Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis

Hiroshi Hoshijima; Takahiro Mihara; Hiroyuki Seki; Shunsuke Hyuga; Norifumi Kuratani; Toshiya Shiga

doi:10.1371/journal.pone.0250909

Incidence of long-term post-acute sequelae of SARS-CoV-2 infection related to pain and other symptoms: A systematic review and meta-analysis

PLoS One. 2023 Nov 29;18(11):e0250909. doi: 10.1371/journal.pone.0250909. eCollection 2023.

Authors

Hiroshi Hoshijima¹, Takahiro Mihara², Hiroyuki Seki³, Shunsuke Hyuga⁴, Norifumi Kuratani⁵, Toshiya Shiga⁶

Affiliations

¹ Division of Dento-oral Anesthesiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan.
² Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
³ Department of Anesthesiology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
⁴ Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
⁵ Department of Anesthesiology, Saitama Children's Medical Center, Saitama, Saitama, Japan.
⁶ Department of Anesthesiology and Pain Medicine, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Chiba, Japan.

Abstract

Background: Persistent symptoms are reported in patients who survive the initial stage of COVID-19, often referred to as "long COVID" or "post-acute sequelae of SARS-CoV-2 infection" (PASC); however, evidence on their incidence is still lacking, and symptoms relevant to pain are yet to be assessed.

Methods: A literature search was performed using the electronic databases PubMed, EMBASE, Scopus, and CHINAL and preprint servers MedRχiv and BioRχiv through January 15, 2021. The primary outcome was pain-related symptoms such as headache or myalgia. Secondary outcomes were symptoms relevant to pain (depression or muscle weakness) and symptoms frequently reported (anosmia and dyspnea). Incidence rates of symptoms were pooled using inverse variance methods with a DerSimonian-Laird random-effects model. The source of heterogeneity was explored using meta-regression, with follow-up period, age and sex as covariates.

Results: In total, 38 studies including 19,460 patients were eligible. Eight pain-related symptoms and 26 other symptoms were identified. The highest pooled incidence among pain-related symptoms was chest pain (17%, 95% confidence interval [CI], 11%-24%), followed by headache (16%, 95% CI, 9%-27%), arthralgia (13%, 95% CI, 7%-24%), neuralgia (12%, 95% CI, 3%-38%) and abdominal pain (11%, 95% CI, 7%-16%). The highest pooled incidence among other symptoms was fatigue (44%, 95% CI, 32%-57%), followed by insomnia (27%, 95% CI, 10%-55%), dyspnea (26%, 95% CI, 17%-38%), weakness (25%, 95% CI, 8%-56%) and anosmia (19%, 95% CI, 13%-27%). Substantial heterogeneity was identified (I2, 50-100%). Meta-regression analyses partially accounted for the source of heterogeneity, and yet, 53% of the symptoms remained unexplained.

Conclusions: The current meta-analysis may provide a complete picture of incidence in PASC. It remains unclear, however, whether post-COVID symptoms progress or regress over time or to what extent PASC are associated with age or sex.

Copyright: © 2023 Hoshijima et al. 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 author and source are credited.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Anosmia
COVID-19* / complications
COVID-19* / epidemiology
Dyspnea / epidemiology
Headache / epidemiology
Headache / etiology
Humans
Incidence
Post-Acute COVID-19 Syndrome
SARS-CoV-2

Grants and funding

This study was supported by International University of Health and Welfare with funding for TS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.