COVID-19: Cardiology Perspective
Michael DiVita
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorMeshe Chonde
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorMegan Kamath
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorDarko Vucicevic
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorAshley M. Fan
Department of Pharmaceutical Services, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorArnold S. Baas
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorJeffrey J. Hsu
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Division of Cardiology, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA
Search for more papers by this authorMichael DiVita
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorMeshe Chonde
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorMegan Kamath
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorDarko Vucicevic
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorAshley M. Fan
Department of Pharmaceutical Services, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorArnold S. Baas
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Search for more papers by this authorJeffrey J. Hsu
Division of Cardiology, Department of Medicine, UCLA Health, Los Angeles, CA, USA
Division of Cardiology, Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA
Search for more papers by this authorAli Gholamrezanezhad MD
Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
Search for more papers by this authorMichael P. Dube MD
Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
Search for more papers by this authorSummary
Coronavirus disease 2019 (COVID-19) most commonly presents primarily with infectious respiratory symptoms, such as fever, shortness of breath, and cough. Yet a variety of cardiovascular manifestations have been observed in infected patients as well, both in the acute phase of the illness and as part of the long-term sequelae of symptoms experienced by some. Cardiovascular involvement in COVID-19 may present in an assortment of ways, such as ischemic or inflammatory myocardial injury, thrombosis, arrhythmias, and dysautonomia. This chapter will review the epidemiology, mechanisms of action, manifestations, and management considerations of cardiovascular diseases associated with COVID-19.
References
- Wang , D. , Hu , B. , Hu , C. et al. ( 2020 ). Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China . JAMA 323 : 1061 – 1069 .
- Zheng , Y.-Y. , Ma , Y.-T. , Zhang , J.-Y. , and Xie , X. ( 2020 ). COVID-19 and the cardiovascular system . Nat. Rev. Cardiol. 17 : 259 – 260 .
- Zhou , F. , Yu , T. , Du , R. et al. ( 2020 ). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study . Lancet 395 : 1054 – 1062 .
- Shi , S. , Qin , M. , Shen , B. et al. ( 2020 ). Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China . JAMA Cardiol. 5 : 802 – 810 .
- Guo , T. , Fan , Y. , Chen , M. et al. ( 2020 ). Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19) . JAMA Cardiol. 5 : 811 – 818 .
- Clerkin , K.J. , Fried , J.A. , Raikhelkar , J. et al. ( 2020 ). COVID-19 and cardiovascular disease . Circulation 141 : 1648 – 1655 .
- Atri , D. , Siddiqi , H.K. , Lang , J.P. et al. ( 2020 ). COVID-19 for the cardiologist: basic virology, epidemiology, cardiac manifestations, and potential therapeutic strategies . JACC Basic Transl. Sci. 5 : 518 – 516 .
- Gheblawi , M. , Wang , K. , Viveiros , A. et al. ( 2020 ). Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2 . Circ. Res. 126 : 1456 – 1474 .
- Tavazzi , G. , Pellegrini , C. , Maurelli , M. et al. ( 2020 ). Myocardial localization of coronavirus in COVID-19 cardiogenic shock . Eur. J. Heart Fail. 22 : 911 – 915 .
- Halushka , M.K. and Vander Heide , R.S. ( 2021 ). Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations . Cardiovasc. Pathol. 50 : 107300 .
- Bikdeli , B. , Madhavan , M.V. , Jimenez , D. et al. ( 2020 ). Global COVID-19 thrombosis collaborative group, endorsed by the ISTH, NATF, ESVM, and the IUA, supported by the ESC working group on pulmonary circulation and right ventricular function. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review . J. Am. Coll. Cardiol. 75 : 2950 – 2973 .
- Connors , J.M. and Levy , J.H. ( 2020 ). COVID-19 and its implications for thrombosis and anticoagulation . Blood 135 : 2033 – 2040 .
- Chen , G. , Wu , D. , Guo , W. et al. ( 2020 ). Clinical and immunological features of severe and moderate coronavirus disease 2019 . J. Clin. Invest. 130 : 2620 – 2629 .
- Pericàs , J.M. , Hernandez-Meneses , M. , Sheahan , T.P. et al. ( 2020 ). Hospital Clínic cardiovascular infections study group. COVID-19: from epidemiology to treatment . Eur. Heart J. 41 : 2092 – 2112 .
- Chen , N. , Zhou , M. , Dong , X. et al. ( 2020 ). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study . Lancet 395 : 507 – 513 .
- Thygesen , K. , Alpert , J.S. , Jaffe , A.S. et al. ( 2018 ). Fourth universal definition of myocardial infarction . Circulation 138 : e618 – e651 . https://doi.org/10.1161/CIR.0000000000000617 .
