#Rhabdomyolysis as Potential Late #Complication Associated with #COVID19 (Emerg Infect Dis., summary)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Summary, edited.]

Volume 26, Number 9—September 2020 | Letter

Rhabdomyolysis as Potential Late Complication Associated with COVID-19

Ying-Chao He and Feng Chen

Author affiliations: Fujian Provincial Hospital, Fuzhou, Fujian, China

Suggested citation for this article: He Y-C, Chen F. Rhabdomyolysis as potential late complication associated with COVID-19. Emerg Infect Dis. 2020 Sep [date cited]. https://doi.org/10.3201/eid2609.201463

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To the Editor: We provide follow-up information on a case discussed in Emerging Infectious Diseases of a man with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who reportedly had late-onset rhabdomyolysis with lower limb pain and fatigue (1). After the patient was stabilized, he was transferred to Wuhan Union Hospital, where he disclosed symmetric weakness (Medical Research Council grade 4/5) in both lower limbs with weakened deep tendon reflexes and decreased sensation to light touch and pinprick distally. Because weakness and paresthesia persisted after biochemistries normalized, we feel that these observations are not explained solely by rhabdomyolysis.

(…)

Keywords: SARS-CoV-2; COVID-19; Rhabdomyolysis.

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Development of #pulmonary #embolism in a nonhospitalized patient with #COVID19 who did not receive venous thromboembolism #prophylaxis (Am J Med Syst Pharm., abstract)

[Source: American Journal of Medicine, System Pharmacy, full page: (LINK). Abstract, edited.]

Development of pulmonary embolism in a nonhospitalized patient with COVID-19 who did not receive venous thromboembolism prophylaxis

Ellen M Uppuluri, PharmD, Nancy L Shapiro, PharmD

American Journal of Health-System Pharmacy,  zxaa286, https://doi.org/10.1093/ajhp/zxaa286

Published: 11 August 2020

 

Abstract

Disclaimer

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Purpose

Coronavirus disease 2019 (COVID-19) has been associated with thrombotic complications such as stroke and venous thromboembolism (VTE), and VTE prophylaxis for hospitalized patients with COVID-19 is recommended. However, extended postdischarge VTE prophylaxis and VTE prophylaxis for nonhospitalized patients with COVID-19 are not routinely recommended due to uncertain benefit in these populations.

Summary

Here we report development of a pulmonary embolism (PE) in a young patient without other VTE risk factors who was treated for COVID-19 in an emergency department (ED) and discharged home without VTE prophylaxis, which was consistent with current recommendations. The patient presented to the ED 12 days later with complaints of chest pain for 1 day and was found to have a PE within the segmental and subsegmental branches of the left lower lobe.

Conclusion

This case suggests that nonhospitalized patients with COVID-19 may be at higher risk for VTE than patients with other medical illnesses and warrants further research into the risk of VTE in outpatients with COVID-19.

anticoagulation, COVID-19, prophylaxis, pulmonary embolism, venous thromboembolism

Issue Section: Case Report

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© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Pulmonary embolism; Coagulopathy.

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#Transmission of #SARS-CoV-2 Involving Residents Receiving #Dialysis in a Nursing Home — #Maryland, April 2020 (MMWR Morb Mortal Wkly Rep., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), MMWR Morbidity and Mortality Weekly Report, full page: (LINK). Abstract, edited.]

Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home — Maryland, April 2020

Early Release / August 11, 2020 / 69

Benjamin F. Bigelow1,*; Olive Tang, PhD1,*; Gregory R. Toci1; Norberth Stracker, MS1,2; Fatima Sheikh, MD1; Kara M. Jacobs Slifka, MD3; Shannon A. Novosad, MD3; John A. Jernigan, MD3; Sujan C. Reddy, MD3; Morgan J. Katz, MD1

Corresponding author: Benjamin F. Bigelow, benbigelow@jhmi.edu.

1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 2Division of Population Health and Disease Prevention, Baltimore City Health Department, Baltimore, Maryland; 3CDC COVID-19 Response Team.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

* These authors contributed equally to this work.

