Viral Illnesses and Sports Performance La

Home , Coxsackie B virus, Infectious mononucleosis

Research Review

Viral Illnesses and Sports Performance lA. Roberts Medical Advisor to the Scottish Amateur Athletic Association and Department of Respiratory Medicine, Western Infirmary, Glasgow

Summary Viruses are ubiquitous and cause numerous infections in humans. These may vary from asymptomatic infection to severe debilitating illness. Viruses enter the host cells to replicate. using host synthetic mechanisms, and. thus, are resistant to conventional anti biotics. The human bodyresponds to viral infection by synthesising specific antibodywhich can be usedto aid diagnosis. Infectious mononucleosis (glandular fever) commonly affects the 15 to 30 yearsage group. It may produce severe debility which may last a month or more. Coxsackie virus infection can produce symptoms ofthe common coldbut may also invadeheartmuscleand produce myocarditis, a potentially serious disease. Otherviruses also produce a wide spectrum ofdisease. Recent evidence has shown that people undergoing severe mental or physical stress may havereduced immunity to viralinfections. Thereare risksassociated withstrenuous physical activityduringthe acutephaseofviralinfection, and thereare reports ofsudden death and serious complications occurring in previously fit young adults who undertake vigorous exercise when in the acute phase of a viral illness. Abnormalities of skeletal musclehavebeen demonstrated in patients with viralinfection and this may explain the loss ofperformance experienced by athletes after upper respiratory tract infection. As a general rule, for all but mild common colds, it is advised that the athleteavoids hard trainingfor the first month after infection.

Viruses are the most common infectious agents ards, it is important that viral infections are re affecting humans. The average adult has between cognised and correctly managed to avoid unnec 1 and 6 upper respiratory tract viral infections per essary complications. Often the desire ofthe athlete year (Beneson 1975). Not only are there innumer to train through an illness or minimise the lay-off able viruses which infect man but also the effect time conflicts with the need to avoid stressful ex of a single species of virus may vary enormously. ercise during an acute viral illness. In addition there Viral illnesses produce the entire spectrum of dis is evidence that athletes in training are more sus ease from fatal disease through mild colds to ceptible to viral illness than the normal popula asymptomatic infections. tion. In this review I will discuss the more common viruses and the illnesses they produce, the effects 1. Mechanism of Viral Infection of viruses on particular organ systems, e.g. muscle and heart, and make particular reference to sports Viruses are distinguished from bacteria by their performance. In sportsmen undergoing strenuous dependence on host cells for replication. Viruses training and aiming for high performance stand- do not have the ability to reproduce their own gen- Viruses and Sports Performance 297

etic material and therefore have to invade a host Table I. Common respiratory viruses and their clinical features cell and take over its synthetic mechanisms to rep Virus group No. of Clinical features licate their own genetic material and multiply. The serotypes majority of viruses enter the body via the respi ratory tract, then individual cells by penetrating the Rhinovirus > 110 Common cold cell membrane and displacing host control mech Coxsackie A 23 Upper respiratory tract anisms. Usually the cell produces many viruses infection which are then released by either cell lysis or by Coxsackie B 6 Infection, especially common budding from the cell. It is important to be aware cold that this method ofreproduction renders the virus Echovirus 31 Common cold resistant to all the common antibiotics. Conse quently, the routine prescription of antibiotics for Adenovirus 33 Upper and lower respiratory tract infection viral upper respiratory tract infections is at best useless and may encourage resistance to antibiotics Coronavirus ? Common cold in potentially harmful bacteria present in the host. Respiratory syncitial Upper respiratory tract The host responds to the viral infection by virus infection bronchiolitis, mobilising antibody and cellular defences and pro pneumonia ducing interferon, which inhibits viral reproduc Influenza (ABCh 3 Influenza: upper respiratory tion. It is only if these defences are. overwhelmed tract infection that severe illness occurs. Immunisation is effec Parainfluenza Upper respiratory tract tive against certain viral illnesses by mobilising host infection defences with a pseudo-infection. However there Herpesvirus: Epstein- Infectious mononucleosis are innumerable viruses which can cause upper Barr virus respiratory tract infections so immunisation is not practical. Table I shows the virus groups which are most commonly implicated in acute coryza (com is not immune to the virus, i.e. has no previous mon cold) in man. exposure, the antibodies present will not recognise the virus. The virus is then able to bind to the cell 1.1 Immune Mechanisms surface on the underlying mucosa. Once the cell is There are 3 main defences of the body to in entered, the viruses multiply, are released and fection. One is the nonspecific humoral system, spread to adjacent cells and via the blood to distant consisting of factors such as complement and in cells. Here the second arm ofthe body's immunity, terferon, and there are specific antibody and cell cell-mediated immunity, is important. When the mediated defences (fig. 1) which are stimulated by body encounters a foreign organism, in addition to exposure to the infecting agent. The ability of a the production ofantibody, lymphocytes and mac virus to infect the human host depends on the abil rophages are activated which infiltrate the virus ity of the virus to survive in the environment and infected tissues, producing an intense inflamma on its successful transmission to host cells. Viruses tory reaction, killing cells containing any viral anti causing upper respiratory tract infections are in gens. haled into the nose and/or mouth. They are usually Acquired immunity consists ofan immunolog trapped by the surface mucus of the upper respi ical 'memory'. This allows rapid production ofspe ratory tract. Here the virus may encounter an anti cific antibody and rapid proliferation of killer T body, secretory 19A, which is produced locally in lymphocytes and macrophages. Immunity to vi the mucosa. The antibody recognises particular ruses may last for life, or only for a few weeks. molecules on the cell surface, binds with them and Prolonged immunity is characteristic of infections initiates the destruction of the virus. If the subject where the virus has entered the blood stream, such Viruses and Sports Performance 298

