Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients

Chaudhary, Rahul; Garg, Jalaj; Houghton, Damon E.; Murad, M. Hassan; Kondur, Ashok; Chaudhary, Rohit; Wysokiński, Waldemar E.; McBane, Robert D.

doi:10.1016/j.mayocpiqo.2021.01.009

Cited by 61 publications

(76 citation statements)

References 111 publications

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“…Similarly, a recent metanalysis reported higher D-Dimer levels in patients with a more severe form of the disease (WMD 0.60, 0.49–0.71, I 2 = 83.85%). Interestingly, this association seems to be independent from race and ethnicity 55 .…”

Section: Discussionmentioning

confidence: 86%

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Polimeni

Leo

Spaccarotella

et al. 2021

Sci Rep

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Coronavirus disease 2019 (COVID-19) is a highly contagious disease that appeared in China in December 2019 and spread rapidly around the world. Several patients with severe COVID-19 infection can develop a coagulopathy according to the ISTH criteria for disseminated intravascular coagulopathy (DIC) with fulminant activation of coagulation, resulting in widespread microvascular thrombosis and consumption of coagulation factors. We conducted a meta-analysis in order to explore differences in coagulopathy indices in patients with severe and non-severe COVID-19. An electronic search was performed within PubMed, Google Scholar and Scopus electronic databases between December 2019 (first confirmed Covid-19 case) up to April 6th, 2020. The primary endpoint was the difference of D-dimer values between Non-Severe vs Severe disease and Survivors vs Non-Survivors. Furthermore, results on additional coagulation parameters (platelet count, prothrombin time, activated partial thromboplastin time) were also analyzed. The primary analysis showed that mean d-dimer was significantly lower in COVID-19 patients with non-severe disease than in those with severe (SMD − 2.15 [− 2.73 to − 1.56], I2 98%, P < 0.0001). Similarly, we found a lower mean d-dimer in Survivors compared to Non-Survivors (SMD − 2.91 [− 3.87 to − 1.96], I2 98%, P < 0.0001). Additional analysis of platelet count showed higher levels of mean PLT in Non-Severe patients than those observed in the Severe group (SMD 0.77 [0.32 to 1.22], I2 96%, P < 0.001). Of note, a similar result was observed even when Survivors were compared to Non-Survivors (SMD 1.84 [1.16 to 2.53], I2 97%, P < 0.0001). Interestingly, shorter mean PT was found in both Non-Severe (SMD − 1.34 [− 2.06 to − 0.62], I2 98%, P < 0.0002) and Survivors groups (SMD − 1.61 [− 2.69 to − 0.54], I2 98%, P < 0.003) compared to Severe and Non-Survivor patients. In conclusion, the results of the present meta-analysis demonstrate that Severe COVID-19 infection is associated with higher D-dimer values, lower platelet count and prolonged PT. This data suggests a possible role of disseminated intravascular coagulation in the pathogenesis of COVID-19 disease complications.

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Section: Discussionmentioning

confidence: 86%

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Polimeni

Leo

Spaccarotella

et al. 2021

Sci Rep

View full text Add to dashboard Cite

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“…Interestingly, the high density of NETs formation containing microthrombi enriched of neutrophils and platelets found during COVID-19 is blocked by therapeutic dose of heparin [37]. Many other biomarkers have been described as associated with the severity of COVID-19 or the risk of thrombosis, such as inflammatory markers (e.g., interleukin-6) or hormonal markers [38][39][40].…”

Section: Discussionmentioning

confidence: 99%

D-Dimer Level and Neutrophils Count as Predictive and Prognostic Factors of Pulmonary Embolism in Severe Non-ICU COVID-19 Patients

Thoreau

Galland

Delrue

et al. 2021

Viruses

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The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55–77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6–4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1–537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4–29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5–67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.

