choc pate Review Artie INQUIRY. The Jour f Hath Care The Effects of the SARS-CoV-2 Virus on the yin '.0 Cardiovascular System and Coagulation Sesaren sitet cae BS iotrtroerssontonien State Leading to Cardiovascular Diseases: A tetueor conn Narrative Review (SAGE Rafiq A. Bhat, PhD', Syed Maqbool, DM, DNB, FNB?, Akanksha Rathi, MD’, ‘Syed Manzoor Ali, DM*, Yoosuf Ali Ashraf Muhammad Hussenbocus, MD® Xiao Wentao, MD', Yongsheng Qu, MD', You Zhang, MD', Yuxiao Sun, MD', Hai-Xia Fu, MD', Ling Yun Wang, MD‘, Atul Dwivedi, PhD’, Javaid Akhter Bhat, PhD®, Raja saqib Iqbal, MD’, Md Monowarul Islam, MD‘, Abhishek Tibrewal, MD'°, and Chuanyu Gao, PhD!!! Abstract “The novel coronavirus pandemic has led to morbidiy and mortalty throughout the world Unt! now, fis 2 highly veulene contagion sacking the respiratory system inhumans, especialy people wih chronic diseases and the elderly who aremostvulperabe- A major of affcted are thote suferng from carchovascuar and coronary diseases. In his review arte, an atempe has been made to dscus and thoroughly cevew the mode of herpes that alevate cardac compleations and compleations due to hyperceaguation in pasents infected with the SARS-CoV-2 virus, Present a host of thrombolyc drugs are in use like Prourokrase, Retelapse, RATNKPA and Urokérase. However, thrombolytic therapy, especially ven inravenousy is associated wih a serous rk of invaerail haemorrhage systemic haemorrhage, immunsioge complains, hypotension and myocardal rupure The elects of the SARS-CoV. vrs upon the cardiovasalar system and coagulation sate ofthe body are being dosely studied. In connection tothe same, cial prognass and compicatons of trombolvic therapy are being scrutized. tis noteworthy to mention that myocardial cxygen supphiderand mismatch, direct myocardial ce injury ard cate plaque ruptre ae te mulpe mecharisms responsible for acute coronary syndrome and eardac compleaons in Covi 9 infecion. However, ths review has lntaon as ama salable in ths context mite, seared and heterogenous that questions the reliably ofthe same. So, more mul-cetrc sues invong representative populstion, carried ou. meteuiusly, coud further asst in responding beter to cardiac completions among Covid-9 paens. ' Deparment ofnerverionl Caeolgy, Fava Central China Carshoracusr Hoepta Zhengzhou Uriversy,Zhergthou, People’ Repub of China: Henan Prova People's Hosp, Zhengrhou Univers, Zhengsou, Peoples Republi of Cine 2Deparmert of Cardology, Government Saperspcaty Horta Sriagi In Deparment of Communsty Medicine, Vadaneaietace of Media cancer, Pagar nda ‘sDepartnent of Cardology. Super Specalty Dison, Goverment Medal Calle, Sina, ina °Daparurert of Rheumatlgy ard Immunology, Naning Orum Tower Hospital Clin Collge of Narng Metical University, Nanjing. Chins ‘Departent of Cardolgy. The Fist Aflaced Hospalof Zhengzhou Universty, Zhengzhou, Peoples Republic of Cha “Department of Cincal and Basic Sciences, Meal Schaal of Hubs Pelytechrie Unversity, Habe, Chia ‘sate Key Laboratory of Crop Genes and Germpas Enhancement, Nang Agata Univers. Nan, People's Repubtc ef China "Deparment of Paedaees, Burs Hospal and Medel Research Cee, New Dal Inds "Deparment of Cemmunty Medi, lsieute of Bost and Epdemiley, Grgren nda "Henan Prowcal Key Laboratory for Conta of Coronary Heart Deas, Zherigiu, People's Republic of Chea Received 27 August 2021; revue 1S March 2022; revised manuscript accepted 21 March 2022 Corresponding Author: {Chiany Gao, Daparement of Cardiology Henan Provncl People's Hospital, Zhengthou Uriversy, Zhenghow 450003, People's Republic of Chia Enatt oy 6802 @163.com [Arbution NowConmercil 40 Lanse (hipslcreatweconimonsorghicenseiy-nl4.0) which permits nor-2 min per. Yes No Medium 