Suggested citation for this article: Bigelow BF, Tang O, Toci GR, et al. Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home — Maryland, April 2020. MMWR Morb Mortal Wkly Rep. ePub: 11 August 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6932e4

 

Summary

  • What is already known about this topic?
    • Residents of long-term care facilities have high COVID-19–associated morbidity and mortality. More information is needed about SARS-CoV-2 introduction and transmission in nursing homes.
  • What is added by this report?
    • Investigation of a COVID-19 outbreak in a Maryland nursing home identified a significantly higher prevalence among residents receiving dialysis (47%) than among those not receiving dialysis (16%); 72% were asymptomatic at the time of testing.
  • What are the implications for public health practice?
    • Nursing home residents undergoing dialysis might be at a higher risk for SARS-CoV-2 infection because of exposures to staff members and community dialysis patients. Attention to infection control practices and surveillance in nursing homes and dialysis centers is critical to preventing nursing home COVID-19 outbreaks.

 

Abstract

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in nursing homes once it is introduced (1,2). To prevent outbreaks, more data are needed to identify sources of introduction and means of transmission within nursing homes. Nursing home residents who receive hemodialysis (dialysis) might be at higher risk for SARS-CoV-2 infections because of their frequent exposures outside the nursing home to both community dialysis patients and staff members at dialysis centers (3). Investigation of a COVID-19 outbreak in a Maryland nursing home (facility A) identified a higher prevalence of infection among residents undergoing dialysis (47%; 15 of 32) than among those not receiving dialysis (16%; 22 of 138) (p<0.001). Among residents with COVID-19, the 30-day hospitalization rate among those receiving dialysis (53%) was higher than that among residents not receiving dialysis (18%) (p = 0.03); the proportion of dialysis patients who died was 40% compared with those who did not receive dialysis (27%) (p = 0.42).Careful consideration of infection control practices throughout the dialysis process (e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting), clear communication between nursing homes and dialysis centers, and coordination of testing practices between these sites are critical to preventing COVID-19 outbreaks in this medically vulnerable population.

(…)

Keywords: SARS-CoV-2; COVID-19; Institutional outbreaks; Maryland; USA.

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#Facility-Wide #Testing for #SARS-CoV-2 in Nursing Homes — Seven #US Jurisdictions, March–June 2020 (MMWR Morb Mortal Wkly Rep., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), MMWR Morbidity and Mortality Weekly Report, full page: (LINK). Abstract, edited.]

Facility-Wide Testing for SARS-CoV-2 in Nursing Homes — Seven U.S. Jurisdictions, March–June 2020

Early Release / August 11, 2020 / 69

Kelly M. Hatfield, MSPH1; Sujan C. Reddy, MD1; Kaitlin Forsberg, MPH1; Lauren Korhonen, MSPH1; Kelley Garner, MPH2; Trent Gulley, MPH2; Allison James, DVM, PhD2; Naveen Patil, MD2; Carla Bezold, ScD3; Najibah Rehman, MD3; Marla Sievers, MPH4; Benjamin Schram, MPH5; Tracy K. Miller, PhD5; Molly Howell, MPH5; Claire Youngblood, MA6; Hannah Ruegner, MPH6; Rachel Radcliffe, DVM6; Allyn Nakashima, MD7; Michael Torre, PhD7; Kayla Donohue, MPH8; Paul Meddaugh, MS8; Mallory Staskus, MS8; Brandon Attell, MA1; Caitlin Biedron, MD1; Peter Boersma, MPH1; Lauren Epstein, MD1; Denise Hughes1; Meghan Lyman, MD1; Leigh E. Preston, DrPH1; Guillermo V. Sanchez, MSHS, MPH1; Sukarma Tanwar, MMed1; Nicola D. Thompson, PhD1; Snigdha Vallabhaneni, MD1; Amber Vasquez, MD1; John A. Jernigan, MD1

Corresponding author: Kelly M. Hatfield, khatfield2@cdc.gov.

1CDC COVID-19 Response Team; 2Arkansas Department of Health; 3Detroit Health Department, Detroit, Michigan; 4New Mexico Department of Health; 5North Dakota Department of Health; 6South Carolina Department of Health and Environmental Control; 7Utah Department of Health; 8Vermont Department of Health.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Kayla Donohue reports full-time employment at United Way of Northwest Vermont with temporary assignment to COVID-19 response at the Vermont Department of Health, which supported her work related to this publication. No other potential conflicts of interest were disclosed.