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“…Although we found no differences in gender, age or comorbidities between hospitalized versus outpatient management, a higher percentage of men 75%, required hospitalization compared with 57.8% of women; a point already observed for COVID-19 complications and viremia [8,18,19]. Additionally, 72% of patients with type 2 diabetes mellitus and 64.7% with hypertension were hospitalized.…”

Section: Discussionmentioning

confidence: 41%

“…Additionally, 72% of patients with type 2 diabetes mellitus and 64.7% with hypertension were hospitalized. These are commonly reported comorbidities in hospitalized COVID-19 patients [8,18,19]. Our analysis revealed that a low plasmatic level of HDL c and elevated Tg/HDL c ratio at the time of COVID-19 diagnosis is linked with requirement of hospitalization and illness severity as critical care patients showed the lowest HDL c concentration and highest Tg/HDL c ratio compared with severe and mild/asymptomatic COVID-19 patients.…”

Section: Discussionmentioning

confidence: 65%

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High triglyceride to HDL-cholesterol ratio as a biochemical marker of severe outcomes in COVID-19 patients

Alcántara-Alonso¹,

Molinar-Ramos

González-López³

et al. 2021

Clinical Nutrition ESPEN

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Background & aims Coronavirus disease 2019 (COVID-19) patients with severe complications have shown comorbidities with cardiovascular-disease, hypertension and type 2 diabetes mellitus; clinical disorders that share the common metabolic alterations of insulin resistance and dyslipidaemia. A high triglyceride to high density lipoprotein cholesterol (Tg/HDL c) ratio has been associated with reduced insulin sensitivity, metabolic syndrome and adverse cardiovascular events. Our aim in this study was to determine the association between different components of the lipid profile and particularly the Tg/HDL c ratio with severe complications like the requirement of invasive mechanical ventilation in COVID-19 patients. Methods We collected demographic, clinical and biochemical data to conduct a cohort study in 43 adult patients with confirmed COVID-19 diagnosis by quantitative polymerase chain reaction (qPCR) at baseline and in the subsequent 15 days. Patients were subjected to a very similar treatment scheme with the JAK1/2 inhibitor ruxolitinib. Descriptive statistics, variable association and logistic regression were applied to identify predictors of disease severity among elements and calculations from the lipid profile. Results Patients were aged 57±14 years; 55.8% were male from which 75% required hospitalization and 44.2% were female who 58% were hospitalized. The most common comorbidities were type 2 diabetes mellitus (58%) and hypertension (40%). Hospitalized and critical care patients showed lower HDL c blood levels and increased Tg/HDL c ratio than those with outpatient management and mild/asymptomatic COVID-19. Tg/HDL c ratio correlated with variables of disease severity such as lactate dehydrogenase (LDH) levels ( r =0.356; p <0.05); the National Early Warning Score 2 (NEWS 2)( r =0.495; p <0.01); quick sequential organ failure assessment (qSOFA)( r =0.538; p <0.001); increased need of oxygen support ( r =0.447; p <0.01) and requirement of mechanical ventilation ( r =0.378; p <0.05). Tg/HDL c ratio have a negative correlation with partial oxygen saturation/fraction of inspired oxygen (SaO2/FiO2) ratio ( r =-0.332; p <0.05). Linear regression analysis showed that Tg/HDL c ratio can predict increases in inflammatory factors like LDH ( p <0.01); ferritin ( p <0.01) and D-dimer ( p <0.001). Logistic regression model indicated that ≥ 7.45 Tg/HDL c ratio predicts requirement of invasive mechanical ventilation (OR 11.815, CI 1.832-76.186, p <0.01). Conclusions The Tg/HDLc ratio can be used...

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Thromboinflammatory Biomarkers in COVID-19: Systematic Review and Meta-analysis of 17,052 Patients

Cited by 61 publications

References 111 publications

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

Differences in coagulopathy indices in patients with severe versus non-severe COVID-19: a meta-analysis of 35 studies and 6427 patients

D-Dimer Level and Neutrophils Count as Predictive and Prognostic Factors of Pulmonary Embolism in Severe Non-ICU COVID-19 Patients

High triglyceride to HDL-cholesterol ratio as a biochemical marker of severe outcomes in COVID-19 patients

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