Risk of mortality in COVID-19 patients: a meta- and network analysis

Abstract

Understanding the most relevant hematological/biochemical characteristics, pre-existing health conditions and complications in survivors and non-survivor will aid in predicting COVID-19 patient mortality, as well as intensive care unit (ICU) referral and death. A literature review was conducted for COVID-19 mortality in PubMed, Scopus, and various preprint servers (bioRxiv, medRxiv and SSRN), with 97 observational studies and preprints, consisting of survivor and non-survivor sub-populations. This meta/network analysis comprised 19,014 COVID-19 patients, consisting of 14,359 survivors and 4655 non-survivors. Meta and network analyses were performed using META-MAR V2.7.0 and PAST software. The study revealed that non-survivors of COVID-19 had elevated levels of gamma-glutamyl transferase and creatinine, as well as a higher number of neutrophils. Non-survivors had fewer lymphocytes and platelets, as well as lower hemoglobin and albumin concentrations. Age, hypertension, and cerebrovascular disease were shown to be the most influential risk factors among non-survivors. The most common complication among non-survivors was heart failure, followed by septic shock and respiratory failure. Platelet counts, creatinine, aspartate aminotransferase, albumin, and blood urea nitrogen levels were all linked to ICU admission. Hemoglobin levels preferred non-ICU patients. Lower levels of hemoglobin, lymphocytes, and albumin were associated with increased mortality in ICU patients. This meta-analysis showed that inexpensive and fast biochemical and hematological tests, as well as pre-existing conditions and complications, can be used to estimate the risk of mortality in COVID-19 patients.

Figure 1

PRISMA flow diagram of the studies identified, screened, reviewed, and included in the meta-analysis.

Figure 2

Correlation-based network analysis. The Pearson correlation threshold of 50% was used to show the network of all variables (a–c). More precisely, the Pearson correlation thresholds of 72% and 93% (d, e) were respectively selected to define the connection between survivors, non-survivors and blood parameters. The Pearson correlation thresholds of 79% and 97% were respectively chosen to assess the relationship between survivors, non-survivors and (f) risk factors or (g) complications. Circles of the network indicate the blood parameters (a, d, e), risk factors (b, f) and complications (c, g). The size of the node reflects the degree of connectivity of the node and the edges display the relationship between the two variables. The thicker edges reveal higher correlations between variables. Nodes with more links are close to each other. Network analysis and visualization was carried out using PAST and Fruchterman-Reingold algorithm or Circular algorithm as a force-directed layout algorithm. Abbreviations in panels (a), (d), and (e): Alb, albumin; HBG, hemoglobin; NEU, neutrophil; PLT, platelet; LYM, lymphocyte; WBC, white blood cells, PCT, procalcitonin; GGT, gamma-glutamyl transferase; CRP, C-reactive protein, CK, creatine kinase; Creat: creatinine, BUN, blood urea nitrogen; Bili, total bilirubin; AST, aspartate aminotransferase; ALT, alanine aminotransferase. Abbreviations in panels (b) and (f): BMI, body mass index; Time to H, time from symptoms appearance to hospitalization; Renal, renal disease; Cereb, cerebrovascular disease; Liver, liver disease; COPD, chronic obstructive pulmonary disease; Cardio, cardiovascular disease. Abbreviations in panels (c) and (g): Fail, failure; Res, respiratory; Liver, liver dysfunction; Sec, secondary; Kidney, acute kidney injury; Cardiac, acute kidney injury.

Figure 3

Forest plot of blood parameters in survivors and non-survivors of COVID-19. The Standardized Mean Difference (SMD) and the 95% confidence intervals (CIs) were used to define the effect size of different blood indices in survivors and non-survivors. S, survivors; GGT, gamma-glutamyl transferase; NEU, neutrophil; WBC, white blood cell; CRP, C-reactive protein; AST, aspartate aminotransferase; CK, creatine kinase; IL-6, interleukin-6; BUN, blood urea nitrogen; ALT, alanine aminotransferase; PCT, procalcitonin; HBG, hemoglobin; PLT, platelet; LYM, lymphocyte; n, population size.

Figure 4

Forest plot of pre-existing health conditions in survivors and non-survivors of COVID-19. The Standardized Mean Difference (SMD) and the 95% confidence intervals (CIs) were used to define the prevalence of various risk factors and complications for survivors and non-survivors of COVID-19. Time to hospital, time from symptoms appearance to hospitalization; Cerebrovascular, cerebrovascular disease; Cardiovascular, cardiovascular disease; Renal, renal disease; Liver, liver disease; BMI, body mass index; COPD, chronic obstructive pulmonary disease; S, survivors; n, population size.

Figure 5

Forest plot of complications in survivors and non-survivors of COVID-19. The Standardized Mean Difference (SMD) and the 95% confidence intervals (CIs) were used to define the prevalence of various risk factors and complications for survivors and non-survivors of COVID-19. ARDS, acute respiratory distress syndrome; S, survivors; n, population size.

Figure 6

Forest plot of (a) pre-existing health issues and (b) blood parameters in COVID-19-infected ICU and non-ICU patients. The Standardized Mean Difference (SMD) and the 95% confidence intervals (CIs) were used to define the effect size. n, population size; D, diseases; COPD, chronic obstructive pulmonary disease; S, survivors; NS, non-survivors; ALT, alanine aminotransferase; WBC, white blood cell; PCT, procalcitonin; BUN, blood urea nitrogen; NEU, neutrophil; AST, aspartate aminotransferase; CRP, C-reactive protein; PLT, platelet; LYM, lymphocyte; HBG, hemoglobin.

Figure 7

Forest plot of (a) pre-existing health conditions and (b) blood parameters in survivors and non-survivors of COVID-19 patients admitted to the intensive care unit (ICU). The Standardized Mean Difference (SMD) and the 95% confidence intervals (CIs) were used to define the effect size. n, population size; D, diseases; COPD, chronic obstructive pulmonary disease; S, survivors; NS, non-survivors; ALT, alanine aminotransferase; WBC, white blood cell; PCT, procalcitonin; BUN, blood urea nitrogen; NEU, neutrophil; AST, aspartate aminotransferase; CRP, C-reactive protein; PLT, platelet; LYM, lymphocyte; HBG, hemoglobin.