Suggested citation for this article: Hatfield KM, Reddy SC, Forsberg K, et al. Facility-Wide Testing for SARS-CoV-2 in Nursing Homes — Seven U.S. Jurisdictions, March–June 2020. MMWR Morb Mortal Wkly Rep. ePub: 11 August 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6932e5

 

Summary

  • What is already known about this topic?
    • Facility-wide testing of health care personnel and nursing home residents for SARS-CoV-2 can inform strategies to prevent transmission.
  • What is added by this report?
    • In two health department jurisdictions, testing in facilities without a previous COVID-19 case identified a prevalence of 0.4%. Five health department jurisdictions that targeted facility-wide testing after identification of a case found a prevalence of 12%; for each additional day before completion of initial facility-wide testing, an estimated 1.3 additional cases were identified.
  • What are the implications for public health practice?
    • Performing facility-wide testing rapidly following identification of a case in a nursing home might facilitate control of transmission among residents and health care personnel. Strategies are needed to optimize facility-wide testing in nursing homes without a reported case.

 

Abstract

Undetected infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) contributes to transmission in nursing homes, settings where large outbreaks with high resident mortality have occurred (1,2). Facility-wide testing of residents and health care personnel (HCP) can identify asymptomatic and presymptomatic infections and facilitate infection prevention and control interventions (3–5). Seven state or local health departments conducted initial facility-wide testing of residents and staff members in 288 nursing homes during March 24–June 14, 2020. Two of the seven health departments conducted testing in 195 nursing homes as part of facility-wide testing all nursing homes in their state, which were in low-incidence areas (i.e., the median preceding 14-day cumulative incidence in the surrounding county for each jurisdiction was 19 and 38 cases per 100,000 persons); 125 of the 195 nursing homes had not reported any COVID-19 cases before the testing. Ninety-five of 22,977 (0.4%) persons tested in 29 (23%) of these 125 facilities had positive SARS-CoV-2 test results. The other five health departments targeted facility-wide testing to 93 nursing homes, where 13,443 persons were tested, and 1,619 (12%) had positive SARS-CoV-2 test results. In regression analyses among 88 of these nursing homes with a documented case before facility-wide testing occurred, each additional day between identification of the first case and completion of facility-wide testing was associated with identification of 1.3 additional cases. Among 62 facilities that could differentiate results by resident and HCP status, an estimated 1.3 HCP cases were identified for every three resident cases. Performing facility-wide testing immediately after identification of a case commonly identifies additional unrecognized cases and, therefore, might maximize the benefits of infection prevention and control interventions. In contrast, facility-wide testing in low-incidence areas without a case has a lower proportion of test positivity; strategies are needed to further optimize testing in these settings.

(…)

Keywords: SARS-CoV-2; COVID-19; Diagnostic tests; Institutional outbreaks; USA.

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#Clinical Characteristics of Moderate #COVID19 #Patients #Aggravation in #Wuhan Stadium Cabin Hospital: A 571 Cases of Retrospective Cohort Study (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Clinical Characteristics of Moderate COVID‐19 Patients Aggravation in Wuhan Stadium Cabin Hospital: A 571 Cases of Retrospective Cohort Study

Lei Shu,  Xiaoyan Wang,  Mingquan Li,  Xiaolin Chen,  Ningfei Ji,  Lei Shi,  Mingjing Wu, Kaili Deng,  Jing Wei,  Xueli Wang,  Yang Cao,  Jiaxin Yan,  Ganzhu Feng

First published: 11 August 2020 | DOI: https://doi.org/10.1002/jmv.26414

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26414

 

Abstract

In order to report the clinical characteristics and potential risk factors of COVID‐19 Patients in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID‐19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID‐19 were fever, cough and dyspnea, hypertension, diabetes and coronary heart diseases were the main comorbidities both in transferred and stable patients. 26 patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 hours to 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation and interstitial abnormalities of CT scanning, lymphopenia and elevated of CRP, the time points of transferred patients mainly between 36 hours to 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Hubei; China.

