OPINION
COVID-19
and physical activity: What is the relation between exercise immunology and the
current pandemic situation?
COVID-19 e atividade
física: qual a relação entre a imunologia do exercício e a atual pandemia?
Guilherme Gomes Azizi1,6,
Marco Orsini2,3,4, Sérgio Duarte Dortas
Júnior1,5, Paulo César Vieira2,6, Ricardo Steiner de
Carvalho6, Cláudio Sérgio da Rocha Pires2,6, Sebastião
Carlos Ferreira da Silva6 Bruno Mendes de Sá Pinto6,7,
Carlos Eduardo Cardoso4, Adalgiza Mafra Moreno2, Marco Antonio Alves Azizi2,6
1Serviço de Imunologia,
Hospital Universitário Clementino Fraga Filho (HUCFF-UFRJ)
2Universidade Iguaçu –
UNIG
3Serviço de
Neurologia/Neurocirurgia Universidade Federal Fluminense – UFF
4Universidade de
Vassouras - USS
5Departamento de Clínica
Médica - Universidade Federal do Rio de Janeiro - UFRJ
6Fluminense Football
Club
7Hospital Casa de
Portugal
Received 2020, May 2; accepted 2020, May 5.
Corresponding author: Guilherme Azizi, Rua Emílio Miranda, 28, 21211720 Rio de Janeiro RJ, Brazil
Guilherme Gomes Azizi: gazizi247@gmail.com
Marco Orsini: orsinimarco@hotmail.com
Sergio Duarte Dortas Júnior: sdortasjr@gmail.com
Paulo César Vieira:
vieira.czar@gmail.com
Ricardo Steiner de
Carvalho: rsteiner21@hotmail.com
Cláudio Sérgio da Rocha
Pires: drclaudiopires@gmail.com
Sebastião Carlos
Ferreira da Silva: drsebastiaocarlos@hotmail.com
Bruno Mendes de Sá
Pinto: bmsp-88@hotmail.com
Carlos Eduardo Cardoso:
prppg@universidadedevassouras.edu.br
Adalgiza Mafra Moreno:
adalgizamoreno@hotmail.com
Marco Antonio Alves Azizi:
marcoazizimed@gmail.com
Exercise immunology is a strong and mysterious science in sports
medicine, but studies were origin more than a 100 years ago, when Schulte had
already described an exercise-induced leukocytosis as early as 1893 [1]. Since
then, both cross-sectional and longitudinal studies in humans have demonstrated
the profound impact that exercise can have on the immune system. That is
exactly why it is fundamentally important in this pandemic time to elucidate
many questions and direct the athletes and non-athletes to the due care.
The current situation started with a cluster of pneumonia patients with
an unidentified cause emerged in Wuhan, Hubei Province, China, in December 2019
[2]. Approximately 2 months later the World Health Organization (WHO) announced
a standard format of Coronavirus Disease-2019 (COVID-19) [3] on the same day
named as SARS-CoV-2 [4].
After sequence and evolutionary tree analysis, SARS-CoV-2 was considered
as a member of b-CoVs [5,6] like SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV)
[7].
Respiratory droplets and contact transmission are the main transmission
routes, but SARS-CoV-2 can be detected in the urine and stool, which gets a
possible risk of fecal-oral transmission [8]. However, there is still no evidence
that corroborates this route, but all possible transmission routes need
vigilance during the physical exercise. COVID-19 has a probable asymptomatic
incubation period (2 -14 days) which the virus can be transmitted [9].
SARS-CoV-2 has a R0 of 2.2-2.6, everyone has the potential to spread the
infection to 2.2 other people [10].
Initially, the most common symptoms were reported in 41 patients with
fever (98%), cough (76%), and myalgia or fatigue (44%) sputum production (28%),
headache (8%), hemoptysis (5%), and diarrhea (3%). More than half of patients
developed dyspnea Blood test showed normal or reduced (25%) leukocytes count
and lymphopenia (65%) [11].
Another study showed 140 patients diagnosed as COVID-19, where the most
common symptoms were fever (91.7%), cough (75%), fatigue (75%) and chest
tightness or dyspnea (36.7%). 39.6% of them complained gastrointestinal
symptoms. 90 (64.3%) patients had comorbidity, the most common of which were
chronic diseases, such as hypertension (30%) and diabetes (12.1%). Only two
COPD patients were identified, and 2 patients reported chronic urticaria. Other
allergic diseases as asthma, allergic rhinitis, food allergy, atopic dermatitis
were not self-reported [12].
