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SARS-CoV-2 proteins

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    Mast Cells and COVID-19 MESHD: a case report implicating a role of mast cell activation in the prevention and treatment of Covid-19 MESHD

    Authors: Isabelle Brock; Anne Maitland

    doi:10.21203/rs.3.rs-330667/v2 Date: 2021-03-15 Source: ResearchSquare

    Coronavirus disease MESHD ( COVID-19 MESHD) is a heterogeneous syndrome MESHD following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD of the upper respiratory tract. ln adults, the clinical condition can range from asymptomatic cases to severe acute respiratory syndrome MESHD and multi-organ dysfunction MESHD. Those at risk of developing COVID-19 MESHD related hyperinflammatory syndrome MESHD likely had an ineffective, innate immune response to this novel pathogen. Mast cells are associated with the epithelium, contributing to tissue homeostasis and epithelial barrier defense. Equipped with an array of pathogen receptors, mast cells exhibit distinct cytokine profiles, dependent on the tissue and the triggered pathogen receptors. Following viral infections, mast cells produce pro-inflammatory chemical mediators, such as interleukin-1 (IL-1) and IL-6 HGNC, and these cytokines has been shown to be elevated in severe COVID-19 MESHD cases. Here, we present a case of a patient with a longstanding history of signs and symptoms, worrisome for a mast cell activation syndrome MESHD ( MCAS MESHD), but never had laboratory confirmation of this non-clonal mast cell activation disorder, until she contracted COVID-19 MESHD. This case illustrates the need to recognize the rate of mast cell activation in SARS-CoV-2 infection MESHD, not only to optimize anti-SARS-CoV-2 therapy, including the development of vaccine, but to potentially curb the risk of SARS­ CoV-2 triggered hyperinflammatory syndrome MESHD.

    Neural epidermal growth factor-like 1 HGNC protein variant increases survival and modulates the inflammatory and immune responses in human ACE-2 HGNC transgenic mice infected with SARS-CoV-2

    Authors: Roopa Biswas; Shannon Eaker; Dharmendra Kumar Soni; Swagata Kar; Denae LoBato; Cymbeline Culiat

    doi:10.1101/2021.02.08.430254 Date: 2021-02-08 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) and is a worsening global pandemic. COVID-19 MESHD has caused at least 1.7 million deaths worldwide and over 300,000 in the United States. Recently, two promising vaccines are being administered in several countries. However, there remains an urgent need for a therapeutic treatment for COVID-19 MESHD patients with severe respiratory damage MESHD that can lead to intensive care, prolonged hospitalization, or mortality. Moreover, an increasing population of patients manifest lingering disabling symptoms (called Long Haulers). Here, we tested the efficacy of a recombinant neural epidermal growth factor like 1 protein variant (NELL1-NV1) in a COVID-19 MESHD mouse model, transgenic mice expressing the human angiotensin I-converting enzyme 2 HGNC ( ACE2 HGNC) receptor (tg-mice hACE2 HGNC) infected with SARS-CoV-2. The administration of NELL1-NV1 to SARS-CoV-2-infected MESHD tg-mice hACE2 HGNC significantly improved clinical health score and increased survival. Analyses of bronchoalveolar (BAL) fluid demonstrated decreased levels of several cytokines and chemokines (IFN-{gamma}, IL-10, IL-12 p70, CXCL-10/IP-10, MIG and Rantes), in NV1-treated treated mice compared to controls. Cytokines including IL-1 HGNC, IL-9 HGNC, IL-6 HGNC, LIX/ CXCL5 HGNC, KC/ CXCL1 HGNC, MIP-2 HGNC/ CXCL2 HGNC, MIP-1 HGNC/ CCL3 HGNC, and G-CSF HGNC, critical to immune responses such as neutrophil recruitment, viral clearance and vascularization, were increased compared to controls. Our data suggest the potential of NELL1 HGNC-NV1-based therapy to mitigate the cytokine storm, modulate the abnormal immune response and repair respiratory tissue damage in COVID-19 MESHD patients.

    Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19 MESHD

    Authors: Suzane Ramos da Silva; Enguo Ju; Wen Meng; Alberto E. Paniz Mondolfi; Sanja Dacic; Anthony Green; Clare Bryce; Zachary Grimes; Mary E Fowkes; Emilia M. Sordillo; Carlos Cordon-Cardo; Haitao Guo; Shou-Jiang Gao

    doi:10.1101/2020.09.25.20195818 Date: 2020-09-29 Source: medRxiv

    Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection MESHD in patients with Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage MESHD (DAD), excess inflammation MESHD, pneumocyte hyperplasia MESHD and proliferation, and formation of platelet aggregates or thromboemboli MESHD. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism MESHD and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD. Findings The lung parenchyma showed severe DAD MESHD with thromboemboli MESHD in all cases. SARS-CoV-2 infection MESHD was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II MESHD (AT2) cells (HT2-280), ciliated cells (tyr--tubulin), goblet cells ( MUC5AC HGNC), club-like cells ( MUC5B HGNC) and endothelial cells ( CD31 HGNC and CD34 HGNC). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes ( CD68 HGNC and CD163 HGNC), neutrophils ( ELA-2 HGNC), natural killer (NK) cells ( CD56 HGNC), B-cells ( CD19 HGNC and CD20 HGNC), and T-cells (CD3{varepsilon}). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 HGNC ( ACE2 HGNC). The numbers of infected and ACE2 HGNC-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3{varepsilon}+ T-cells consisting of mainly T helper cells ( CD4 HGNC), few cytotoxic T cells (CTL, CD8 HGNC), and no T regulatory cell ( FOXP3 HGNC). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 HGNC ( IL-6 HGNC) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 MESHD patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation MESHD and compromised adaptive immune responses.

    Daytime variation in SARS-CoV-2 infection MESHD and cytokine production

    Authors: Aissatou Bailo Diallo; Laetitia Gay; Benjamin Coiffard; Marc Leone; Soraya Mezouar; Jean-Louis Mège; Elisa Ghelfi; Chhinder Sodhi; David Hackam; Lester Kobzik; Ben Croker; Douglas Brownfield; Hongpeng Jia; Kristopher A. Sarosiek; Paige D. Hall; Maud Jansen; Kumaran Shanmugarajah; Jessica S. Donington; Florian Krammer; Daved Fremont; Andrzej Joachimiak; Yoshihiro Kawaoka; Vera Tesic; Maria Lucia Madariaga; Patrick C Wilson; Martin Pettersson; Mattew R. Reese; Thomas Rogers; Michelle I Rossulek; Jean G Sathish; Claire Steppan; Martyn Ticehurst; Lawrence W. Updyke; Yuao Zhu; Jun Wang; Arnab K Chatterjee; Andrew D Mesecar; Annaliesa S. Anderson; Charlotte Allerton

    doi:10.1101/2020.09.09.290718 Date: 2020-09-12 Source: bioRxiv

    S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which is the causative agent of the coronavirus disease MESHD ( Covid-19 MESHD). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections MESHD. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection MESHD of isolated human monocytes, key actor cells in Covid-19 MESHD disease, from healthy subjects. The circadian gene expression of Bmal1 HGNC and Clock genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection MESHD was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6 HGNC, IL-1{beta HGNC} and IL-10 HGNC levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that Bmal1 HGNC and Clock transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Zeitgeber Time (ZT)6 and ZT17. After forty-eight hours, the amount of SARS-CoV-2 virus increased in the monocyte infected at ZT6 compared to ZT17. The high virus amount at ZT6 was associated with significant increased release in IL-6 HGNC, IL-1{beta HGNC} and IL-10 HGNC compared to ZT17. Our results suggest that time day of SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHD affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease MESHD progression and we propose circadian rhythm as a novel target for managing viral progression. ImportanceThe implication of circadian rhythm (CR) in pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recently anticipated. The time of day of infection is critical for illness progression as reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. In this study, we wondered if SARS-CoV-2 infection MESHD and cytokine production by human monocytes, innate immune cells affected by Covid-19 MESHD, were regulated by CR. Our results suggest that time day of SARS-CoV-2 infection MESHD affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression.

