Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

Sajuthi, Satria; DeFord, Peter; Li, Yingchun; Jackson, Nathan D.; Montgomery, Michael T.; Everman, Jamie L.; Rios, Cydney; Pruesse, Elmar; Nolin, James D.; Plender, Elizabeth G.; Wechsler, Michael E.; Mak, Angel C. Y.; Eng, Celeste; Salazar, Sandra; Medina, Vivian; Wohlford, Eric M.; Huntsman, Scott; Nickerson, Deborah A.; Germer, Søren; Zody, Michael C.; Abecasis, Gonçalo R.; Kang, Hyun Min; Rice, Kenneth; Kumar, Rajesh; Oh, Sam S.; Rodríguez‐Santana, José; Burchard, Esteban G.; Seibold, Max A.

doi:10.1038/s41467-020-18781-2

Cited by 153 publications

(150 citation statements)

References 84 publications

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“…However, transcriptional levels still remain reduced on day 6 p.i., albeit testosterone levels already start to recover on day 6 p.i.. This observation is in line with previous reports on ACE2 and TMPRSS2 downregulation in SARS-CoV infected cells [15][16][17] . These data might suggest that the transcription of SARS-CoV-2 entry factors might not be exclusively controlled by testosterone.…”

Section: Sars-cov-2 Infection In the Lung Correlates With Reduced Acesupporting

confidence: 92%

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

Stanelle-Bertram

Schaumburg

Kouassi

et al. 2020

Preprint

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SARS-CoV-2 infection is associated with increased morbidities in men compared to women. Androgens are believed to play an important role in SARS-CoV-2 pathogenesis in men due to the postulated androgen-dependency of ACE2 and TMPRSS2. However, it is yet unclear whether the sex bias is mediated by SARS-CoV-2 infection itself or by other confounding factors. Here, using the golden hamster model, we show that SARS-CoV-2 infection attacks reproductive organs, causes massive dysregulation of sex hormones and induces elevated transcription of the androgen-to-estrogen converting enzyme aromatase CYP19A1 in the lung. In male hamsters, SARS-CoV-2 infection causes severely depleted testosterone and highly elevated estradiol levels. In female hamsters, SARS-CoV-2 infection causes reduced estradiol levels. Hormonal dysregulation in infected animals is followed by severe weight loss compared to control groups treated with poly(I:C) or PBS. Lungs of SARS-CoV-2 infected animals present abundant CYP19A1 expression in the endothelium and in macrophages, particularly in males. Prominent CYP19A1 expression in endothelial cells and macrophages was verified in lung sections of deceased Covid-19 males compared to females. Our results demonstrate that SARS-CoV-2 infection leads to massive dysregulation of sex hormones, which may increase the risk for sex-specific disease outcome particularly in combination with comorbidities. These findings provide insights into the complex metabolic cross talk between SARS-CoV-2 infection and sex hormones.

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Section: Sars-cov-2 Infection In the Lung Correlates With Reduced Acesupporting

confidence: 92%

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

Stanelle-Bertram

Schaumburg

Kouassi

et al. 2020

Preprint

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“…Moreover, our analysis shows that TMPRSS2 expression is not altered by interferon Accordingly, it has recently been reported that interferon inflammation does not modulate TMPRSS2 expression but upregulates ACE2 expression [12]. Instead, TMPRSS2 expression in airway epithelia is highly upregulated by IL-13 [12,14], a highly expressed cytokine in plasma of COVID-19 patients that require ventilation [13]. Furthermore, IL-13 is also involved in allergic airway type 2 inflammation, asthma and chronic obstructive pulmonary disease (COPD) [12,14], thus suggesting a further mechanism for COVID-19 susceptibility and severity.…”

Section: Analysis Of Tmprss2 Expression Datasupporting

confidence: 50%

“…This evidence suggests that concomitance with other infections, and some workplace pollutants could make lung cells more susceptible to the SARS-CoVs. Moreover, our analysis shows that TMPRSS2 expression is not altered by interferon Accordingly, it has recently been reported that interferon inflammation does not modulate TMPRSS2 expression but upregulates ACE2 expression [12]. Instead, TMPRSS2 expression in airway epithelia is highly upregulated by IL-13 [12,14], a highly expressed cytokine in plasma of COVID-19 patients that require ventilation [13].…”

