IntroductionCoagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity.MethodsElectronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies.ResultsOverall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias.ConclusionsThe hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.
Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID-19 and its comorbidities have not been established. Methods. In total, 312 patients with long COVID-19 from 21 primary care centers were included in the study. At the six-month follow-up, their lung function was assessed by computerized tomography (CT) and spirometry, whereas cardiac function was assessed by electrocardiogram (ECG), Holter ECG, echocardiography, 24 h blood pressure monitoring, and a six-minute walk test (6MWT). Results. Of the 312 persons investigated, significantly higher systolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP were revealed in participants with hypertension or type 2 diabetes. Left ventricular diastolic dysfunction was more frequently present in patients with hypertension. The most common registered CT abnormalities were fibrotic changes (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Among the tested biochemical parameters, three associations were found in long COVID-19 patients with hypertension but not diabetes: increased hemoglobin, fibrinogen, and ferritin. Nine patients had persisting IgM antibodies to SARS-CoV-2. Conclusions. We demonstrated a strong association between signs of cardiac dysfunction and lung fibrotic changes with comorbidities in a cohort of long COVID-19 subjects.
Introduction. Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the early hemostatic parameters in retrospective studies in association with severity of infection. Methods. Ovid, PubMed, Web of Sciences, and Google Scholar were searched for research articles that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference with 95% CI for each of five coagulation parameters (D-dimers, fibrinogen, prothrombin time, platelets count, activated partial thromboplastin time). Two authors independently extracted data and assessed study quality. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger test by linear regression. Results. Overall, 41 original studies (17601 patients) on SARS-CoV2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group (SMD 0.6985 with 95%CI [0.5155; 0.8815]); SMD 0.661with 95%CI [0.3387; 0.9833]; SMD 0.2683 with 95%CI [0.1357; 0.4009]; SMD 0.284 with 95%CI [0.1472; 0.4208]). In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 (SMD -0.1684 with 95%CI [-0.2826; -0.0542]). Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias. Conclusions. The standard coagulation laboratory parameters with exception of platelets counts are significantly elevated in patients with severe COVID-19. However, fibrinolysis shutdown requires evaluation outside conventional coagulation tests and analysis of additional specific markers related to clotting formation and PLT characteristics. We hypothesize that a proportion and parameters of immature reticulated platelets may serve as additional biomarkers for prediction of adverse events.
Background. Long COVID-19 symptoms appeared in many COVID-19 survivors. However, the prevalence and symptoms associated with long COVID and its comorbidities have not been established. Methods. Between May and September 2020 we included 312 patients with post-COVID-19 from 21 primary care centers if they had any persistent symptoms for at least three months from the first onset of the disease. On the 6 months follow up, their lung function was assessed by CT and spirometry, whereas cardiac function was assessed by electrocardiogram (ECG), Holter ECG, Echocardiography, and 24-hour blood pressure monitoring. A six-minute test (6MWT) was conducted on 308 participants during the follow-up visit. All participants were given a questionnaire with items on demographic information, current complaints, comorbidities, and medications, and Chalder Fatigue Scale (CFS) questionnaire. Statistical analysis was done using R vs. 4.1.2. Two-group comparison of continuous variables was performed using a T-test for normally distributed data, and the Mann-Whitney Wilcoxon test, ANOVA, and Kruskal-Wallis tests were applied for multiple comparisons following with Tukey and Dunn tests as post-hoc methods. Hochberg p-value adjustment was used to reduce the false discovery rate during multiple comparisons. Categorical variables were analyzed with Fishers Exact test. Results. Of 312 persons investigated, there was no significant gender difference between post-COVID-19 clinical manifestations except for memory dysfunction and anxiety, more prevalent among female participants. Chalder Fatigue Score was predominant in female participants (243, 78%). 39 (12.5%) participants reported having type 2 diabetes mellitus, and 158 (50.64%) had hypertension. Among the tested parameters, those positively correlated with comorbid conditions include age, BMI, D-dimers, NT-proBNP, C-reactive protein, neutrophils, fasting glucose, and HbA1c; hypertension also shows three associations that were not found in patients when examining the role of diabetes: increased hemoglobin, fibrinogen, and ferritin. 24-hour blood pressure monitoring revealed significantly higher systolic and diastolic blood pressure, left ventricular hypertrophy, and elevated NT-proBNP in participants with hypertension and subjects with type 2 diabetes. Left ventricular diastolic dysfunction is more frequently present in patients with hypertension. Chest CT was conducted on 227 (72.8%) participants 5.8+/-0.9 months after the onset of COVID-19. The most common registered CT abnormality was chronic bronchitis (198, 87.2%), followed by fibrotic changes in (83, 36.6%) and mediastinal lymphadenopathy (23, 10.1%). Immunological test results showed that SARS-CoV19 IgG antibodies were present in 241 subjects (77.2%), and SARS-CoV19 IgM antibodies were present in 9 subjects (2.88%). Conclusions. Our study provides valuable clues for long-term post-sequelae in a cohort of the Long COVID-19 subjects. We demonstrated a strong association of signs of cardiac dysfunction, lung fibrotic changes, increased hemoglobin, fibrinogen, and ferritin with hypertension but not with other comorbidities. Our results are of importance for understanding the Long Covid-19 syndrome.
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