Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis

Abstract

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19.

Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently.

Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23-1.71), dyspnea (RR 2.55, 95%CI 1.88-2.46), diabetes (RR 1.59, 95%CI 1.41-1.78), hypertension (RR 1.90, 95%CI 1.69-2.15). Congestive heart failure (OR 4.76, 95%CI 1.34-16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57-27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19-7.39) and reticular pattern (OR 5.54, 95%CI 1.24-24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality.

Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

Fig 1. Stages of the analysis process, assessing inclusion and exclusion criteria that amounted to the articles addressed in this review.

Fig 2

Meta-analysis to assess risk of mortality for (A) smoking status. (B) hypertension. (C) diabetes mellitus. (D) COPD. (E) acute cardiac injury. (F) acute kidney injury. (G) bilateral lung involvement. (H) Lung consolidation. COPD = chronic obstructive pulmonary disease. !Shenzhen Third People’s Hospital, Shenzhen, China. #Tongji Hospital, Wuhan, China. $Wuhan Jinyintan Hospital, Wuhan, China. *Zhongnan Hospital of Wuhan University, Wuhan, China. %Tianyou Hospital, Wuhan, China. &Taizhou Public Health Medical Center, Zhejiang, China. +Chongqing Three Gorges Central Hospital, Chongqing, China. @Renmin Hospital of Wuhan University, Wuhan, China. ^General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, China.

Fig 3. Meta-analysis to assess odds of severe disease for (A) smoking status (B) hypertension (C) diabetes mellitus (D) COPD E. bilateral lung involvement (F) Lung consolidation.

COPD = chronic obstructive pulmonary disease. !Shenzhen Third People’s Hospital, Shenzhen, China. # Tongji Hospital, Wuhan, China. $Wuhan Jinyintan Hospital, Wuhan, China. *Zhongnan Hospital of Wuhan University, Wuhan, China. %Tianyou Hospital, Wuhan, China. &Central hospital of Wuhan, Wuhan. +Chongqing Three Gorges Central Hospital, Chongqing, China. @Renmin Hospital of Wuhan University, Wuhan, China. ^General Hospital of Central Theater Command of People’s Liberation Army, Wuhan, China.

Fig 4

Meta-regression plot showing the proportion increase in mortality among COVID-19 patients regressed against (A) mean age. (B) mean leukocyte count. (C) mean lymphocyte count. (D) mean serum albumin. (E) mean C-reactive protein. (F) mean D-dimer.

Fig 5

Meta-regression plot shows the proportion increase in severity among COVID-19 patients regressed against (A) mean age. (B) mean leukocyte count. (C) mean lymphocyte count. (D) mean serum albumin. (E) mean C-reactive protein. (F) mean D-dimer.