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HGNC Genes

SARS-CoV-2 proteins

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    Targeting of the NLRP3 HGNC Inflammasome for early COVID-19 MESHD

    Authors: Carlo Marchetti; Kara Mould; Isak W. Tengesdal; William J. Janssen; Charles A. Dinarello

    doi:10.1101/2021.02.24.432734 Date: 2021-02-24 Source: bioRxiv

    Following entry and replication of Severe Acute Respiratory Syndrome-coronavirus MESHD 2 (SARS-CoV-2) into ACE2 expressing cells, the infected cells undergo lysis releasing more virus but also cell contents. In the lung, constitutive cytokines such as IL-1 HGNC are released together with other cell contents. A cascade of inflammatory cytokines ensues, including chemokines and IL-1{beta}, triggering both local as well as systemic inflammation MESHD. This cascade of inflammatory cytokines in patients with COVID-19 MESHD is termed Cytokine Release Syndrome ( CRS MESHD), and is associated with poor outcomes and death MESHD. Many studies reveal that blocking IL-1{beta HGNC} activities in COVID-19 MESHD patients reduces disease severity and deaths MESHD. Here we report highly significant circulating levels of IL-1{beta HGNC}, IL-1 Receptor antagonist HGNC, IL-6 HGNC, TNF HGNC, IL-10 HGNC and soluble urokinase plasminogen activator receptor HGNC in COVID-19 MESHD patients with mild or no symptoms. We also report that in circulating myeloid cells from the same patients, there is increased expression of the NOD-, LRR- and pyrin domain-containing 3 ( NLRP3 HGNC) early in the infection. We observed increased NLRP3 HGNC gene expression in myeloid cells correlated with IL-1{beta HGNC} gene expression and also with elevated circulating IL-1{beta HGNC} levels. We conclude that early in SARS-CoV-2 infection MESHD, NLRP3 HGNC activation takes place and initiates the CRS. Thus, NLRP3 HGNC is a target to reduce the organ damage of inflammatory cytokines of the CRS.

    Chyawanprash for the prevention of COVID-19 MESHD infection among healthcare workers: A Randomized Controlled Trial

    Authors: Arun Gupta; Amit Madan; Babita Yadav; Richa Singhal; Pallavi Suresh Mundada; Yogesh Kumar Pandey; Riju Agarwal; Rakesh Rana; Arunabh Tripathi; Bhagwan Sahay Sharma; BCS Rao; Bharti Gupta; Narayanam Srikanth; Kartar Singh Dhiman

    doi:10.1101/2021.02.17.21251899 Date: 2021-02-19 Source: medRxiv

    Background: Coronavirus disease 2019 MESHD ( Covid19 MESHD) occurs after exposure to severe acute respiratory syndrome coronavirus 2 MESHD (SARSCoV2). For persons who are at high risk of exposure, the standard of care is personal protection from getting infected. Whether Ayurvedic rasayana drug like Chyawanprash can prevent symptomatic infection in frontline health care workers is unknown. Objective: To evaluate the effect of the combination of Chyawanprash and Standard Preventive Regimen compared to the use of Standard Preventive Regimen alone on the proportion of RT-PCR confirmed COVID 19 infections among frontline healthcare workers (HCWs). Methods: An open label randomized controlled trial was conducted in the HCWs between 25 to 60 years age currently working in an environment with chance of direct exposure to COVID 19 cases. The interventions to be compared in this trial were Standard Preventive Regimen as per institutional guidelines and based on their roles (Group I) and Ayurvedic Intervention viz., Chyawanprash 12 g twice for 30 days from day of randomization plus Standard Preventive Regimen (Group II). The incidence of RT PCR confirmed COVID19 MESHD cases in both groups, was the primary outcome measure. Evaluation of the safety of the study drug (by any statistically significant change in various biochemical and hematological parameters and occurrence of any adverse drug reactions); incidence of any other infective diseases (bacterial / viral / fungal / etc.) like upper respiratory tract illness during the study period and any change in the immunoglobulins like IgG, IgM and IgE and inflammatory markers like TNF alpha HGNC, IL6 HGNC and IL10 HGNC were the secondary outcome measures. Results: Out of 193 participants who completed the study, no participant in both groups was COVID 19 positive at the end of one month. In post intervention follow up, 4 subjects in Group I and 2 subjects in Group II were COVID 19 positive. No adverse drug reaction or any serious adverse event was reported during the study. No clinically significant change in the safety parameters was observed before and after the study. Statistically significant rise in Serum IgG level was seen in Group II but other inflammatory and immune markers did not show statistically significant difference. Conclusion: Chyawanprash was well tolerated by all the participants in the intervention group but to prove its adaptogenic effect and efficacy as an add-on to the standard care in preventing the occurrence of COVID 19, clinical trial for longer duration with larger sample size is needed. Trial registration: Clinical Trials Registry of India vide CTRI/2020/05/025275 dated 20/05/2020 Date of IEC approval: 19.5.2020 Keywords: Adaptogen, Ayurveda, Health personnel, Prophylaxis, Rasayana, SARS CoV 2

    Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology

    Authors: Andrew H Karaba; Weiqiang Zhou; Leon L Hsieh; Alexis Figueroa; Guido Massaccesi; Richard E Rothman; Katherine ZJ Fenstermacher; Lauren Sauer; Kathryn Shaw-Saliba; Paul W Blair; Sherry Leung; Russell Wesson; Nada Alachkar; Ramy El-Diwany; Hongkai Ji; Andrea L Cox

    doi:10.1101/2021.01.29.21250317 Date: 2021-02-01 Source: medRxiv

    Background: Several inflammatory cytokines are upregulated in severe COVID-19 MESHD. We compared cytokines in COVID-19 MESHD versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19 MESHD, we examined the relationship of BMI to cytokines associated with severe disease. Methods: Thirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19 MESHD, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 MESHD and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity. Results: IL-18 HGNC, IL-1{beta HGNC}, IL-6 HGNC, and TNF HGNC- were significantly increased in COVID-19 MESHD versus influenza patients while GM-CSF HGNC, IFN-{gamma}, IFN-{lambda}1, IL-10 HGNC, IL-15 HGNC, and MCP-2 HGNC were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18 HGNC, IL-6 HGNC, and TNF HGNC- were elevated in severe COVID-19 MESHD, but not severe influenza. Random forest analysis identified high IL-6 HGNC and low IFN-{lambda}1 HGNC levels as the most distinct between severe COVID-19 MESHD and severe influenza. Finally, IL-1RA HGNC was identified as a potential mediator of the effects of BMI on COVID-19 MESHD severity. Conclusions: These findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection MESHD, and emphasize drivers of severe COVID-19 MESHD to focus both mechanistic and therapeutic investigations.

    The Significance of KL-6 HGNC as Prognosis Monitoring Biomarker in Patients With Severe COVID-19 MESHD From Stabilized Stage Toward Convalescence

    Authors: Long He; Liu Lu; Ming Zong; Huang Zhou; Lan Wang; Nian Zhen Chen; Jia Yi Yuan; Er Peng Jiang; Liang Zheng; Qiang Li; Lie Ying Fan; Zhong Min Liu

