Background and AimsDiabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 . We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. MethodsSystematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. ResultsThere were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88,3.03], p<0.001; I 2 : 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p<0.001; I 2 : 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p<0.001; I 2 : 45%), ARDS (RR 4.64 [1.86,11.58], p=0.001; I 2 : 9%), and disease progression (RR 3.31 [1.08, 10.14], p=0.04; I 2 : 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p=0.003) and hypertension (p<0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) ConclusionDM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.

Objective: Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Methods: Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restrictedmaximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. Results: There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I 2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I 2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I 2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I 2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I 2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I 2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). Conclusion: This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.

Background: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. Methods: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. Results: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. Conclusion: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.

Background: We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. Results: A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I 2 : 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I 2 : 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I 2 : 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I 2 : 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I 2 : 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I 2 : 76%). Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. Conclusion: Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with

Objective: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. Results: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender ( p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). Conclusion: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.

Background: In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods: We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) N99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results: There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p b 0.001; I 2 : 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I 2 : 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p b 0.001; I 2 : 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I 2 : 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I 2 : 0%). Conclusion: Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

Background and aims The ongoing COVID-19 pandemic is disproportionately affecting patients with comorbidities. Therefore, thorough comorbidities assessment can help establish risk stratification of patients with COVID-19, upon hospital admission. Charlson Comorbidity Index (CCI) is a validated, simple, and readily applicable method of estimating the risk of death from comorbid disease and has been widely used as a predictor of long-term prognosis and survival. Methods We performed a systematic review and meta-analysis of CCI score and a composite of poor outcomes through several databases. Results Compared to a CCI score of 0, a CCI score of 1–2 and CCI score of ≥3 was prognostically associated with mortality and associated with a composite of poor outcomes. Per point increase of CCI score also increased mortality risk by 16%. Moreover, a higher mean CCI score also significantly associated with mortality and disease severity. Conclusion CCI score should be utilized for risk stratifications of hospitalized COVID-19 patients.

Highlights Obesity was associated with mortality and severity in patients with COVID-19. Dose–response meta-analysis demonstrate an increase of 5% risk for poor outcome for every 5 kg/mg 2 increase in body mass index. The relationship departed from linearity and became steeper from 30–35 kg/mg 2 onwards.