352 0 Alteplace 100 me, 90 min Yer No il 7 sa RHINK4PA 16mg (5~I0s) projectile Yer No Minimum 8 6 intravenous injecten Urolénase 15 milion v, 30 min No No. Obvious Unknown Unknown Source: Orga are intracranial haemorthage, systemic haemorrhage, im- ‘munologic complications, hypotension and myocardial rupture. Theoretically, thromboembolism is also a risk but it is rarely come across in clinical practice. Similarly, re- perfusion archythmias, which are cardiac rhythm disturbances atthe time of reperfusion, also do not pose a significant risk to the lives of the patients on thrombolytic therapy. Systemic hhacmorthages are also uncomman, especially in the absence ‘of major vascular punctures, and the chances of fatal out- The risk with using streptokinase or agents with a streptokinase moiety, including anisteplase (an isolated plasminogen — streptokinase activator complex, APSAC), is the development of anaphylaxis which, again is rare, Con- trarily, hypotension is much more common in these pa tients” “However, most clinicians are worried about devastating intracranial haemorrhage, which occurs in 0.2 1% of the patients on thrombolytic therapy.” Clinicians should be wary of using thrombolysis late, as myocardial rupture is increasingly being recognised as an associated ‘outcome of the same, Clinical risks should always be weighed against the po- tential benefits and thus it is often seen that those at the highest risk are the ones who gain the most from the therapy. Critical Issues in Management of Cardiac Patients during Covid-19 Pandemic Im many parts of the world, hospital admissions have been greatly reduced, reducing the number of admissions from cardiac complaints by 75% in the worst hit areas.” On the other hand, lack of healtheare manpower andior fear of Covid-19 precludes the delivery of elficient healtheare ser- vices to cardiac patients in many regions.”” There isa need for 4 protocol indicating the feasibility of performing PCI pro- cedures on ACS patients, Keeping into consideration the safety of healthcare workers and welfare of the patient ‘Thrombolytic agents, though safe to use, have thei limita- tions in presence of a Covid infection. Clopidogrel and ti- ccagrelor showed interaction with anti-viral drags used to treat coronavirus infections in animal models, however, these claims are yet to be replicated in a randomised control twial.”"" Additionally, aspirin and NSAIDS can also be used without a threat of an adverse reaction in these patients.”” Critically ill ACS patients itrespective of their Covid-19 status should be sent for angiography with the intent to re- vascularize mechanically and for clinically stable patients too primary PCI remains the treatment of choice. The reperfusion strategies among STEMI patients having suspected Novel Coronavirus Pneumonia (NCP) has been depicted in detail in (Figure 1), Critical Issues in Management of Cardiac Complications in Covid-19 Patients Elevated troponin levels are sometimes (7%-27.8%) reported in patients with Covid-19 infections, and are associated with increased morbidity and mortality among these patients""*"° The pathogenesis for high troponin levels in ‘these patients is multi-factrial, however, common clinical conditions should be frst ruled out in these patients such as MI, arrhythmia, heart failure, renal failure, hypotension and hypoxemia,”* The widespread inflammation in the body of a Covid-19 patient might theoretically increase the risk of MI but there is no direct evidence available for this assumption, though, this is the case in other viral infections like influ: cenza.”