Persons older than 60 years old with hypertension, diabetes, COPD,
cardiovascular, cerebrovascular, liver, kidney, and gastrointestinal diseases
are more susceptible to the infection by SARS-CoV-2 and experience higher
mortality when they develop COVID-19 [13-15].
These clinical features suggested the possibility of involvement of
highly pro-inflammatory condition in the disease progression and severity. This
early high rise in the serum levels of pro-inflammatory cytokines were also
observed in SARS-CoV and MERS-CoV
infection, suggesting a potential similar cytokine storm-mediated disease
severity [16,17].
In severe cases of SARS-CoV or MERS-CoV infection, there is an increased neutrophil and
monocyte-macrophages influx [18,19]. With all knowledge accumulated about
previous coronavirus infections, innate immune response plays a crucial role in
antiviral and against coronavirus responses.
Thereby, we need to understand immune and inflammatory conditions that
involve COVID-19. A recent study of 41 hospitalized patients with high-levels
of pro-inflammatory cytokines including IL-2, IL-7, IL-10, G-CSF, IP-10, MCP-1,
MIP-1A, and TNF-α were observed in the COVID-19 severe cases [11].
Another report demonstrated increased cytokine levels (IL-6, IL-10, and
TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-g expression in CD4+ T cells are associated with severe COVID-19 [20].
Named “cytokine storm” it may have a major role in the pathogenesis of
COVID-19 may to be related a downstream cytokine cascade involving IL-1, IL-6,
IL-12 and TNF-α [21], followed by the development of lung tissue damage
resulting in ARDS, sepsis, and organ failure. The risk of respiratory failure
in patients with circulating IL-6 > 80 pg/ml was
22-fold higher with a median time to mechanical ventilation of 1.5 days [22].
Recently, a histopathological study with 4 patients in pos-mortem
presented a rigorous lungs examination showing a bilateral diffuse alveolar
damage with a comparatively mild-to-moderate lymphocytic infiltrate, composed
of a mixture of CD4+ and CD8+ lymphocytes. The dominant process in all cases
was consistent with diffuse alveolar damage, with a mild to moderate
mononuclear response consisting of notable CD4+ aggregates around thrombosed
small vessels, and significant associated hemorrhage [23].
A rapid and well-coordinated innate immune response is the first line of
defense against viral infections, but dysregulated immune responses may cause
immunopathology [24-26]. The innate immune system utilizes pathogen associated
molecular patterns (PAMPs) to recognize the invasion of the virus. After a long
intracellular signaling cascade, transcription factors induce expression of
type I IFN and other pro-inflammatory cytokines and respond at the first-line
defense [27]. The interferon (IFN) type I is essential to the innate immune
response against viral infection in association with controlling viral
replication and effective adaptive immune response. However, SARS-CoV and MERS-CoV, a SARS-COV-2
similar virus employs multiple strategies to interfere with the signaling
leading to production, function or associated to type I IFN cascade [27-29].
When talking about social isolation and pandemic, there is a need to
understand behavioral aspects that can influence the health of population,
being exercise a factor of interest, which can have both positive and negative
effects on immune function and possible susceptibility to illnesses and upper
respiratory diseases.
A single bout of exercise has a profound effect on total number and
composition of circulating leukocytes. After a dynamic exercise (minutes) the
total leukocyte count increases two- to threefold whereas prolonged endurance
exercise (30min-3h) counts for a fivefold increment. Exercise-induced leukocytosis,
mainly neutrophils and lymphocytes with a smaller contribution being made from
monocytes, is a transient phenomenon, with normal counts returning to pre
exercise levels (6-24 h) after exercise cessation. 30–60 min after exercise
cessation, a rapid lymphocytopenia [30-32] occurs concomitantly with a
sustained neutrophilia [30,33].
Acute exercise causes substantial increases in hemodynamics, which place
greater mechanical forces on the endothelium, thereby the leukocytes to
demarginate and enter the free-flowing circulation, in association there are
more levels of shear stress within the capillary structures, driving more
leukocytes into the peripheral circulation.
Physical activity results in the secretion of catecholamines and
corticotropin releasing hormone and cortisol, which are importantly responsible
for the mobilization of monocyte during exercise, lymphocyte within minutes of
engaging in dynamic exercise and neutrophil that continue their increase, often
reaching peak values within a few hours after exercise cessation [34,35].