- Mahmud , E. , Dauerman , H.L. , Welt , F.G.P. et al. ( 2020 ). Management of Acute Myocardial Infarction during the COVID-19 pandemic: a position statement from the Society for Cardiovascular Angiography and Interventions (SCAI), the American College of Cardiology (ACC), and the American College of Emergency Physicians (ACEP) . J. Am. Coll. Cardiol. 76 : 1375 – 1384 .
- Choudry , F.A. , Hamshere , S.M. , Rathod , K.S. et al. ( 2020 ). High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction . J. Am. Coll. Cardiol. 76 : 1168 – 1176 .
- Klok , F.A. , Kruip , M.J.H.A. , van der Meer , N.J.M. et al. ( 2020 ). Incidence of thrombotic complications in critically ill ICU patients with COVID-19 . Thromb. Res. 191 : 145 – 147 .
- The REMAP-CAP, ACTIV-4a, ATTACC Investigators and Zarychanski , R. ( 2021 ). Therapeutic anticoagulation in critically Ill patients with Covid-19 – preliminary Report . medRxiv https://doi.org/10.1101/2021.03.10.21252749 .
10.1101/2021.03.10.21252749 Google Scholar
- INSPIRATION Investigators , Sadeghipour , P. , Talasaz , A.H. et al. ( 2021 ). Effect of intermediate-dose vs standard-dose prophylactic anticoagulation on thrombotic events, extracorporeal membrane oxygenation treatment, or mortality among patients with COVID-19 admitted to the intensive care unit: the INSPIRATION randomized clinical trial . JAMA 325 : 1620 .
- National Institutes of Health ( 2021 ). Full-dose blood thinners decreased need for life support and improved outcome in hospitalized COVID-19 patients . https://www.nih.gov/news-events/news-releases/full-dose-blood-thinners-decreased-need-life-support-improved-outcome-hospitalized-covid-19-patients (accessed 4 May 2021).
- Driggin , E. , Madhavan , M.V. , Bikdeli , B. et al. ( 2020 ). Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic . J. Am. Coll. Cardiol. 75 : 2352 – 2371 .
- Kariyanna , P.T. , Sutarjono , B. , Grewal , E. et al. ( 2020 ). A systematic review of COVID-19 and myocarditis . Am. J. Med. Case Rep. 8 : 299 – 305 .
- Kociol , R.D. , Cooper , L.T. , Fang , J.C. et al. ( 2020 ). Recognition and initial management of fulminant myocarditis: a scientific statement from the American Heart Association . Circulation 141 : e69 – e92 .
- Siripanthong , B. , Nazarian , S. , Muser , D. et al. ( 2020 ). Recognizing COVID-19-related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management . Heart Rhythm 17 : 1463 – 1471 .
- Hendren , N.S. , Drazner , M.H. , Bozkurt , B. , and Cooper , L.T. ( 2020 ). Description and proposed management of the acute COVID-19 cardiovascular syndrome . Circulation 141 : 1903 – 1914 .
- Lippi , G. , Lavie , C.J. , and Sanchis-Gomar , F. ( 2020 ). Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): evidence from a meta-analysis . Prog. Cardiovasc. Dis. 63 : 390 – 391 .
- Ruan , Q. , Yang , K. , Wang , W. et al. ( 2020 ). Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China . Intensive Care Med. 46 : 846 – 848 .
- Puntmann , V.O. , Carerj , M.L. , Wieters , I. et al. ( 2020 ). Outcomes of cardiovascular magnetic resonance imaging in patients recently recovered from coronavirus disease 2019 (COVID-19) . JAMA Cardiol. 5 : 1265 – 1273 .
- Martinez , M.W. , Tucker , A.M. , Bloom , O.J. et al. ( 2021 ). Prevalence of inflammatory heart disease among professional athletes with prior COVID-19 infection who received systematic return-to-play cardiac screening . JAMA Cardiol. 2021 : e210565 .
- Moulson , N. , Petek , B.J. , Drezner , J.A. et al. ( 2021 ). SARS-CoV-2 cardiac involvement in young competitive athletes . Circulation 144 https://doi.org/10.1161/CIRCULATIONAHA.121.054824 .
- Hu , H. , Ma , F. , Wei , X. , and Fang , Y. ( 2021 ). Coronavirus fulminant myocarditis treated with glucocorticoid and human immunoglobulin . Eur. Heart J. 42 : 206 .
- Sala , S. , Peretto , G. , Gramegna , M. et al. ( 2020 ). Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection . Eur. Heart J. 41 : 1861 – 1862 .