* Just like high troponin levels, hypertension is also commonly seen to be co-existing in as many as 15%-35% of | Covid-19 patients.” There are two confounding factors that account for this observation ~ frst is the high prevalence of | hypertension in the population and second is the people admitted with Covidel9 are usually of advanced age.” There js a major knowledge gap about the role of hypertension as a risk factor for Covid-19 and it will take lange, representative, ‘population-based, prospective studies to fill this gap. Like- wise, there is a paucity of good epidemiological data re- porting the increased risk of a cardiac event during Covid-19 infection, and just one study reported an increased risk of stroke during the infection.”* As discussed earlier in this review, cytokine storm in Covid-19 may lead to a systemic inflammatory response and multi-organ failure, But though cardiovascular complications are recognised, the incidence of © sexed with OK ScannerBhat et a 7 _[ ence ommemounf tcl el - = " — “| ro _ — saerate| lon 1 os ar er ee ee ee oo a ae =e) Lo | [ES T oe Sees Be So bee Figure |. ST segment elevation myocar infarction reperfusion ereatment strategy for suspected Novel Coronavirus Pneumonia (NCP) patients during the Covi: 19 epidemic, Source: Original n STEM patient the course of ation ders if the patient receives first medical contact before or after 12 hours, irespecdve of suspicion of NCP. If the patents a suspected NCP patient and he receives medial are before 12 hours then contraindication to thrombalyss is asressd. the patent has contraindcatons then PC is danein isolation catheter lb andif there are no contraindicacions to thrombolytic therapy then onsite thrombolysis one. However. the patents presenslatr than | 2hours then emergency PCIis done after assessing the risks and benofits of the same, or conservative therapy sgvenand the patient iskept ina NCP CCU. ifthe patiet isa non-suspected NCP, presenting before 12 hours then reperfusion is done with the help of PCI within 90 ‘minutes. However, ifthe patents presents later chan Zhours then emergency PClis done afer assessing the risks and benefits ofthe same, ‘or conservative therapy is ven, First Medical Contact PCI: Percutaneous Coronary Intervention, ER: Emergency Room, CCU: Cardiac Care Unie cardiac arrhythmias in affected patients is infrequently re- ported among these patients, despite of many Covid-19 drugs having a pro-arthythmic potential. Even 0, the use of both (hydroxy)chloroquine and lopinavirrtonavir should be avoided in patients at increased risk of arrhythmias like the ones having a congenital or acquired long-QT syndrome, and there is a need to keep theit clectrolyte imbalance in check in order to timely detect hypokalemia.” The concomitant use of other QT-interval prolonging drugs should also be avoided.” Statins, however, have shown no deleterious effect on the cardiovascular system in Covid-19 infection, rather they may ‘be beneficial owing to their innate ability to regulate immune response through post-translational modification of intra- cellular signalling molecules."* Additionally, other COVID- 19-related effects on the heart, or massive pulmonary em- bolism remains elusive. Conclusions and Perspectives Despite of the low admission rates, cardiac illness still accounts for a large proportion of the morbidity and mortality of the population in both the developed and developing world. COVID-19 infection can lead to different cardiae complica: tions by way of different inflammatory mechanisms which can increase the morality, especially in patents with risk factors Indeed, there are various thrombolytic therapies available in the world today that can greatly improve the prognosis of patients with STEMI, but we should not downplay or un- derestimate