Immune response to viral invasion ! •

B lymphocyte T lymphOCyte !

Activated Plasma cells Macrophage T lymphOCyte ! 1

Specific Cytotoxic Killer cells antibodies lymphocyte I ~ ~ ~ IgM II IgA II IgG I

Fig. 1. Schematic representation of the interactions in the specific immune system. as mononucleosis. Common cold viruses which 1975). Once infected, an individual carries the vi produce only local effectsmay produce only a short rus in his or her lymphocytoid cells in a latent form lived immunity. Other nonspecific factors, such as for life, but, despite this, clinically identifiable white cell phagocytosis, interferon and comple reactivation of Epstein-Barr virus is rare. ment, also help the body fight infection. Most patients with infectious mononucleosis re call a 3 to 5 day prodromal period of malaise, fa 2. Common Viral Illnesses tigue,anorexia and mild headache. The patient then 2.1 Epstein-Barr Virus develops pharyngitis, with fever, and enlarged cer vicallymph nodes. By the second week, 50 to 70% Epstein-Barr virus is the causative agent of the have an enlarged spleen and occasionally the liver disease infectious mononucleosis, also known as is enlarged. The acute phase of the illness lasts 5 glandular fever, common in adolescents and young to 15 days (Hoagland 1967) and is followed by a adults (Henle et al.1974; Neiderman et aI. 1968). period of gradual improvement. Occasionally a It is estimated that it affects between 2 and 6 per prolonged symptomatic illness can occur (Chretien 10,000of the population in anyone year (Edmond et al. 1977). Viruses and Sports Performance 299