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#Mutational #spectra of #SARS‐CoV‐2 #orf1ab polyprotein and signature mutations in the #USA (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Mutational spectra of SARS‐CoV‐2 orf1ab polyprotein and signature mutations in the United States of America

Shuvam Banerjee M.Tech (Bioinformatics),  Sohan Seal,  Riju Dey,  Kousik Kr. Mondal, Pritha Bhattacharjee PhD

First published: 11 August 2020 | DOI:  https://doi.org/10.1002/jmv.26417

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26417

 

Abstract

Pandemic COVID‐19 outbreak has been caused due to SARS‐CoV‐2 pathogen, resulting millions of infection and death worldwide, USA being on top at the present moment. The long, complex orf1ab polyproteins of SARS‐CoV‐2 play an important role in viral RNA synthesis. To assess the impact of mutations in this important domain, we analyzed 1134 complete protein sequences of orf1ab polyprotein from NCBI Virus database from affected patients across various states of USA from December 2019 to 25th April 2020. Multiple sequence alignment using Clustal Omega followed by statistical significance was calculated. Four significant mutations T265I (nsp 2), P4715L (nsp 12) and P5828L and Y5865C (both at nsp 13) were identified in important non‐structural proteins, which function either as replicase or helicase. A comparative analysis shows 265T→I, 5828P→L and 5865Y→C are unique to USA and not reported from Europe or Asia; while one, 4715P→L is predominant in both Europe and USA. Mutational changes in amino acids are predicted to alter structure and function of corresponding proteins, thereby it is imperative to consider the mutational spectra while designing new antiviral therapeutics targeting viral orf1ab.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Virology.

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#SARS-CoV-2 Neutralizing #Antibody #Titers in #Convalescent #Plasma and Recipients in New Mexico: An Open #Treatment Study in #COVID19 Patients (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

SARS-CoV-2 Neutralizing Antibody Titers in Convalescent Plasma and Recipients in New Mexico: An Open Treatment Study in COVID-19 Patients

Steven B Bradfute, PhD, Ivy Hurwitz, PhD, Alexandra V Yingling, MSc, Chunyan Ye, MSc, Qiuying Cheng, PhD, Timothy P Noonan, MD, Jay S Raval, MD, Nestor R Sosa, MD, Gregory J Mertz, MD, Douglas J Perkins, PhD, Michelle S Harkins, MD

The Journal of Infectious Diseases, jiaa505, https://doi.org/10.1093/infdis/jiaa505

Published: 11 August 2020

 

Abstract

Background

Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in acute COVID-19 patients remains largely undetermined. We measured NAb titers in CP and in acute COVID-19 patients before and after transfusion through the traditional FDA IND pathway.

Methods

We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. Trial Registration: Clinicaltrials.gov identifier: NCT04434131 (https://clinicaltrials.gov/ct2/show/NCT04434131)

Results

NAb titers in the donor CP units were low (<1:40 to 1:160) and had no effect on recipient neutralizing activity one day after transfusion. NAb titers were detected in 6/12 patients upon enrollment and in 11/12 patients during at least two timepoints. Average titers peaked on day 7 and declined towards day 14 (P=0.004). NAb and IgG titers were correlated in donor plasma units (ρ=0.938, P<0.0001) and in the cumulative patient measures (ρ=0.781, P<0.0001).

Conclusions

CP infusion did not alter recipient NAb titers. Pre-screening of CP may be necessary for selecting donors with high levels of neutralizing activity for infusion into patients with COVID-19.

SARS-CoV-2, coronavirus, antibodies, neutralizing, convalescent, plasma

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: SARS-CoV-2; COVID-19; Serotherapy; New Mexico; USA.

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#Pathogenetic #profiling of #COVID19 and #SARS-like viruses (Brief Bioinformat., abstract)

[Source: Briefings in Bioinformatics, full page: (LINK). Abstract, edited.]

Pathogenetic profiling of COVID-19 and SARS-like viruses

Zulkar Nain, Humayan Kabir Rana, Pietro Liò, Sheikh Mohammed Shariful Islam, Matthew A Summers, Mohammad Ali Moni

Briefings in Bioinformatics, bbaa173, https://doi.org/10.1093/bib/bbaa173

Published: 11 August 2020

 

