Covid-19: One of the many Obesity related co-morbidities?
Thousands of academic articles have been published on Covid-19 over recent weeks, reflecting the amount of data being generated and the importance of finding ways to fight the SARS-CoV-2 virus. The more we learn about the disease, the more complex it appears to be, with as many questions as answers arising (1). However, one aspect of the disease is now quite well established – the major risk factors that make individuals more susceptible to severe Covid-19 illness. After advanced age and male sex, the major risk factors are obesity and other, related underlying health conditions such as hypertension, cardiovascular disease (CVD), type 2 diabetes (T2D) and respiratory diseases (2).
Obesity is a major risk factor for CVD, T2D, hypertension and many other serious conditions, including a number of cancers, and its role in the development of these diseases is the reason it is such a major public health concern. However, Covid-19 has cruelly exposed another health issue associated with obesity – increased susceptibility to infections, particularly respiratory infections. Individuals with obesity often have respiratory dysfunction due to the presence of large fat deposits around the chest and upper abdomen. This is characterised by altered respiratory mechanisms, increased airway resistance, impaired gas exchange and low lung volume and muscle strength (3). As a result, obesity increases the risk of contracting respiratory tract infections including influenza and pneumonia (4, 5).
In the 2009 Influenza A H1N1 pandemic, patients with obesity were disproportionately affected by the virus, with more than twice the mortality rate of people with normal weight (6). Although this was an influenza virus, not a coronavirus, this should nevertheless have been a warning sign that people with obesity are likely to be at greater risk during viral respiratory pandemics. This warning was enhanced by a later study which looked at the response to the H1N1 vaccine. People with obesity initially produced high levels of antibodies, but within 12 months their antibody titres had dropped significantly, and they had double the risk of contracting the virus (7). This suggests that obesity compromises the immune system and its ability to fight viral respiratory infections.
In the case of Covid-19, it is most likely that the impact of obesity on the severity of the disease is due primarily to immune system dysfunction. A range of functional abnormalities have been identified in obesity, but in viral infections the dysfunction of Natural Killer (NK) cells is particularly relevant as they are important in both the initial stage of infection and then clearing the virally infected cells (8). The low-grade, chronic inflammation caused by excess visceral adipose tissue surrounding vital organs in the abdominal cavity, which is implicated in cardiometabolic complications of obesity, has also been highlighted as a possible cause of the over-exaggerated immune response seen in many Covid-19 fatalities (9).
It has also been suggested that visceral adipose tissue may act as a ‘reservoir’ for Covid-19. Adipose tissue expresses the protein ACE2 which is the entry point for SARS-CoV-2 into cells, so it is feasible the virus could infect visceral adipose tissue which then becomes a reservoir for more extensive viral spread, increased viral shedding, immune activation, cytokine amplification and systemic tissue damage (10).
Research into this disease will be ongoing for many years, and it is important to elucidate the mechanisms by which obesity contributes to the severity of Covid-19 illness, in order to identify potential targets for treatment. Two relatively simple areas for investigation would be zinc deficiency and vitamin D deficiency. Both these nutrients are essential for effective regulation of the immune system, and obesity increases the risk of deficiency of both (11, 12). Testing patients for zinc and vitamin D status would therefore be warranted, so that deficiencies could be corrected. In addition to playing a vital role in immune function, zinc also acts intracellularly to inhibit the RNA polymerase enzyme which replicates viral RNA (13), so any deficiency in circulating zinc could hinder the body’s attempts to fight the virus.
While it is vital we understand as much as possible about this new virus and learn how we might be able to minimise the impact of similar future outbreaks, it is arguably even more important to renew and re-invigorate our efforts to tackle obesity. We need to reduce obesity rates, not just to help limit the impact of future pandemics, but also to reduce the devastating effects of CVD, T2D and other obesity-related illnesses on the health and well-being of the millions of people with obesity, and ease the burden these diseases place on our healthcare systems. Unfortunately, healthcare professionals are not generally well trained to manage patients with obesity. A 2015 analysis of the NHS workforce estimated that fewer than 0.1% had received any specialised obesity training (14), which may be due to the fact obesity is not considered a disease in the UK. In the US, where obesity is recognised a disease, obesity is higher on the agenda but a very recent study revealed that U.S. medical schools “are not adequately preparing their students to manage patients with obesity” (15). It is vital that the curricula of medical and nursing courses are reviewed in relation to obesity, and that specialised training is provided to existing health professionals, to ensure they have the knowledge and skills to support and treat patients with obesity.
References
1. Bernstein L and Cha AE (2020) Doctors keep discovering new ways the coronavirus attacks the body. Washington Post. Published 10 May 2020. https://www.washingtonpost.com/health/2020/05/10/coronavirus-attacks-body-symptoms/?arc404=true
2. Centres for Disease Control and Prevention (2020) Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/groups-at-higher-risk.html
3. Murugan, A. T. & Sharma, G (2008) Obesity and respiratory diseases. Chron. Respir. Dis. 5: 233–242
4. Phung DT, Wang Z, Rutherford S, Huang C, Chu C (2013) Body mass index and risk of pneumonia: a systematic review and meta-analysis. Obes Rev. 14: 839e57.
5. Gounder AP, Boon ACM (2019) Influenza Pathogenesis: The Effect of Host Factors on Severity of Disease. J Immunol. 202: 341‐350.
6. Louie JK, Acosta M, Winter K, et al. (2009) Factors Associated With Death or Hospitalization Due to Pandemic 2009 Influenza A(H1N1) Infection in California. JAMA. 302: 1896–1902.
7. Green WD, Beck MA (2017) Obesity Impairs the Adaptive Immune Response to Influenza Virus. Ann Am Thorac Soc. 14: S406-S409
8. O’Shea D, Hogan AE (2019) Dysregulation of Natural Killer Cells in Obesity. Cancers (Basel). 11: 573. doi:10.3390/cancers11040573
9. Sattar N, McInnes IB, McMurray JJV (2020) Obesity a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.120.047659
10. Ryan PD and Caplice NM (2020) Is Adipose Tissue a Reservoir for Viral Spread, Immune Activation and Cytokine Amplification in COVID‐19. Obesity. doi:10.1002/oby.22843
11. Vimaleswaran KS, Berry DJ, Lu C, et al. (2013) Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 10: e1001383. doi:10.1371/journal.pmed.1001383
12. Gu K, Xiang W, Zhang Y, Sun K, Jiang X (2019) The association between serum zinc level and overweight/obesity: a meta-analysis. Eur J Nutr. 58: 2971-2982
13. te Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ(2010) Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity invitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 6: e1001176. doi:10.1371/journal.ppat.1001176
14. Candesic (2015) College of Contemporary Health: Training Market for Obesity.
15. Butsch WS, Kushner RF, Alford S et al. (2020) Low priority of obesity education leads to lack of medical students’ preparedness to effectively treat patients with obesity: results from the U.S. medical school obesity education curriculum benchmark study. BMC Med Educ 20: 23. https://doi.org/10.1186/s12909-020-1925-z