It has been suggested that infectious mononuc ally produces a short term infection without long leosis is a less severe disease in athletes (Dalrymple term effects. Infections in children are nearly al 1965) and I have seen 2 athletes with deterioration ways symptomless, but in young adolescents, the ofathletic performance as their only symptom both ratio of overt to symptomless infection increases of whom had evidence of recent infectious mono to between one-third and two-thirds. Occasionally nucleosis (Roberts 1985). Further evidence in sup patients do not fully recover for months or years port of this suggestion comes from a survey of and there is increasing evidence that this prolonged physically active army cadets in whom 75% of Ep illness is related to a latent infection of the B stein-Barr virus infections were asymptomatic (Le lymphocytes which is subject to reactivation. Tobi hane 1970). However, fatigue and lassitude in nor et al. (I 982) and Straus et al. (1985) have reported mal subjects could be equivalent to poor abnormalities ofimmune function in patients with performance or loss of form in trained athletes. apparent persisting infection, but Jones et al. (1985) Most patients have recovered within 2 months after found no consistent difference in lymphocyte func the onset of illness, although athletes may take tion. Whether this abnormality is cause or effect longer to attain full fitness. could only be determined by a prospective study Complications of infectious mononucleosis in of a large population of young adults. clude splenic rupture which has been reported as occurring in 0.1 to 0.2% ofall cases (Hoagland 1967) 2.2 Coxsackie Group but Rutkow (I978) on analysis of world literature found spontaneous splenic rupture to be very rare. Coxsackie viruses are part of the enterovirus Splenic rupture occurs when the spleen is enlarged, group. Coxsackie virus infection may be asymp although this may not be clinically detectable (Maki tomatic or cause mild common cold symptoms. & Reich 1982). Splenic ruptures occur predomi However, Coxsackie infections have also been as nantly (90%) in males and there appears to be no sociated with myocarditis and aseptic meningitis relationship between severity of illness and likeli (Grist et al. 1978). There is naturally a bias towards hood of splenic rupture (Maki et al. 1982). If am investigation ofpatients with symptoms, so the true picillin is given during an acute attack ofinfectious incidence of subclinical infection is unknown, but mononucleosis, a maculopapular rash develops, re 2 out of 12 athletes that I have seen (Roberts 1985) gardless of previous exposure to the antibiotic in with loss of form and no other symptoms of viral 90% of cases (McKenzie et al. 1986). infection have evidence ofrecent Coxsackie B group The condition is diagnosed by examining the infection shown by rising antibody titres. There is blood film for atypical lymphocytes (Downey et al. a high prevalence of immunity to Coxsackie vi 1923) and by serological testing. There are no spe ruses (Lau 1983) which makes assessment of cur cific treatments for the condition. Ampicillin should rent disease difficult. The development of reliable be avoided. A recent report of a pilot study using antiviral IgM antibody assays, high levels ofwhich cephalexin in infectious mononucleosis seemed to are evidence ofrecent infection, should help clarify shorten the course of the disease (Lakic 1983), but the situation (Dories & Ter Meulen 1983). a properly controlled trial would be required to Lau (1983) surveyed cardiac and non-cardiac confirm this observation. Corticosteroids have also patients and also a normal population for evidence been used to accelerate the resolution ofsymptoms of recent Coxsackie virus infection. Between 30 and (Bolden 1972) but there is no evidence that they 60% of normal subjects had evidence of previous reduce the complication rate. Coxsackie BI-5 infection; 8.6% of non-cardiac patients had evidence ofrecent Coxsackie infection 2.1.1 Prolonged Illness after Infectious and 8.9% of non-cardiac patients had evidence of Mononucleosis recent Coxsackie infection. Thus, Coxsackie virus Primary infection with Epstein-Barr virus usu- infection is a common condition. Viruses and Sports Performance 300

Postviral fatigue syndrome (or epidemic myalgic and cell-mediated immunity. A direct action ofthe encephalomyelitis) is an increasingly recognised central nervous system on thymus (Bullock & condition. It usually occurs after Coxsackie virus Moore 1980) or spleen (Williams et al. 1981) may infection (Behan & Behan 1980), although it has modulate the immune system and corticosteroids also been diagnosed after influenza and varicella which are elevated by stress may also be import virus infections. The patient complains of persist ant. Dorian et al. (1981) have shown that lympho ing malaise, fatigue, lassitude and aching muscles. cyte response to mitogens is impaired when under Recent work has demonstrated subtle abnormali stress. Strenuous exercise in mice has been shown ties of skeletal muscle metabolism (Arnold et al. to increase susceptibility to Coxsackie B3 infection 1984)confirming that the condition has a physical (Reyes & Lerner 1976) and Douglas & Hanson basis. Unfortunately, symptoms may persist for (1978) have reported an increased incidence of up months or years and there is no treatment. Ob per respiratory tract infection in training athletes. viously, this condition would have a devastating Thomasi et al. (1982) examined secretory IgA lev effect on sports performance. els in Nordic cross-country skiers before and after national cross-country races. They found a signifi 2.3 Other Viruses cant fall in mucus IgA, one of the main defences of the upper respiratory tract to infection. Thus, Rhinoviruses are in the same family as the either exercise itself, or the emotional stress at Coxsackie group. There are more than 100 differ tached to athletic competition may render the ath ent viruses in this group that produce the common lete more susceptible to various infectious diseases cold symptoms in man. Adenovirus produce mainly of the respiratory tract, although this is by no means eye disease and pharyngitis, but a few serotypes proven (Simon 1984). (types 3,4,14,21) produce upper respiratory symp toms. Influenza A produces an upper respiratory 4. Physical Exercise and Viral Infections tract infection with an associated malaise which is usually quite severe. It tends to occur in pandem If upper respiratory tract infections are subclin ics. Influenza Band C have a more sporadic pat ical, do they matter? Sudden death occurs in young tern to outbreaks and produce less severe symp people associated with vigorous exercise. In a sur toms (see table I). Most of the viruses listed in table vey of 78 sudden deaths during, or immediately I have been associated with nonspecific debilitat after, exercise, Jokl and Mclellan (1971) found a ing illnesses. history of recent upper respiratory tract infection in 5 out of78, cardiovascular problems accounting 3. Are Athletes at Increased Risk of for most of the remainder. It is difficult to prove Infection? that intercurrent viral illness increases the risk of death during exercise, but there are numerous The fact that most athletes are gregariousin their anecdotal reports ofdeath in young healthy people training habits will expose them to an increased who undertake vigorous exercise during an acute risk of cross-infection from their fellows. However, viral illness. The predilection of Coxsackie virus there may also be more subtle reasons for in for the heart muscle to produce myocarditis or per creased susceptibility to infection. Various forms icarditis (Smith 1966) could explain, by increasing of stress have been shown to alter immune func the risk of acute arrhythmias, sudden death in tion. Jemmott et al. (1983) showed in a group of young fit people. Burch (1979) advised that young dental students, that levels of secretory IgA in sa people who stress themselves with vigorous, pro liva fell during the stress of major examinations. longed physical exercise during upper respiratory They suggestedthat the increased adrenaline levels tract infections have an increased risk of devel associated with stress may inhibit both humoral oping viral cardiomyopathy, causing irreversible Viruses and Sports Performance 301

