Semin Thromb Hemost 2020; 46(07): 807-814
DOI: 10.1055/s-0040-1715094
Review Article

Coronavirus (COVID-19), Coagulation, and Exercise: Interactions That May Influence Health Outcomes

Emma Kate Zadow
1   Holsworth Research Initiative, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
,
Daniel William Taylor Wundersitz
1   Holsworth Research Initiative, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
,
Diane Louise Hughes
1   Holsworth Research Initiative, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
2   Department of Pharmacy and Biomedical Sciences, School of Molecular Sciences, La Trobe University, Bendigo, Victoria, Australia
,
Murray John Adams
3   College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia, Australia
,
Michael Ian Charles Kingsley
1   Holsworth Research Initiative, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
4   Department of Exercise Sciences, University of Auckland, Auckland, New Zealand
,
Hilary Anne Blacklock
5   Department of Haematology, Middlemore Hospital, Auckland, New Zealand
,
Sam Shi Xuan Wu
6   Department of Health and Medical Sciences, Swinburne University of Technology, Hawthorn, Victoria, Australia
,
Amanda Clare Benson
6   Department of Health and Medical Sciences, Swinburne University of Technology, Hawthorn, Victoria, Australia
,
Frédéric Dutheil
7   Université Clermont Auvergne, CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, University Hospital of Clermont-Ferrand, Preventive and Occupational Medicine, Witty Fit, Clermont-Ferrand, France
,
Brett Ashley Gordon
1   Holsworth Research Initiative, La Trobe Rural Health School, La Trobe University, Bendigo, Victoria, Australia
› Author Affiliations

Abstract

The proinflammatory cytokine storm associated with coronavirus disease 2019 (COVID-19) negatively affects the hematological system, leading to coagulation activation and endothelial dysfunction and thereby increasing the risk of venous and arterial thrombosis. Coagulopathy has been reported as associated with mortality in people with COVID-19 and is partially reflected by enhanced D-dimer levels. Poor vascular health, which is associated with the cardiometabolic health conditions frequently reported in people with severer forms of COVID-19, might exacerbate the risk of coagulopathy and mortality. Sedentary lifestyles might also contribute to the development of coagulopathy, and physical activity participation has been inherently lowered due to at-home regulations established to slow the spread of this highly infectious disease. It is possible that COVID-19, coagulation, and reduced physical activity may contribute to generate a “perfect storm,” where each fuels the other and potentially increases mortality risk. Several pharmaceutical agents are being explored to treat COVID-19, but potential negative consequences are associated with their use. Exercise is known to mitigate many of the identified side effects from the pharmaceutical agents being trialled but has not yet been considered as part of management for COVID-19. From the limited available evidence in people with cardiometabolic health conditions, low- to moderate-intensity exercise might have the potential to positively influence biochemical markers of coagulopathy, whereas high-intensity exercise is likely to increase thrombotic risk. Therefore, low- to moderate-intensity exercise could be an adjuvant therapy for people with mild-to-moderate COVID-19 and reduce the risk of developing severe symptoms of illness that are associated with enhanced mortality.



Publication History

Article published online:
03 September 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 
  • References

  • 1 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
  • 2 Wen J, Aston J, Liu X, Ying T. Effects of misleading media coverage on public health crisis: a case of the 2019 novel coronavirus outbreak in China. Anatolia 2020; 31: 331-336
  • 3 WHO. WHO Coronavirus Disease (COVID-19) Dashboard. Available at: https://covid19.who.int/ . Accessed 22 May, 2020
  • 4 UNCTAD. Coronavirus: can policymakers avert a trillion-dollar crisis?. Available at: https://unctad.org/en/pages/newsdetails.aspx?OriginalVersionID=2300 . Accessed April 30, 2020
  • 5 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020; 506: 145-148
  • 6 Liu Y, Yang Y, Zhang C. et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci 2020; 63 (03) 364-374
  • 7 Peng YD, Meng K, Guan HQ. et al. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV [in Chinese]. Zhonghua Xin Xue Guan Bing Za Zhi 2020; 48 (00) E004
  • 8 Terpos E, Ntanasis-Stathopoulos I, Elalamy I. et al. Hematological findings and complications of COVID-19. Am J Hematol 2020; 95 (07) 834-847
  • 9 Gao Y, Li T, Han M. et al. Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J Med Virol 2020; 92 (07) 791-796
  • 10 Cannegieter SC, Klok FA. COVID-19 associated coagulopathy and thromboembolic disease: commentary on an interim expert guidance. Res Pract Thromb Haemost 2020; 4 (04) 439-445
  • 11 Pallister CJ, Watson MS. Haematology. 2nd ed. Banbury, UK: Scion Publishing; 2010
  • 12 Lowe GD. Virchow's triad revisited: abnormal flow. Pathophysiol Haemost Thromb 2003; 33 (5-6): 455-457
  • 13 Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med 2020; 58 (07) 1021-1028
  • 14 Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 2020; 7 (06) e438-e440
  • 15 Bikdeli B, Madhavan MV, Gupta A. et al; Global COVID-19 Thrombosis Collaborative Group. Pharmacological agents targeting thromboinflammation in COVID-19: review and implications for future research. Thromb Haemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1713152.