Abstract

The novel coronavirus (2019-nCoV) has recently emerged, causing COVID-19 outbreaks and significant societal/global disruption. Importantly, COVID-19 infection resembles SARS-like complications. However, the lack of knowledge about the underlying genetic mechanisms of COVID-19 warrants the development of prospective control measures. In this study, we employed whole-genome alignment and digital DNA–DNA hybridization analyses to assess genomic linkage between 2019-nCoV and other coronaviruses. To understand the pathogenetic behavior of 2019-nCoV, we compared gene expression datasets of viral infections closest to 2019-nCoV with four COVID-19 clinical presentations followed by functional enrichment of shared dysregulated genes. Potential chemical antagonists were also identified using protein–chemical interaction analysis. Based on phylogram analysis, the 2019-nCoV was found genetically closest to SARS-CoVs. In addition, we identified 562 upregulated and 738 downregulated genes (adj. P ≤ 0.05) with SARS-CoV infection. Among the dysregulated genes, SARS-CoV shared ≤19 upregulated and ≤22 downregulated genes with each of different COVID-19 complications. Notably, upregulation of BCL6 and PFKFB3 genes was common to SARS-CoV, pneumonia and severe acute respiratory syndrome, while they shared CRIP2, NSG1 and TNFRSF21 genes in downregulation. Besides, 14 genes were common to different SARS-CoV comorbidities that might influence COVID-19 disease. We also observed similarities in pathways that can lead to COVID-19 and SARS-CoV diseases. Finally, protein–chemical interactions suggest cyclosporine, resveratrol and quercetin as promising drug candidates against COVID-19 as well as other SARS-like viral infections. The pathogenetic analyses, along with identified biomarkers, signaling pathways and chemical antagonists, could prove useful for novel drug development in the fight against the current global 2019-nCoV pandemic.

2019-nCoV, coronavirus, COVID-19, microarray, SARS-CoV-2, comorbidities

Issue Section: Case study

Keywords: SARS-CoV-2; COVID-19; Viral pathogenesis.

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#Systems #biological #assessment of #immunity to #mild versus #severe #COVID19 infection in humans (Science, abstract)

[Source: Science, full page: (LINK). Abstract, edited.]

Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans

Prabhu S. Arunachalam1,*, Florian Wimmers1,*, Chris Ka Pun Mok2,*, Ranawaka A. P. M. Perera3,*, Madeleine Scott1,4,†, Thomas Hagan1,†, Natalia Sigal1,†, Yupeng Feng1,†, Laurel Bristow5, Owen Tak-Yin Tsang6, Dhananjay Wagh7, John Coller7, Kathryn L. Pellegrini8, Dmitri Kazmin1, Ghina Alaaeddine5, Wai Shing Leung6, Jacky Man Chun Chan6, Thomas Shiu Hong Chik6, Chris Yau Chung Choi6, Christopher Huerta5, Michele Paine McCullough5, Huibin Lv2, Evan Anderson9, Srilatha Edupuganti5, Amit A. Upadhyay8, Steve E. Bosinger8,10, Holden Terry Maecker1, Purvesh Khatri1,4, Nadine Rouphael5, Malik Peiris2,3, Bali Pulendran1,11,12,‡

1 Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA. 2 HKU-Pasteur Research Pole, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong (HKU), Hong Kong. 3 Centre of Influenza Research, School of Public Health, HKU Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. 4 Center for Biomedical informatics, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. 5 Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Decatur, GA 30030, USA. 6 Infectious Diseases Centre, Princess Margaret Hospital, Hospital Authority of Hong Kong, Hong Kong. 7 Stanford Functional Genomics Facility, Stanford University School of Medicine, Stanford, CA 94305, USA. 8 Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. 9 Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA. 10 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30329, USA. 11 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. 12 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.

‡Corresponding author. Email: bpulend@stanford.edu

* These authors contributed equally to this work.

† These authors contributed equally to this work.

Science  11 Aug 2020: eabc6261 | DOI: 10.1126/science.abc6261

 

Abstract

COVID-19 represents a global crisis, yet major knowledge gaps remain about human immunity to SARS-CoV-2. We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta. In PBMCs of COVID-19 patients, there was reduced expression of HLA-DR and pro-inflammatory cytokines by myeloid cells, and impaired mTOR-signaling and IFN-α production by plasmacytoid DCs. In contrast, there were enhanced plasma levels of inflammatory mediators, including EN-RAGE, TNFSF14, and oncostatin-M, which correlated with disease severity and increased bacterial products in human plasma. Single-cell transcriptomics revealed no type-I IFN, reduced HLA-DR in myeloid cells of severe patients, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics, and transient, low plasma IFN-α levels during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.

Keywords: SARS-CoV-2; COVID-19; Immunopathology; Immunology.

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