- Guan , W.-J. , Ni , Z.-Y. , Hu , Y. et al. ( 2020 ). Clinical characteristics of coronavirus disease 2019 in China . N. Engl. J. Med. 382 : 1708 – 1720 .
- Friedrich , M.G. , Sechtem , U. , Schulz-Menger , J. et al. ( 2009 ). International consensus group on cardiovascular magnetic resonance in myocarditis. Cardiovascular magnetic resonance in myocarditis: a JACC white paper . J. Am. Coll. Cardiol. 53 : 1475 – 1487 .
- Inciardi , R.M. , Lupi , L. , Zaccone , G. et al. ( 2020 ). Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19) . JAMA Cardiol. 5 : 819 .
- Mason , J.W. , O'Connell , J.B. , Herskowitz , A. et al. ( 1995 ). A clinical trial of immunosuppressive therapy for myocarditis. The myocarditis treatment trial Investigators . N. Engl. J. Med. 333 : 269 – 275 .
- McNamara , D.M. , Holubkov , R. , Starling , R.C. et al. ( 2001 ). Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy . Circulation 103 : 2254 – 2259 .
- Chen , H.S. , Wang , W. , Wu , S.N. , and Liu , J.P. ( 2013 ). Corticosteroids for viral myocarditis . Cochrane Database Syst. Rev. 2013 : CD004471.
- Cao , W. , Liu , X. , Bai , T. et al. ( 2020 ). High-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019 . Open Forum Infect. Dis. 7 : ofaa102 .
- Li , A. , Garcia-Bengochea , Y. , Stechel , R. , and Azari , B.M. ( 2020 ). Management of COVID-19 myopericarditis with reversal of cardiac dysfunction after blunting of cytokine storm: a case report . Eur. Heart. J. Case Rep. 4 : 1 – 6 .
- Magnani , J.W. and Dec , G.W. ( 2006 ). Myocarditis: current trends in diagnosis and treatment . Circulation 113 : 876 – 890 .
- Brito , D. , Meester , S. , Yanamala , N. et al. ( 2021 ). High prevalence of pericardial involvement in college student athletes recovering from COVID-19 . JACC Cardiovasc. Imaging 14 : 541 – 555 .
- Imazio , M. , Gaita , F. , and LeWinter , M. ( 2015 ). Evaluation and treatment of pericarditis: a systematic review . JAMA 314 : 1498 – 1506 .
- Imazio , M. , Cecchi , E. , Demichelis , B. et al. ( 2008 ). Myopericarditis versus viral or idiopathic acute pericarditis . Heart 94 : 498 – 501 .
- Kytö , V. , Sipilä , J. , and Rautava , P. ( 2014 ). Clinical profile and influences on outcomes in patients hospitalized for acute pericarditis . Circulation 130 : 1601 – 1606 .
- Cooper , L.T. ( 2009 ). Myocarditis . N. Engl. J. Med. 360 : 1526 – 1538 .
- Faraj , R. , Belkhayat , C. , Bouchlarhem , A. et al. ( 2021 ). Acute pericarditis revealing COVID-19 infection: case report . Ann. Med. Surg. (Lond.) 62 : 225 – 227 .
- Kumar , R. , Kumar , J. , Daly , C. , and Edroos , S.A. ( 2020 ). Acute pericarditis as a primary presentation of COVID-19 . BMJ Case Rep. 13 : e237617 .
- Hua , A. , O'Gallagher , K. , Sado , D. , and Byrne , J. ( 2020 ). Life-threatening cardiac tamponade complicating myo-pericarditis in COVID-19 . Eur. Heart J. 41 : 2130 – 2120 .
- Dabbagh , M.F. , Aurora , L. , D'Souza , P. et al. ( 2020 ). Cardiac tamponade secondary to COVID-19 . JACC Case Rep. 2 : 1326 – 1330 .
- Sauer , F. , Dagrenat , C. , Couppie , P. et al. ( 2020 ). Pericardial effusion in patients with COVID-19: case series . Eur. Heart J. Case Rep. 4 : 1 – 7 .
- Cremer , P.C. , Kumar , A. , Kontzias , A. et al. ( 2016 ). Complicated pericarditis: understanding risk factors and pathophysiology to inform imaging and treatment . J. Am. Coll. Cardiol. 68 : 2311 – 2328 .
- Klein , A.L. , Abbara , S. , Agler , D.A. et al. ( 2013 ). American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of cardiovascular computed tomography . J. Am. Soc. Echocardiogr. 26 : 965 – 1012.e15 .
- Imazio , M. , Brucato , A. , Lazaros , G. et al. ( 2020 ). Anti-inflammatory therapies for pericardial diseases in the COVID-19 pandemic: safety and potentiality . J. Cardiovasc. Med. (Hagerstown) 21 : 625 – 629 .