  • 16 Hashemi A, Madhavan MV, Bikdeli B. Pharmacotherapy for prevention and management of thrombosis in COVID-19. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1714273.
  • 17 Monroe DM, Hoffman M. What does it take to make the perfect clot?. Arterioscler Thromb Vasc Biol 2006; 26 (01) 41-48
  • 18 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93 (01) 327-358
  • 19 Verhamme P, Hoylaerts MF. The pivotal role of the endothelium in haemostasis and thrombosis. Acta Clin Belg 2006; 61 (05) 213-219
  • 20 Kleinegris MC, Ten Cate-Hoek AJ, Ten Cate H. Coagulation and the vessel wall in thrombosis and atherosclerosis. Pol Arch Med Wewn 2012; 122 (11) 557-566
  • 21 Siahkouhian M, Khodadadi D, Bolboli L. Diurnal variation of haemostatic response to exercise in young sedentary males. Biol Sport 2013; 30 (02) 125-130
  • 22 Page MJ, Pretorius E. A champion of host defense: a generic large-scale cause for platelet dysfunction and depletion in infection. Semin Thromb Hemost 2020; 46 (03) 302-319
  • 23 Larsen JB, Pasalic L, Hvas AM. Platelets in coronavirus disease 2019. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1710006.
  • 24 Wang D, Hu B, Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; (e-pub ahead of print) DOI: 10.1001/jama.2020.1585.
  • 25 Prchal JT. Hypoxia and thrombosis. Blood 2018; 132 (04) 348-349
  • 26 Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res 2019; 181: 77-83
  • 27 Thachil J, Srivastava A. SARS-2 coronavirus-associated hemostatic lung abnormality in COVID-19: is it pulmonary thrombosis or pulmonary embolism?. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1712155.
  • 28 Kwaan HC. Coronavirus disease 2019: the role of the fibrinolytic system from transmission to organ injury and sequelae. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1709996.
  • 29 Chen T, Wu D, Chen H. et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ 2020; 368: m1091
  • 30 Guan WJ, Ni ZY, Hu Y. et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020; 382 (18) 1708-1720
  • 31 Grasselli G, Zangrillo A, Zanella A. et al; COVID-19 Lombardy ICU Network. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA 2020; 323 (16) 1574-1581
  • 32 Dutheil F, Gordon BA, Naughton G. et al. Cardiovascular risk of adipokines: a review. J Int Med Res 2018; 46 (06) 2082-2095
  • 33 Gaertner F, Massberg S. Blood coagulation in immunothrombosis-at the frontline of intravascular immunity. Semin Immunol 2016; 28 (06) 561-569
  • 34 Lodigiani C, Iapichino G, Carenzo L. et al; Humanitas COVID-19 Task Force. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020; 191: 9-14
  • 35 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18 (04) 844-847
  • 36 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
  • 37 Prisco D, Paniccia R, Bandinelli B. et al. Evaluation of clotting and fibrinolytic activation after protracted physical exercise. Thromb Res 1998; 89 (02) 73-78
  • 38 Schobersberger W, Wirleitner B, Puschendorf B. et al. Influence of an ultramarathon race at moderate altitude on coagulation and fibrinolysis. Fibrinolysis 1995; 10 (01) 37-42
  • 39 Nguyen NT, Owings JT, Gosselin R. et al. Systemic coagulation and fibrinolysis after laparoscopic and open gastric bypass. Arch Surg 2001; 136 (08) 909-916
  • 40 Parker BA, Augeri AL, Capizzi JA. et al. Effect of marathon run and air travel on pre- and post-run soluble d-dimer, microparticle procoagulant activity, and p-selectin levels. Am J Cardiol 2012; 109 (10) 1521-1525
  • 41 Wells PS, Anderson DR, Rodger M. et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003; 349 (13) 1227-1235
  • 42 Koehler KS, Bottoni T. The effect of exercise on D-dimer levels. Mil Med 2014; 179 (02) 225-230
  • 43 Henke PK, Pannucci CJ. Venous thromboembolism risk factor assessment and prophylaxis. Phlebology 2010; 25 (05) 219-223
  • 44 Kelly J, Rudd A, Lewis RR, Hunt BJ. Plasma D-dimers in the diagnosis of venous thromboembolism. Arch Intern Med 2002; 162 (07) 747-756
  • 45 Schulman S. Coronavirus disease 2019, prothrombotic factors, and venous thromboembolism. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1710337.