    Natural Killer cell activation, reduced ACE2 HGNC, TMPRSS2 HGNC, cytokines G-CSF HGNC, M-CSF HGNC and SARS-CoV-2-S pseudovirus infectivity by MEK HGNC inhibitor treatment of human cells

    Authors: Lanlan Zhou; Kelsey Huntington; Shengliang Zhang; Lindsey Carlsen; Eui-Young So; Cassandra Parker; Ilyas Sahin; Howard Safran; Suchitra Kamle; Chang-Min Lee; Chun-Geun Lee; Jack A. Elias; Kerry S. Campbell; Mandar T. Naik; Walter J. Atwood; Emile Youssef; Jonathan A. Pachter; Arunasalam Navaraj; Attila A. Seyhan; Olin Liang; Wafik El-Deiry

    doi:10.1101/2020.08.02.230839 Date: 2020-08-03 Source: bioRxiv

    COVID-19 MESHD affects vulnerable populations including elderly individuals and patients with cancer MESHD. Natural Killer (NK) cells and innate-immune TRAIL HGNC suppress transformed and virally-infected cells. ACE2 HGNC, and TMPRSS2 HGNC protease promote SARS-CoV-2 infectivity MESHD, while inflammatory cytokines IL-6 HGNC, or G-CSF HGNC worsen COVID-19 MESHD severity. We show MEK HGNC inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 HGNC expression in human cells. Chloroquine or hydroxychloroquine increase cleaved active SP-domain of TMPRSS2 HGNC, and this is potentiated by MEKi. In some human cells, remdesivir increases ACE2 HGNC-promoter luciferase-reporter expression, ACE2 HGNC mRNA and protein, and ACE2 HGNC expression is attenuated by MEKi. We show elevated cytokines in COVID-19 MESHD- (+) patient plasma (N=9) versus control (N=11). TMPRSS2 HGNC, inflammatory cytokines G-CSF HGNC, M- CSF HGNC, IL-1a HGNC, IL-6 HGNC and MCP-1 HGNC are suppressed by MEKi alone or in combination with remdesivir. MEKi enhance NK cell (but not T-cell) killing of target-cells, without suppressing TRAIL HGNC-mediated cytotoxicity MESHD. We generated a pseudotyped SARS-CoV-2 virus with a lentiviral core but with the SARS-CoV-2 D614 or G614 SPIKE (S) protein PROTEIN on its envelope and used VSV-G lentivirus as a negative control. Our results show infection of human bronchial epithelial cells or lung cancer MESHD cells and that MEKi suppress infectivity of the SARS-CoV-2-S pseudovirus following infection MESHD. We show a drug class-effect with MEKi to promote immune responses involving NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection MESHD leading also to suppression of SARS-CoV-2-S pseudovirus infection MESHD of human cells in a model system. MEKi may attenuate coronavirus infection MESHD to allow immune responses and antiviral agents to control COVID-19 MESHD disease progression and severity.

    Use of a humanized anti- CD6 HGNC monoclonal antibody (itolizumab) in elderly patients with moderate COVID-19 MESHD

    Authors: Mayra Ramos-Suzarte; Yayquier Diaz; Yordanis Martin; Nestor Antonio Calderon; William Santiago; Orlando Vinet; Yulieski La O; Jorge Perez; Augusto Oyarzabal; Yoan Perez; Geidy Lorenzo; Meylan Cepeda; Danay Saavedra; Zayma Mazorra; Daymys Estevez; Patricia Lorenzo-Luaces; Carmen Valenzuela; Armando Caballero; Kalet leon; Tania Crombet; Carlos Jorge Hidalgo

