Cell-type-specific immune dysregulation in severely ill COVID-19 patients

Yao, Changfu; Bora, Stephanie A.; Parimon, Tanyalak; Zaman, Tanzira; Friedman, Oren; Palatinus, Joseph A.; Surapaneni, N.; Matusov, Yuri; Chiang, Giuliana Cerro; Kassar, A.; Patel, Nayan; Green, Chelsi E.R.; Aziz, Adam; Suri, Harshpreet; Suda, Jo; Lopez, Andres A.; Martins, Gislâine A.; Stripp, Barry R.; Gharib, Sina A.; Goodridge, Helen S.; Chen, Peter

doi:10.1016/j.celrep.2021.108943

Cited by 33 publications

(25 citation statements)

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“…IRF1 was significantly augmented in monocytes with upregulated surface markers from patients later experiencing a benign course of the disease. Consistently, previous reports have shown that IRF1 expression in classical monocytes was lower in severe than in moderate COVID-19 patients [ 57 ]. IRF1 mediates anti-viral defense by multiple constitutive and inducible mechanisms, the later including pathways dependent from RIG-I-like, toll-like, IFN and TNF-α receptors [ 58 ].…”

Section: Discussionsupporting

confidence: 91%

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

et al. 2021

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An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

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Section: Discussionsupporting

confidence: 91%

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

et al. 2021

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“…The increased risk of secondary infection in patients with COVID-19 could be explained by four not mutually exclusive factors. First, the immune system dysregulation mostly due to two mechanisms: the "cytokine storm", triggered in response to the virus ( McGonagle et al, 2020 ) ( E et al, 2020 ) ( Fajgenbaum and June, 2020 ), and the marked reduction in IFN-γ production with the consequent reduction of Th1 polarization of CD4+ T cells and cytotoxic activity ( Diao et al, 2020 ) ( Qin et al, 2020 ) ( Yao et al, 2021 ). Second, the longer hospitalization time with higher rate of admission in ICUs, which increases the risk of contracting nosocomial infections ( Timsit et al, 2020 ) ( Ripa et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Bloodstream infections in the COVID-19 era: results from an Italian multi-centre study

Pasquini¹,

Barocci²,

Brescini³

et al. 2021

International Journal of Infectious Diseases

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Background Correlation between COVID-19 and superinfections has been investigated, but remains to be fully assessed. In this multicenter study we report the impact of the pandemic on bloodstream infections. Methods This study includes all patients with a BSI admitted to four Italian hospitals between January 1st and June 30th, 2020. Clinical, demographic, and microbiologic data were compared with those of patients hospitalized during the same period of 2019. Results Among 26,012 patients admitted in the first semester of 2020, 1,182 had COVID-19. In patients with COVID-19, we observed 107 BSIs, with an incidence rate of 8.19 episodes per 1000 patient-days. This incidence was significantly higher than in patients without COVID-19 (2.72/1000 patient-days) and in patients admitted in 2019 (2.76/1000 patient-days). In comparison with patients without COVID-19, BSIs onset in patients with COVID-19 was delayed during the course of hospitalization (16.0 vs 5 days). Thirty-day mortality among patients with COVID-19 was 40.2%, significantly higher than in patients without COVID-19 (23.7%). BSIs in patients with COVID-19 were frequently caused by MDR pathogens, which were often center-dependent. Conclusions BSIs are a frequent secondary infection in patients with COVID-19, characterized by an increased risk during hospitalization and potentially burdened with high mortality.

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“…28 Later in the disease course, particularly with severe disease, excessive inflammatory responses or immune dysfunction have a greater impact on disease progression than viral load. [29][30][31][32] Moreover, molecular presence of SARS-CoV-2 does not guarantee infectivity, and measures of viral load and viral clearance may also be impacted by collection method and definition of clearance. Nevertheless, the observed correlation between time from symptom onset and change from baseline viral load…”

Section: Development Of Natural Immunity Through Formation Of Endogenous Antibodies Against the Sars-mentioning

confidence: 99%

First‐in‐Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID‐19

Chen

Datta

et al. 2021

Clin Pharma and Therapeutics

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Pfizer and Meissa Vaccines. WF reports research funding provided to UNC from Ridgeback Biopharmaceuticals, Eli Lilly and Company, and Regeneron, consultancy fees from Merck and Roche and served on adjudication committee for Janssen and Syneos. MD reports personal fees from Genentech-Roche, Partner Therapeutics, Tillots Pharma, ORIC Pharmaceuticals, Moderna, AzurRx, SQZ, and WebMD, grants from Novartis and Eli Lilly and Company, and scientific advisory board member for Neoleukin Therapeutics. AS is an advisory board member for Eli Lilly and Company.

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Cell-type-specific immune dysregulation in severely ill COVID-19 patients

Cited by 33 publications

References 0 publications

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery

Bloodstream infections in the COVID-19 era: results from an Italian multi-centre study

First‐in‐Human Study of Bamlanivimab in a Randomized Trial of Hospitalized Patients With COVID‐19

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