complications these therapies present, like © sexed with OK ScannerINQUIRY intracranial haemorthage, systemic haemorrhage, immu- rnologic complications, hypotension and myocardial rupture. Hence, during this pandemic, fining a balance between risks relatedto the untimely treatment of STEMI patients and SARS- CoV-2 infection, control has become a global challenge. To ‘summarise, there isa dire need for more studies to explain the cardiac effects of Covid-19. It was also seen that the data available in this context is limited, scattered and heterogenous that questions the reliability ofthe same. So, more multi-centre studies involving representative population, carried out me- ticulously could futherassistinalleviationof the current crisis. Till then, the patients who are on cardio-protective therapies shouldcontinueas suchand patients developing cardiovascular ‘complications owing to Covid-19 should be put on tried and tested therapies if no contraindications are there. Declaration of conflicting interests ‘The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication ofthis article Funk e ‘The author(s) received no financial support for the research, a ‘horship, andlor publication of this ate Ethical Statement (Our study didnot require an ethical board approval because it isnot applicable ‘ORCID iD ‘Yoosuf Ali Ashraf Muhammad Hussenbocus © tpsorid org! (0000.0002-3650-260% References | World Heatth Organization. Cardiovascular diseases (CVD). Fact sheet No. 317. 2011. hipvww.who %420in/ media controlfctsheetsf31 T/enindex hil, Accessed October 10 2020, 2. Goldstein JA, Demetrou D, Grines CL etal. Multiple complex ‘coronary plagues in patients with acute myocardial infarction. 1N Eng J Med, 2000;343(13)915.922. 3. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCE/ AHA guideline for the management of ST-clevation myo. cardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Foree on Practice Guidelines. Circulation, 2013;127: 529-555, 4. Baral G, Rossini R, Musumeci G. Antplatelet therapy in STEMI undergoing primary PCI: when, which one and how long. Minerva Cardioangiol. 2018:66(4}-422-428, 5. Renttop KP, Blanke H, Karsch KR, et al. Acute myocar infarction: intracoronaty application of sitroglycerin and streptokinase. Clin Cardiol, 1979;2(5)354-363. 16. 20. 21 2. Carville SF, Henderson R, Gray H, The acute management of ‘ST-segmentlevaton myocardial infarction. Clin Med. 2015; 15(4)362-367, Woo PC, Huang ¥, Lau SK, eal. Coronavius genomics and bioinformatics analysis. Viruses. 2010;2-1804-1820. Drosten C, Gunther S, Preiser W, etal. Kdentifcation of a novel ‘coronavirus in patients with severe acute respiratory syndrome. 1N Bing J Med, 2003:348;1967-1976. ‘Zaki AM, van Bolcemen S, Bestebroct TM, etal. Isolation of novel coonavinis fa man with pneumonia Saud Arabia, 1N Bing J Med, 2012:367-1814-1820. Zh N, Zhang D, Wang W, etal. China novel coronavirus Investigating and research team. @ novel coronavius from ‘atients with pneumonia in China, 2019. N Engl J Med. 2 382(8):727-733 Wang D, Hu B, Hu C, etal. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirs-infected ‘pneumonia in Wuhan, Chia, JAMA. 2020:323(11):106 Huang C, Wang ¥, Li X, etal. Clinical features of| infected with 2019 novel coronavieas in Wohan, China, Lancet. 2020;395(10223):497-506. Libby P, Lescalzo J, Ridker PM, etal. Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the ‘week, J dm Coll Cano, 2018;72:2071-2081 Masher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med, 2019;380:171-176 Kwong JC, Schwartz KL, Campitelli MA. Acute myocardial infarction after Liboratory-confirmed infenza infection. N Engl J Med, 2018;378:2540-2541, ‘The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characterises of an ‘outbreak of 2019 novel coronavirus diseases (COVID-19): China. China CDC Weekly, 2020:2:113-122. ‘van Bohemen S, de Graaf SM, Lavber C, et a. Genomic characterization of a newly discovered coronavirus associated ‘with acute respiratory distess syndrome in humans, mBo 2012;3(6):<00473-12. Raj VS, Mow H, Smits SL, et sl. Dipeptidy! peptidase 4 is» functional receptor for the emerging human coronavius-EMC. ‘Nature, 2013:495(7440)251.254 Petlman S, Netland J. Coronavirus post SARS: update on replication and pathogenesis. Nat Rev Microbial. 2009;7(6): 439-450, Glowacka 1, Bertam S, Miller MA, et al, Evidence shat ‘TMPRSS? activates the severe acute respirory syndrome coronavins spike protein for membrane fusion and reduces ‘irl conto! by the humoral immune response. J Virol, 2011; 85(9):4122-4134 Bertram S, Glowacka 1, Miller MA, etal. Cleavage and ac- tivation ofthe severe acute respiratory syndrome coronavirus spike protein by human airway trypsin-ike protease. Virol 2011;85(24): 13363-13372. Wu F, Zhao S, Yu B, eal A new coronavins associated with Ihuman respiratory disease in China, Nate. 2020:579: 265-200. © sexed with OK ScannerBhat et a 23. Zhou P, Yang X, Wang X, tal. A pneumonia outbreak as- sociated with a new coronavirus of probable bat origin. Nature 2020;579:270-273, 24, XX, Chen P, Wang h etal Evolution ofthe novel eoronavinas from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sei. 2020,63(8) 457-460. 25. Bansal M. Cardiovascular disease and COVID-19, Diabetes ‘Metab Syndr. 2020:14(3}247-250, 26. ShiS, Qin M, Shen B, etal. Assocation of cardia injury with ‘mortality in hospitalized patients with COVID-19 in Wuhan, (China. JAMA Cardiol 2020:5:802-810. 27. Zhou F, Yu, Du R, et al. Clinical couse and risk factors for ‘mortality of adult inpatients with COVID-19 in Wuhan, China retrospective cohort study. Lancet. 2020;395(10229): ns4-1062 28. WuZ, MeGoogan JM. Characteristic of and important lessons fiom the Coronavirus Disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 eases from the Chinese centre for disease control and prevention, JAMA. 2020;323(13): 1239-1242 29. ‘Xiong TY, Redwood S, Prendergast B, etal. Coronaviuses and the cardiovascular system: acute and long-term implications. Eur Heart J. 2020:41(19}1 798-1800, 30. Frisoni P, Neri M, D'ExicoS, et al. Cytokine storm and hise topathological findings in 60 cases of COVID-19-related death From viral load research to immanohistochemical quantification of major players IL-1f, IL-6, IL-15 and TNF-a. Forensic Sei Med Pathol, 2021;18(1)120. 31. XZ, ShiL, Wang ¥, etal. Pathological ndings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respir Med. 2020;(8)420-422. 32. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cate diovascular system. Nat Rev Cardiol. 2020;17(8)259-260. 33. Clerkin KJ Fried JA, Raikhlkar J, etal. Coronavirus Disease 2019 (COVID-19) and cardiovascular disease. Cirelaton 2020;14120)-1648-1685. 34, Babapoor-Farokhran S, Gill D, Walker J, et al. Myocardial injury and COVID-19: possible mechanisms, Life Se. 2020; 253117723, 435. Schocahagen P, Tuzcu EM, Ellis SG, Plague vulnerability plague rupture, and acute cononary syndromes: (mul)-focal ‘manifestation of a systemic disease proces, Cireuarion, 2002; 106(7): 760-62. 36. Maiese A, Frat P, Del Duca F, et al, Myocardial pathology in COVID-10-ssociated cardine injury: a systematic review. hagnostis. 2021:11(9):1647 37. BegbieM, Notley C,Tilin, tal, The Factor VI acute phase response requites the participation of NFkappaB and C/EBP, Thrombtlaemost. 2000;84:216-222, 38. Mapro C, Mulvey JJ, Belin D, etal. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020;220:1-13 3. 