    doi:10.1101/2020.07.24.20153833 Date: 2020-07-30 Source: medRxiv

    Abstract Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) has caused a recent outbreak of Coronavirus Disease MESHD ( COVID-19 MESHD). In Cuba, the first case of COVID-19 MESHD was reported on March 11 HGNC. Elderly with multiple comorbidities are particularly susceptible to adverse clinical outcomes in the course of SARS CoV-2 infection MESHD. During the outbreak, a local transmission event took place in a nursing home in Villa Clara province, Cuba, in which nineteen elderly residents were positive for SARS-CoV-2. Methods: Based on the increased susceptibility to viral-induced cytokine release syndrome inducing respiratory MESHD and systemic complications in this population, the patients were included in an expanded access clinical trial to receive itolizumab, an anti- CD6 HGNC monoclonal antibody. Results: All the patients had underlying medical conditions. The product was well tolerated. After the first dose, the course of the disease was favorable and 18 out of 19 (94.7%) patients were discharged clinically recovered with negative RT-PCR at 13 days (median). One dose of itolizumab, circulating IL-6 HGNC decreased in the first 24-48 hours in patients with high baseline values, whereas in patients with low levels, this concentration remained over low values. To preliminary assess the effect of itolizumab, a control group was selected among the Cuban COVID-19 MESHD patients, which did not receive immunomodulatory therapy. Control subjects were well-matched regarding age, comorbidities and severity of the disease. Every three moderately ill patients treated with itolizumab, one admission in intensive care unit (ICU) was prevented. Discussion/Conclusion: Itolizumab was well tolerated. Its effect is associated with a reduction and controlling IL-6 HGNC serum levels. Moreover, treated patients had a favorable clinical outcome, considering their poor prognosis. This treatment is associated significantly with a decrease the risk to be admitted in ICU and reduced 10 times the risk of death MESHD. This study corroborates that the timely use of itolizumab, in combination with other antiviral and anticoagulant therapies, is associated with a reduction the COVID-19 MESHD disease worsening and mortality. The humanized antibody itolizumab emerges as a therapeutic alternative for patients with COVID-19 MESHD and suggests its possible use in patients with cytokine release syndrome from other pathologies.

    The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2

    Authors: Carolina Q. Sacramento; Natalia Fintelman-Rodrigues; Jairo R. Temerozo; Suelen da Silva Gomes Dias; Andre C. Ferreira; Mayara Mattos; Camila R. R. Pao; Caroline S. de Freitas; Vinicius Cardoso Soares; Fernando A. Bozza; Dumith Chequer Bou-Habib; Patricia T. Bozza; Thiago Moreno L. Souza

    doi:10.1101/2020.06.15.153411 Date: 2020-06-16 Source: bioRxiv

    The infection by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes major public health concern and economic burden. Although clinically approved drugs have been repurposed to treat individuals with 2019 Coronavirus disease MESHD ( COVID-19 MESHD), the lack of safety studies and limited efficiency as well jeopardize clinical benefits. Daclatasvir and sofosbuvir (SFV) are clinically approved direct-acting antivirals (DAA) against hepatitis C virus MESHD ( HCV MESHD), with satisfactory safety profile. In the HCV MESHD replicative cycle, daclatasvir and SFV target the viral enzymes NS5A and NS5B, respectively. NS5A is endowed with pleotropic activities, which overlap with several proteins from SARS-CoV-2. HCV MESHD NS5B and SARS-CoV-2 nsp12 are RNA polymerases that share homology in the nucleotide uptake channel. These characteristics of the HCV MESHD and SARS-CoV-2 motivated us to further study the activity of daclatasvir and SFV against the new coronavirus. Daclatasvir consistently inhibited the production of infectious SARS-CoV-2 MESHD virus particles in Vero cells, in the hepatoma MESHD cell line HuH-7 HGNC and in type II pneumocytes (Calu-3), with potencies of 0.8, 0.6 and 1.1 M, respectively. Daclatasvir targeted early events during SARS-CoV-2 replication cycle and prevented the induction of IL-6 HGNC and TNF HGNC-, inflammatory mediators associated with the cytokine storm typical of SARS-CoV-2 infection MESHD. Sofosbuvir, although inactive in Vero cells, displayed EC50 values of 6.2 and 9.5 M in HuH-7 HGNC and Calu-3 cells, respectively. Our data point to additional antiviral candidates, in especial daclatasvir, among drugs overlooked for COVID-19 MESHD, that could immediately enter clinical trials.

