Physical Activity, Natural Killer cells and Covid-19 (SARS-CoV-2)

As part of its programme Beat the Street in North Lanarkshire, Intelligent Health sent out this tweet to encourage people to become more active at a time when physical inactivity levels have risen particularly in those most vulnerable to Covid-19 mortality.

“Being physically active, by walking, wheeling or running, boosts our body’s natural killer cells which are known to strengthen our immunity by helping to fight off viruses – including coronavirus. @nlcpeople @PathsforAll”

There are two statements and one implication in this tweet.

Statement 1: Being physically active boosts our body’s Natural Killer Cells

Statement 2: Natural Killer cells are known to strengthen our immunity by helping to fight off SARS-CoV-2 infection.

Implication: Being Physically Active could help to fight off Coronavirus

Statement 1: Being physically active boosts our body’s Natural Killer Cells

There is good evidence that physical activity can benefit both the innate and adaptive immune system that can result in reduced viral infections in those who are more active compared to those who are inactive.[1]

Natural Killer Cells are large granular lymphocytes with natural cytotoxity. They represent one component of the innate immune system that can destroy certain virally infected  and tumour cells without prior sensitisation.

Evidence shows that regular activity can enhance the status of our immune status and in particular the level of Natural Killer Cells.

In a study[2] of 12,000 asymptomatic subjects, those who were regularly active had higher levels of Natural Killer Cells with the Odds Ratio being 1.23 meaning that there is a 23% difference between those who are inactive compared to those who are active as measured by IPAQ. There is also good evidence that a bout of physical activity of 30 mins (fast walking) raises levels of Natural Killer Cells in the circulation by 2 fold and this appears to be greater in older untrained individuals than those who already walk regularly[3]. It appears that the rise in Adrenaline levels reduces the stickiness of the Natural Killer Cell releasing it into the circulation and adrenaline levels are higher during exercise of the untrained compared to the trained elderly. There is also the “shear” affect of increased blood flow in the muscles that helps release more Natural Killer cells.

A review of this subject by the group at McMaster University[4] found that there is a significant increase in NK cells following exercise and that the different effect of exercise on different types of NK cells could have exciting treatment possibilities for immunocompromised children and patients with MS.

Statement 2:Natural Killer cells are known to strengthen our immunity by helping to fight off Coronavirus

Natural Killer cells are essential to fight off all viral infections[5] and have been shown to be key role in combating SARS-CoV-2 infection[6] Perhaps the most compelling evidence of their importance in fighting off viral infections is in those patients with selective dysfunction of the NK cells who suffer from frequent and severe viral infections.[7]

During SARS-CoV-2 infection there is a fall in circulating NK cells[8] as they home towards the lung where the virus will be activating the innate immune system. The numbers in the lung increase significantly and they become highly activated and proliferate significantly[9].  The evidence shows that NK cells in the nasal mucosa and lung tissue not only prevent SARS-CoV-2 infection from infecting the person in the first place but even in mild infections NK cells provide the second line of defence as part of the innnate immune system[10].

Implication: Being Physically Active could help to fight off Coronavirus

Given that physical activity is related to larger numbers and greater impact of Natural Killer Cells and that Natural Killer Cells are key to the first line of defence for SARS-CoV-2 infection then there is a strong indication that being active is likely to help protect someone from SARS-CoV-2 infection or help reduce its severity. Using the precautionary principle[11] then the inaction to prevent people from being active is likely to be of greater harm than getting people active on the plausible understanding that they may be protecting themselves.

