Comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatment strategies, and outcomes in adult and pediatric patients with COVID-19: A systematic review and meta-analysis

Abstract

Introduction: Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a world-wide pandemic with an enormous medical and societal-economic toll. Thus, our aim was to gather all available information regarding comorbidities, clinical signs and symptoms, outcomes, laboratory findings, imaging features, and treatments in patients with coronavirus disease 2019 (COVID-19).

Methods: EMBASE, PubMed/Medline, Scopus, and Web of Science were searched for studies published in any language between December 1st, 2019 and March 28th, 2020. Original studies were included if the exposure of interest was an infection with SARS-CoV-2 or confirmed COVID-19. The primary outcome was the risk ratio of comorbidities, clinical signs and symptoms, laboratory findings, imaging features, treatments, outcomes, and complications associated with COVID-19 morbidity and mortality. We performed random-effects pairwise meta-analyses for proportions and relative risks, I², T², and Cochrane Q, sensitivity analyses, and assessed publication bias.

Results: 148 studies met the inclusion criteria for the systematic review and meta-analysis with 12'149 patients (5'739 female) and a median age of 47.0 [35.0-64.6] years. 617 patients died from COVID-19 and its complication. 297 patients were reported as asymptomatic. Older age (SMD: 1.25 [0.78-1.72]; p < 0.001), being male (RR = 1.32 [1.13-1.54], p = 0.005) and pre-existing comorbidity (RR = 1.69 [1.48-1.94]; p < 0.001) were identified as risk factors of in-hospital mortality. The heterogeneity between studies varied substantially (I²; range: 1.5-98.2%). Publication bias was only found in eight studies (Egger's test: p < 0.05).

Conclusions: Our meta-analyses revealed important risk factors that are associated with severity and mortality of COVID-19.

Keywords: COVID-19; Clinical characteristics; Comorbidities; Imaging features; Laboratory findings; Meta-analysis; Outcomes; SARS-CoV-2; Systematic review; Treatment.

Fig. 1

Flow-chart of the search strategy. A total of 148 studies were eligible for the literature review and the first part of the meta-analysis (i.e., prevalence). Nineteen studies were included in the second part of the meta-analysis (i.e., severity and mortality).

Fig. 2

Proportion of female and male patients in adult (A) and pediatric/neonatal cohort (B). All case studies/reports were pooled together for visualization (CS_adult, and CS_children [pediatric/neonatal]). The key to the study identifier can be found in Table 1 (adults) and Table 3 (children).

Fig. 3

Age of adult (A), pregnant (B), and pediatric/neonatal COVID-19 patients (C) included in eligible studies. Median age and interquartile ranges (IQR) are represented by the midpoints and error bars, respectively. The studies have been sorted by patients' median age in years. The size of the midpoint (circle, square, triangle) indicates the study sample size. The red line represents the pooled median age of the respective cohort. All adult case studies/reports (CS_adult) were pooled for the visualization reasons. The key to the study identifier can be found in Table 1 (adults), Table 2 (pregnant women), and Table 3 (children). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Comorbidities (A), clinical signs and symptoms (B), outcomes (C), and treatments administered (D) to adult COVID-19 patients. The colors indicated the proportion of patients (%, 0 = yellow, 100 = dark purple). Note: Missing values are colored in white. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

Age of non-severe (A), severe (B), survivor (C), and non-survivor (D) COVID-19 patients included in eligible studies. The median age and Interquartile ranges (IQR) are represented by the midpoints and error bars, respectively. The studies have been sorted by patients' median age in years. The size of the midpoint indicates the study sample size. The red line indicates the pooled median age of the respective cohort. The key to the study identifier can be found in Table 1. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 6

Relative risks of comorbidities (i.e., hypertension, diabetes mellitus, and COPD) and complications (i.e., ARDS) in patients with a severe COVID-19 disease progression. Funnel plots indicate the potential of publication bias. The key to the study identifier can be found in Table 1.

Fig. 7

Relative risks of comorbidity (i.e., any heart condition), treatment (i.e., mechanical ventilation), and complications (i.e., acute kidney injury and ARDS) in survivors and non-survivors. Funnel plots indicate the potential of publication bias. The key to the study identifier can be found in Table 1.