Many studies demonstrated an important innate cells response to acute
moderate-intensity exercise, for example, it enhances neutrophil chemotaxis
[36], as phagocytosis is enhanced immediately after a single exercise bout
[37], but neutrophil degranulation in response to bacterial stimulation appears
to be impaired [38]. After moderate intensity exercise the neutrophil oxidative
burst continues to be enhanced, however, this is not true after exhaustive or
prolonged exercise [38,39], other findings are related to well-trained athletes
that are sensitive to the increases of training load, what present loss-making
alterations in the neutrophil-monocyte oxidative burst, CD4/CD8 ratios,
lymphocyte proliferation, antibody synthesis, and NK-cell cytotoxic activity
[41-45]. What can occur during 1-3 weeks of intensified training, generating
reductions in neutrophil function, lymphocyte proliferation and mucosal IgA
[42,43,46].
Immunoglobulin A (IgA) is an important part of the mucosal immune
system. There is not a consensus on the impact of acute exercise on salivary
IgA (sIgA), because many factors may influence the
response like a training status, intensity and duration of the exercise bout,
saliva collection, nutrition [30].
The inverse relationship between sIgA
concentrations and risk of airway infections in exercising and non-exercising
populations has demonstrated differences between these two populations [46-48].
The impact of exercise intensity on sIgA
concentrations and secretion rates has demonstrated greater decreases in sIgA associated with prolonged high intensity exercise,
whereas moderate increases in sIgA occur in response
to short duration moderate intensity exercise [48-51].
A study monitored the stress-induced alteration in concentrations of sIgA and cortisol, and the incidence of upper respiratory
tract infections over the course of a 9-week season in college. 14
student-athletes and 14 college students, all being young and women, demonstrate
decreased levels of sIgA and increase in the indices
of training (load, strain, and monotony) were associated with an increase in
the incidence of illness during the 9-week competitive soccer season [52].
The “open window” hypothesis is an important idea that explains when an
endurance athlete repeats bouts of acute strenuous exercise without adequate
recovery why opportunistic infections may enjoy this till 72h after the
exercise [53]. Although exercise immunology researchers discuss the “open
window” and if it is the only real association between upper respiratory
infections or symptoms and the strenuous exercise, a large body of evidence
supports the proposition that elite athletes undertaking prolonged heavy
intensive exercise can exhibit immune changes, in association with
physiological, metabolic, and psychological stressors, and pathogen/allergen
exposure, that increase the risk of infection and/or airway inflammation [54].
Otherwise, regular moderate-intensity exercise has been linked a to
better vaccine responses [55,56], lower numbers of exhausted T-cells [57],
increased T-cell proliferation [58] lower levels of circulating inflammatory
cytokines [59], increased neutrophil phagocytic activity [60], greater NK-cell
cytotoxic activity [61], indicating that regular moderate-intensity exercise is
capable of improving, or maintaining, immunity across the life [62]. In
addition, may help prolong or reinvigorate thymic activity, which we can
observe with increased plasma levels of IL-7 [63].
Concurrently, subtle elevations in stress hormones released from
skeletal muscle, notably interleukin-6 (IL-6), is observed during acute bouts
of moderate-intensity exercise; however, the pleiotropic nature of IL-6 appears
to provide protection (versus harm) to immunity via directly suppressing potent
inflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α)] in the
lungs, creating an anti-inflammatory milieu for several hours post-exercise
[64].
The literature presents many studies about competitions that
demonstrates the profile between athlete high-level moment and illness. In the
Rio Olympic Games, in a total, 11 274 athletes (5089 women, 45%; 6185 men, 55%)
was reported for Rio 2016 medical staff 651 illnesses over the 17-day period
(47% affected the respiratory and 21% the gastrointestinal systems) [65].
In the 2010 Fifa World Cup Ninety-nine
illnesses were reported in 89 players (12.1% of all players). Most illnesses
affected either the respiratory (40; 40.4%) or the digestive (26; 26.3%)
system. The most frequent diagnoses were acute upper respiratory tract
infection (31; 31.3%) and gastroenteritis (21; 21.2%) [66].
Another factor is the carbohydrate availability, which an essential
component to the immune performance, because to perform in a state of glycogen
depletion there is an increased catecholamine and glucocorticoid, creating a
greater decline of the T-cell, NK-cell, and neutrophil and depressed immune
function compared to exercise on a normal or high carbohydrate diet [67,68].
Therefore, the previous extensive medicine and immunological knowledge
provide us with the understanding that the increased incidence of infection in
athletes is multifactorial maybe physical, psychological, environmental or
nutritional what suppress the immune system [69]. In addition, a variety of
causes can be an association with airway symptoms and could include physical
damage such as drying of the airways [70], asthma and allergic airway
inflammation [71] and psychological impacts of exercise on membrane integrity
[72].
