The search strategy generated 23,934 citations, but 14,393 articles were left after duplicates were removed (Figure 1). Of these, 14,031 studies were excluded after a review of the title and abstract. After reading the full text of the remaining 362 studies, we found that 87 studies, representing 1,349,931 COVID-19 patients, fulfilled the eligibility criteria. Among these, 12 studies were from the Americas (United States: 9, Canada: 1, Bolivia: 1, Mexico: 1), 61 studies from Asia (China: 51, South Korea: 4, Japan: 2, Singapore: 1, Iran: 1, India: 1, Iraq: 1), 12 studies from Europe (Italy: 5, France: 2, Norway: 1, Switzerland: 1, the United Kingdom: 2, multiple European countries merged: 1) , and 2 studies from Oceania (Australia: 2) (Table S2).
Proportion of severe COVID-19 patients
Of the 87 studies, 51 reported the severity rate of COVID-19 patients. The rate ranged from 26% in Asia, 20% in the Americas and Europe, and 3% in Oceania, with a pooled rate of 24% (95%CI 20‒30, I2 = 99.8%) (Figure 2, Table S3). The severity rate in Oceania was the lowest among all region studied (20%, 95%CI 12‒29). Twenty-six percent of male COVID-19 patients (95%CI 20‒30%) developed severe symptoms, compared to 19% of female patients (95%CI 14‒24%); this gender trend was seen in COVID-19 patients from all four regions (Figure 2, Appendix Table 3). SARS-CoV-2 infection in the low-latitude regions showed a tendency for a high prevalence of severe cases among both men and women (Figure 2, Table S3).
Sixty studies, comprising 1,418,194 COVID-19 patients, reported comorbidities. Hypertension was the most common comorbidity in the pooled COVID-19 patients, accounting for 26% (95%CI 22‒31%), followed by diabetes (13%, 95%CI 10‒15%), cardiovascular diseases without hypertension (8%, 95%CI 7‒10%), lung diseases (4%, 95%CI 4‒5%), and cancer (3%, 95%CI 2‒4%) (Figure 3). Geographically, the rate of comorbidities among COVID-19 patients in the Americas was significantly higher than that among patients in Asia, and the prevalence of cancer and lung diseases among COVID-19 patients in Europe was significantly higher than that among patients in Asia (Figure 3, Table S4). The proportion of comorbidities in COVID-19 patients showed an upward trend with the increase in latitude (Figure 3).
In the overall comparison of mild and severe cases, diabetes (odds ratio [OR] 2.70, 95%CI 1.96‒3.71) and cardiovascular diseases (OR 2.62, 95%CI 1.22‒5.64) were more closely related to severe cases. Hypertension (OR 2.08, 95%CI 1.26‒3.42) and cancer (OR 2.07, 95%CI 1.75‒2.57) were more closely related to severe cases than lung diseases (OR 1.79, 95%CI 1.15‒2.79) (Table S5).
In Asia, hypertension (OR 2.77, 95%CI 1.27‒4.07), cardiovascular disease (OR 2.91, 95%CI 2.14‒3.94), lung disease (OR 2.11, 95%CI 1.15‒3.88), and cancer (OR 2.68, 95%CI 2.15‒3.34) were more clearly correlated with the severity of COVID-19 than in other regions (Table 2). In contrast, diabetes (OR 3.41, 95%CI 1.71‒6.78) showed the strongest correlation with the severity of COVID-19 in the Americas. There was no significant correlation between comorbidities and COVID-19 severity among Europeans (Table 2). In latitude level comparisons, the low-latitude countries showed the strongest correlation between cancer and severe COVID-19 (OR 4.72, 95%CI 14.50‒4.89), and the rate of each comorbidity among COVID-19 patients was higher than that in the mid-latitude countries (Table S6).
Prevalence of severity and clinical manifestations
Fever (75%, 95%CI 67‒75%) and cough (58%, 95%CI 55‒62%) were the most common clinical manifestations in all COVID-19 patients, with the highest rate of fever in Asia (76%, 95%CI 70‒81%) and the highest rate of cough (69%, 95%CI 68‒70%) in Oceania (Figure 4). Dyspnea was more common in COVID-19 patients from the Americas (48%, 95%CI 33‒64%), Europe (49%, 95%CI 29‒64%), and high-latitude countries (69%, 95%CI 53‒82). In addition, European COVID-19 patients experienced significantly higher rates of loss of olfaction and taste (83%, 95%CI 60‒97%) and upper digestive tract symptoms, such as nausea (19%, 95%CI 17‒21%) and loss of appetite (35%, 95%CI 28‒42) than in other regions (Figure 4, Table S4).
In the overall comparison of common and severe COVID-19 patients, dyspnea (OR 6.49, 95%CI 3.60‒11.72), anorexia (OR 2.41, 95%CI 1.34‒4.33), abdominal pain (OR 2.22, 95%CI 1.17‒4.23), and fatigue (OR 1.83, 95%CI 1.48‒2.27) correlated strongly with illness severity (Table 3). Rhinitis (OR 0.84, 95%CI 0.47‒1.52), cough (OR 1.12, 95%CI 0.78‒1.62), diarrhea (OR 1.19, 95%CI 0.79‒1.78), and myalgia (OR 1.25, 95%CI 0.98‒1.60) were not significantly related to the severity of COVID-19 (Figure 5).
In Asia, dyspnea (OR 9.55, 95%CI 4.67‒19.54), fatigue (OR 1.83, 95%CI 1.48‒2.27) and anorexia (OR 2.41, 95%CI 1.34‒4.33) showed some association with COVID-19 severity (Table 4, Appendix Table 5). Dyspnea (OR 2.0, 95%CI 1.29‒3.08) and abdominal pain (OR 3.61, 95%CI 1.21‒10.72) were related to the severity of COVID-19 in the Americas (Figure 6, Table S7).
In COVID-19 patients from low-latitude countries, dyspnea (OR 2.46, 95%CI 1.04‒5.86) and diarrhea (OR 2.46, 95%CI 1.04‒5.86) were closely related to the disease severity, but in mid-latitude regions, patients manifested mainly with fatigue (OR 1.85, 95%CI 1.46‒2.35), dyspnea (OR 5.68, 95%CI 3.05‒10.61), abdominal pain (OR 2.88, 95%CI 1.45‒5.73), and anorexia (OR 2.16, 95%CI 1.14‒4.09) (Figure 7, Table S7).