    doi:10.21203/rs.3.rs-191056/v1 Date: 2021-01-30 Source: ResearchSquare

    Background: This study aims to identify some biomarkers for monitoring the recovery of lung injury MESHD in severe COVID-19 MESHD patients from stabilized stage toward convalescence.Methods: We enrolled participants who diagnosed with severe COVID-19 MESHD (n = 28) and health volunteers (n = 25) from Taikang Tongji (Wuhan) Hospital. The patients were in a stabilized stage and had a course of 48.1±12.8 days. We followed these patients for 90 days. The blood routine, cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC, TNF-α HGNC, IFN-α, IFN-γ HGNC), type II alveolar epithelium injury MESHD indicators ( Surfactant protein A HGNC ( SP-A HGNC), Krebs von den Lungen-6 HGNC von MESHD den Lungen-6 ( KL-6 HGNC)) and chest CT were tested on the 1, 30, 60, and 90 days after enrollment. Results: In stabilized stage, the parameters of blood routine and some cytokines ( IL-1β HGNC, IL-2 HGNC, IL-4 HGNC, IL-12p70, TNF-α HGNC) had bounced back to normal (p>0.05). Some cytokines ( IL-5 HGNC, IL-6 HGNC, IL-10 HGNC, IL-17A HGNC, IFN-α, IFN-γ HGNC) and type II alveolar epithelium injury MESHD indicators ( SP-A HGNC and KL-6 HGNC) were still higher than normal (p<0.05). During the stabilized stage to convalescence, in spite of the variation of monocyte count, monocyte/lymphocyte ratio, IL-5 HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC IFN-γ HGNC, IFN-α, SP-A HGNC and KL-6 HGNC were downward trend (p<0.05), only KL-6 HGNC level (p<0.05) could simultaneously reflect the lung injury MESHD volume which be measured by CT. Conclusions: Our preliminary data indicated that KL-6 HGNC could be an effective prognostic biomarker for monitoring the recovery of lung function in patients with severe COVID-19 MESHD from stabilized stage toward convalescence.

    Cerebrospinal fluid in COVID-19 MESHD neurological complications: no cytokine storm or neuroinflammation.

    Authors: Maria A. Garcia; Paula V. Barreras; Allie Lewis; Gabriel Pinilla; Lori J. Sokoll; Thomas Kickler; Heba Mostafa; Mario Caturegli; Abhay Moghekar; Kathryn C. Fitzgerald; - Hopkins Neuro-COVID-19 Group; Carlos A Pardo

    doi:10.1101/2021.01.10.20249014 Date: 2021-01-12 Source: medRxiv

    BACKGROUND. Neurological complications MESHD occur in COVID-19 MESHD. We aimed to examine cerebrospinal fluid (CSF) of COVID-19 MESHD subjects with neurological complications MESHD and determine presence of neuroinflammatory changes implicated in pathogenesis. METHODS. Cross-sectional study of CSF neuroinflammatory profiles from 18 COVID-19 MESHD subjects with neurological complications categorized by diagnosis ( stroke MESHD, encephalopathy MESHD, headache MESHD) and illness severity (critical, severe, moderate, mild). COVID-19 MESHD CSF was compared with CSF from healthy, infectious and neuroinflammatory disorders MESHD and stroke MESHD controls (n=82). Cytokines ( IL-6 HGNC, TNF-alpha HGNC, IFN-gamma HGNC, IL-10 HGNC, IL-12p70, IL-17A HGNC), inflammation MESHD and coagulation markers (high-sensitivity- C Reactive Protein HGNC [hsCRP], ferritin, fibrinogen HGNC, D-dimer, Factor VIII) and neurofilament light chain ( NF-L HGNC), were quantified. SARS-CoV2 RNA and SARS-CoV2 IgG and IgA antibodies in CSF were tested with RT-PCR and ELISA. RESULTS. CSF from COVID-19 MESHD subjects showed a paucity of neuroinflammatory changes, absence of pleocytosis MESHD or specific increases in pro-inflammatory markers or cytokines ( IL-6 HGNC, ferritin, or D-dimer). Anti-SARS-CoV2 antibodies in CSF of COVID-19 MESHD subjects (77%) were observed despite no evidence of SARS-CoV2 viral RNA. A similar increase of pro-inflammatory cytokines ( IL-6 HGNC, TNF-alpha HGNC;, IL-12p70) and IL-10 HGNC in CSF of COVID-19 MESHD and non- COVID-19 MESHD stroke MESHD subjects was observed compared to controls. CSF-NF-L was elevated in subjects with stroke MESHD and critical COVID-19 MESHD. CSF-hsCRP was present almost exclusively in COVID-19 MESHD cases. CONCLUSION. The paucity of neuroinflammatory changes in CSF of COVID-19 MESHD subjects and lack of SARS-CoV2 RNA do not support the presumed neurovirulence of SARS-CoV2 or neuroinflammation MESHD in pathogenesis of neurological complications in COVID-19 MESHD. Elevated CSF-NF-L indicates neuroaxonal injury MESHD in COVID-19 MESHD cases. The role of CSF SARS-CoV2 IgG antibodies is still undetermined.