  • 46 Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019: a pooled analysis. Thromb Haemost 2020; 120 (05) 876-878
  • 47 Haskell WL, Lee IM, Pate RR. et al; American College of Sports Medicine; American Heart Association. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation 2007; 116 (09) 1081-1093
  • 48 Lippi G, Henry BM, Sanchis-Gomar F. Physical inactivity and cardiovascular disease at the time of coronavirus disease 2019 (COVID-19). Eur J Prev Cardiol 2020; 27 (09) 906-908
  • 49 FitbitStaff. The impact of coronavirus on global activity. Available at: https://blog.fitbit.com/covid-19-global-activity/ . Accessed May 29, 2020
  • 50 Evidation Health. COVID-19 Pulse Study. Available at: https://evidation.com/news/covid-19-pulse-first-data-evidation/ . Accessed May 28, 2020
  • 51 Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012; 379 (9828): 1835-1846
  • 52 Hull CM, Harris JA. Cardiology Patient Page. Venous thromboembolism and marathon athletes. Circulation 2013; 128 (25) e469-e471
  • 53 Gregson J, Kaptoge S, Bolton T. et al; Emerging Risk Factors Collaboration. Cardiovascular risk factors associated with venous thromboembolism. JAMA Cardiol 2019; 4 (02) 163-173
  • 54 Lippi G, Favaloro EJ, Sanchis-Gomar F. Sudden cardiac and noncardiac death in sports: epidemiology, causes, pathogenesis, and prevention. Semin Thromb Hemost 2018; 44 (08) 780-786
  • 55 Lippi G, Sanchis-Gomar F, Henry BM. Coronavirus disease 2019 (COVID-19): the portrait of a perfect storm. Ann Transl Med 2020; 8 (07) 497
  • 56 Garber CE, Blissmer B, Deschenes MR. et al; American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43 (07) 1334-1359
  • 57 Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA. et al; American College of Sports Medicine. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Med Sci Sports Exerc 2009; 41 (07) 1510-1530
  • 58 Panagiotakos DB, Pitsavos C, Chrysohoou C, Kavouras S, Stefanadis C. ATTICA Study. The associations between leisure-time physical activity and inflammatory and coagulation markers related to cardiovascular disease: the ATTICA Study. Prev Med 2005; 40 (04) 432-437
  • 59 Pitsavos C, Panagiotakos DB, Chrysohoou C, Kavouras S, Stefanadis C. The associations between physical activity, inflammation, and coagulation markers, in people with metabolic syndrome: the ATTICA study. Eur J Cardiovasc Prev Rehabil 2005; 12 (02) 151-158
  • 60 Zbinden-Foncea H, Francaux M, Deldicque L, Hawley JA. Does high cardiorespiratory fitness confer some protection against pro-inflammatory responses after infection by SARS-CoV-2?. Obesity (Silver Spring) 2020; (Apr): 23
  • 61 Chen P, Mao L, Nassis GP, Harmer P, Ainsworth BE, Li F. Coronavirus disease (COVID-19): the need to maintain regular physical activity while taking precautions. J Sport Health Sci 2020; 9 (02) 103-104
  • 62 Szymanski LM, Pate RR. Fibrinolytic responses to moderate intensity exercise. Comparison of physically active and inactive men. Arterioscler Thromb 1994; 14 (11) 1746-1750
  • 63 Thrall G, Lane D, Carroll D, Lip GYH. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: implications for the pathogenesis of acute coronary syndromes. Thromb Res 2007; 120 (06) 819-847
  • 64 el-Sayed MS. Effects of exercise on blood coagulation, fibrinolysis and platelet aggregation. Sports Med 1996; 22 (05) 282-298
  • 65 Ferguson EW, Bernier LL, Banta GR, Yu-Yahiro J, Schoomaker EB. Effects of exercise and conditioning on clotting and fibrinolytic activity in men. J Appl Physiol (1985) 1987; 62 (04) 1416-1421
  • 66 Karampour S, Gaeini AA. Response of coagulation and anti-coagulant factors of elite athletes following acute resistance and high-intensity interval training. J Sports Med Phys Fitness 2018; 58 (1-2): 120-126
  • 67 Kupchak BR, Creighton BC, Aristizabal JC. et al. Beneficial effects of habitual resistance exercise training on coagulation and fibrinolytic responses. Thromb Res 2013; 131 (06) e227-e234
  • 68 Eriksson-Berg M, Egberg N, Eksborg S, Schenck-Gustafsson K. Retained fibrinolytic response and no coagulation activation after acute physical exercise in middle-aged women with previous myocardial infarction. Thromb Res 2002; 105 (06) 481-486
