Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?

Abstract

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19.

Methods: We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31^st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies.

Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73).

Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.

Keywords: Covid-19; meta-analysis; mortality; outcome prediction; risk factors.

Figure 1 -

PRISMA Flow Diagram

Figure 2 -

Risk of bias assessment

Figure 3a -

Pooled odds ratios among ICU vs. non ICU groups COPD = chronic obstructive pulmonary disease, ART = anti-retroviral therapy, NIV = non-invasive ventilation, OR = odds ratio, CI = Confidence Interval

Figure 3b -

Pooled odds ratios among mortality vs. survival groups COPD = chronic obstructive pulmonary disease, ART = anti-retroviral therapy, NIV = non-invasive ventilation, ECMO = extra corporal membrane oxygenation, OR = odds ratio, CI = Confidence Interval

Figure 4 -

Pooled median estimates of selected indicators along with their normal laboratory ranges among patients who died, patients who survived, ICU-admitted patients, and non-ICU admitted patients Normal range (grey) was used as stated in included publications. If different normal ranges are reported in included publications, we used the lowest and highest values. For Leukocytes and Lymphocytes upper range of the normal range is 11.0×10^9/L and 4.0×10^9/, respectively. CRP = C-reactive protein; LDH = Lactate dehydrogenase;