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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.

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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

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