be paid to the region-or age-specifc incubation period.

Endothelial activation and dysfunction in COVID-19: frombasic mechanisms to potential therapeutic approaches

On 12 March 2020,the outbreak of coronavirus disease 2019(COVID-19)was declared a pandemic by the World Health Organization.As of 4 August 2020,more than 18 million confirmed infections had been reported globally.Most patients have mild symptoms,but some patients develop respiratory failure which is the leading cause of death among COVID-19 patients.Endothelial cells with high levels of angiotensin-converting enzyme 2 expression are major participants and regulators of inflammatory reactions and coagulation.Accumulating evidence suggests that endothelial activation and dysfunction participate in COVID-19 pathogenesis by altering the integrity of vessel barrier,promoting pro-coagulative state,inducing endothelial inflammation,and even mediating leukocyte infiltration.This review describes the proposed cellular and molecular mechanisms of endothelial activation and dysfunction during COVID-19 emphasizing the principal mediators and therapeutic implications.