Abstract:

The patho-physiology of COVID19 is still not clear. This study investigated the status of coagulation, LDH activity, and inflammation in SARS-CoV-2 infected patients. One hundred and thirty-four newly diagnosed COVID19 infected patients (age ranged65-82years) attending Mullingar Regional Hospital, Mullingar, Republic of Ireland, volunteered to participate in this study. They all presented with a pulmonary disorder, pyrexia, vomiting, body pains, etc. SARS-CoV-2 confirmatory test was done with RT-PCR molecular test using Cepheid Genexpert System. The data of another 121 plasma samples of apparently normal, non-COVID19 infected individuals taken before the emergence of COVID19 served as controls. Levels of blood platelets was determined in the participants using Siemen ADVIA 2120 Haematological System, and plasma D-dimer was determined in the participants using Star Max-Stago–Automatic Coagulation Analyzer LDH activity, plasma ferritin, and C-reactive protein (CRP) were determined in the participants using Beckman AU680-Chemistry Analyser. SARS-CoV-2 –infected patients showed significantly (p<0.001) higher levels of D-dimer (1522.95+1395.45ng/ml), CRP (125.3+116.4mg/l), ferritin (488.5+514.9pg/l), and LDH activity (574.4+446.7iu/l) compared to controls (78.8+18.1ng/ml, 2.4+1.7mg/l, 61.3+58.2pg/l, 304.1+76.6iu/l respectively). The blood platelet count did not show significant (p>0.05) change in the COVID19 patients (252.2 x 10⁹+101 x 10⁹) compared to controls (256.4 x 10⁹+63.2 x 10⁹). Elevated LDH activity could indicate tissue breakdown in the SARS-Cov-2 infected patients. Hyper-coagulation and inflammation are imminent in the COVID19 patients. Adjuvant anticoagulant and anti-inflammatory therapies may be useful as part of therapeutic regimen in the SARS-CoV-2 infected patients.

Keywords: COVID19, Coagulopathy, CRP and ferritin, LDH.

References:

Hinojosa-Velasco A, Bobadilla-Montes de Oca VP, García-Sosa LE, Mendoza-Durán JD, Pérez-Méndez MJ, Eduardo Dávila-González, Dolores G Ramírez-Hernández, Jaime García-Mena, Zárate-Segura P, Reyes-Ruiz JM, Bastida-González F., 2020. A Case Report of Newborn Infant with Severe COVID-19 in Mexico: Detection of SARS-CoV-2 in Human Breast Milk and Stool. Int J Infect Dis. 26; S1201-9712(20)30684-6.

DOI: 10.1016/j.ijid.2020.08.055. Online ahead of print.

[2] Guo Y , Qing-Dong Cao, Zhong-Si Hong, Yuan-Yang Tan, Shou-Deng Chen, Hong-Jun Jin, Kai-Sen Tan, De-Yun Wang, Yan Jinn 2020. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 13;7(1):11. doi: 10.1186/s40779-020-00240-0.

[3] Singhal T. 2020. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 87(4):281-286. doi: 10.1007/s12098-020-03263-6. Epub 2020.

[4] Boermeester MA, van Leeuwen PAM, Coyle SM, et al., 1995. Interleukin-1 receptor blockade in patients with sepsis syndrome: evidence that interleukin-1 contributes to the release of interleukin-6, elastase phospholipase A2, and to the activation of the complement, coagulation, and fibrinolytic systems, Arch Surg, vol. 130 (pg. 739-48).

[5] Ur A and Verma K. 2020. Cytokine Storm in Covid19: A Neural Hypothesis ACS Chemical Neuroscience. 11 (13), 1868-1870.

[6] Gaertner F, Massberg S., 2016. Blood coagulation in immunothrombosis‐At the frontline of intravascular immunity. Semin Immunol. 28: 561– 9.

[7] Antoniak S, Nigel Mackman., 2014. Multiple roles of the coagulation protease cascade during virus infection. Bood. 123 (17): 2605–2613. https://doi.org/10.1182/blood-2013-09-526277.

[8] Collard C.D., Vakeva A., Morrissey M.A., Agah A., Rollins S.A., Reenstra W.R., Buras J.A., Meri S., Stahl G.L. 2000. Complement activation after oxidative stress: role of the lectin complement pathway. Am. J. Pathol. 156:1549–1556.

[9] Antoniak S, Owens AP, Baunacke M, et al., 2013. PAR-1 contributes to the innate immune response during viral infection. J Clin Invest. 123:3; 1310-1322.

[10] Grover SP, Mackman N. 2018. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol. 38: 709– 25.

[11] Drake TA, Morrissey JH, Edgington TS. 1989. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 134: 1087– 97.

[12] Herpers BL, Endeman H, de Jong BA, de Jongh BM, Grutters JC, Biesma DH, van Velzen-Blad H 2009. “Acute-phase responsiveness of mannose-binding lectin in community-acquired pneumonia is highly dependent upon MBL2 genotypes”. Clin Exp Immunol. 156 (3): 488–94. doi:10.1111/j.1365-2249.2009. 03929.x. PMC 2691978. PMID 19438602.

[13] Feelders RA et al. 1998. Regulation of iron metabolism in the acute phase response: interferon g tumour necrosis factors a induce hypoferraemia, ferritin production, and a decrease in circulating transferrin receptors in cancer patients. European Journal of Clinical Investigation, 28:520–527.