    A blood-based comprehensive and systems-level analysis of disease stages, immune regulation and symptoms in COVID-19 MESHD patients

    Authors: Anguraj Sadanandam; Tobias Bopp; Santosh Dixit; David JHF Knapp; Chitra Priya Emperumal; Krishnaraj Rajalingam; Alan Melcher; Nagarajan Kannan

    doi:10.21203/rs.3.rs-30473/v1 Date: 2020-05-20 Source: ResearchSquare

    COVID-19 MESHD patients show significant clinical heterogeneity in presentation and outcomes that makes pandemic control and strategy difficult; optimising management requires a systems biology approach of understanding the disease. Here we sought to understand and infer complex system-wide changes in patients infected with coronaviruses ( SARS-CoV and SARS-CoV-2 MESHD; n=38 and 57 samples) at two different disease stages compared with healthy individuals (n=16) and patients with other infections (n=144). We applied inferential statistics/machine-learning approaches (the COVID-engine platform) to RNA profiles derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, an integrated blood-based gene signatures distinguished acute-like (mimicking coronavirus-infected MESHD patients with prolonged hospitalisation) from recovering-like patients. These signatures also hierarchically represented systems-level parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle confirmatory observations included PBMC-associated increases in ACE2 HGNC, cytokine storm-associated IL6 HGNC, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage had significantly enhanced TNF HGNC, IFN-g HGNC, anti-viral, HLA-DQA1 HGNC, and HLA-F HGNC gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, PBMC-derived surrogate-based approach revealed overlapping genes associated with comorbidities (associated diabetes MESHD), and disease-like symptoms (associated with thromboembolism MESHD, pneumonia MESHD, lung disease MESHD and septicaemia MESHD). Overall, our study involving PBMC-based RNA profiling may further help understand complex and variable systems-wide responses displayed by coronavirus-infected MESHD patients.

    Epidemiological,clinical and radiological findings in medical staff with COVID-19 MESHD in Wuhan, China: a single-centered, retrospective cohort study

    Authors: Jie Liu; Liu Ouyang; Pi Guo; Haisheng Wu; Peng Fu; Yuliang Chen; Dan Yang; Xiaoyu Han; Yukun Cao; Osamah Alwalid; Hanping Wu; Heshui Shi; Fan Yang; Yu Hu; Chuansheng Zheng

    doi:10.21203/rs.3.rs-28753/v1 Date: 2020-05-14 Source: ResearchSquare

    Backgrounds In December 2019, a pneumonia MESHD associated with the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in Wuhan city, China. As of 20 Feb 2020, a total of 2,055 medical staff infected with SARS-Cov-2 in China had been reported. The predominant cause of the infection and the failure of protection among medical staff remains unclear. We sought to explore the epidemiological, clinical characteristics and prognosis of novel coronavirus-infected MESHD medical staff.Methods Medical staff who infected with SARS-Cov-2 and admitted to Union Hospital, Wuhan between 16 Jan, 2020 to 25 Feb, 2020 were included retrospectively. Epidemiological, clinical and radiological data were compared by occupation and analyzed with the Kaplan-Meier and Cox regression methods.Results A total of 101 medical staff (32 males and 69 females; median age: 33 years old) were included in this study and 74% were nurses. None had an exposure to Huanan seafood wholesale market or wildlife. A small proportion of the cohort had contact with specimens (3%) as well as patients infected with SARS-Cov-2 in fever clinics (15%) and isolation wards (3%). 80% of medical staff showed abnormal IL-6 HGNC levels and 33% had lymphocytopenia MESHD. Chest CT mainly manifested as bilateral (62%), septal/subpleural (77%) and ground­glass opacities (48%). The major differences between doctors and nurses manifested in laboratory indicators. As of the last observed date, no patient was transferred to intensive care unit or died, and 98 (97%) had been discharged. Fever MESHD (HR=0.57; 95% CI 0.36-0.90) and IL-6 HGNC levels greater than >2.9 pg/ml (HR=0.50; 95% CI 0.30-0.86) on admission were unfavorable factors for discharge.Conclusions Our findings suggested that the infection of medical staff mainly occurred at the early stages of SARS-CoV-2 epidemic MESHD in Wuhan, and only a small proportion of infection had an exact mode. Meanwhile, medical staff infected with COVID-19 MESHD have relatively milder symptoms and favorable clinical course than other ordinary patients, which may be partly due to their medical expertise, younger age and less underlying diseases. The potential risk factors of presence of fever MESHD and IL-6 HGNC levels greater than >2.9 pg/ml could help to identify medical staff with poor prognosis at an early stage.