Special considerations regarding exercise and immune health must be
addressed for older adults who represent the growing population globally, and
incidentally are the most sensitive to developing infectious disease. Immunosenescence described as the phenomenon responsible
for the inextricable deterioration of immune competency that occurs with
increasing age, is believed to be the primary factor explaining the lowered
immune vigilance, poorer responses to vaccinations and the greater risk, and
morbidity, associated with infectious diseases, including COVID-19 outbreak.
Given the already described beneficial effects of habitual moderate-intensity
exercise on aspects of immunity in younger populations, physical activity is
suggested to be a logical therapeutic strategy to abate aging effect son the
immune system. It is well supported by a growing body of evidence from
epidemiological and experimental studies in older adults indicating that
regular participation in moderate-intensity exercise attenuates age-related
oxidative stress and reduces the frequency of various immune biomarkers that
are associated with compromised immunity, thereby suggesting that exercise may
delay the onset of immunosenescence and attenuate the
risk of infection [73].
Suggestions
In consideration of the knowledge previously explained and possible
association to doubt moment and SARS-COV-2 risk contagion, this research group
proposed some suggestions from athletes and non-athletes during the COVID-19
pandemic, looking up a health manutention and good conditions to a future
return to the competitions. Thereby, avoid SARS-COV-2 infection and/or severe
complications.
- We
considered that this moment is not adequate to a high level of training/extreme
physical effort. Preserve your regular physical activity and moderate
intensity, avoiding greater risks of contamination and detraining. You must
know that for each week of total inactivity, you can loss of up to 10% of
fitness [64].
- Measures
to reduce or stop smoking has fundamental importance. Approximately six million
people worldwide die due to tobacco use each year [74]. The cigarette
contributes to the pathogenesis and a recognized risk factor of chronic
obstructive pulmonary disease (COPD), hypertension, cardiovascular disease,
cancer, chronic systemic diseases with inflammatory components such as
atherosclerosis, and type 2 diabetes mellitus [75,76]. Smokers are vulnerable
to respiratory viruses and the tobacco upregulates the angiotensin-converting
enzyme-2 (ACE2) receptor compared to non-smokers, irrespective of tissue subset
or COPD status, increasing pulmonary ACE2 expression by 25%, which is the
receptor for both the severe acute respiratory syndrome (SARS)-coronavirus
SARS-CoV and SARS-CoV-2. Thereby, smokers can be more
susceptible to the development of COVID-19 [77,78].
- Avoid
changes in your treatment for chronic diseases, pulmonary or not, without the
advice of your physiciam.
- Avoid
medications and formulas without a scientific basis for prevention and
treatment to COVID-19 infection
- Avoid
alcohol ingest and maintain your sleep quality
- Aerobic
or resistance activities in safe environments and respecting the adequate
social distance. Preferably, in covered and closed places that can be
thoroughly cleaned after the activity and following the recommendations of the
competent local authorities. It is so necessary because droplets travel a
distance 1.8 meters in the air and the average life of COVID-19 is 2.7 hours in
the air and 13 hours on steel [77].
- Maintain
the hygiene of your sports equipment.
- Make
an adequate ingest of proteins and carbohydrates, always consulting your
support professional, prioritizing a multidisciplinary work between
nutritionists, doctors, physical educators, in addition to your mental health,
and those around you, seek assistance from your sports psychologist and other
competent professionals for your health.
- We
do not recommend training in case of fever in a COVID infection or others
suggest symptoms.
- Exercise
at home using various safe, simple, and easily implementable exercises is well
suited to avoid the airborne coronavirus and maintain fitness levels. Examples
of home exercises include walking in the house, lifting and carrying food bags,
alternating leg, stair climbing, stand-to-sit and sit-to-stand using a chair
and from the floor, and sit-ups and pushups [78-80].
Conclusion
In conclusion, regular exercise training of moderate intensity is
believed to exert beneficial effects on immune function and must be associated
to the suggestions.
We sought to clarify the importance of the regular exercise of a
moderate intensity and the likely risks evolvement to inadequate exercise
associated with poor diet and habits, and physiological alteration. In this
way, we advise moderation, tranquility, and patience in this pandemic period.
References
- Shephard
RJ. The history of exercise immunology. In: Tipton C, ed. The history of
exercise physiology. Champaign, IL: Human Kinetics; 2010
- Li
Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY et
al. Early transmission dynamics in Wuhan, China, of novel coronavirus–infected
pneumonia. N Engl J Med 2020;382(13):1199-207
https://doi.org/10.1056/nejmoa2001316
- World
Health Organization Press Conference. The World Health Organization (WHO) has
officially named the disease caused by the novel coronavirus as COVID-19.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
- Gorbalenya AE, Baker SC, Baric
RS, de Groot RJ, Drosten C, Gulyaeva
AA, Haagmans BL, Lauber C, Leontovich
AM, Neuman BW et al. Severe acute respiratory syndrome-related coronavirus: The
species and its viruses—A statement of the Coronavirus Study Group. Nature
Microbiology 2020. https://doi.org/10.1038/s41564-020-0695-z
- Zhu
N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R et al. A
novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020;382(8):727-33.
https://doi.org/10.1056/nejmoa2001017
- Zhou
P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL et
al. A pneumonia outbreak associated with a new coronavirus of probable bat
origin. Nature 2020;579(7798):270-3.
https://doi.org/10.1038/s41586-020-2012-7
- Weiss SR, Leibowitz JL.