Section: Analysis Of Tmprss2 Expression Datamentioning

confidence: 50%

“…Instead, TMPRSS2 expression in airway epithelia is highly upregulated by IL-13 [12,14], a highly expressed cytokine in plasma of COVID-19 patients that require ventilation [13]. Furthermore, IL-13 is also involved in allergic airway type 2 inflammation, asthma and chronic obstructive pulmonary disease (COPD) [12,14], thus suggesting a further mechanism for COVID-19 susceptibility and severity.…”

Section: Analysis Of Tmprss2 Expression Datamentioning

confidence: 99%

“…However, since the observed expression variations are enough to increase influenza susceptibility, it is possible that many other eQTLs in TMPRSS2 gene could alter the susceptibility to SARS-CoV-2 infection. For example, some new eQTLs [12] and missense SNPs altering TMPRSS2 expression and function have been recently suggested to influence SARS-CoV-2 entry and Fig. 2 Violin plots of TMPRSS rs2070788 (left) and rs383510 (right) eQTLs in the lung, as reported in GTEx portal.…”

Section: Polymorphismsmentioning

confidence: 99%

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Expression and co-expression analyses of TMPRSS2, a key element in COVID-19

Piva¹,

Sabanovic²,

Cecati³

et al. 2020

Eur J Clin Microbiol Infect Dis

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The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, diabetes, smoking habits, exposure to pollutant and other stimuli, in order to highlight which factors might alter TMPRSS2 expression, and thus impact the susceptibility to infection and COVID-19 prognosis. Moreover, we reported TMPRSS2 polymorphisms affecting its expression and suggested the ethnic groups more prone to COVID-19. Finally, we also highlighted a gender-specific co-expression between TMPRSS2 and other genes related to SARS-CoV-2 entry, maybe explaining the higher observed susceptibility of infection in men. Our results could be useful in designing potential prevention and treatment strategies regarding the COVID-19.

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Recent advances and developments in COVID‐19 in the context of allergic diseases

Ding

Sun

Sokołowska

et al. 2021

Clinical & Translational All

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Background Since the first reports of coronavirus disease 2019 (COVID‐19) in Wuhan, China, in December 2019, there have been 198 million confirmed cases worldwide as of August 2021. The scientific community has joined efforts to gain knowledge of the newly emerged virus named severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the immunopathological mechanisms leading to COVID‐19, and its significance for patients with allergies and asthma. Methods Based on the current literature, recent advances and developments in COVID‐19 in the context of allergic diseases were reviewed. Results and Conclusions In this review, we discuss the prevalence of COVID‐19 in subjects with asthma, attacks of hereditary angioedema, and other allergic diseases during COVID‐19. Underlying mechanisms suggest a protective role of allergy in COVID‐19, involving eosinophilia, SARS‐CoV‐2 receptors expression, interferon responses, and other immunological events, but further studies are needed to fully understand those associations. There has been significant progress in disease evaluation and management of COVID‐19, and allergy care should continue during the COVID‐19 pandemic. The European Academy of Allergy & Clinical Immunology (EAACI) launched a series of statements and position papers providing recommendations on the organization of the allergy clinic, handling of allergen immunotherapy, asthma, drug hypersensitivity, allergic rhinitis, and other allergic diseases. Treatment of allergies using biologics during the COVID‐19 pandemic has also been discussed. Allergic reactions to the COVID‐19 vaccines, including severe anaphylaxis, have been reported. Vaccination is a prophylactic strategy that can lead to a significant reduction in the mortality and morbidity associated with SARS‐CoV‐2 infection, and in this review, we discuss the proposed culprit components causing rare adverse reactions and recommendations to mitigate the risk of anaphylactic events during the administration of the vaccines.

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Type 2 and interferon inflammation regulate SARS-CoV-2 entry factor expression in the airway epithelium

Cited by 153 publications

References 84 publications

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

SARS-CoV-2 induced CYP19A1 expression in the lung correlates with increased aromatization of testosterone-to-estradiol in male golden hamsters

Expression and co-expression analyses of TMPRSS2, a key element in COVID-19

Recent advances and developments in COVID‐19 in the context of allergic diseases

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