ABSTRACT
ABSTRACT COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1 , can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin . Graphical Abstract
Subject(s)
COVID-19ABSTRACT
Background Specialised pro-resolution molecules (SPMs) halt the transition to chronic pathogenic inflammation. We aimed to quantify serum levels of pro- and anti-inflammatory bioactive lipids in SARS-CoV-2 patients, and to identify potential relationships with innate responses and clinical outcome. Methods Serum from 50 hospital admitted inpatients (22 female, 28 male) with confirmed symptomatic SARS-CoV-2 infection and 94 age and sex matched cohort collected prior to the pandemic, were processed for quantification of bioactive lipids. Anti-nucleocapsid and anti-spike quantitative binding assays were performed. Results SARS-CoV-2 serum had significantly higher concentrations of omega-6 derived pro-inflammatory lipids and omega-6 and omega-3 derived SPMs, compared to age and sex matched controls. Levels of SPMs were not markedly altered by age. There were significant positive correlations between SPMs and other bioactive lipids and anti-spike antibody binding. Levels of some SPMs were significantly higher in patients with an anti-spike antibody value >0.5. Levels of linoleic acid (LA) and 5,6-dihydroxy-8Z,11Z,14Z-eicosatrienoic acid (5,6-DHET) were significantly lower in SARS-COV-2 patients who died. Discussion SARS-COV-2 infection was associated with a robust activation of the pathways that generate the specialised pro-resolution molecules and other anti-inflammatory bioactive lipids, supporting the future investigation of these pathways which may inform the development of novel treatments.
Subject(s)
COVID-19 , Inflammation , Severe Acute Respiratory SyndromeABSTRACT
Younger age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent COVID waves, which are believed to be driven by new SARS-CoV-2 variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhanced key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the ACE2 receptor in the host cells, increased glycosylation of spike protein at antigenic sites, and proteolytic cleavage of the spike protein, leading to improved host cell entry and replication of the virus. The putative changes in the virus-host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host expressions of ACE2 and other proteases. The new variants can act more efficiently, and even on the lower concentrations of the viral entry receptor and associated proteases, thus can have more efficient host cell entry and greater replication resulting in higher viral load and prolonged viral shedding, and widespread tissue injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence that multiple new variants show reduced neutralization by natural and vaccine acquired antibodies, indicating repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.
Subject(s)
COVID-19 , Wounds and InjuriesABSTRACT
India recently witnessed a devastating second wave of COVID-19, which peaked by the end of the first week of May 2021. We aimed to understand formation and spread of the second wave in the country. We analyzed time series distribution of the genomic sequence data for SARS-CoV-2 and correlated that with the epidemiological data for new cases and deaths, for the corresponding period of the second wave. Further we analyzed the phylodynamics of the circulating SARS-CoV-2 variants in the Indian population in the period of study. Our analysis shows that the first indications of arrival of the second wave were observable by the end of January 2021, and by the end of March, 2021 it was clearly indicated. B.1.617 lineage variants drove the wave, particularly B.1.617.2 (a.k.a. delta variant). Based on the observations of this study, we propose that genomic surveillance of the SARS-CoV-2 variants augmented with epidemiological data can be a promising tool for forecasting imminent COVID-19 waves.