An epidemic within the novel coronavirus pandemic

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As the world struggles with the novel coronavirus (COVID-19) pandemic, a clearer picture of the risk factors for severe infection and even death has started to emerge. Obesity and the metabolic changes that accompany it now stand out as leading risk factors for COVID-19 infection.

The U.S. Centers for Disease Control and Prevention (CDC) lists severe obesity at any age as a high-risk condition for COVID-19. The high risk from obesity spotlights how the obesity epidemic in America has collided with the pandemic.

The obesity epidemic in the U.S. has been building for decades. According to the CDC, from 1999 to 2000 through 2017 to 2018, the prevalence of obesity, defined as a body mass index (BMI) of 30 or above, increased from 30.5 percent of the population to 42.4 percent. The prevalence of severe obesity, defined as a BMI of 40 or above, increased from 4.7 percent to 9.2 percent.

The collision of the obesity epidemic with the COVID-19 pandemic has been happening since COVID-19 was first detected in December 2019. Much remains to be learned about this disease, but it’s clear that high BMI is a significant risk factor for severe COVID-19 infection. Any degree of obesity is associated with poor prognosis for COVID-19 patients. Individuals who are overweight are more likely to need hospitalization and intubation and are at greater risk of death, regardless of age, sex, or race and ethnicity. They also seem to shed the virus and remain infectious for longer.

The question remains if obesity is the real risk factor, or the chronic conditions associated with obesity, such as metabolic syndrome, diabetes, and hypertension. In a published case series that included 5,700 patients hospitalized with COVID-19 between March 1 and April 4 in the New York City area, the most common comorbidities were hypertension, obesity, and diabetes. Of the 553 patients who died, those with diabetes were more likely to have received invasive mechanical ventilation or care in the intensive care unit (ICU) compared with those who did not have diabetes.

The evidence for obesity as the primary risk factor, and not other possible comorbidities such as social determinants of health and obesity’s association with chronic conditions, comes from a retrospective cohort study conducted from February through May 2020 at Kaiser Permanente Southern California, a large integrated healthcare organization. The researchers looked at 6,916 patients with COVID-19 and found a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a healthy BMI of 18.5 to 24, those with BMIs of 40 or greater had a 2.68 relative risk of death. The researchers report that the risk was most striking among those aged 60 years or younger and men.

Very similar results were found in a retrospective cohort study of 2,466 patients hospitalized for COVID-19 in March 2020 in New York City. Here too, the researchers found that obesity was associated with an increased risk for death or intubation—independent of age, sex, race and ethnicity, and comorbid conditions. Younger age again stood out, and obesity was strongly associated with intubation or death among adults younger than 65.

We don’t know all the answers yet in terms of what makes obesity dangerous in COVID-19, but researchers have some good evidence for several ideas. One is the role of angiotensin-converting enzyme 2 (ACE2) receptors. Because the virus seems to enter the body by binding to ACE2 receptors on the cell surface, having more receptors increases vulnerability to infection and increases the viral load. In addition, in obese patients, expression of ACE2, a hormone that is proinflammatory, prothrombotic, and vasoconstrictive, is already upregulated by visceral fat. We know from recent research that the virus binds to the ACE2 receptor more quickly in the presence of inflammation. The COVID-19 virus further upregulates the hormone when it binds to the receptor, accelerating damage from this pathway.

Obese patients may already have compromised respiratory function before infection with COVID-19. Abdominal obesity can cause compression of the diaphragm and lungs and reduce lung function. Also, obese patients may already have poor lung function caused by hypertension, sleep-disordered breathing, obstructive sleep apnea, and chronic hypoventilation. Obesity also causes chronic low-grade inflammation and an increase in circulating proinflammatory cytokines, which seem to play a role in the worst COVID-19 outcomes.