40 4 2 8 45, 46, 0 4 # 50. si 2 83 st 3s Panigada M, Botti N, Taglabue P tal Hypercoagulbility ‘of COVID-I9 patients in Intensive Care Unit. A Report of Thrombo-clastogrphy findings and other parameters of he- mostasis J Thromh Haemost. 2020;18(17) 1738-1742, Ranucei M, Ballot A, Di Dedda U, etal. The procoagulant pattem of patients with COVID-I9 acate respiratory distress syndrome. J Thromb Haemost, 2020;18(7) 1747-1751, Covid 19 Resources, American Society of Haematology COVID-19 and VTE/Anticcagulation: Frequently Asked ‘Questions, _hiips/vww:hematology.orpiovid-19/covid-19- and-coagulopathy. Accessed April 20 2020. Connors JM, Levy JH, Thrombo-inflammation and the by- peteoagulabity of COVID-I9. J Thromb Haemost. 2020; 18(7:1559-1561 Helms J, Tacguard C, Severa F, eta, High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter Prospective cohort study. Iensine Care Med. 2020:46 1089-1098 Vin S, Huang M, LiD, etal, Difference of coagulation features between severe pneumonin induced by SARS-CoV? and non: SARS-CoV2J Thromb Thrombolysis. 2021:51-1 Maiese A, Manetii AC, La Russa R, etal Autopsy findings in ‘COVID-19-related deaths: literature review. Forensic Sei Med Pathol. 2021;17:279-296 Maiese A, Manetti AC, BosetiC, eta. SARS-CoV.2 and the brain: a review of the cutent knowledge on neuropathology in COVID.I9, Brain Pathol. 2021;31(6)e13018. ‘Tang N, LiD, Wang X, etal Abnormal coagulation parameters are associated with poor prognosis in patients with novel co ronavinus pneumonia, J Thromb Haemost. 2020;18:844-847 Anpsian A, Ota M. Exploring possile mechanisms for ‘COVID-19 induced thrombocytopenia: unanswered questions. J Thromb Haemost, 2020;18(6) 1514-1516 ‘Thachil J. The versatile heparin in COVID-I9. J Thromb Haomost,2020,18:1020-1022. Tang N, Bai H, Chen X, etal. Anticoagulant treatment is 35- sociated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020;18 1094-1090 Thomas W, Varley J, Johnston A, et al. Thrombotic compli- «ations of patents admitted to intensive care with COVID-19 at a teaching hospital inthe United Kingdom. Thvomb Res. 2020; 191:76-77, Bowles L, Paton S, Yartey N, etal. Lupus anticoagulant and abnormal coagulation tess inpatients with Covid-19. Engl J Med, 2020;383:288.200. Levi M, Toh CH, Thachil Jel. Guidelines forthe diagnosis and management of disseminated intravascular coagulation, fi J Haematol, 2009;145:24-33, Iba T, Levy JH, Levi M, etal. Coagulopathy of coronavinas disease 2019. Crit Care Med, 2020;48(9)-1358-1364 Kok FA, Kruip M, van der Meer NIM, etal Incidence of thrombotic complications in critically ill ICU patients with COVID.19. Thromb Res. 2020:191:145-147 © sexed with OK ScannerINQUIRY 56, 3. 58 59 60, 61 2 6 6s, Danchin N, Puymirat E, Steg PG, eal. FAST-ME 2005 in ‘vestgators. five-year survival in patints with STsegment- levation myocardial infarction according to modalities of reperfusion therapy: the French registry on acute STElevation and non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 (Cobort. Circulation, 2014; 129(16):1629-1636, ‘Welsh RC, Van de Wert F, Westerhout CM, etal, Outcomes oF a pharmacoinvasive strategy for successful versus failed fb nolysis and primary percutaneous intervention in acute myo- cardial infarction (fiom the Strategic Reperfusion Early after Myocardial Infarction [STREAM] study). Am J Cardiol. 2014; 446): 811-819, Franzosi MG, Santoro E, De Vita C, etl. Ten-year follw-up of | ‘the fist megatial testing thrombotic therapy in patents with acute myocar infrction: esas ofthe Gruppe Ialiano por lo Studio dell Sopravvivenza nel Infarto-I Study. Circulation. 