Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 May 12:12:657363.
doi: 10.3389/fimmu.2021.657363. eCollection 2021.

Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis

Rafaela Pires da Silva  1 , João Ismael Budelon Gonçalves  2 , Rafael Fernandes Zanin  3 , Felipe Barreto Schuch  4 , Ana Paula Duarte de Souza  2
Affiliations
Meta-Analysis

Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis

Rafaela Pires da Silva et al. Front Immunol. .

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resulting in a range of clinical manifestations and outcomes. Laboratory and immunological alterations have been considered as potential markers of disease severity and clinical evolution. Type I interferons (IFN-I), mainly represented by IFN-α and β, are a group of cytokines with an important function in antiviral responses and have played a complex role in COVID-19. Some studies have demonstrated that IFN-I levels and interferon response is elevated in mild cases, while other studies have noted this in severe cases. The involvement of IFN-I on the pathogenesis and outcomes of SARS-CoV-2 infection remains unclear. In this study, we summarize the available evidence of the association of plasma protein levels of type I IFN with the severity of COVID-19.

Methods: The PRISMA checklist guided the reporting of the data. A systematic search of the MEDLINE (PubMed), EMBASE, and Web of Science databases was performed up to March of 2021, looking for articles that evaluated plasma protein levels of IFN-I in mild, severe, or critical COVID-19 patients. Comparative meta-analyses with random effects were performed to compare the standardized mean differences in plasma protein levels of IFN-I of mild versus severe and mild versus critical patients. Meta-regressions were performed to test the moderating role of age, sex, time that the IFN-I was measured, and limit of detection of the assay used in the difference between the means.

Results: There was no significant difference in plasma levels of IFN-α when comparing between mild and severe patients (SMD = -0.236, 95% CI -0.645 to 0.173, p = 0.258, I2 = 82.11), nor when comparing between patients mild and critical (SMD = 0.203, 95% CI -0.363 to 0.770, p = 0.481, I2 = 64.06). However, there was a significant difference between healthy individuals and patients with mild disease (SMD = 0.447, 95% CI 0.085 to 0.810, p = 0.016, I2 = 62.89).

Conclusions: Peripheral IFN-α cannot be used as a severity marker as it does not determine the clinical status presented by COVID-19 patients.

Keywords: COVID-19; IFN-α; biomarker; severity; type I interferon.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of article selection.
Figure 2
Figure 2
Comparison of plasma IFN-α concentration between mild and severe patients.
Figure 3
Figure 3
Comparison of plasma IFN-α concentration between mild and critical patients.
Figure 4
Figure 4
Comparison of plasma IFN-α concentration between mild patients and healthy individuals.
Figure 5
Figure 5
Comparison of plasma IFN-α concentration between severe patients and healthy individuals and.
See this image and copyright information in PMC

References

    1. World Health Organization . Who Coronavirus Disease (Covid-19) Dashboard (2020). Available at: https://covid19.who.int/ (Accessed April 09, 2021).
    1. García LF. Immune Response, Inflammation, and the Clinical Spectrum of COVID-19. Front Immunol (2020) 11:144. 10.3389/fimmu.2020.0144 - DOI - PMC - PubMed
    1. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med (2020) 382:13. 10.1056/NEJMoa2001316 - DOI - PMC - PubMed
    1. Xu XW, Jiang XG, Xu KJ, Ying LJ, Ma CL, Li SB, et al. Clinical Findings in a Group of Patients Infected With the 2019 Novel Coronavirus (SARS-Cov-2) Outside of Wuhan, China: Retrospective Case Series. BMJ (2020) 368:606. 10.1136/bmj.m606 - DOI - PMC - PubMed
    1. Zhang JJ, Dong X, Cao YY, Yuan YD, Yan YB, Yan YQ, et al. Clinical Characteristics of 140 Patients Infected With SARS-CoV-2 in Wuhan, China. Allergy: Eur J Allergy Clin Immunol (2020) 75:7. 10.1111/all.14238 - DOI - PubMed

Publication types