- Little , P. ( 2020 ). Non-steroidal anti-inflammatory drugs and covid-19 . BMJ 368 : m1185 .
- Imazio , M. and Adler , Y. ( 2013 ). Treatment with aspirin, NSAID, corticosteroids, and colchicine in acute and recurrent pericarditis . Heart Fail. Rev. 18 : 355 – 360 .
- Kawasaki , T. , Kosaki , F. , Okawa , S. et al. ( 1974 ). A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan . Pediatrics 54 : 271 – 276 .
- McCrindle , B.W. , Rowley , A.H. , Newburger , J.W. et al. ( 2017 ). Diagnosis, treatment, and long-term Management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association . Circulation 135 : e927 – e999 .
- Riphagen , S. , Gomez , X. , Gonzalez-Martinez , C. et al. ( 2020 ). Hyperinflammatory shock in children during COVID-19 pandemic . Lancet 395 : 1607 – 1608 .
- Whittaker , E. , Bamford , A. , Kenny , J. et al. ( 2020 ). Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 . JAMA 324 : 259 – 269 .
- Verdoni , L. , Mazza , A. , Gervasoni , A. et al. ( 2020 ). An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study . Lancet 395 : 1771 – 1778 .
- Moraleda , C. , Serna-Pascual , M. , Soriano-Arandes , A. et al. ( 2021 ). Multi-inflammatory syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain . Clin. Infect. Dis. 72 : e397 – e401 .
- Cheung , E.W. , Zachariah , P. , Gorelik , M. et al. ( 2020 ). Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City . JAMA 324 : 294 – 296 .
- Lee , E.H. , Kepler , K.L. , Geevarughese , A. et al. ( 2020 ). Race/ethnicity among children with COVID-19–associated multisystem inflammatory syndrome . JAMA Netw. Open 3 : e2030280 .
- Feldstein , L.R. , Rose , E.B. , Horwitz , S.M. et al. ( 2020 ). Multisystem inflammatory syndrome in U.S. children and adolescents . N. Engl. J. Med. 383 : 34 – 346 .
- Kaushik , A. , Gupta , S. , Sood , M. et al. ( 2020 ). A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection . Pediatr. Infect. Dis. J. 39 : e340 – e346 .
- Consiglio , C.R. , Cotugno , N. , Sardh , F. et al. ( 2020 ). The immunology of multisystem inflammatory syndrome in children with COVID-19 . Cell 183 : 968 – 81.e7 .
- Morris , S.B. , Schwartz , N.G. , Patel , P. et al. ( 2020 ). Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection - United Kingdom and United States, march-august 2020 . MMWR Morb. Mortal. Wkly Rep. 69 : 1450 – 1456 .
- Most , Z.M. , Hendren , N. , Drazner , M.H. , and Perl , T.M. ( 2021 ). Striking similarities of multisystem inflammatory syndrome in children and a myocarditis-like syndrome in adults: overlapping manifestations of COVID-19 . Circulation 143 : 4 – 6 .
- Centers for Disease Control and Prevention ( 2020 ). Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) . https://emergency.cdc.gov/han/2020/han00432.asp .
- Matsubara , D. , Kauffman , H.L. , Wang , Y. et al. ( 2020 ). Echocardiographic findings in pediatric multisystem inflammatory syndrome associated with COVID-19 in the United States . J. Am. Coll. Cardiol. 76 : 1947 – 1961 .
- van Stijn-Bringas , D.D. , Planken , R.N. , Groenink , M. et al. ( 2020 ). Coronary artery assessment in Kawasaki disease with dual-source CT angiography to uncover vascular pathology . Eur. Radiol. 30 : 432 – 441 .
- Goyal , P. , Choi , J.J. , Pinheiro , L.C. et al. ( 2020 ). Clinical characteristics of Covid-19 in New York City . N. Engl. J. Med. 382 : 2372 – 2374 .
- Bhatla , A. , Mayer , M.M. , Adusumalli , S. et al. ( 2020 ). COVID-19 and cardiac arrhythmias . Heart Rhythm 17 : 1439 – 1444 .
- Colon , C.M. , Barrios , J.G. , Chiles , J.W. et al. ( 2020 ). Atrial arrhythmias in COVID-19 patients . JACC Clin Electrophysiol. 6 : 1189 – 1190 .
- Sala , S. , Peretto , G. , De Luca , G. et al. ( 2020 ). Low prevalence of arrhythmias in clinically stable COVID-19 patients . Pacing Clin. Electrophysiol. 43 : 891 – 893 .
