Context.— An abundance of clinical reports focused on specific laboratory parameters have been reported on coronavirus disease 19 (COVID-19), but a systematic analysis synthesizing these findings has not been performed. Objective.— To review and summarize the current available literature on the predictive role of various biomarkers in COVID-19 patients. Data sources.— A literature search was performed using databases including PubMed, medRxiv, and bioRxiv. A total of 72 papers were reviewed, including 54 peer-reviewed papers and 18 non-peer-reviewed preprints. Conclusions.— Although the markers are considered nonspecific, acute-phase reactants, including C-reactive protein (CRP), ferritin, serum amyloid A (SAA), and procalcitonin, were reported as sensitive markers of acute COVID-19 disease. Significantly elevated white blood cell count; marked lymphopenia; decreased CD3, CD4, or CD8 T-lymphocyte counts; high neutrophil count; thrombocytopenia; and markedly elevated inflammatory biomarkers were associated with severe disease and the risk of developing sepsis with rapid progression. Trends observed by serial laboratory measurements during hospitalization, including progressive decrease of lymphocyte count, thrombocytopenia, elevated CRP, procalcitonin, increased liver enzymes, decreased renal function, and coagulation derangements, were more common in critically ill patient groups and associated with a high incidence of clinical complications. Elevated interleukin 6 level and markedly increased SAA were most often reported in severely and critically ill patients. Indicators of systemic inflammation, such as neutrophil to lymphocyte ratio, systemic immune-inflammation index, or COVID-19 Severity Score, may be used to predict disease severity, outcome, and mortality. Interpretation of the data reported in the studies reviewed here is limited because of the study design (mostly retrospective), limited sample size, and a lack of defined clinical criteria.

/pdf/predicting-disease-severity-and-outcome-in-covid-19-patients-3wkhiy0aqa.pdf

Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers.

Thromboinflammation in COVID-19 acute lung injury.

The serological testing of anti-SARS-CoV-2 immunoglobulin G (IgG) and/or IgM is widely used in the diagnosis of COVID-19 However, its diagnostic efficacy remains unclear In this study, we searched for diagnostic studies from the Web of Science, PubMed, Embase, CNKI, and Wanfang databases to calculate the pooled diagnostic accuracy measures using bivariate random-effects model meta-analysis As a result, 22 from a total of 1613 articles, including 2282 patients with SARS-CoV-2 and 1485 healthy persons or patients without SARS-CoV-2, were selected for a meta-analysis Pooled sensitivity, specificity, and area under curve of the summary receiver operator curve (SROC) were: (a) 085 (95% confidence interval [CI]: 079-090), 099 (95% CI: 098-100), and 099 (95% CI: 097-099) for anti-SARS-CoV-2 IgG and (b) 074 (95% CI: 065-081), 099 (95% CI: 097-100), and 095 (95% CI: 093-097) for IgM A subgroup analysis among detection methods indicated the sensitivity of IgG and IgM using enzyme-linked immunosorbent assay were slightly lower than those using gold immunochromatography assay (GICA) and chemiluminescence immunoassay (P > 05) These results showed that the detection of anti-SARS-CoV-2 IgG and IgM had high diagnostic efficiency to assist the diagnosis of SARS-CoV-2 infection And, GICA might be used as the preferred method for its accuracy and simplicity

Diagnostic efficacy of anti-SARS-CoV-2 IgG/IgM test for COVID-19: A meta-analysis.

Background Accumulating evidence indicates toward an association between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and procoagulatory state in blood. Thromboelastographic investigations are useful point-of-care devices to assess coagulation and fibrinolysis. Objectives We investigated the hypothesis that the procoagulatory state in COVID-19 patients is associated with impaired fibrinolysis system. Methods Altogether, 29 COVID-19 patients admitted to normal wards or to the intensive care unit (ICU) were included in this descriptive study. Whole blood samples were investigated by thromboelastography to assess coagulation and fibrinolysis. Additionally, standard routine coagulation testing and immunoassays for factors of fibrinolysis as plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), plasminogen activity and α2-antiplasmin (A2AP) were performed. Results A significantly increased lysis resistance and a significantly longer time of lysis after adding tissue plasminogen activator were observed in blood samples from ICU COVID-19 patients compared with healthy controls (maximal lysis: 3.25 ± 0.56 vs. 6.20 ± 0.89%, p = 0.0127; lysis time: 365.7 ± 44.6 vs. 193.2 ± 16.3 seconds, p = 0.0014). PAI-1 activity was significantly higher in plasma samples of ICU COVID-19 patients (PAI-1: 4.92 ± 0.91 vs. 1.28 ± 0.33 U/mL, p = 0.001). A positive correlation between the activity of PAI-1 and lysis time of the formed clot (r = 0.70, p = 0.0006) was observed. Conclusion Our data suggest that severe SARS-CoV-2 infection is associated with impaired fibrinolytic activity in blood, where fibrinolytic inhibitors are elevated leading to an increased resistance to clot lysis. Thromboelastography could offer a tool to investigate the contribution of the fibrinolytic status to the procoagulatory condition in COVID-19.

/pdf/severe-sars-cov-2-infection-inhibits-fibrinolysis-leading-to-22w0d52zip.pdf

Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19.

http://www.thelancet.com/article/S2352396422000019/pdf

Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 patient lungs

Objective To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. Methods We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). Result The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What’s more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. Conclusion Most COVID-19 patients with inordinate coagulation systems, dynamic monitoring of coagulation parameters might be a key in the control of COVID-19 death.

/pdf/the-values-of-coagulation-function-in-covid-19-patients-3bk6lfs17f.pdf

The values of coagulation function in COVID-19 patients.

Objective: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. 
Methods: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), 2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT).
Result: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What9s more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. 
Conclusion: The coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.

/pdf/the-values-of-coagulation-function-in-covid-19-patients-2kpc3whw21.pdf

Tengfei Bao

Papers

The values of coagulation function in COVID-19 patients.

The values of coagulation function in COVID-19 patients

Clinical application value of immunochromatography in detecting SARS-CoV-2 IgM and IgG antibodies