Overweight and obese patients face a worse prognosis from COVID-19 infection. For these patients, avoiding infection through effective preventive measures is even more critical. For the duration of the pandemic, practitioners should encourage all patients, but especially obese patients, to practice strict social distancing, wear masks, and follow careful hand hygiene. Flu shots should also be strongly encouraged.

An individualized program of diet, supplements, exercise, and mindset is needed for an optimal outcome. For overweight and obese patients who already have high markers of inflammation, a diet plan that emphasizes anti-inflammatory and antioxidant nutrients may help improve immunity while also encouraging weight loss. A diet high in fruits and vegetables may help improve immunity for these patients through the anti-inflammatory phytochemicals they contain. Quercetin found abundantly in apples and onions, and luteolin, a flavonoid found in celery, green peppers, and many other vegetables, bind to the ACE2 receptor, potentially blocking the COVID-19 virus from entering cells. Other phytochemicals may have a similar effect.

Good micronutrient status is also vital for preventing viral infection. Patients at risk of COVID-19 should consider supplements for antiviral support, including quercetin, EGCG, melatonin, PEA, lipoic acid, pomegranate, omega-3 fatty acid, and vitamin D. Some research indicates that low vitamin D status is associated with a greater risk of respiratory virus infection. Consider supplementation for patients with suboptimal vitamin D levels.

Overweight and obese patients may also be more receptive to lifestyle improvements if they understand how important these are for fighting off a viral infection. More physical activity and more sleep are both factors well known to help improve immunity and help keep viral infections from being as severe if they do occur.

The pandemic is a rare teachable moment for patients with weight issues. Explaining the genuine risk of a poor outcome or even death may convince some obese patients that the time has come to focus on weight loss and better health. An integrated healthcare practice is uniquely positioned to help these patients through personalized lifestyle medicine.

References

Anderson, M.R., Geleris, J., and Anderson, D.R., et al. (2020) Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection: A Retrospective Cohort Study. Annals of Internal Medicine. Retrieved from: https://www.acpjournals.org/doi/10.7326/M20-3214

Hales, C.M., Carroll, M.D., Fryar, C.D., and Ogden, C.L. (2020) Prevalence of obesity and severe obesity among adults: the United States, 2017–2018. U.S. Centers for Disease Control and Prevention. Retrieved from: https://www.cdc.gov/nchs/data/databriefs/db360-h.pdf

Martineau, A.R. and Forouhi, N.G. (2020) Vitamin D for COVID-19: a case to answer? Lancet Diabetes & Endocrinology. Retrieved from: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30268-0/fulltext

Richardson, S., Hirsch, J.S., and Narasimhan, M., et al. (2020) Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. Retrieved from: https://jamanetwork.com/journals/jama/fullarticle/2765184  

Sanchis-Gomar, F., Lavie, C.J., Mehra, M.R., Henry, B.M., and Lippi, G. (2020) Obesity and Outcomes in COVID-19: When an Epidemic and Pandemic Collide. Mayo Clinic Proceedings. Retrieved from: https://www.mayoclinicproceedings.org/article/S0025-6196(20)30477-8/pdf

Smith, M. and Smith, J.C. (2020) Repurposing Therapeutics for COVID-19: Supercomputer-Based Docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface. ChemRxiv. Retrieved from: https://chemrxiv.org/articles/Repurposing_Therapeutics_for_the_Wuhan_Coronavirus_nCov-2019_Supercomputer-Based_Docking_to_the_Viral_S_Protein_and_Human_ACE2_Interface/11871402

Tarto,f S.Y., Qian, L., Hong, V., et al. (2020) Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization. Annals of Internal Medicine. Retrieved from: https://www.acpjournals.org/doi/10.7326/M20-3742

U.S. Centers for Disease Control and Prevention. (2019) People who are at increased risk for severe illness. Retrieved from: at www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-higher-risk.html

Ziegler, C.G.K., Allon, S.J., and Nyquist, S.K., et al. (2020) SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. Retrieved from: https://www.sciencedirect.com/science/article/pii/S0092867420305006

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