Clinical manifestations of human monkeypox infection: a systematic review and meta-analysis

Little is known about the ongoing monkeypox (mpox) outbreak, and the clinical features of mpox in patients worldwide have not been rigorously analysed. Thus, we aimed to investigate the clinical features associated with mpox infection and understand the pathophysiology and characteristics of the disease. For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and the Cochrane Database of Systematic Reviews for articles published till 16 September 2022. We used a random effects model to calculate the pooled prevalence and 95% confidence interval (CI). We used the I2 statistic to assess heterogeneity, Egger's test to assess publication bias, 95% prediction interval to determine the level of uncertainty, and the Newcastle-Ottawa Scale and Joanna Briggs Institute quality assessment tool to assess the risk of bias. Twenty-six relevant articles from 19 countries across 5 continents were included, and data on 5472 mpox patients with 18 unique features were analysed. The pooled prevalence of clinical features of mpox were rash (85.7%, 95% CI: 68.3–94.3; k = 21), chills (77.8%, 95% CI: 70.5–83.7; k = 3), and fever (62.3%, 95% CI: 51.3–71.6; k = 25), lymphadenopathy (58.6%, 95% CI: 47.2–69.2; k = 21), lethargy or exhaustion (46.8%, 95% CI: 30.7–63.5; k = 14), pruritus (40.6%, 95% CI: 28.5–54.0; k = 5), myalgia (36.0%, 95% CI: 24.3–49.7; k = 16), headache (34.6%, 95% CI: 23.4–47.8; k = 17), skin ulcer (31.1%, 95% CI: 18.6–47.1; k = 7), abdomen symptom (24.2%, 95% CI: 17.9–31.9; k = 11), pharyngitis (23.0%, 95% CI: 12.7–37.9; k = 14), respiratory symptom (19.5%, 95% CI: 6.8–44.6; k = 6), nausea or vomiting (13.0%, 95% CI: 4.6–31.9; k = 3), scrotal or penile oedema (10.7%, 95% CI: 6.3–17.7; k = 4), conjunctivitis (7.1%, 95% CI: 2.4–18.9; k = 6), and death (0.9%, 95% CI: 0.4–2.0; k = 26). This is the first international and comprehensive study to examine all clinical presentations of human mpox infection. Our systematic review proposes a comprehensive understanding of the current mpox outbreak and may serve as key data for future studies on the pathological mechanisms and epidemiology of mpox infections.