- Turagam , M.K. , Musikantow , D. , Goldman , M.E. et al. ( 2020 ). Malignant arrhythmias in patients with covid-19: incidence, mechanisms, and outcomes . Circulation: Arrhythmia Electrophysiol. 2020 13 : e008920 . https://doi.org/10.1161/CIRCEP.120.008920 .
- Chen , D. , Li , X. , Song , Q. et al. ( 2020 ). Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China . JAMA Netw. Open 3 : e2011122 .
- Moreno-P , O. , Leon-Ramirez , J.-M. , Fuertes-Kenneally , L. et al. ( 2020 ). COVID19-ALC research group. Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: a case series of 306 Mediterranean patients . Int. J. Infect. Dis. 100 : 449 – 454 .
- Bielecka-Dabrowa , A. , Mikhailidis , D.P. , Jones , L. et al. ( 2012 ). The meaning of hypokalemia in heart failure . Int. J. Cardiol. 158 : 12 – 17 .
- Digby , G.C. , Pérez Riera , A.R. , Barbosa Barros , R. et al. ( 2011 ). Acquired long QT interval: a case series of multifactorial QT prolongation . Clin. Cardiol. 34 : 577 – 582 .
- Lakkireddy , D.R. , Chung , M.K. , Gopinathannair , R. et al. ( 2020 ). Guidance for cardiac electrophysiology during the COVID-19 pandemic from the Heart Rhythm Society COVID-19 task force; electrophysiology section of the American College of Cardiology; and the electrocardiography and arrhythmias Committee of the Council on clinical cardiology, American Heart Association . Heart Rhythm 17 : e233 – e241 .
- Dherange , P. , Lang , J. , Qian , P. et al. ( 2020 ). Arrhythmias and COVID-19: a review . JACC Clin Electrophysiol. 6 : 1193 – 1204 .
- Saenz , L.C. , Miranda , A. , Speranza , R. et al. ( 2020 ). Recommendations for the organization of electrophysiology and cardiac pacing services during the COVID-19 pandemic: Latin American Heart Rhythm Society (LAHRS) in collaboration with: Colombian College of Electrophysiology, Argentinian Society of Cardiac Electrophysiology (SADEC), Brazilian Society of Cardiac Arrhythmias (SOBRAC), Mexican Society of Cardiac Electrophysiology (SOMEEC) . J. Interv. Card. Electrophysiol. 59 : 307 – 313 .
- Russo , V. , Rago , A. , Carbone , A. et al. ( 2020 ). Atrial fibrillation in COVID-19: from epidemiological association to pharmacological implications . J. Cardiovasc. Pharmacol. 76 : 138 – 145 .
- Kenney , M.J. and Ganta , C.K. ( 2014 ). Autonomic nervous system and immune system interactions . Compr. Physiol. 4 : 1177 – 1200 .
- Goldstein , D.S. ( 2020 ). The extended autonomic system, dyshomeostasis, and COVID-19 . Clin. Auton. Res. 30 : 299 – 315 .
- Fudim , M. , Qadri , Y.J. , Ghadimi , K. et al. ( 2020 ). Implications for Neuromodulation therapy to control inflammation and related organ dysfunction in COVID-19 . J. Cardiovasc. Transl. Res. 13 : 894 – 899 .
- Díaz , H.S. , Toledo , C. , Andrade , D.C. et al. ( 2020 ). Neuroinflammation in heart failure: new insights for an old disease . J. Physiol. 598 : 33 – 59 .
- Verstrepen , K. , Baisier , L. , and De Cauwer , H. ( 2020 ). Neurological manifestations of COVID-19, SARS and MERS . Acta Neurol. Belg. 120 : 1051 – 1060 .
- Miglis , M.G. , Prieto , T. , Shaik , R. et al. ( 2020 ). A case report of postural tachycardia syndrome after COVID-19 . Clin. Auton. Res. 30 : 449 – 451 .
- Thieben , M.J. , Sandroni , P. , Sletten , D.M. et al. ( 2007 ). Postural orthostatic tachycardia syndrome: the Mayo clinic experience . Mayo Clin. Proc. 82 : 308 – 313 .
- Lo , Y.L. , Leong , H.N. , Hsu , L.Y. et al. ( 2005 ). Autonomic dysfunction in recovered severe acute respiratory syndrome patients . Can. J. Neurol. Sci. 32 : 264 .
- Fedorowski , A. ( 2019 ). Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management . J. Intern. Med. 285 : 352 – 366 .
- Dani , M. , Dirksen , A. , Taraborrelli , P. et al. ( 2021 ). Autonomic dysfunction in ‘long COVID’: rationale, physiology and management strategies . Clin. Med. 21 : e63 – e67 .