damage to the heart muscle. This illness may have the virus may be disseminated via the blood stream a fatal outcome. Burch (1979) stated that strenuous to many organs. Furthermore, I have already de physical exercise should be avoided for 2 weeks scribed evidence that infections may run a pro after the infection has resolved. tracted course. One way in which viruses could af Sutton et al. (1967) described a case of a pre fect performance is by a direct effect on skeletal viously fit 42-year-old patient who undertook a muscle. Friman (1977) tested a group of subjects vigorous swimming session while recovering from who had recent viral infections. He assessed iso an upper respiratory tract infection. He subse metric strength in the recently infected subjects and quently died of heart failure. At postmortem exam in a matched control group. There was a significant ination, Coxsackie B4 virus was isolated from the reduction (up to 15%) in isometric strength in the myocardium. Pether (1982) described 2 patients infected subjects which had not fully recovered to who exercised while convalescing from influenza B reference values one month after illness. Astrom et upper respiratory tract infections. Both contracted al. (1976), in a controlled test, examined muscle bacterial meningitis and one died. Pether suggested tissue obtained from patients recovering from re that heavy exercise might have been a contributory cent viral or mycoplasma illnesses. They found sig factor to the increased susceptibility to infection nificantly reduced muscle enzyme activity (glycer and advised against strenuous exercise for 1 week aldehyde phosphate, lactate dehydrogenase, after a flu-like illness. Jodselson et al. (1980) de cytochrome oxidase and citrate synthetase) in in scribed a 26-year-old runner who developed acute fected patients. Furthermore, electron microscopy rhabdomyolysis (acute muscle destruction) follow showed focal abnormalities in muscle ultrastruc ing a training run. He required emergency treat ture. These changes had almost completely re ment to prevent renal failure developing. He had solved when muscle biopsy was repeated 3 months no symptoms suggestive of recent viral illness, but after illness. The muscle enzyme changes described investigation revealed evidence of acute echovirus were similar to those found in certain muscle dis 9 infection. eases with muscle weakness as a main symptom. In people with overt asthma, or who have an Electron microscopic appearances were nonspe asthmatic tendency, it is well-recognisedthat upper cific, as occurs in most muscle diseases. Excess gly respiratory tract viral infections may worsen asth cogen stored in abnormal muscle would suggestthat matic symptoms (Empey et al. 1976). Exercise in muscle energy utilisation had been altered. duces an asthmatic attack in 70%of susceptible in A recent case report (Arnold et al. 1984) de dividuals (McNeill et al. 1966)which, in turn, may scribed a patient with postviral (herpes zoster) fa lead to an influx of inflammatory cells, termed the tigue syndrome. Using nuclear magnetic resonance 'late response' (Durham & Kay 1985), thereby in they demonstrated early excessive intracellular creasing the asthmatic state. The late, or inflam acidosis during muscular exercise. They suggested matory, response may be prevented by appropriate that the defect might involve the interaction be treatment so it is important to ensure athletes with tween glycolytic and oxidative metabolism within asthmatic tendencies are carefully monitored dur the muscle cell. In contrast, a study by Friman et ing upper respiratory tract infections, avoid stren al. (1985) using inoculated virus (sandfly fever vi uous exercise and have optimum anti-asthma rus) to produce pyrexia found that isometric treatment. strength was reduced during the pyrexial phase but recovered when the body temperature returned to 5. Athlete's Performance normal. However, this is an unusual viral infection and may not be representative of viral illnesses in Why should viral illness affect an athlete's per man. formance? Despite the occurrence of either local There is a well-known phenomenon in horse upper respiratory symptoms or even none at all, racing circles called 'the poor performance syn- Viruses and Sports Performance 302

