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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. Restricted-maximum 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.

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.

Several comorbidities have been associated with an increased risk of severity and mortality in coronavirus disease 2019 (COVID-19), including hypertension, diabetes, cerebrovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease. In this systematic review and meta-analysis, we attempted to investigate the association between heart failure (HF) and poor outcome in patients with COVID-19. We performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, “Heart failure” and “COVID-19”. The outcome of interest was mortality and poor prognosis (defined by incidence of severe COVID-19 infection, admission to ICU, and use of ventilator) in patients with preexisting heart failure with coronavirus disease. We identified 204 potential articles from our search, and 22 duplicates were removed. After screening of the titles and abstracts of the remaining 182 articles we identified 92 potentially relevant articles. We excluded 74 studies due to the following reasons: four studies were systematic reviews, two studies were meta-analyses, three articles were literature reviews, and 65 articles did not report on the outcome of interest. Finally, we included the remaining 18 studies in our qualitative synthesis and meta-analysis. There were 21,640 patients from 18 studies. HF was associated with hospitalization in COVID19 HR was 2.37 [1.48, 3.79; p < 0.001], high heterogeneity [I2, 82%; p < 0.001]. HF was associated with a poor outcome demonstrated by an OR of 2.86 [2.07; 3.95; p < 0.001] high heterogeneity [I2, 80%; p < 0.001]. Patient with preexisting HF was associated with higher mortality OR of 3.46 [2.52, 4.75; p < 0.001] moderately high heterogeneity [I2, 77%; p < 0.001]. Patients with heart failure are at increased risk for hospitalization, poor outcome, and death from COVID-19. A significant difference in mortality between patients with and without heart failure was observed, patients with heart failure having a higher mortality. •Individuals with preexisting cardiovascular diseases are associated with poor outcomes with COVID 19.•Decreased circulatory and physiological reserves in heart failure, are linked to a more severe course of the disease.•Patients with Heart Failure are at increased risk for poor outcomes such as hospitalization, and death from COVID-19.•Patients with heart failure have higher mortality rates compared to those without.

Background This systematic review and meta-analysis aimed to synthesize the latest evidence on the efficacy and safety of tranexamic acid (TXA) on traumatic brain injury (TBI). Methods We performed a systematic literature search on topics that compared intravenous TXA to placebo in patients with TBI up until January 2020 from several electronic databases. Results There were 30.522 patients from 7 studies. Meta-analysis showed that TXA was associated with reduced mortality (RR 0.92 [0.88, 0.97], p  = 0.002; I 2 : 0%) and hemorrhagic expansion (RR 0.79 [0.64, 0.97], p  = 0.03; I 2 : 0%). Both TXA and control group has a similar need for neurosurgical intervention ( p  = 0.87) and unfavourable Glasgow Outcome Scale (GOS) ( p  = 0.59). The rate for vascular occlusive events ( p  = 0.09), and its deep vein thrombosis subgroup ( p  = 0.23), pulmonary embolism subgroup ( p  = 1), stroke subgroup ( p  = 0.38), and myocardial infarction subgroup ( p  = 0.15) were similar in both groups. Subgroup analysis on RCTs with low risk of bias showed that TXA was associated with reduced mortality and hemorrhagic expansion. TXA was associated with reduced vascular occlusive events (RR 0.85 [0.73, 0.99], p  = 0.04; I 2 : 4%). GRADE was performed for the RCT with low risk of bias subgroup, it showed a high certainty of evidence for lower mortality, less hemorrhage expansion, and similar need for neurosurgical intervention in TXA group compared to placebo group. Conclusion TXA was associated with reduced mortality and hemorrhagic expansion but similar need for neurosurgical intervention and unfavorable GOS. Vascular occlusive events were slightly lower in TXA group on subgroup analysis of RCTs with low risk of bias.

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. 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) >99th 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. 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 < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 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; I2: 0%). Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19. •Cardiac injury is associated with higher mortality in patients with COVID-19.•Cardiac injury is associated with higher need for ICU care and risk of severe COVID-19.•Level of highly-sensitive cardiac troponin I was higher in patients with secondary outcomes.