Coronavirus pathogenesis. Advance in virus research; 2011. p.85-164.
https://doi.org/10.1016/b978-0-12-385885-6.00009-2
- General
Office of National Health Commission; General Office of National Administration
of Traditional Chinese Medicine. Diagnostic and treatment protocol for Novel
Coronavirus Pneumonia.
https://www.chinadaily.com.cn/pdf/2020/1.Clinical.Protocols.for.the.Diagnosis.and.Treatment.of.COVID-19.V7.pdf
- Center
for Disease Control and Prevention. Atlanta: CDC. Symptoms of Novel Coronavirus
(2019-nCoV). 2020 https://www.cdc.gov/coronavirus/2019-ncov/
- Wu
F, Zhao S, Yu B, Chen YM, Wang W, Song ZG et al. A new coronavirus associated
with human respiratory disease in China. Nature
2020;580(7803):E7. https://doi.org/10.1038/s41586-020-2202-3
- Huang
C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X et al. Clinical features of patients infected with 2019 novel coronavirus in
Wuhan, China. Lancet 2020;395(10223):497-506.
https://doi.org/10.1016/s0140-6736(20)30183-5
- Zhang
JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, Akdis CA, D. Clinical characteristics of 140 patients
infected with SARS-CoV-2 in Wuhan, China. Allergy 27/02/2020.
https://doi.org/10.1111/all.14238
- Arentz M, Yim
E, Klaff L, Lokhandwala S, Riedo FX, Chong M, Lee M. Characteristics and outcomes of
21 critically Ill patients with COVID-19 in Washington State. JAMA
2020;323(16):1612. https://doi.org/10.1001/jama.2020.4326
- Team
TNCPERE. The epidemiological characteristics of an outbreak of 2019 novel
coronavirus diseases (COVID-19) - China, 2020. China CDC Weekly 2020;2:113-22.
- Zhou
F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei
Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk
factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a
retrospective cohort study. Lancet 2020;395(10229):1054-62.
https://doi.org/10.1016/S0140-6736(1020)30566-30563
- Mahallawi WH, Khabour OF, Zhang Q, Makhdoum HM,
Suliman BA. MERS-CoV infection in humans is
associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine 2018;104:8-13.
https://doi.org/10.1016/j.cyto.2018.01.025
- Wong
CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH et al. Plasma inflammatory cytokines
and chemokines in severe acute respiratory syndrome. Clin Exp Immunol
2004;136(1):95-103. https://doi.org/10.1111/j.1365-2249.2004.02415.x
- Perlman
S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for
SARS. Nat Rev Immunol 2005;5(12):917-27. https://doi.org/10.1038/nri1732
- Zumla A, Hui DS, Perlman S. Middle East
respiratory syndrome. Lancet 2015;386(9997):995-1007.
https://doi.org/10.1016/s0140-6736(15)60454-8
- Pedersen
SF, Ho YC. SARS-CoV-2: a storm is raging. J Clin Invest 2020;130(5):2202-5.
https://doi.org/10.1172/jci137647
- Mehta
P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ et al. COVID-19: consider cytokine storm syndromes and immunosuppression.
Lancet 2020;395(10229):1033-4.
https://doi.org/10.1016/s0140-6736(20)30628-0
- Herold
TVJ, Arnreich C, Hellmuth JC, von Bergwelt-Baildon
M, Klein M, Weinberger T. Level of IL-6 predicts respiratory failure in
hospitalized symptomatic COVID-19 patients. medRxiv 2020
https://doi.org/10.1101/2020.04.01.20047381
- Fox
SE, Akmatbekov A, JHarbert
JL, Li G, 3Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in
Covid-19: the first autopsy series from New Orleans. medRxiv
2020. https://doi.org/10.1101/2020.04.06.2005057
- Channappanavar R et al. Dysregulated
type I interferon and inflammatory monocyte-macrophage responses cause lethal
pneumonia in SARS-CoV-infected mice. Cell Host
Microbe 2016;19(2):181-93. https://doi.org/10.1016/j.chom.2016.01.007
- Davidson
S et al. Disease-promoting effects of type I interferons in viral, bacterial
and coinfections. J Interf Cytokine Res 2015;35(4):252-64.
https://doi.org/10.1089/jir.2014.0227
- Shaw
AC et al. Age-dependent dysregulation of innate immunity. Nat Rev Immunol 2013;13(12):875-87. https://doi.org/10.1038/nri3547
- de Wit
E, van Doremalen N, Falzarano
D, Munster VJ. SARS
and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol
2016;14(8):523-34. https://doi.org/10.1038/nrmicro.2016.81
- Channappanavar R, Perlman S.