drome' (Mumford & Rossdale 1980). It is associ 7. Conclusions ated with upper respiratory tract infections in horses. A prospective study of British horse racing Viral infections are common. They can be stables was organised by the Horse Betting Levy asymptomatic or debilitating. Viruses enter the cell board with 600 horses being sampled annually for and take over cellular mechanisms to reproduce. 8 years. They found evidence of frequent subclin As a result, they are not affected by conventional ical infections, some of which were associated with antibiotics. There are various humoral and cell the 'poor performance syndrome' (Powell et at. mediated mechanisms which aid recovery from 1978). There are obvious parallels with athletes in viral infections. Various viruses produce well-re training and horse-racing training, although defi cognised acute effects but may also be followed by nite conclusions cannot be drawn. more subtle changes. There are risks of serious complications including death, if strenuous exer cise is undertaken during an acute viral infection. 6. Resumption of Training Viral infections may present with loss of perform ance as the only symptom. There are many pos When should an athlete resume activity? The sible explanations of this loss of form, but there is best studied ofviral infections affecting sportsmen evidence from several approaches that skeletal is infectious mononucleosis. The main complica muscle function may be altered. tion of this infection is splenic rupture which may Exercise perse may alter the immune response be spontaneous and occurs in the first 21 days of such that the individual is more susceptible to viral the illness (Hoagland 1967)or later (Rutkow 1978). infection. Some surveys have confirmed that ath Most physicians therefore arbitrarily recommend letes in training have an increased incidence ofup that strenuous activity be avoided for I month after per respiratory tract infections. onset of illness (Shields 1983; Van et at. 1978), al Athletes should not undertake strenuous train though Rutkow (1978) recommends a 6 month rest ing routines when they have any symptoms of in after resolution of the illness before full athletic ac fection. Furthermore, it is worth arranging a medi tivity is resumed. An alternative approach is to cal check-up to exclude a viral cause if an athlete monitor the size of the spleen by x-ray of the ab develops unexplained loss of form. domen (Riemenschneider & Whelan 1965) or ultrasonography (Kardel et al. 1971) and to delay References the return to activity until the spleen has returned Arnold DL. Bone PJ, Radda GK, Taylor DJ. Excessive intra to normal size. cellular acidosis of skeletal muscle on exercise in a patient with post viral exhaustion syndrome. Lancet I: 1367-1369, 1984 With other viral infections there are no hard and Astrom E, Friman G, Pilstrom L. Effectof viral and mycoplasma fast rules. The article by Friman (1977) demon infections on ultrastructure and enzyme activities in human skeletal muscle. Acta Pathologica Microbiologica et Imrnu strated that muscle abnormalities had not fully re nologica Scandinavica (Section A) 84: 113-122, 1976 solved I month after the onset of symptoms due Behan PO, Behan WMH. Epidemic myalgic Encephalomyelitis. In Rose FC (Ed.) Clinical Neuroepidemiology, pp.374-383, to a variety of viral infections. I suggest that if the Pitman Medical, Tunbridge Wells, 1980 athlete has symptoms of a common cold with no Beneson AS. Acute viral respiratory disease in control of com municable diseases in man, pp. 262-266, American Public constitutional upset then training may be safely re Health Association, Washington, 1975 sumed a few days after the resolution of symptoms. Bolden KJ. Corticosteroids in the treatment of infectious mono nucleosis. Journal of the Royal College of General Practition However, if there are symptoms or signs of sys ers 22: 87-95, 1972 temic involvement, e.g. extreme tiredness, muscle Bullock K, Moore RY. Nucleus ambiguous projections of the thy mus gland: possible pathways for regulation of the immune aches or swollen lymph glands, then a full month response and the neuro-endocrine network. (Abstract.) Anat should be allowed before resumption of full train omy Records 196: 25, 1980 Burch GE. Viral diseases of the heart. Acta Cardiologica I: 5-9, ing. 1979 Viruses and Sports Performance 303

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