Haematological abnormalities and pharmacotherapy in severe acute respiratory syndrome corona virus 2
Keywords:COVID-19, Lymphocytopenia, Neutrophilia, 2-DG, COVAX
The first case of SARS-CoV-2 (severe acute respiratory syndrome corona virus 2) was reported in Wuhan, China at the end of year 2019. It shows flu-like symptoms, but anosmia, fatigue, persistent cough and loss of appetite, that collectively might spot individuals with COVID-19. The aim of writing this review was to gather the information about blood abnormalities and pharmacotherapy for COVID-19 as a resource for healthcare professionals. A blood workup as well as continuous tracking hematological changes could divulge the risks of disease progression. The indirect indicators such as C-reactive protein (CRP), D-dimer, albumin, ferritin and LDH levels which are used as markers to estimate the severity of COVID-19 infection and prognosis. The most common hematological findings include lymphocytopenia, neutrophilia, eosinopenia, mild thrombocytopenia and less frequently, thrombocytosis. Clinical management includes prophylactic and therapeutic measures. Supportive care including supplemental oxygen and mechanical ventilatory support as and when indicated. Several class of drugs like anti-malarial, anti-viral, anti-inflammatory drugs are being used for the treatment and prevention of COVID-19. The target for development of most of the vaccine for COVID-19 is S protein of the corona virus. Various vaccines available for use across the globe are COVAX, Covishield, Moderna, Johnson and Johnson, Sputnik V, Novavax, Sinopharm, SinoVac. Serial monitoring of hematological manifestations is recommended and the treating doctor should stay vigilant and consider proper screening. The therapeutic intention is to decrease viral load and pharmacological thrombo-prophylaxis in high risk patients.
Menni C, Valdes AM, Freidin MB, Sudre CH, Nguyen LH, Drew DA, et al. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nat Med. 2020;26(7):1037-40.
Mina A, Besien K, Platanias L. Hematological manifestations of COVID-19. Leukem Lymph. 2020;61(12):2790-8.
Liu X, Zhang R, He G. Hematological findings in coronavirus disease 2019: indications of progression of disease. Ann Hematol. 2020;99(7):1421-8.
Khartabil TA, Russcher H, Ven VDA, Rijke YB. A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients. Crit Rev Clin Lab Sci. 2020;57(6):415-31.
Debuc B, Smadja DM. Is COVID-19 a new hematologic disease? Stem Cell Rev Rep. 2021;17(1):4-8.
Sun S, Cai X, Wang H, He G, Lin Y, Lu B, et al. Abnormalities of peripheral blood system in patients with COVID-19 in Wenzhou, China. Clin Chim Acta. 2020;507:174-80.
Shetty S, Padijnayayveetil J, Tucker T, Stankowska D, Idell S. The fibrinolytic system and the regulation of lung epithelial cell proteolysis, signaling, and cellular viability. Am J Physiol Lung Cell Mol Physiol. 2008;295(6):967-75.
Thachil J. All those D-dimers in COVID-19. J Thromb Haemost. 2020;18(8):2075-6.
Saini RK, Saini N, Ram S, Soni SL, Suri V, Malhotra P, et al. COVID-19 associated variations in liver function parameters: a retrospective study. Postgrad Med J. 2020:1-7.
Burugu H, Kandi V, Kutikuppala L, Suvvari TK. Activities of serum ferritin and treatment outcomes among COVID-19 patients treated with vitamin c and dexamethasone: an uncontrolled single-center observational study. Cureus. 2020;12(11):11442.
Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg. 2003;237(3):319-34.
Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457-60.
Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875-9.
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74.
Deng Y, Liu W, Liu K, Fang Y, Shang J, Zhou L, et al. Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 in Wuhan, China: a retrospective study. Chin Med J (Engl). 2020;133(11):1261-7.
Lippi G, Plebani M. Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chim Acta. 2020;505:190-1.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-43.
Fathi N, Rezaei N. Lymphopenia in COVID-19: therapeutic opportunities. Cell Biol Int. 2020;44(9):1792-7.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
Tan L, Wang Q, Zhang D, Ding J, Huang Q, Tang Y, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduct Target Ther. 2020;5(1):33.
Bhandari S, Bhargava A, Sharma S, Keshwani P, Sharma R, Banerjee S. Clinical Profile of Covid-19 Infected Patients Admitted in a Tertiary Care Hospital in North India. J Assoc Physicians India. 2020;68(5):13-7.
Sharma D, Dayama A, Banerjee S, Bhandhari S, Chatterjee A, Chatterjee D. To study the role of absolute lymphocyte count and RDW in COVID-19 patients and their association with appearance of symptoms and severity. J Assoc Physicians India. 2020;68(8):39-42.
Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20.
Bao C, Tao X, Cui W, Yi B, Pan T, Young K, et al. SARS-CoV-2 induced thrombocytopenia as an important biomarker significantly correlated with abnormal coagulation function, increased intravascular blood clot risk and mortality in COVID-19 patients. Experiment Hematol Oncol. 2020;9:16.
Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020;99(6):1205-8.
Ahmed S, Jafri L, Hoodbhoy Z, Siddiqui I. Prognostic value of serum procalcitonin in COVID-19 patients: a systematic review. Indian J Crit Care Med. 2021;25(1):77-84.
Chen X, Yan L, Fei Y, Zhang C. Laboratory abnormalities and risk factors associated with in‐hospital death in patients with severe COVID‐19. J Clin Lab Anal. 2020;34(10):23467.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020;71(15):732-9.
World Health Organization. WHO clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. Available at: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infectionwhen-novel-coronavirus-nc. Accessed on 5th April 2021.
Gao J , Tian Z , Yang X . Breakthrough: chloroquine phosphate has shown apparent efficacy in the treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020;14(1):72-3.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.
Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A. Pharmacotherapy in COVID-19; A narrative review for emergency providers. Am J Emerg Med. 2020;38(7):1488-93.
Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med. 2020;382(24):2327-36.
US FDA. Fact sheet: Frequently asked questions on the emergency use authorization for veklury (remdesivir) for hospitalized COVID-19 patients. Available at: https://www.fda.gov/media/137574/download. Accessed on 5 April 2021.
Guo YR, Cao QD, Hong ZS, Tan Y, Chen S, Jin H, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak-an update on the status. Mil Med Res. 2020;7(1):11.
Agrawal U, Raju R, Udwadia ZF. Favipiravir: a new and emerging antiviral option in COVID-19. Med J Armed Forces India. 2020;76(4):370-6.
CDSCO. Fact sheet: Approval of favipiravir tablets to glenmark pharmaceuticals and remdesivir injection to Cipla Ltd and Hetero drugs. Available at: https://www.cdsco.gov.in/opencms/resources/UploadCDSCOWeb/2018/UploadPublic_NoticesFiles/NOTICE_REM_FAV.pdf. Accessed on 5 April 2021.
Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study. Engineering (Beijing). 2020;6(10):1192-8.
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA approved drug ivermectin inhibits replication of SARS-CoV2 in vitro. Antiviral Res. 2020;178:104787.
NIH. Fact sheet: COVID-19 treatment guidelines-ivermectin, 2021. Available at: https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/. Accessed on 5 April 2021.
Vora A, Arora VK, Behera D, Tripathy SK. White paper on Ivermectin as a potential therapy for COVID-19. Indian J Tuberc. 2020;67(3):448-51.
Isglobal. Fact sheet: Usefulness of Ivermectin in COVID-19 Illness. Available at: https://www.isglobal.org/documents/10179/6022921/Patel+et+al.+2020+version+2.pdf/adf390e0-7099-4c70-91d0-e0f7a0b69e14. Accessed on 5 April 2021.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704.
Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Hemost. 2020;18:1094-9.
Barrett CD, Moore HB, Moore EE, MacIntyre RC, Moore PK, Burke J, et al. Fibrinolytic therapy for refractory COVID-19 acute respiratory distress syndrome: Scientific rationale and review. Res Pract Thromb Haemost. 2020;4(4):524-31.
Dashti-Khavidaki S, Khalili H. Considerations for Statin Therapy in Patients with COVID-19. Pharmacotherapy. 2020;40(5):484-6.
WHO. Fact sheet: The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with COVID-19. Available at: https://www.who.int/news-room/commentaries/detail/the-use-of-non-steroidal-anti-inflammatory-drugs-(nsaids)-in-patients-with-covid-19. Accessed on 5 April 2021.
Pandit A, Bhalani N, Bhushan B, Koradiad P, Gargiya S, Bhomia V, et al. Efficacy and safety of pegylated interferon alfa-2b in moderate COVID-19: A phase II, randomized, controlled, open-label study. Int J Infect Dis. 2021;105:516-21.
DRDO’s Newspaper Clippings. Fact sheet: All you need to know about DRDO’s new anti-COVID-19 drug 2-DG. Available at: https://www.drdo.gov.in/sites/default/files/drdo-news-documents/NPC_11_May_2021.pdf. Accessed on 5 April 2021.
Chakraborty R, Parvez S. COVID-19: An overview of the current pharmacological interventions, vaccines, and clinical trials. Biochem Pharmacol. 2020;180:114184.
Luo P, Liu Y, Qiu L, Liu X, Liu D, Li J. Tocilizumab treatment in COVID-19: A single center experience. J Med Virol. 2020;92(7):814-8.
Tanne J. COVID-19: FDA approves use of convalescent plasma to treat critically ill patients. BMJ. 2020;368:1256.
Graham BS, Mascola JR, Fauci AS. Novel vaccine technologies: essential components of an adequate response to emerging viral diseases. JAMA. 2018;319(14):1431-2.
Lapipette. Fact sheet: COVID-19 vaccine cards. Available at: https://lapipette.com/vaccine_cards. Accessed on 5 April 2021.
Cutolo M, Paolino S, Smith V. Evidence for a protective role of vitamin D in COVID-19. RMD Open. 2020;6:001454.