Pathogenic human coronavirus infections: causes and
consequences of cytokine storm and immunopathology. Semin
Immunopathol 2017;39(5):529-39.
https://doi.org/10.1007/s00281-017-0629-x
- Kindler
E, Thiel V, Weber F. Interaction of SARS and MERS coronaviruses with the
antiviral interferon response. Coronaviruses 2016. p.219-43.
https://doi.org/10.1016/bs.aivir.2016.08.006
- Walsh
NP, Gleeson M, Shephard RJ et al. Position statement. Part one: immune function
and exercise. Exerc Immunol Rev 2011;17:6–63.
https://www.ncbi.nlm.nih.gov/pubmed/21446352
- Campbell
JP, Riddell NE, Burns VE et al. Acute exercise mobilises CD8+ T lymphocytes
exhibiting an effector-memory phenotype. Brain Behav Immun 2009;23(6):767-75.
https://doi.org/10.1016/j.bbi.2009.02.011
- Simpson
RJ, Florida-James GD, Whyte GP, Black JR, Ross JA, Guy K. Apoptosis does not
contribute to the blood lymphocytopenia observed after intensive and downhill
treadmill running in humans. Res Sports Med 2007;15(3):157-74.
https://doi.org/10.1080/15438620701405339
- Simpson
RJ. The effects of exercise on blood leukocyte numbers. In: Gleeson M, Bishop
NC, Walsh NP, eds. Exercise Immunology. Oxford, UK, New York, USA: Routledge;
2013. p.64-105. https://doi.org/10.4324/9780203126417
- Okutsu M, Suzuki K, Ishijima
T, Peake J, Higuchi M. The effects of acute exerciseinduced
cortisol on CCR2 expression on human monocytes. Brain Behav
Immun 2008;22(7):1066-71.
https://doi.org/10.1016/j.bbi.2008.03.006
- Okutsu M, Ishii K, Niu
KJ, Nagatomi R. Cortisol-induced CXCR4 augmentation
mobilizes T lymphocytes after acute physical stress. Am J Physiol
Regul Integr Comp Physiol 2005;288(3):R591–R599.
https://doi.org/10.1152/ajpregu.00438.2004
- Ortega
E, Collazos ME, Maynar M, Barriga C, De la Fuente M. Stimulation of the phagocytic
function of neutrophils in sedentary men after acute moderate exercise. Eur J Appl Physiol Occup Physiol 1993;66(1):60-4.
https://doi.org/10.1007/bf00863401
- Nieman
DC, Nehlsen-Cannarella SL, Fagoaga OR et al. Effects
of mode and carbohydrate on the granulocyte and monocyte response to intensive,
prolonged exercise. J Appl Physiol 1998;84(4):1252-9.
https://doi.org/10.1152/jappl.1998.84.4.1252
- Bishop
NC, Gleeson M, Nicholas CW, Ali A. Influence of carbohydrate supplementation on
plasma cytokine and neutrophil degranulation responses to high intensity
intermittent exercise. Int J Sport Nutr Exerc Metab
2002;12(2):145-56. https://doi.org/10.1123/ijsnem.12.2.145
- Pyne DB. Regulation of neutrophil
function during exercise. Sports Med 1994;17(4):245-58.
https://doi.org/10.2165/00007256-199417040-00005
- Suzuki
K, Nakaji S, Yamada M et al. Impact of a competitive
marathon race on systemic cytokine and neutrophil responses. Med Sci Sports Exerc 2003;35(2):348-55.
https://doi.org/10.1249/01.mss.0000048861.57899.04
- Gleeson
M, McDonald WA, Cripps AW, Pyne DB, Clancy RL,
Fricker PA. The effect on immunity of long-term intensive training in elite
swimmers. Clin Exp Immunol 1995;102:210-6.