1998,98(24).2659.2666. Danchin N, Blanchard D, Steg PG, ea. Impact of prehospital thrombolysis for acute myocardial infarction on I-year out ‘came results from the French Natonseide USIC 2000 Registry. Circulation. 20041 10(14): 1908-1915, YerasiC, Case BC, Forrestal BJ, eal. Treatment ofT-segment levaton myocardial infuction during COVID-19 pandemic. Cardiovasc Revase Med. 2020:21(8):1024-1029, Chinese Society of Cardiology of Chinese Medical Associ tion. 2019 Chinese Society af Cardiology (CSC) guidelines for the disgnosis and management of patients with ST-segment levation myocardial infarction [I], Chin J Cardiol, 2019; 47(10) 766-783, Zhao YY, Yang JG, Xu HB, et al. Association between the composite measures of hospital performance and in-hospital mortality for patients with acule STseyment elevation myo- ‘eardal infarction in china corelatonal analysis of mortality (CAML study) [J]. Chin Cire J. 20195345) 497-443, Zhang Y, Gao C, Duan G, et al. Survey on the early ve perfusion therapy status in patients wth ST-segment elevation ‘myocardial infarction hospitalized in tertiary and secondary hospitals in Henan province, Chin J Cardiol. 2018;43(10): S580 Xinyun L, You Z, Muwei L, etal EMcaey of thrombolytic therapy using reteplase in cases with acute ST-segment ele ‘ation myocardial infarction: esuts from multicenter clinical tal, Chin J Cardiol. 2016;449): 766-770. Lakshmanadoss U. Novel strategies in ischemic heart disease Intec, 2012:123-134, 66. 6. 6, ©, 1 2. na. 14 15. 16 n. 18 7, Kase CS, O'Neal AM, Fisher M, etal. Intracranial hae- rmorthage after use of tissue plasminogen activator for ‘coronary thrombolysis, Ann frtern Med. 1990;112:17-21 Stinivasan G, Bosehman C, Roth SI, etal. Unsuspected vas- cults and intracranial hemorrhage following thrombolysis. Clin Cardiol. 1997:20(1):84-86, Sloan M, Gore JM. Ischemic stoke and intracranial haemorhage following thrombolytic therapy for acute myocardial infarction: 3 risk-benofit analysis. ov J Cardiol. 1992:60:212- 38a De Rosa 8, Spaccarotella C, Basso C, et al. Reduction of hospitalizations for myocardial infarction in Healy in the ‘COVID-19 era, Eur Heurt J. 2020;41(22):2083-2088. ‘Tam CF, Cheung KS, Lam S, etal, Impact of coronavirus lisease 2019 (COVID-19) outbreak on STsegmen-elevation ‘myocardial infarction care in Hong Kong, China, Cire Cardiovase Qual Outcomes, 2020,13(4) 006631 ‘Chu CM, Cheng VC. Hung IF, eal. Role of lopinairrtonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004;59(3) 252-256 Cao B, Wang Y, Wen D, etal. til of LopinavirRitonavir in adults hospitalized with severe Covid-19.N Engl J Med. 2020, '382(19) 1787-1799. World Health Organisation, The use of now-steroidalantiin- flammatory drugs (NSAIDs) in Patients with COVID-19. -ntps: hw. wo itinews-roomicommentaresdetailthe-use- ‘of-non-steroidal-ant-nftammatory-drugs-(osaids) in-patients: swithcovid-19, Accessed May 18 2020, Gupea AK, ood H, Addison D, eal Curent pespectves on ‘oro disease 2019 and cacovascur disease white paper by the JAHA Ears J Am Heart soe, 2000;(12}<017013, Yang X. Vu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARSCoV-2 pneumonia in Wuhan, China: a single-centered, retospectve, observational study Lancet Respir Med. 2020:8:475-481 Kwong JC, Schwartz KL, Campitelli MA, etal. Acute myo- cardial infarction afferIaboratory-confrmed influenza infec- tion N Eng! J Med. 2018:378:345-253 ‘Guan W5, NiZV, Hu ¥, eta. Clinical chances of coronavins disease 2019 in Chins. N Engl F Med. 2020382:1708-1720, Mao L, Jin H, Wang M, etal. Neurologic manifestations of | ‘hospitalized patients with coronavirus disease 2019 in Wuhan, China, JAMA Neurol, 2020;77.683-690. Wu CC. Postma PG, Arbelo E, etal. SARS-CoV:2, COVID- 19, and inherited arrhythmia syndromes. Heart Rhythm 2020; 17456-1462, © sexed with OK Scanner