Natural killer cell immunotypes related to COVID-19 disease severity

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Abstract

The NK cell activation landscape in acute SARS-CoV-2 infection is associated with COVID-19 disease severity.

Activated NK cells in severe COVID-19

Natural killer (NK) cells are cytotoxic lymphocytes that provide innate immune defense against viral infections and cancer, but little is known about their involvement in the host response to COVID-19. Maucourant et al. used high-dimensional flow cytometry to characterize NK cells in patients with moderate or severe COVID-19. SARS-CoV-2 infection was associated with fewer blood NK cells but a higher activation state in circulating NK cells. Severe COVID-19 resulted in an increase in “armed” NK cells containing high levels of cytotoxic proteins such as perforin. The adaptive NK subset was markedly expanded in a subset of severe patients. These findings lay the groundwork for future studies examining the mechanisms of NK cell activation in COVID-19 and their potential roles in host protection and immunopathology.

Abstract

Understanding innate immune responses in coronavirus disease 2019 (COVID-19) is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in single-cell RNA sequencing signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Last, arming of CD56 ^bright NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical Characteristics of Coronavirus Disease 2019 in China

Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)

Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)

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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Mervyn Singer, Clifford S Deutschman, Christopher Warren Seymour … (2016)

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

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Author and article information

Journal

Journal ID (nlm-ta): Sci Immunol

Journal ID (iso-abbrev): Sci Immunol

Journal ID (publisher-id): SciImmunol

Journal ID (hwp): immunology

Title: Science Immunology

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2470-9468

Publication date (Print): 21 August 2020

Volume: 5

Issue: 50

Electronic Location Identifier: eabd6832

Affiliations

[1 ]Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

[2 ]Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.

[3 ]Division of Infectious Diseases and Dermatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.

[4 ]Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

[5 ]Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

[6 ]K.G. Jebsen Centre for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

[7 ]SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

[8 ]Division of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

[9 ]Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden.

[10 ]Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.

[11 ]Department of Clinical Science, Intervention, and Technology (CLINTEC), Division for Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, Sweden.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: niklas.bjorkstrom@ 123456ki.se

[‡]

The members of the Karolinksa COVID-19 Study Group can be found in the Acknowledgments.

Author information

Christopher Maucourant http://orcid.org/0000-0003-1033-2992

Iva Filipovic http://orcid.org/0000-0002-8166-5500

Andrea Ponzetta http://orcid.org/0000-0003-3224-802X

Martin Cornillet http://orcid.org/0000-0001-7981-0927

Laura Hertwig http://orcid.org/0000-0002-1170-0948

Antonio Lentini http://orcid.org/0000-0003-1239-5495

Demi Brownlie http://orcid.org/0000-0001-5932-6425

Eivind Heggernes Ask http://orcid.org/0000-0001-8655-1433

Ryan M. Hull http://orcid.org/0000-0001-7153-4198

Alvaro Haroun-Izquierdo http://orcid.org/0000-0003-4557-3606

Jonas Klingström http://orcid.org/0000-0001-9076-1441

Elin Folkesson http://orcid.org/0000-0002-6585-6235

Marcus Buggert http://orcid.org/0000-0003-0633-1719

Johan K. Sandberg http://orcid.org/0000-0002-6275-0750

Olav Rooyackers http://orcid.org/0000-0002-3391-5448

Nicole Marquardt http://orcid.org/0000-0003-3186-4752

Quirin Hammer http://orcid.org/0000-0003-2968-6061

Kristoffer Strålin http://orcid.org/0000-0002-8801-3169

Niklas K. Björkström http://orcid.org/0000-0002-0967-076X

Article

Publisher ID: abd6832

DOI: 10.1126/sciimmunol.abd6832

PMC ID: 7665314

PubMed ID: 32826343

SO-VID: 2ad42e4f-4801-4321-a195-c20e77304cbe

Copyright © Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 06 July 2020

Date accepted : 19 August 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/501100001729, Swedish Foundation for Strategic Research;

Funded by: doi http://dx.doi.org/10.13039/501100004047, Karolinska Institutet;

Funded by: doi http://dx.doi.org/10.13039/501100004063, Knut och Alice Wallenbergs Stiftelse;

Funded by: doi http://dx.doi.org/10.13039/501100004348, Stockholms Läns Landsting;

Funded by: doi http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;

Funded by: Nordstjernan AB;

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Copyeditor Fritzie Benzon

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Natural killer cell immunotypes related to COVID-19 disease severity

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Abstract

Activated NK cells in severe COVID-19

Abstract

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Novel Coronavirus Disease COVID-19

Most cited references 58

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical Characteristics of Coronavirus Disease 2019 in China

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

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