  • 69 Gram AS, Petersen M, Quist JS, Rosenkilde M, Stallknecht B, Bladbjerg EM. Effects of 6 months of active commuting and leisure-time exercise on fibrin turnover in sedentary individuals with overweight and obesity: a randomised controlled trial. J Obes 2018; 2018: 7140754
  • 70 Braschi A. Acute exercise-induced changes in hemostatic and fibrinolytic properties: analogies, similarities, and differences between normotensive subjects and patients with essential hypertension. Platelets 2019; 30 (06) 675-689
  • 71 Posthuma JJ, van der Meijden PE, Ten Cate H, Spronk HM. Short- and long-term exercise induced alterations in haemostasis: a review of the literature. Blood Rev 2015; 29 (03) 171-178
  • 72 Weiss C, Welsch B, Albert M. et al. Coagulation and thrombomodulin in response to exercise of different type and duration. Med Sci Sports Exerc 1998; 30 (08) 1205-1210
  • 73 Lippi G, Salvagno GL, Tarperi C. et al. Prothrombotic state induced by middle-distance endurance exercise in middle-aged athletes. Semin Thromb Hemost 2018; 44 (08) 747-755
  • 74 el-Sayed MS. Exercise intensity-related responses of fibrinolytic activity and vasopressin in man. Med Sci Sports Exerc 1990; 22 (04) 494-500
  • 75 Menzel K, Hilberg T. Blood coagulation and fibrinolysis in healthy, untrained subjects: effects of different exercise intensities controlled by individual anaerobic threshold. Eur J Appl Physiol 2011; 111 (02) 253-260
  • 76 Röcker L, Möckel M, Westpfahl KP, Gunga HC. Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system. Thromb Haemost 1996; 75 (04) 612-616
  • 77 Gunga HC, Kirsch K, Beneke R. et al. Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels. Int J Sports Med 2002; 23 (07) 495-499
  • 78 Hilberg T, Prasa D, Stürzebecher J, Gläser D, Schneider K, Gabriel HH. Blood coagulation and fibrinolysis after extreme short-term exercise. Thromb Res 2003; 109 (5-6): 271-277
  • 79 Zadow EK, Kitic CM, Wu SSX, Fell JW, Adams MJ. Time of day and short-duration high-intensity exercise influences on coagulation and fibrinolysis. Eur J Sport Sci 2018; 18 (03) 367-375
  • 80 Cuzzolin L, Lussignoli S, Crivellente F. et al. Influence of an acute exercise on neutrophil and platelet adhesion, nitric oxide plasma metabolites in inactive and active subjects. Int J Sports Med 2000; 21 (04) 289-293
  • 81 Kvernmo HD, Osterud B. The effect of physical conditioning suggests adaptation in procoagulant and fibrinolytic potential. Thromb Res 1997; 87 (06) 559-569
  • 82 Szymanski LM, Pate RR, Durstine JL. Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men. J Appl Physiol (1985) 1994; 77 (05) 2305-2310
  • 83 Gonzales F, Mañas M, Seiquer I. et al. Blood platelet function in healthy individuals of different ages. Effects of exercise and exercise conditioning. J Sports Med Phys Fitness 1996; 36 (02) 112-116
  • 84 Womack CJ, Ivey FM, Gardner AW, Macko RF. Fibrinolytic response to acute exercise in patients with peripheral arterial disease. Med Sci Sports Exerc 2001; 33 (02) 214-219
  • 85 DeSouza CA, Dengel DR, Rogers MA, Cox K, Macko RF. Fibrinolytic responses to acute physical activity in older hypertensive men. J Appl Physiol (1985) 1997; 82 (06) 1765-1770
  • 86 Morris PJ, Packianathan CI, Van Blerk CJ, Finer N. Moderate exercise and fibrinolytic potential in obese sedentary men with metabolic syndrome. Obes Res 2003; 11 (11) 1333-1338
  • 87 Ivey FM, Womack CJ, Kulaputana O, Dobrovolny CL, Wiley LA, Macko RF. A single bout of walking exercise enhances endogenous fibrinolysis in stroke patients. Med Sci Sports Exerc 2003; 35 (02) 193-198
  • 88 Shetty R, Ghosh A, Honavar SG, Khamar P, Sethu S. Therapeutic opportunities to manage COVID-19/SARS-CoV-2 infection: present and future. Indian J Ophthalmol 2020; 68 (05) 693-702
  • 89 Abd El-Aziz TM, Stockand JD. Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status. Infect Genet Evol 2020; 83: 104327
  • 90 Hendren NS, Drazner MH, Bozkurt B, Cooper Jr LT. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation 2020; 141 (23) 1903-1914
  • 91 Bhimraj A, Morgan RL, Shumaker AH. et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. Clin Infect Dis 2020; 2000: ciaa478
  • 92 Franchini M, Del Fante C, Klersy C. et al. Challenges in the production of convalescent hyperimmune plasma in the age of COVID-19. Semin Thromb Hemost 2020; (e-pub ahead of print) DOI: 10.1055/s-0040-1713433.