    Humoral and cell-mediated response in colostrum after exposure to severe acute respiratory syndrome coronavirus 2 MESHD

    Authors: Vignesh Narayanaswamy; Brian Pentecost; Dominique Alfandari; Emily Chin; Kathleen Minor; Alyssa Kastrinakis; Tanya Lieberman; Kathleen F Arcaro; Heidi Leftwich

    doi:10.1101/2021.01.03.20248715 Date: 2021-01-04 Source: medRxiv

    BackgroundColostrum provides an immune sharing between a mother and her infant. The transfer in colostrum of antibodies against SARS-CoV-2 and the elicited cytokines may provide crucial protection to the infant. There is limited literature on the immune response to SARS-CoV-2 present in colostrum. ObjectiveTo evaluate the presence of antibodies specific to SARS-CoV-2 and the associated cytokines in colostrum from women who tested positive for the virus. Study DesignBetween March and September 2020 we obtained bilateral colostrum samples collected on spot cards within 48 hours of delivery from 15 new mothers who had previously tested positive for SARS-CoV-2. Five of these 15 COVID-19 MESHD positive women also provided bilateral liquid colostrum within 1-2 days of providing the spot card samples. Archived bilateral colostrum samples collected from 8 women during 2011-2013 were used as pre- COVID-19 MESHD controls. All samples were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike PROTEIN protein using an ELISA that measures SARS-CoV-2 RBD-specific IgA, IgG, and IgM, and for concentrations of 10 inflammatory cytokines ( IFN{gamma HGNC}, TNF HGNC, IL-1{beta HGNC}, IL-2 HGNC, IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-12, IL-13 HGNC) using a multiplex electrochemiluminescent sandwich assay. ResultsBilateral colostrum samples from 73%, 73% and 33% of the 15 COVID-19 MESHD mothers exhibited IgA, IgG, and IgM reactivity to RBD respectively. Colostrum samples from two of the 8 pre-pandemic controls showed IgA and IgG reactivity to RBD. Additionally, COVID-19 MESHD mothers had significantly higher levels of 9 of the 10 inflammatory markers (all except IFN{gamma HGNC}) as compared to the pre- COVID-19 MESHD controls. Comparable results were obtained with both the spot card-eluates and liquid samples. ConclusionsA strong humoral immune response is present in the colostrum of women who were infected with SARS-CoV-2 before delivering. High levels of 9 inflammatory markers were also present in the colostrum. The evolution and duration of the antibody response, as well as dynamics of the cytokine response, remain to be determined. Our results also indicate that future large-scale studies can be conducted with milk easily collected on paper spot cards.

    Kinetics of Plasma Cytokines During and After Two Different Modalities of Extracorporeal Blood Purification in Critically Ill COVID-19 MESHD Patients

    Authors: Daniela Ponce; Welder Zamoner; Luis Eduardo Magalhães; Paula Gabriela Souza de Oliveira; Patricia Polla; Alexandre Naime Barbosa; Marjorie de Assis Golim; Andre Luis Balbi

