UMass Chan Medical School Faculty Publications
UMMS Affiliation
Program in Molecular Medicine; Medical Scientist Training Program; Graduate School of Biomedical Sciences, MD/PhD Program; Department of Biochemistry and Molecular Pharmacology
Publication Date
2021-01-15
Document Type
Article Preprint
Disciplines
Epidemiology | Immunity | Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virology | Virus Diseases
Abstract
BACKGROUND: Risk of severe coronavirus disease 2019 (COVID-19) increases with age, is greater in males, and is associated with decreased numbers of blood lymphoid cells. Though the reasons for these robust associations are unclear, effects of age and sex on innate and adaptive lymphoid subsets, including on homeostatic innate lymphoid cells (ILCs) implicated in disease tolerance, may underlie the effects of age and sex on COVID-19 morbidity and mortality.
METHODS: Flow cytometry was used to quantitate subsets of blood lymphoid cells from people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comparing those hospitalized with severe COVID-19 (n=40) and those treated as outpatients for less severe disease (n=51). 86 healthy individuals served as controls. The relationship between abundance of specific blood lymphoid cell types, age, sex, hospitalization, duration of hospitalization, and elevation of blood markers for systemic inflammation, was determined using multiple regression.
RESULTS: After accounting for effects of age and sex, hospitalization for COVID-19 was associated with 1.78-fold fewer ILCs (95%CI: 2.34–1.36; p = 4.55 x 10−5) and 2.31-fold fewer CD16+ natural killer (NK) cells (95%CI: 3.1–1.71; p = 1.04 x 10−7), when compared to uninfected controls. Among people infected with SARS-CoV-2, the odds ratio for hospitalization, adjusted for age, sex, and duration of symptoms, was 0.413 (95%CI: 0.197–0.724; p = 0.00691) for every 2-fold increase in ILCs. In addition, higher ILC abundance was associated with less time spent in the hospital and lower levels of blood markers associated with COVID-19 severity: each two-fold increase in ILC abundance was associated with a 9.38 day decrease in duration of hospital stay (95% CI: 15.76–3.01; p= 0.0054), and decrease in blood C-reactive protein (CRP) by 46.29 mg/L (95% CI: 71.34–21.24; p = 6.25 x 10−4), erythrocyte sedimentation rate (ESR) by 11.04 mm/h (95% CI: 21.94–0.13; p = 0.047), and the fibrin degradation product D-dimer by 1098.52 ng/mL (95% CI: 1932.84–264.19; p = 0.011).
CONCLUSIONS: Both ILCs and NK cells were depleted in the blood of people hospitalized for severe COVID-19, but, among lymphoid cell subsets, only ILC abundance was independently associated with the need for hospitalization, duration of hospital stay, and severity of inflammation. These results indicate that, by promoting disease tolerance, homeostatic ILCs protect against morbidity and mortality in SARS-CoV-2 infection, and suggest that reduction in the number of ILCs with age and in males accounts for the increased risk of severe COVID-19 in these demographic groups.
Keywords
Infectious Diseases, COVID-19, SARS-CoV-2 infection, age, sex, morbidity, mortality, severity, blood lymphoid cells
Rights and Permissions
The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
DOI of Published Version
10.1101/2021.01.14.21249839
Source
medRxiv 2021.01.14.21249839; doi: https://doi.org/10.1101/2021.01.14.21249839. Link to preprint on medRxiv
Journal/Book/Conference Title
medRxiv
Repository Citation
Silverstein NJ, Wang Y, Manickas-Hill Z, Carbone CC, Dauphin A, MGH COVID-19 Collection & Processing Team, Li JZ, Walker BD, Yu XG, Luban J. (2021). Innate lymphoid cells and disease tolerance in SARS-CoV-2 infection [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.01.14.21249839. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1921
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Epidemiology Commons, Immunity Commons, Immunology of Infectious Disease Commons, Immunopathology Commons, Infectious Disease Commons, Virology Commons, Virus Diseases Commons
Comments
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.