- Brignole , M. , Moya , A. , de Lange , F.J. et al. ( 2018 ). ESC scientific document group. Practical instructions for the 2018 ESC guidelines for the diagnosis and management of syncope . Eur. Heart J. 39 : e43 – e80 .
- The American Autonomic Society , Figueroa , J.J. , Cheshire , W.P. et al. ( 2020 ). Autonomic function testing in the COVID-19 pandemic: an American autonomic society position statement . Clin. Auton. Res. 30 : 295 – 297 .
- Taub , P.R. , Zadourian , A. , Lo , H.C. et al. ( 2021 ). Randomized trial of Ivabradine in patients with hyperadrenergic postural orthostatic tachycardia syndrome . J. Am. Coll. Cardiol. 77 : 861 – 871 .
- Gorna , R. , MacDermott , N. , Rayner , C. et al. ( 2021 ). Long COVID guidelines need to reflect lived experience . Lancet 397 : 455 – 457 .
- Mahase , E. ( 2020 ). Covid-19: what do we know about “long covid”? BMJ 370 : m2815 .
- Carfì , A. , Bernabei , R. , and Landi , F. ( 2020 ). Gemelli against COVID-19 post-acute care study group. Persistent symptoms in patients after acute COVID-19 . JAMA 324 : 603 – 605 .
- Huang , C. , Huang , L. , Wang , Y. et al. ( 2021 ). 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study . Lancet 397 : 220 – 232 .
- Mitrani , R.D. , Dabas , N. , and Goldberger , J.J. ( 2020 ). COVID-19 cardiac injury: implications for long-term surveillance and outcomes in survivors . Heart Rhythm 17 : 1984 – 1990 .
- Bhatraju , P.K. , Ghassemieh , B.J. , Nichols , M. et al. ( 2020 ). Covid-19 in critically ill patients in the Seattle region - case series . N. Engl. J. Med. 382 : 2012 – 2022 .
- Suthahar , N. , Meijers , W.C. , Silljé , H.H.W. , and de Boer , R.A. ( 2017 ). From inflammation to fibrosis-molecular and cellular mechanisms of myocardial tissue Remodelling and perspectives on differential treatment opportunities . Curr. Heart Fail. Rep. 14 : 235 – 250 .
- Maron , B.J. , Udelson , J.E. , Bonow , R.O. et al. ( 2015 ). Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology . Circulation 132 : e273 – e280 .
- Kim , J.H. , Levine , B.D. , Phelan , D. et al. ( 2021 ). Coronavirus disease 2019 and the athletic heart: emerging perspectives on pathology, risks, and return to play . JAMA Cardiol. 6 : 219 – 227 .
- Yancy , C.W. , Jessup , M. , Bozkurt , B. et al. ( 2017 ). 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the Management of Heart Failure: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Failure Society of America . Circulation ; 136 ; e137 – 61 . doi: https://doi.org/10.1161/CIR.0000000000000509 .
- Al-Khatib , S.M. , Stevenson , W.G. , Ackerman , M.J. et al. ( 2018 ). 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society . Circulation 138 : e272 – e391 . https://doi.org/10.1161/CIR.0000000000000549 .
- Becker , R.C. ( 2020 ). Anticipating the long-term cardiovascular effects of COVID-19 . J. Thromb. Thrombolysis 50 : 512 – 524 .
- Khuroo , M.S. ( 2020 ). Chloroquine and hydroxychloroquine in coronavirus disease 2019 (COVID-19). Facts, fiction and the hype: a critical appraisal . Int. J. Antimicrob. Agents 56 : 106101 .
- Centers for Disease Control and Prevention ( 2021 ). COVID-19 treatment guidelines panel . https://www.covid19treatmentguidelines.nih.gov .
- RECOVERY Collaborative Group , Horby , P. , Mafham , M. et al. ( 2020 ). Effect of hydroxychloroquine in hospitalized patients with Covid-19 . N. Engl. J. Med. 383 : 2030 – 2040 .
- Geleris , J. , Sun , Y. , Platt , J. et al. ( 2020 ). Observational study of hydroxychloroquine in hospitalized patients with Covid-19 . N. Engl. J. Med. 382 : 2411 – 2418 .
- Cavalcanti , A.B. , Zampieri , F.G. , Rosa , R.G. et al. ( 2020 ). Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19 . N. Engl. J. Med. 383 : 2041 – 2052 .
- Bhimraj , A. , Morgan , R.L. , Shumaker , A.H. et al. ( 2020 ). Infectious diseases society of America guidelines on the treatment and Management of Patients with COVID-19 . Clin. Infect. Dis. 2020 : ciaa478 .