However there are some early papers that explained the logic of why physical activity should be protective against SARS-CoV-2 infection. There is also a much deeper understanding of SARS-CoV-2 infection and how physical activity can protect us all from getting SARS-CoV-2 infection or if we do get it how the impact can be attenuated.[12]

However now 18 months into the pandemic we have more empirical data. A major study published in the British Journal of Sports Medicine[13] showed a significant protection in those who were active compared to being inactive. The benefits were right across the board from less chance of becoming infected to reduced hospitalisation and mortality.[14]

In summary

The evidence that physical activity increases the numbers and activity of Natural Killer cells and our immunity in generally is overwhelming. The evidence that NK cells are key to the defence from SARS-CoV -2 infection is equally solid. The evidence that physical activity protects or attenuates the impact of SARS-CoV-2 infection is becoming stronger with some cross sectional studies leading the way. No paper has doubted that one of the main protective

[1] Chastin, S.F.M., Abaraogu, U., Bourgois, J.G. et al. Effects of Regular Physical Activity on the Immune System, Vaccination and Risk of Community-Acquired Infectious Disease in the General Population: Systematic Review and Meta-Analysis. Sports Med 51, 1673–1686 (2021). https://doi.org/10.1007/s40279-021-01466-1

[2] Jung, Y.S., Park, J.H., Park, D.I., Sohn, C.I., Lee, J.M. and Kim, T.I., 2018. Physical inactivity and unhealthy metabolic status are associated with decreased natural killer cell activity. Yonsei medical journal, 59(4), pp.554-562.

[3] Ogawa, K., Oka, J., Yamakawa, J. and Higuchi, M., 2005. A single bout of exercise influences natural killer cells in elderly women, especially those who are habitually active. Journal of strength and conditioning research, 19(1), p.45.

[4] Timmons, B.W. and Cieslak, T., 2008. Human natural killer cell subsets and acute exercise: a brief review. Exerc Immunol Rev, 14(905), pp.8-23.

[5] Jost, S. and Altfeld, M., 2013. Control of human viral infections by natural killer cells. Annual review of immunology, 31, pp.163-194.

[6] Björkström, N.K. and Ponzetta, A., 2021. Natural killer cells and unconventional T cells in COVID-19. Current Opinion in Virology.

[7] Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S., 2008. Functions of natural killer cells. Nature immunology, 9(5), pp.503-510.

[8] Maucourant, C., Filipovic, I., Ponzetta, A., Aleman, S., Cornillet, M., Hertwig, L., Strunz, B., Lentini, A., Reinius, B., Brownlie, D. and Cuapio, A., 2020. Natural killer cell immunotypes related to COVID-19 disease severity. Science immunology, 5(50), p.eabd6832.

[9] Han, X., Zhou, Z., Fei, L., Sun, H., Wang, R., Chen, Y., Chen, H., Wang, J., Tang, H., Ge, W. and Zhou, Y., 2020. Construction of a human cell landscape at single-cell level. Nature, 581(7808), pp.303-309.

[10] Market, M., Angka, L., Martel, A.B., Bastin, D., Olanubi, O., Tennakoon, G., Boucher, D.M., Ng, J., Ardolino, M. and Auer, R.C., 2020. Flattening the COVID-19 curve with natural killer cell based immunotherapies. Frontiers in Immunology, 11, p.1512.

[11] Foster, K.R., Vecchia, P. and Repacholi, M.H., 2000. Science and the precautionary principle. Science, 288(5468), pp.979-981.

[12] Jakobsson, J., Cotgreave, I., Furberg, M., Arnberg, N. and Svensson, M., 2021. Potential physiological and cellular mechanisms of exercise that decrease the risk of severe complications and mortality following sars-cov-2 infection. Sports, 9(9), p.121.

[13] Lee, S.W., Lee, J., Moon, S.Y., Jin, H.Y., Yang, J.M., Ogino, S., Song, M., Hong, S.H., Abou Ghayda, R., Kronbichler, A. and Koyanagi, A., 2021. Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study. British Journal of Sports Medicine.

[14] da Silveira, M.P., da Silva Fagundes, K.K., Bizuti, M.R., Starck, É., Rossi, R.C. and e Silva, D.T.D.R., 2021. Physical exercise as a tool to help the immune system against COVID-19: an integrative review of the current literature. Clinical and experimental medicine, 21(1), pp.15-28.

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