Background: Abnormalities in hematologic, biochemical, and immunologic biomarkers have been shown to be associated with severity and mortality in Coronavirus Disease 2019 (COVID-19). Therefore, early evaluation and monitoring of both liver and kidney functions, as well as hematologic parameters, are pivotal to forecast the progression of COVID-19. Objectives: In this study, we performed a systematic review and meta-analysis to investigate the association between several complications, including acute kidney injury (AKI), acute liver injury (ALI), and coagulopathy, with poor outcomes in COVID-19. Design: Systematic review and meta-analysis Setting: Observational studies reporting AKI, ALI, and coagulopathy along with the outcomes of clinically validated death, severe COVID-19, or intensive care unit (ICU) care were included in this study. The exclusion criteria were abstract-only publications, review articles, commentaries, letters, case reports, non-English language articles, and studies that did not report key exposures or outcomes of interest. Patients: Adult patients diagnosed with COVID-19. Measurements: Data extracted included author, year, study design, age, sex, cardiovascular diseases, hypertension, diabetes mellitus, respiratory comorbidities, chronic kidney disease, mortality, severe COVID-19, and need for ICU care. Methods: We performed a systematic literature search from PubMed, SCOPUS, EuropePMC, and the Cochrane Central Database. AKI and ALI follow the definition of the included studies. Coagulopathy refers to the coagulopathy or disseminated intravascular coagulation defined in the included studies. The outcome of interest was a composite of mortality, need for ICU care, and severe COVID-19. We used random-effects models regardless of heterogeneity to calculate risk ratios (RRs) for dichotomous variables. Heterogeneity was assessed using I2. Random effects meta-regression was conducted for comorbidities and the analysis was performed for one covariate at a time. Results: There were 3615 patients from 15 studies. The mean Newcastle-Ottawa scale of the included studies was 7.3 ± 1.2. The AKI was associated with an increased the composite outcome (RR: 10.55 [7.68, 14.50], P < .001; I2: 0%). Subgroup analysis showed that AKI was associated with increased mortality (RR: 13.38 [8.15, 21.95], P < .001; I2: 24%), severe COVID-19 (RR: 8.12 [4.43, 14.86], P < .001; I2: 0%), and the need for ICU care (RR: 5.90 [1.32, 26.35], P = .02; I2: 0%). The ALI was associated with increased mortality (RR: 4.02 [1.51, 10.68], P = .005; I2: 88%) in COVID-19. Mortality was higher in COVID-19 with coagulopathy (RR: 7.55 [3.24, 17.59], P < .001; I2: 69%). The AKI was associated with the composite outcome and was not influenced by age (P = .182), sex (P = .104), hypertension (P = .788), cardiovascular diseases (P = .068), diabetes (P = .097), respiratory comorbidity (P = .762), and chronic kidney disease (P = .77). Limitations: There are several limitations of this study. Many of these studies did not define the extent of AKI (grade), which may affect the outcome. Acute liver injury and coagulopathy were not defined in most of the studies. The definition of severe COVID-19 differed across studies. Several articles included in the study were published at preprint servers and are not yet peer-reviewed. Most of the studies were from China; thus, some patients might overlap across the reports. Most of the included studies were retrospective in design. Conclusions: This meta-analysis showed that the presence of AKI, ALI, and coagulopathy was associated with poor outcomes in patients with COVID-19.

BackgroundThe evidence for subperiosteal drainage (SPD) versus subdural drainage (SDD) in chronic subdural hematoma (CSDH) remains controversial, and most surgeons prefer to use SDD over SPD. We aim to assess the latest evidence on the use of SPD compared to SDD in patients with CSDH undergoing burr hole evacuation.MethodsWe performed a systematic literature search on topics that assesses the use of SPD compared to SDD in patients with CSDH up until November 2019 from PubMed, EuropePMC, Cochrane Central Database, ScienceDirect, ProQuest, and ClinicalTrials.gov. The primary outcome was recurrent CSDH, and the secondary outcomes were mortality, surgical morbidities, and modified Rankin Score (mRS).ResultsThere were a total of 3241 subjects from 10 studies. SPD was shown to reduce recurrent CSDH (OR 0.66 [0.52, 0.84], p < 0.001; I2: 17%, p = 0.30) compared to SDD. Recurrent CSDH was lower in SPD group in subgroup analysis at 3-months (OR 0.63 [0.49, 0.81]; I2: 68%, p = 0.04) and 6-months (OR 0.66 [0.51, 0.85], p = 0.001; I2: 77%, p = 0.01) follow-up. However, there was no difference in CSDH recurrence upon subgroup analysis of RCTs. Similar mortality was demonstrated between SPD and SDD group (p = 0.13). The occurrence of parenchymal injury/new neurological deficit was significantly lower in SPD group (OR 0.26 [0.14, 0.51], p < 0.001; I2: 49%, p = 0.08). The rate of seizure, (p = 0.57), postoperative bleeding (p = 0.29), and infection (p = 0.25) were shown to be similar in both SPD and SDD group. Overall, the rate of surgical morbidity was significantly lower in SPD group (OR 0.61 [0.44, 0.85], p = 0.003; I2: 16%, p = 0.25). mRS at the end of follow-up was similar in SPD and SDD group (p = 0.12).ConclusionSPD was associated with less CSDH recurrence, but similar rate of mortality, seizures, postoperative bleeding, and infections compared to SDD. The rate of parenchymal injury/new neurological deficit was lower in the SPD group.

In this systematic review and dose–response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1 960 731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case–control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, P non-linearity = 0·140) were associated with lower risk of glioma. Dose–response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, P non-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.