10.1093/cid/ciaa478 Google Scholar
- Tett , S.E. ( 1993 ). Clinical pharmacokinetics of slow-acting antirheumatic drugs . Clin. Pharmacokinet. 25 : 392 – 407 .
- Kanoh , S. and Rubin , B.K. ( 2010 ). Mechanisms of action and clinical application of macrolides as immunomodulatory medications . Clin. Microbiol. Rev. 23 : 590 – 615 .
- Kawamura , K. , Ichikado , K. , Takaki , M. et al. ( 2018 ). Adjunctive therapy with azithromycin for moderate and severe acute respiratory distress syndrome: a retrospective, propensity score-matching analysis of prospectively collected data at a single center . Int. J. Antimicrob. Agents 51 : 918 – 924 .
- Rosenberg , E.S. , Dufort , E.M. , Udo , T. et al. ( 2020 ). Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York state . JAMA 323 : 2493 – 2502 .
- Furtado , R.H.M. , Berwanger , O. , Fonseca , H.A. et al. ( 2020 ). Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial . Lancet 396 : 959 – 967 .
- Ramireddy , A. , Chugh , H. , Reinier , K. et al. ( 2020 ). Experience with Hydroxychloroquine and azithromycin in the coronavirus disease 2019 pandemic: implications for QT interval monitoring . J. Am. Heart Assoc. 9 : e017144 .
- Bessière , F. , Roccia , H. , Delinière , A. et al. ( 2020 ). Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with Hydroxychloroquine alone or in combination with azithromycin in an intensive care unit . JAMA Cardiol. 5 : 1067 – 1069 .
- Metlay , J.P. and Waterer , G.W. ( 2020 ). Treatment of community-acquired pneumonia during the coronavirus disease 2019 (COVID-19) pandemic . Ann. Intern. Med. 173 : 304 – 305 .
- Gubitosa , J.C. , Kakar , P. , Gerula , C. et al. ( 2020 ). Marked sinus Bradycardia associated with Remdesivir in COVID-19: a case and literature review . JACC Case Rep. 2 : 2260 – 2264 .
- Gupta , A.K. , Parker , B.M. , Priyadarshi , V. , and Parker , J. ( 2020 ). Cardiac adverse events with Remdesivir in COVID-19 infection . Cureus 12 : e11132 .
- Grein , J. , Ohmagari , N. , Shin , D. et al. ( 2020 ). Compassionate use of Remdesivir for patients with severe Covid-19 . N. Engl. J. Med. 382 : 2327 – 2336 .
- Beigel , J.H. , Tomashek , K.M. , Dodd , L.E. et al. ( 2020 ). Remdesivir for the treatment of Covid-19- final report . N. Engl. J. Med. 383 : 1813 – 1826 .
- Zhang , P. , Zhu , L. , Cai , J. et al. ( 2020 ). Association of Inpatient use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19 . Circ. Res. 126 : 1671 – 1681 .
- Wan , Y. , Shang , J. , Graham , R. et al. ( 2020 ). Receptor recognition by the novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS coronavirus . J. Virol. 94 : e00127-20 .
- Solaru , K.W. and Wright Jr. J.T. 2020 . COVID-19 and use of drugs targeting the renin-angiotensin-system . American College of Cardiology . https://www.acc.org/latest-in-cardiology/articles/2020/07/15/13/12/covid-19-and-use-of-drugs-targeting-the-renin-angiotensin-system .
- Fang , L. , Karakiulakis , G. , and Roth , M. ( 2020 ). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir. Med. 8 : e21 .
- Bozkurt , B. , Kovacs , R. , and Harrington , B. ( 2020 ). Joint HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19 . J. Card. Fail. 26 : 370 .
- Reynolds , H.R. , Adhikari , S. , Pulgarin , C. et al. ( 2020 ). Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19 . N. Engl. J. Med. 382 : 2441 – 2448 .
- Mancia , G. , Rea , F. , Ludergnani , M. et al. ( 2020 ). Renin-angiotensin-aldosterone system blockers and the risk of Covid-19 . N. Engl. J. Med. 382 : 2431 – 2440 .
- Hakeam , H.A. , Alsemari , M. , Duhailib , Z.A. et al. ( 2021 ). Association of angiotensin-converting enzyme inhibitors and angiotensin II blockers with severity of COVID-19: a multicenter, prospective study . J. Cardiovasc. Pharmacol. Ther. 26 : 244 – 252 .
- European Society of Cardiology 2020 . Position statement of the ESC council on hypertension on ACE-inhibitors and angiotensin receptor blockers . https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang .
- Vaduganathan , M. , Vardeny , O. , Michel , T. et al. ( 2020 ). Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19 . N. Engl. J. Med. 382 : 1653 – 1659 .
- Lee , K.C.H. , Sewa , D.W. , and Phua , G.C. ( 2020 ). Potential role of statins in COVID-19 . Int. J. Infect. Dis. 96 : 615 – 617 .
- Castiglione , V. , Chiriacò , M. , Emdin , M. et al. ( 2020 ). Statin therapy in COVID-19 infection . Eur. Heart J. Cardiovasc. Pharmacother. 6 : 258 – 259 .
- Scheen , A.J. ( 2020 ). Statins and clinical outcomes with COVID-19: meta-analyses of observational studies . Diabetes Metab. 47 : 101220 .
- Butt , J.H. , Gerds , T.A. , Schou , M. et al. ( 2020 ). Association between statin use and outcomes in patients with coronavirus disease 2019 (COVID-19): a nationwide cohort study . BMJ Open 10 : e044421 .
- Fan , Y. , Guo , T. , Yan , F. et al. ( 2020 ). Association of Statin use with the in-hospital outcomes of 2019-coronavirus disease patients: a retrospective study . Front. Med. (Lausanne) 7 : 584870 .
- Matsushita , K. , Ding , N. , Kou , M. et al. ( 2020 ). The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: a systematic review and meta-analysis . Glob. Heart 15 : 64 .
- Alvarez-Garcia , J. , Lee , S. , Gupta , A. et al. ( 2020 ). Prognostic impact of prior heart failure in patients hospitalized with COVID-19 . J. Am. Coll. Cardiol. 76 : 2334 – 2348 .
- Kytömaa , S. , Hegde , S. , Claggett , B. et al. ( 2019 ). Association of influenza-like illness activity with hospitalizations for heart failure: the atherosclerosis risk in communities study . JAMA Cardiol. 4 : 363 – 369 .
- Wadhera , R.K. , Shen , C. , Gondi , S. et al. ( 2021 ). Cardiovascular deaths during the COVID-19 pandemic in the United States . J. Am. Coll. Cardiol. 77 : 159 – 169 .
- Pereira , M.R. , Mohan , S. , Cohen , D.J. et al. ( 2020 ). COVID-19 in solid organ transplant recipients: initial report from the US epicenter . Am. J. Transplant. 20 : 1800 – 1808 .
- Bottio , T. , Bagozzi , L. , Fiocco , A. et al. ( 2021 ). COVID-19 in heart transplant recipients: a multicenter analysis of the northern Italian outbreak . JACC Heart Fail. 9 : 52 – 61 .
- Latif , F. , Farr , M.A. , Clerkin , K.J. et al. ( 2020 ). Characteristics and outcomes of recipients of heart transplant with coronavirus disease 2019 . JAMA Cardiol. 5 : 1165 – 1169 .
- Zheng , Z. , Peng , F. , Xu , B. et al. ( 2020 ). Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis . J. Infect. 81 : e16 – e25 .
- Rivinius , R. , Kaya , Z. , Schramm , R. et al. ( 2020 ). COVID-19 among heart transplant recipients in Germany: a multicenter survey . Clin. Res. Cardiol. 109 : 1531 – 1539 .
- International Society for Heart and Lung Transplantation 2021 . Guidance from the ISHLT regarding the SARS CoV-2 pandemic . https://ishlt.org/covid-19-information (accessed 14 April 2021).
- RECOVERY Collaborative Group , Horby , P. , Lim , W.S. et al. ( 2021 ). Dexamethasone in hospitalized patients with Covid-19 . N. Engl. J. Med. 384 : 693 – 704 .
- National Institutes of Health 2020 . Special considerations in solid organ transplant, hematopoietic stem cell transplant, and cellular therapy candidates, donors, and recipients . https://www.covid19treatmentguidelines.nih.gov/special-populations/transplant (accessed 14 April 2021).
- Boyarsky , B.J. , Ou , M.T. , Greenberg , R.S. et al. ( 2021 ). Safety of the first dose of SARS-CoV-2 vaccination in solid organ transplant recipients . Transplantation 105 : e56 – e57 .
- Widge , A.T. , Rouphael , N.G. , Jackson , L.A. et al. ( 2021 ). Durability of responses after SARS-CoV-2 mRNA-1273 vaccination . N. Engl. J. Med. 384 : 80 – 82 .
- American Society of Transplantation 2021 . COVID-19 vaccine FAQ sheet . https://www.myast.org/sites/default/files/Education/2021%2003%2002%20COVID19%20VACCINE%20FAQS_update%20v4%20FINAL%20%281%29.pdf (accessed 3 March 2021).