    The majority of male patients with COVID-19 MESHD present low testosterone levels on admission to Intensive Care in Hamburg, Germany: a retrospective cohort study.

    Authors: Maria Schroeder; Berfin Schaumburg; Zacharias Mueller; Ann Parplys; Dominik Jarczak; Axel Nierhaus; Andreas Kloetgen; Bettina Schneider; Manuela Peschka; Fabian Stoll; Tian Bai; Henning Jacobsen; Martin Zickler; Stephanie Stanelle-Bertram; Geraldine de Heer; Thomas Renne; Andreas Meinhardt; Joerg Heeren; Jens Aberle; Alice C McHardy; Hartmut Schlueter; Jens Hiller; Sven Peine; Lothar Kreienbrock; Karin Klingel; Stefan Kluge; Guelsah Gabriel

    doi:10.1101/2020.05.07.20073817 Date: 2020-05-11 Source: medRxiv

    Background. Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) continues to spread worldwide and pose a major public health burden. There is increasing evidence that men are more likely to die from SARS-CoV-2 infection MESHD than women. However, underlying factors that mediate the observed sex bias in coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) remain unknown. Methods. In this retrospective cohort, we included COVID-19 MESHD patients who were admitted to an Intensive Care Unit at the University Hospital Hamburg-Eppendorf, Germany. We obtained demographic data of all patients who were discharged or had died by 29th April 2020. We systematically analyzed sex hormones as well as cytokine and chemokine responses in male and female patients with laboratory-confirmed SARS-CoV-2 infections MESHD upon hospital admission. We used uni- and multivariable linear regression methods to identify potential risk factors for disease severity in males and females. Findings. All enrolled patients (n=45; n=35 males and n=10 females) presented comorbidities with hypertension MESHD being the most common (45.7% in males; 40% in females), followed by cancer MESHD (35% in males; 40% in females), obesity MESHD (34.3% in males and 30% in females), type II diabetes MESHD (25.7% in males and 20% in females) and chronic heart diseases MESHD (8.6% in males and 0% in females). We detected that the vast majority of male COVID-19 MESHD patients present low testosterone (68.6%) and low dihydrotestosterone (48.6%) levels. In contrast, most female COVID-19 MESHD patients have elevated testosterone levels (60%) without alterations in dihydrotestosterone levels. Both, female and male COVID-19 MESHD patients may present elevated estradiol levels (45.7% in males and 40% in females). Disease severity defined by SOFA score correlates with elevated cytokine responses (e.g. IL-6 HGNC) in males and IL-2 HGNC in females. In male COVID-19 MESHD patients, testosterone levels negatively correlate with inflammatory IL-2 HGNC and IFN-{gamma HGNC}, whereas estradiol levels positively correlate with the inflammatory cytokine IL-6 HGNC. Vice versa, in female COVID-19 MESHD patients, testosterone levels positively correlate with inflammatory cytokines (e.g. IL-6 HGNC). Interpretation. We here show that critically ill male COVID-19 MESHD patients suffer from severe testosterone and dihydrotestosterone deficiencies MESHD. Both androgens are required to mount antiviral immune responses to combat infection in males.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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