[14] Chen G, Di Wu, Wei Guo, Yong Cao, Da Huang, Hongwu Wang, Tao Wang, Xiaoyun Zhang, Huilong Chen, Haijing Yu, Xiaoping Zhang, Minxia Zhang, Shiji Wu, Jianxin Song, Tao Chen, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning., 2020. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 1;130(5):2620-2629. DOI: 10.1172/JCI137244.

[15] Rambaldi A, Giuseppe Gritti, Maria Caterina Micò, Marco Frigeni, Gianmaria Borleri , Anna Salvi, Francesco Landi, Chiara Pavoni, Aurelio Sonzogni, Andrea Gianatti, Francesca Binda, Stefano Fagiuoli, Fabiano Di Marco, Luca Lorini, Giuseppe Remuzzi, Steve Whitaker, Gregory Demopulos. 2020. Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab. Immunobiology. 225(6):152001. doi: 10.1016/j.imbio. 152001. Epub 2020 Aug 9.

[16] Pagana KD, Pagana TJ, Pagana TN. 2019. Mosby’s Diagnostic & Laboratory Test Reference. 14th ed. St. Louis, Mo: Elsevier.

[17] Rostami M, Mansouritorghabeh H., 2020. D-dimer level in COVID-19 infection: a systematic review. Expert Rev Hematol. 13(11):1265-1275. DOI: 10.1080/17474086. 2020. 1831383. Epub 2020 Oct 12.

[18] Al-Samkari H, Rebecca S Karp Leaf, Walter H Dzik, Jonathan C T Carlson, Annemarie E Fogerty, Anem Waheed, Katayoon Goodarzi, Pavan K Bendapudi, Larissa Bornikova, Shruti Gupta, David E Leaf, David J Kuter, Rachel P Rosovsky., 2020. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 23; 136 (4):489-500. DOI: 10.1182/blood.2020006520.

[19] Bousquet G, Falgarone G, Deutsch D, Derolez S, Lopez-Sublet M, Goudot F, Amari K, Uzunhan Y, Bouchaud O, and Pamoukdjian F. 2020. ADL-dependency, D-Dimers, LDH, and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19. Aging (Albany NY). 30; 12(12): 11306–11313.

[20] Watkins LR, Milligan ED, Maier SF., 2003. Glial proinflammatory cytokines mediate exaggerated pain states: implications for clinical pain. Adv Exp Med Biol. 521:1–21. [PubMed].

[21] Xiang-Hua Y, et al., 2020. severe acute respiratory syndrome and venous thromboembolism in multiple organs. Am. J. respire. Crit. Care Med. 182, 436-437.

[22] Rienhoff HY Jr., 1990. Molecular and cellular biology of serum amyloid A. Molecular Biology and Medicine. 7: 287-298.

[23] Birgegård G, Hällgren R, Killander A, Venge P, Wide. 1979. Serum ferritin during infection. A longitudinal study in renal transplant patients. L.Acta Med Scand. 205 (7):641-5.

[24] Gómez-Pastora J, Weigand M, Kim J, Wu X, Strayer J, Palmer AF, Zborowski M, Yazer M, Chalmers JJ., 2020. Hyperferritinemia in critically ill COVID-19 patients - Is ferritin the product of inflammation or a pathogenic mediator? Clin Chim Acta. 2020 Oct; 509:249-251. DOI: 10.1016/j.cca. 06.033. Epub 2020 Jun 21.

[25] Assandri R, Buscarini E, Canetta C, Scartabellati A, Viganò G, Montanelli A., 2020. Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room. Arch Med Res. 51 (6):598-599. DOI: 10.1016/j.arcmed.2020.05.011.

[26] Guan WJ, Ni ZY, Hu Y, et al. 2020. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 382: 1708–20.

[27] Feld J , Douglas Tremblay , Santiago Thibaud , Alaina Kessler , Leonard Naymagon . 2020. Ferritin levels in patients with COVID-19: A poor predictor of mortality and hemophagocytic lymphohistiocytosis. Int J Lab Hematol. 42 (6):773-779. DOI: 10.1111/ijlh.13309. Epub 2020 Aug 13.

[28] Schumann G, Bonora R, Ceriotti F, Clerc-Renaud P, Ferrero CA, Férard G, Franck PF, Gella FJ, Hoelzel W, Jørgensen PJ, Kanno T, Kessner A, Klauke R, Kristiansen N, Lessinger JM, Linsinger TP, Misaki H, Panteghini M, Pauwels J, Schimmel HG, Vialle A, Weidemann G, Siekmann L. 2002. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. Part 3. Reference procedure for the measurement of catalytic concentration of lactate dehydrogenase. Clin Chem Lab Med. 40(6):643-8.

[29] Li X, Xu S, Yu M, Wang K, Tao Y, Zhou Y, Shi J, Zhou M, Wu B, Yang Z, Zhang C, Yue J, Zhang Z, Renz H, Liu X, Xie J, Xie M, Zhao J., 2020. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol. 146(1):110-118.

[30] Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 28; 395(10229):1054-1062. (PubMed).

[31] Tang N et al. 2020. Anticoagulant treatment is associated with decreased mortality in severe
coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost.

http://doi.org/10.1111/jth.14817.

[32] Yang W., Lee H.W., Hellinga H., Yang J.J., 2002. Structural analysis, identification, and design of calcium-binding sites in proteins. Proteins. 47:344–356.

[33] Manne BK, Denorme F, Middleton EA, et al., 2020. Platelet gene expression and function in patients with COVID-19. Blood. 136 (11):1317-1329.

[34] Hottz ED, Azevedo-Quintanilha IG, Palhinha L, et al., 2020. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood. 136(11):1330-1341. Google Scholar.