SARS-CoV-2 and COVID-19: The most important research questions

Yuen, Kit‐San; Ye, Zi Wei; Fung, Sin‐Yee; Chan, Chi-Ping; Jin, Dong Yan

doi:10.1186/s13578-020-00404-4

Cited by 605 publications

(591 citation statements)

References 12 publications

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“…To further understand the importance of the ACE2 variants in susceptibility, it will be important to correlate clinical outcomes with ACE2 genotypes at population scale. The extremes in COVID-19 clinical symptoms reported ranging from asymptomatic infected adult individuals to those that show acute respiratory syndrome leading to death (Cao et al, 2020b;Cascella et al, 2020;Yuen et al, 2020), suggest a role for additional factors, including the role of innate and adaptive immunity, besides ACE2 variants in modifying disease outcomes.…”

Section: Discussionmentioning

confidence: 99%

Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

Stawiski

Diwanji

Suryamohan

et al. 2020

Preprint

148

172

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in ~3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by ~10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 Sprotein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-proteininteracting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

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Section: Discussionmentioning

confidence: 99%

Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

Stawiski

Diwanji

Suryamohan

et al. 2020

Preprint

148

172

View full text Add to dashboard Cite

show abstract

“…(32,33) This recommendation is based on experience with influenza, SARS-CoV, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), where OCS use prolonged viral replication and was associated with prolonged viral clearance, increased complication rates, increased risk of mechanical ventilation and higher mortality rates (34)(35)(36)(37). It has been noted that OCS therapy increases the risk of nosocomial infection and secondary infection (38). However, there is a distinction between OCS use as a therapy for COVID-19, and OCS use as a treatment of asthma exacerbations (8).…”

mentioning

confidence: 99%

Managing Asthma during Coronavirus Disease-2019: An Example for Other Chronic Conditions in Children and Adolescents

Abrams

Szefler

2020

The Journal of Pediatrics

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“…At present, healthcare systems all over the world are coping with the new coronavirus infection [1]. In particular, tremendous efforts are being made in order to support governments in the policy of infection spread containment and early detection, and researchers are working on causal treatment and the treatment of the severe and critical manifestations downstream from the viral infection [2]. As largely known, coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with droplets and contact as the main way of transmission.…”

Section: Introductionmentioning

confidence: 99%