https://doi.org/10.1111/j.1365-2249.1995.tb06658.x
- Lancaster
GI, Halson SL, Khan Q, Drysdale P, Jeukendrup AE, Drayson MT,
Gleeson M. Effect of acute exhaustive exercise and a 6-day period of
intensified training on immune function in cyclists. J Physiol
2003;548P:O96. https://www.physoc.org/abstracts/effect-of-acute-exhaustive-exercise-and-a-6-day-period-of-intensified-training-on-immune-function-in-cyclists/
- Lancaster
GI, Halson SL, Khan Q, Drysdale P, Jeukendrup AE, Drayson MT,
Gleeson M. The effects of acute exhaustive exercise and intensified training on
type 1/type 2 T cell distribution and cytokine production. Exerc Immunol Rev 2004;10:91-106.
https://www.ncbi.nlm.nih.gov/pubmed/15633589
- Robson
PJ, Blannin AK, Walsh NP, Bishop NC, Gleeson M. The
effect of an acute period of intense interval training on human neutrophil
function and plasma glutamine in endurance-trained male runners. J Physiol 1999;515:84-5.
- Verde
TJ, Thomas SG, Moore RW, Shek P, Shephard RJ. Immune
responses and increased training of the elite athlete. J Appl Physiol 1992;73:1494-9.
https://doi.org/10.1152/jappl.1992.73.4.1494
- Gleeson
M. Mucosal immune responses and risk of respiratory illness in elite athletes. Exerc Immunol Rev 2000;6:5-42.
- Francis
JL, Gleeson M, Pyne DB, Callister R and Clancy RL.
Variation of salivary immunoglobulins in exercising and sedentary populations.
Med Sci Sports Exerc 2005;37:571-8.
https://doi.org/10.1249/01.mss.0000158191.08331.04
- Gleeson
M, Pyne DB and Callister R. The missing links in
exercise effects on mucosal immunity. Exerc Immunol
Rev 2004;10:107-28.
- Allgrove
JE, Gomes E, Hough J and Gleeson M. Effects of exercise intensity on salivary
antimicrobial proteins and markers of stress in active men. J Sports Sci 2008;26:653-61. https://doi.org/10.1080/02640410701716790
- Bishop
NC and Gleeson M. Acute and chronic effects of exercise on markers of mucosal
immunity. Front Biosci 2009;14:4444-56.
- Klentrou P, Cieslak
T, MacNeil M, Vintinner A and Plyley
M. Effect of moderate exercise on salivary immunoglobulin A and infection risk
in humans. Eur J Appl Physiol 2002;87:153-8.
https://doi.org/10.1007/s00421-002-0609-1
- Putlur P, Foster C, Miskowski
JA, Kane MK, SBurton SE, Scheett
TP, McGuigan MR. Alteration of immune function in women collegiate soccer
players and college students. J Sports Sci Med 2004;3;234-43.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938062/
- Pedersen
BK, Ullum H. NK cell response to physical activity:
possible mechanisms of action. Med Sci Sports Exerc
1994;26(2):140-6. https://doi.org/10.1249/00005768-199402000-00003
- Simpson
RJ, Campbell JP, Gleeson M et al. Can exercise affect immune function to
increase susceptibility to infection? Exerc Immunol Rev
2020;26:8–22. http://eir-isei.de/2020/eir-2020-008-article.pdf
- Kohut
ML, Arntson BA, Lee W et al. Moderate exercise
improves antibody response to influenza immunization in older adults. Vaccine
2004;22(17/18):2298-306. https://doi.org/10.1016/j.vaccine.2003.11.023
- Woods
JA, Keylock KT, Lowder T et al. Cardiovascular
exercise training extends influenza vaccine seroprotection
in sedentary older adults: the immune function intervention trial. J Am Geriatr Soc 2009;57(12):2183-91.
https://doi.org/10.1111/j.1532-5415.2009.02563.x
- Spielmann G, McFarlin BK,
O’Connor DP, Smith PJ, Pircher H, Simpson RJ. Aerobic
fitness is associated with lower proportions of senescent blood T-cells in man.
Brain Behav Immun
2011;25(8):1521-9. https://doi.org/10.1016/j.bbi.2011.07.226
- Shinkai S, Kohno H, Kimura K
et al. Physical activity and immune senescence in men. Med Sci Sports Exerc 1995;27(11):1516-26.
https://doi.org/10.1249/00005768-199511000-00008
- Pedersen
BK, Bruunsgaard H. Possible beneficial role of
exercise in modulating lowgrade inflammation in the
elderly. Scand J Med Sci Sports 2003;13(1):56-62.
https://doi.org/10.1034/j.1600-0838.2003.20218.x
- Yan
H, Kuroiwa A, Tanaka H, Shindo
M, Kiyonaga A, Nagayama A. Effect of moderate
exercise on immune senescence in men. Eur J Appl Physiol
2001;86(2):105-11. https://doi.org/10.1007/s004210100521
- Woods
JA, Ceddia MA, Wolters BW, Evans JK, Lu Q, McAuley E.