  • 93 Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm 2008; 65 (15) 1413-1418
  • 94 Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 2011; 1813 (05) 878-888
  • 95 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 Haemost 2020; 18 (05) 1094-1099
  • 96 Żebrowska A, Jastrzębski D, Sadowska-Krępa E, Sikora M, Di Giulio C. Comparison of the effectiveness of high-intensity interval training in hypoxia and normoxia in healthy male volunteers: a pilot study. BioMed Res Int 2019; 2019: 7315714
  • 97 Jahangir M, Muheem A, Rizvi M. Coronavirus (COVID-19): history, current knowledge and pipeline medications. Int J Pharm 2020; 4 (01) 2581-3080
  • 98 Hung IF-N, Lung K-C, Tso EY-K. et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 2020; 395 (10238): 1695-1704
  • 99 Monto AS. The role of antivirals in the control of influenza. Vaccine 2003; 21 (16) 1796-1800
  • 100 Chutaputti A. Adverse effects and other safety aspects of the hepatitis C antivirals. J Gastroenterol Hepatol 2000; 15 (Suppl): E156-E163
  • 101 Yu WC, Hui DSC, Chan-Yeung M. Antiviral agents and corticosteroids in the treatment of severe acute respiratory syndrome (SARS). Thorax 2004; 59 (08) 643-645
  • 102 Veinot JP, Mai KT, Zarychanski R. Chloroquine related cardiac toxicity. J Rheumatol 1998; 25 (06) 1221-1225
  • 103 Marrelli MT, Brotto M. The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles. Malar J 2016; 15 (01) 524
  • 104 Verny C, de Gennes C, Sébastien P. et al. Heart conduction disorders in long-term treatment with chloroquine. Two new cases [in French]. Presse Med 1992; 21 (17) 800-804
  • 105 Friis-Møller N, Reiss P, Sabin CA. et al; DAD Study Group. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356 (17) 1723-1735
  • 106 Mondy KE, Gottdiener J, Overton ET. et al; SUN Study Investigators. High prevalence of echocardiographic abnormalities among HIV-infected persons in the era of highly active antiretroviral therapy. Clin Infect Dis 2011; 52 (03) 378-386
  • 107 Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1-protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998; 351 (9119): 1881-1883
  • 108 Hui DY. Effects of HIV protease inhibitor therapy on lipid metabolism. Prog Lipid Res 2003; 42 (02) 81-92
  • 109 Polman R, Kaiseler M, Borkoles E. Effect of a single bout of exercise on the mood of pregnant women. J Sports Med Phys Fitness 2007; 47 (01) 103-111
  • 110 Yeung RR. The acute effects of exercise on mood state. J Psychosom Res 1996; 40 (02) 123-141
  • 111 Pollock MLGG, Butcher JD. et al. American College of Sports Medicine position stand. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults. Med Sci Sports Exerc 1998; 30 (06) 975-991
  • 112 Lippi G, Henry BM, Bovo C, Sanchis-Gomar F. Health risks and potential remedies during prolonged lockdowns for coronavirus disease 2019 (COVID-19). Diagnosis (Berl) 2020; 7 (02) 85-90
  • 113 Halabchi F, Ahmadinejad Z, Selk-Ghaffari M. COVID-19 epidemic: exercise or not to exercise; that is the question!. Asian J Sports Med 2020; (e-pub ahead of print) DOI: 10.5812/asjsm.102630.