    doi:10.21203/rs.3.rs-136018/v1 Date: 2020-12-25 Source: ResearchSquare

    Cytokine storm syndrome ( CSS MESHD) has been documented in coronavirus disease 2019 MESHD ( COVID-19 MESHD) since the first reports of this disease. In the absence of vaccines or direct therapy for COVID-19 MESHD, extracorporeal blood treatment (EBT) could represent an option for the removal of cytokines and may be beneficial to improve the clinical outcome of critically ill MESHD patients. Intermittent haemodialysis ( IHD MESHD), using high flux (HF) or high cut-off membranes, and continuous renal replacement therapy (CRRT) could be used for blood purification in COVID-19 MESHD patients with CSS. To the best of our knowledge, cytokine kinetics during and after different types of EBT on COVID-19 MESHD patients have never been studied. In this study, we describe cytokine variation and removal during and after IHD MESHD and CRRT in COVID-19 MESHD patients with acute kidney injury MESHD ( AKI MESHD). Methods: Patients with COVID-19 MESHD-related AKI MESHD according to Kidney Disease MESHD Improving Global Outcomes (KDIGO) criteria and admitted at Intensive Care Unit (ICU) were studied. Blood samples were collected at the start and end of both IHD MESHD using HF membranes (10 patients) and continuous venovenous haemodiafiltration (CVVHDF: 10 patients) in two sessions for measuring 13 different plasma interleukins and calculating the cytokine removal rate. Results: We evaluated cytokine removal in patients with COVID-19 MESHD-related AKI MESHD undergoing either prolonged IHD MESHD (10 patients) or CRRT (CVVHDF: 10 patients). There was no difference between the IHD MESHD and CVVHDF groups regarding mechanical ventilation, vasoactive drug use, age or prognostic scores. Patients treated by CRRT presented higher levels of IL-2 HGNC and IL-8 HGNC than patients treated by prolonged IHD at the start of dialysis. Cytokine removal ranged from 9–78%. Patients treated by CRRT presented higher cytokine removal rates than those treated by prolonged IHD for IL-2 HGNC, IL-6 IL-8, IP-10 HGNC and TNF HGNC. The removal rates of IL-4 HGNC, IL-10 HGNC, IL-1β HGNC, IL-17A HGNC, IFN HGNC, MCP-1 HGNC and free active TGF-B1 HGNC were similar in the two groups. After one session of CVVHDF (24 h) the IL-2 HGNC and IL-1β HGNC levels did not vary significantly, whereas IL-4 HGNC, IL-6 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17A HGNC, TNF HGNC, IFN HGNC, IP-10 HGNC, MCP-1 HGNC, IL-12p70 and free active TGF-B1 HGNC decreased by 33.8–76%, and this decrease was maintained over the next 24 h. In the prolonged IHD groups, IL-2 HGNC, IL-6 HGNC, TNF HGNC, IP-10 HGNC and IL-1β HGNC levels did not decrease significantly whereas IL-4 HGNC, IL-8 HGNC, IL-10 HGNC, IL-17A HGNC, IFN HGNC, MCP-1 HGNC, IL-12p70 and free active TGF-B1 HGNC decreased by 21.8–72%. However, all cytokine levels returned to their initial values after 24 h, despite their removal. Conclusions: Cytokine removal is lower using prolonged IHD MESHD with HF membranes than by using CVVHDF, and IHD MESHD allows a transient and selective decrease in cytokines that can be correlated with mortality during CSS-related COVID-19 MESHD.

    Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection MESHD

    Authors: Nina Le Bert; Hannah E Clapham; Anthony T Tan; Wan Ni Chia; Christine YL Tham; Jane M Lim; Kamini Kunasegaran; Linda Tan; Charles-Antoine Dutertre; Nivedita Shankar; Joey ME Lim; Louisa Jin Sun; Marina Zahari; Zaw M Tun; Vishakha Kumar; Beng Lee Lim; Siew Hoon Lim; Adeline Chia; Yee-Joo Tan; Paul Anantharajah Tambyah; Shirin Kalimuddin; David CB Lye; Jenny GH Low; Lin-Fa Wang; Wei Yee Wan; Li Yang Hsu; Antonio Bertoletti; Clarence C Tam; Martina Recalde; Paula Casajust; Jitendra Jonnagaddala; Vignesh Subbian; David Vizcaya; Lana YH Lai; Fredrik Nyberg; Daniel R. Morales; Jose D. Posada; Nigam H. Shah; Mengchun Gong; Arani Vivekanantham; Aaron Abend; Evan P Minty; Marc A. Suchard; Peter Rijnbeek; Patrick B Ryan; Daniel Prieto-Alhambra

    doi:10.1101/2020.11.25.399139 Date: 2020-11-27 Source: bioRxiv

    The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection MESHD without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 MESHD patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M PROTEIN, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion ( IL-2 HGNC, IFN-{gamma HGNC}, IL-4 HGNC, IL-6 HGNC, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma HGNC} and IL-2 HGNC production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 HGNC and pro-inflammatory cytokines ( IL-6 HGNC, TNF HGNC- and IL-1{beta} HGNC) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected MESHD individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 HGNC might help to reduce inflammatory events during viral clearance.

    Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC are associated with the outcome of patients with severe COVID-19 MESHD in ICU

    Authors: Jia Li; Liu Rong; Ran Cui; Jiaqi Feng; Yuyang Jin; Yuetian Yu; Xiaoxiang Chen; Renying Xu

    doi:10.21203/rs.3.rs-83336/v1 Date: 2020-09-25 Source: ResearchSquare

    Background: Biomarkers that would help prognosticate outcomes and guide treatment of patients with severe coronavirus disease 2019 MESHD ( COVID-19 MESHD) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to an intensive care unit (ICU).Methods: A retrospective study was performed on 40 patients with COVID-19 MESHD admitted to an ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum cytokines were kinetically assessed. A multivariable- adjusted generalized linear regression model was used to evaluate the differences in serum cytokine levels between survivor and non-survivors.Results: Among the 40 patients included, a significant positive correlation was found between multiple cytokines. Serum levels of IL-6 HGNC, IL-10 HGNC, and tumor MESHD tumor HGNC necrosis MESHD factor alpha in non-survivors were consistently elevated compared to that of the survivors. Kinetic variations of IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC were associated with a fatal outcome in severe patients with COVID-19 MESHD, independent of sex, age, absolute lymphocyte count, direct bilirubin, hypertension MESHD, chronic obstructive pulmonary disease MESHD, and cancer MESHD.Conclusion: Dynamic changes in serum IL-6 HGNC, IL-8 HGNC, and IL-10 HGNC levels were associated with survival in ICU and could serve as a predictive biomarker in patients with severe COVID-19 MESHD to determine therapeutic options.

    SARS-CoV-2 cellular immune response in uninfected health care workers with prolonged and close exposure to COVID-19 MESHD patients

    Authors: Alejandro Vallejo; Pilar Vizcarra; Carmen Quereda; Ana Moreno; Jose L Casado

    doi:10.21203/rs.3.rs-55720/v1 Date: 2020-08-07 Source: ResearchSquare

    Health care workers (HCW) are at an increased risk since they are directly exposed to SARS-CoV-2 infected MESHD patients, nevertheless, some remained without the development of anti-SARS-CoV-2 antibodies, suggesting lesser susceptibility to infection1-5. This study aimed to ascertain a potential specific cellular immune response to SARS-CoV-2 in these largely exposed HCWs.In this cross-sectional, case-control study, we analyzed 39 exposed uninfected HCWs and 17 convalescent HCWs. Cellular immune response was evaluated after SARS-CoV-2 stimulation with peptide pools ( proteins S PROTEIN, M, and N), using bead-based multiplex assay (12 cytokines).Overall, 94.8% of uninfected HCWs had some degree of specific cellular response to SARS-CoV-2 structural proteins that could be classified, according to the number of cytokine production, as strong (61.5%), partial (33.3%), and weak/no response (5.1%). Strong responders showed a higher anti-inflammatory cytokine production ( IL5 HGNC and IL10 HGNC, p<0.001 and 0.002, respectively), and similar ( IFN-γ HGNC and TNF-α HGNC, p=0.435 and 0.532, respectively) or higher (IL12, p=0.021) pro-inflammatory production compared to convalescents, resulted in a predominantly Th2 response. This study demonstrated a consistent and polyfunctional immune cellular response after stimulation with SARS-CoV-2 peptides in extensively exposed individuals that should be considered to establish the infection susceptibility, the impact in herd immunity, and the risk of relapses.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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