Effects of 6 months of moderate aerobic exercise training on immune function in
the elderly. Mech Ageing Dev 1999;109(1):1-19.
https://doi.org/10.1016/s0047-6374(99)00014-7
- Simpson
RJ, Lowder TW, Spielmann G,
Bigley AB, Lavoy EC, Kunz H. Exercise and the aging
immune system. Ageing Res Rev 2012;11:404-20.
https://doi.org/10.1016/j.arr.2012.03.003
- ElKassar N, Gress
RE. An overview of IL-7 biology and its use in immunotherapy. J Immunotoxicol 2010;7(1):1-7. https://doi.org/10.3109/15476910903453296
- Laddu
DR, Lavie CJ, Phillips SA, Arena R. Physical activity
for immunity protection: Inoculating populations with healthy living medicine
in preparation for the next pandemic [published ahead of print, 2020 Apr 9]. Prog Cardiovasc Dis 2020. https://doi.org/10.1016/j.pcad.2020.04.006
- Soligard
T, Steffen K, Palmer D, et al. Sports injury and
illness incidence in the Rio de Janeiro 2016 Olympic Summer Games: A
prospective study of 11274 athletes from 207 countries. Br J Sports Med
2017;51(17):1265-71. https://doi.org/10.1136/bjsports-2017-097956
- Dvorak
J, Junge A, Derman W, Schwellnus M. Injuries and illnesses of football players
during the 2010 FIFA World Cup. Br J Sports Med 2011;45(8):626-30.
https://doi.org/10.1136/bjsm.2010.079905
- Davison
G, Simpson RJ. Immunity. In: Lanham-New SA, Stear SJ,
Shirreffs SM, Collins AL, eds. Sport and exercise
nutrition. Oxford, UK: Wiley-Blackwell; 2011. p.281-303.
- Walsh
NP, Gleeson M, Pyne DB et al. Position statement. Part two: maintaining
immune health. Exerc Immunol Rev 2011;17:64-103.
- Gleeson
M, ed. Immune function in sport and exercise. Edinburgh: Elsevier; 2005.
- Bermon S. Airway inflammation and upper
respiratory tract infection in athletes: is there a link? Exerc
Immunol Rev 2007;13:6-14.
- Helenius I, Lumme
A, Haahtela T. Asthma, airway inflammation and
treatment in elite athletes. Sports Med 2005;35:565-574.
https://doi.org/10.2165/00007256-200535070-00002
- Bjermer L, Anderson SD.
Bronchial hyperresponsiveness in athletes: mechanisms for development. Eur
Respir Mon 2005;33:19-34.
https://doi.org/10.1183/1025448x.00033004
- Varandas F, Medina D, Gomez A,
Della Villa S. Late rehabilitation on the field. In: Injury and health problem
in football. Berlin Heidelberg: Springer; 2017. p.571-9.
- World
Health Organization. Global report on trends in prevalence of tobacco smoking.
Geneva, Switzerland: WHO; 2015.
- Sopori M. Effects of cigarette smoke on
the immune system. Nat Rev Immunol 2002;2:372-7.
https://doi.org/10.1038/nri803
- Stampfli MR, Anderson GP. How
cigarette smoke skews immune responses to promote infection, lung disease and
cancer. Nat Rev Immunol 2009;9:377-84.
https://doi.org/10.1038/nri2530
- Brake
SJ, Barnsley K, Lu W, McAlinden
KD, Eapen MS, Sohal SS.
smoking upregulates angiotensin-converting enzyme-2 receptor: a potential
adhesion site for novel coronavirus SARS-CoV-2 (Covid-19). J Clin Med 2020;9(3):841. https://doi.org/10.3390/jcm9030841
- Cai
G, Bossé Y, Xiao F, Kheradmand F, Amos CI. Tobacco
smoking increases the lung gene expression of ACE2, the receptor of SARS-CoV-2
[published online ahead of print, 2020 Apr 24]. Am J Respir Crit Care Med 2020.
https://doi.org/10.1164/rccm.202003-0693LE
- Kampf G, Todt
D, Pfaender S, Steinmann E. Persistence of
coronaviruses on inanimate surfaces and their inactivation with biocidal
agents. J Hosp Infect 2020;104(3):246-51.
https://doi.org/10.1016/j.jhin.2020.01.022
- 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(2):103-4. https://doi.org/10.1016/j.jshs.2020.02.001