Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients

Zhou, Zhuo; Ren, Lili; Zhang, Li; Zhong, Jiaxin; Yan, Xiao; Jia, Zhilong; Guo, Li; Yang, Jing; Wang, Chun; Jiang, Shuai; Yang, Donghong; Zhang, Guoliang; Li, Hongru; Chen, Fuhui; Xu, Yu; Chen, Mingwei; Gao, Zhancheng; Yang, Jian; Dong, Jie; Liu, Bo; Zhang, Xiannian; Wang, Weidong; He, Kunlun; Jin, Qi; Li, Mingkun; Wang, Jianwei

doi:10.1016/j.chom.2020.04.017

Cited by 910 publications

(1,067 citation statements)

References 53 publications

Supporting

Mentioning

962

Contrasting

Unclassified

Order By: Relevance

“…In sum, here is an answer to the first question: neutrophils appear to be prevalent in the alveoli of living COVID-19 patients (Zhou et al, 2020), have been found in the alveoli of about one-fifth of autopsied COVID-19 patients at the time of their death, and were plausibly present in many others earlier. While interstitial neutrophils have been documented very rarely in the lungs of COVID-19 patients at death, they likely passed through the interstitium on their way to the alveoli.…”

Section: Neutrophils or Not?mentioning

confidence: 80%

“…This lends support to the idea that the intraalveolar neutrophils found at autopsy in 20.6% of the 277 cases surveyed above are often a feature of COVID-19 itself, rather than the result of superinfection. The elevated CXCL8, CXCL1, and CXCL2 also detected in the BALF (Zhou et al, 2020) may account for the accumulation of neutrophils in the pulmonary alveoli. As neutrophils migrate up a concentration gradient of chemokines, they can encounter concentrations that activate them to secrete cytotoxic products, as discussed below.…”

Section: Neutrophils or Not?mentioning

confidence: 95%

“…Examining bronchoalveolar lavage fluid (BALF) from living subjects, Zhou et al (2020) compared the cells recovered from eight individuals with COVID-19 to those from 46 subjects with community-acquired pneumonia, which is generally bacterial in origin, and from 20 healthy subjects. Neutrophils were the one cell type most selectively elevated in the BALF of subjects with COVID-19 (Zhou et al, 2020). This lends support to the idea that the intraalveolar neutrophils found at autopsy in 20.6% of the 277 cases surveyed above are often a feature of COVID-19 itself, rather than the result of superinfection.…”

Section: Neutrophils or Not?mentioning

confidence: 99%

See 2 more Smart Citations

Neutrophils and COVID-19: Nots, NETs, and knots

Nathan

2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

Section: Neutrophils or Not?mentioning

confidence: 80%

Section: Neutrophils or Not?mentioning

confidence: 95%

Section: Neutrophils or Not?mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils and COVID-19: Nots, NETs, and knots

Nathan

2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Thus, it is reasoned that a mutation affecting nsp16 activity could result in early immune detection followed by more rapid clearance of virus. In support of this, recent studies have suggested that stimulation of an interferon response early in SARS-CoV-2 infection could result in less severe disease, particularly in younger individuals (46). In addition, previous reports for Mouse Hepatitis Virus (MHV) showed that mice treated with a 29 amino acid peptide derived from the loops of nsp10 that interact with nsp16 inhibit the MTase activity of nsp16.…”

Section: Discussionmentioning

confidence: 89%

Structure of SARS-CoV-2 2′-O-methyltransferase heterodimer with RNA Cap analog and sulfates bound reveals new strategies for structure-based inhibitor design

Rosas‐Lemus

Minasov

Shuvalova

et al. 2020

Preprint

View full text Add to dashboard Cite

There are currently no antiviral therapies specific against SARS-CoV-2, the virus responsible for the global pandemic disease COVID-19. To facilitate structure-based drug design, we conducted an X-ray crystallographic study of the nsp16/nsp10 2'-O-methyltransferase complex that methylates Cap-0 viral mRNAs to improve viral protein translation and to avoid host immune detection. Heterodimer structures are determined with the methyl donor S-adenosylmethionine (SAM), the reaction product S-adenosylhomocysteine (SAH) or the SAH analog sinefungin (SFG). Furthermore, structures of nsp16/nsp10 with the methylated Cap-0 analog (m7GpppA) and SAM or SAH bound were obtained. Comparative analysis revealed flexible loops in open and closed conformations at the m7GpppA binding pocket. Bound sulfates in several structures suggested the location of the phosphates in the ribonucleotide binding groove. Additional nucleotide binding sites were found on the face of the protein opposite the active site. These various sites and the conserved dimer interface could be exploited for development of antiviral inhibitors.

show abstract

“…B.1. SARS-CoV-2 associated genes: DEGs in COVID-19 positive patients, henceforth referred to as "SARS-CoV2-associated DEGs" were obtained from two recent studies: i) DEGs in BALFs identified comparing laboratory-confirmed COVID-19 patients (SARS2) (n = 8, median age 50.5 years) with healthy controls without known respiratory diseases (healthy) (n = 20) 24 . ii)…”

Section: Resourcesmentioning

confidence: 99%

Cumulative effect of aging and SARS-CoV2 infection on poor prognosis in the elderly: Insights from transcriptomic analysis of lung and blood

Bhattacharyya

Thelma

2020

Preprint

View full text Add to dashboard Cite

IntroductionThe ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has affected millions of people worldwide and with notable heterogeneity in its clinical presentation. Probability of contracting this highly contagious infection is similar across age groups but disease severity and fatality among aged patients with or without comorbidities are higher. We hypothesized that SARS-CoV-2 infection may augment aging-related gene expression alterations resulting in severe outcomes in elderly patients.MethodologyWe performed a comparative analysis of publicly available transcriptome data from Broncho Alveolar Lavage Fluid (BALF)/lung/blood of healthy aging group with i) COVID-19 patients; and ii) data of host genes interacting with SARS-CoV-2 proteins.ResultsWe observed i) a significant overlap of gene expression profiles of patients’ BALF and blood with lung and blood of the healthy group respectively; ii) a more pronounced overlap in blood compared to lung; and iii) a similar overlap between host genes interacting with SARS-CoV-2 and aging blood transcriptome.ConclusionsPathway enrichment analysis of overlapping gene sets suggests that infection alters expression of genes already dysregulated in the elderly, which together may lead to poor prognosis. eQTLs in these genes may also confer poor outcome in young patients worsening with age and co-morbidities. Furthermore, the pronounced overlap observed in blood may explain clinical symptoms including blood clots, strokes, heart attack, multi-organ failure etc. in severe cases. This model based on a limited patient dataset seems robust and holds promise for testing larger tissue specific datasets from patients with varied severity and across populations.

show abstract

Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients

Abstract: Highlights d BALF cell transcriptome indicates robust innate immune responses in COVID-19 patients d COVID-19 patients exhibit chemokine-dominant hypercytokinemia d ISGs are highly expressed in COVID-19 patients and exhibit pathogenic potential

Cited by 910 publications

References 53 publications

Neutrophils and COVID-19: Nots, NETs, and knots

Neutrophils and COVID-19: Nots, NETs, and knots

Structure of SARS-CoV-2 2′-O-methyltransferase heterodimer with RNA Cap analog and sulfates bound reveals new strategies for structure-based inhibitor design

Cumulative effect of aging and SARS-CoV2 infection on poor prognosis in the elderly: Insights from transcriptomic analysis of lung and blood

Contact Info

Product

Resources

About