Research Blog

July 23, 2021

COVID-19: ODX's Series - Biomarkers, Patterns, and Nutritional Intervention

Welcome to our series of posts on COVID 19. In this series we will focus on comorbidities, overlapping risk factors of COVID and chronic disease, nutritional status and covid 19, blood biomarker patterns, and what we can do to encourage long-term risk reduction. 

COVID-19: The Pandemic That Has Become Endemic

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

The ODX COVID-19 Series

  1. COVID-19: The pandemic that has become endemic
  2. COVID-19: Overlapping risk factors and chronic disease
  3. Nutritional status COVID-19: A covert factor in disease susceptibility
  4. COVID-19: Blood chemistry biomarker patterns - Clues and patterns lurking just under the surface
  5. COVID-19: Blood chemistry biomarker patterns - Down the research rabbit hole
  6. COVID-19: Blood Biomarkers - Neutrophils
  7. COVID-19: Blood Biomarkers - Albumin
  8. COVID-19: BloodBiomarkers - Cytokines
  9. COVID-19: Blood Biomarkers - Interleukin-6
  10. COVID-19: Blood Biomarkers - Interleukin-10
  11. COVID-19: Blood Biomarkers - Vitamin C
  12. COVID-19: Blood Biomarkers - Vitamin D
  13. COVID-19: Blood Biomarkers - Zinc
  14. Biomarker characteristics and blood type - help sharpen the COVID-19 clinical picture
  15. COVID-19: Initial indications and conventional interventions
  16. COVID-19: Long-term risk reduction - Naturopathic, functional medicine, and nutrition-based approaches to prevention
  17. A healthy diet is primary prevention for COVID-19
  18. You should have a gut feeling about COVID-19
  19. Beyond dietary food patterns…plant-based compounds may mitigate COVID-19 risk
  20. Targeted nutrition support in the battle against COVID-19
  21. Targeted nutrition support in COVID-19: Armed with vitamin C
  22. Targeted nutrition support in COVID-19: In sync with zinc
  23. Targeted nutrition support in COVID-19: Micronutrients and phytonutrients are important players
  24. Optimal Takeaways for improving immunity and reducing susceptibility to COVID-19
  25. Optimal - The Podcast: Episode 8 -Blood Biomarkers and Risk Factors for COVID-19 and its Comorbidities

The coronavirus disease 2019 pandemic (COVID-19) has brought significant morbidity and mortality to populations around the globe. It is caused by the novel SARS-CoV-2 virus (severe respiratory syndrome coronavirus-2).

COVID-19 was declared a pandemic in March of 2020. According to Johns Hopkins Coronavirus Resource Center: [1]

  • By the end of December 2020, there were 83,037,387 cases and 1,822,128 deaths worldwide.
  • By April 1, 2021 there were 129,245,588 cases and 2,820,503 deaths worldwide.

The SARS-CoV-2 virus belongs to the family Coronaviridae, named for the crown-shaped spikes on its surface.[2] It appears those spike proteins facilitate adhesion to epithelial tissue, making this novel coronavirus extremely contagious.

Early in the pandemic, clinicians and researchers noted that the most severe cases and fatalities due to COVID-19 tend to be older and have underlying chronic disorders such as cardiovascular disease, diabetes, hypertension, obesity, respiratory compromise, cancer, liver disease, or kidney disease. Notably, these same disorders are characterized by nutrient imbalances and insufficiencies.[3] Early nutrition intervention appears to reduce the risk of severe disease and mortality.

COVID-19 comorbidities, characteristics, and risk factors

A systemic review and meta-analysis of studies from January 1 to April 6, 2020 revealed that severe disease occurs in approximately 23% of infected patients, who in turn had a mortality rate of ~6%. Severity was statistically significantly higher in those with immunosuppression, malignancy, and chronic diseases such as diabetes, heart disease, hypertension, lung, liver, and kidney disease. Inflammatory markers were significantly higher in those with severe disease as well.[4]

Comorbidities and characteristics associated with symptomatic and severe COVID-19 include:[5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]

  • Age greater than 50[16], especially over 80
  • Asthma, especially on oral corticosteroids
  • Autoimmune disease e.g., lupus, psoriasis, rheumatoid arthritis
  • Cancer- especially recent diagnosis and hematological malignancy
  • Cardiovascular disease
  • Cerebrovascular disease
  • Chronic pulmonary disease, COPD
  • Comorbidities with strong ACE-2 receptor expression
  • Darker skin, increased melanin
  • Dementia
  • Diabetes mellitus
  • Disadvantaged social or economic status
  • Ethnicity: Black, South Asian
  • Exposure to pollution
  • Hemoglobin A1C greater than 7.5% (58 mmol/mol, 9.3 mmol/L)[17]
    • Elevated HbA1c is associated with hypercoagulation, inflammation, high mortality[18]
  • HIV
  • Hypercoagulability, thrombosis
  • Hypertension (increased risk up to age 70)
  • Immunosuppressive conditions
  • Kidney disease, reduced eGFR 30-59.9, dialysis
  • Lack of sunlight exposure
  • Lifestyle factors, smoking, excessive alcohol intake
  • Liver disease
  • Male gender
  • Medications
  • Neurological disease
  • Obesity, especially BMI of greater than 40
    • BMI greater than 30 associated with reduced oxygen saturation and is also a strong predictor of more severe COVID-19
  • Organ transplant recipients
  • Oxidative stress
  • Poverty
  • Pregnancy
  • Pulmonary disease
  • Respiratory disease
  • Sickle cell disease
  • Smoking
  • Stroke
  • Unhealthy Western-style diet
  • Vegetarian diet if low in B12, zinc, copper, iron, selenium, vitamin D, and omega-3 EPA and DHA

Fatality rate comparison[19]

  • No pre-existing conditions Less than 1%
  • Cancer 6%
  • Hypertension 6%
  • COPD 3%
  • Diabetes 3%
  • Cardiovascular disease 5%

The elderly appear to be particularly susceptible to severe COVID-19 for many of the reasons they are susceptible to nutrient deficiencies and complications:[20]

  • Comorbidities (especially diabetes, CVD, hypertension, respiratory disease, obesity, sarcopenia, GI disease, malabsorption, and liver and kidney disease).
  • Indoor confinement
  • Medications (e.g., antibiotics, anti-hypertensives, anti-inflammatories, anti-seizure, and endocrine drugs that interfere with vitamin D function).
  • Poor appetite and intake
  • Imbalance and poor diversity of gut microbiota[21]

The bad news is that the COVID-19 pandemic has entered its second year globally. The good news is that known risk factors can be mitigated with many of the same strategies that reduce the risk and severity of chronic diseases associated with COVID-19, including optimizing nutritional status and lifestyle. There is much more to come regarding these simple yet necessary steps.

Next Up - COVID-19: Overlapping risk factors and chronic disease


[1]Johns Hopkins University of Medicine Coronavirus Resource Center.

[2] Souza, Ana Carolina Remondi, et al. "Zinc, Vitamin D and Vitamin C: Perspectives for COVID-19 With a Focus on Physical Tissue Barrier Integrity." Frontiers in Nutrition 7 (2020): 295.

[3] Caccialanza, Riccardo et al. “Early nutritional supplementation in non-critically ill patients hospitalized for the 2019 novel coronavirus disease (COVID-19): Rationale and feasibility of a shared pragmatic protocol.” Nutrition (Burbank, Los Angeles County, Calif.) vol. 74 (2020): 110835. 

[4] Li, Jie et al. “Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes.” Journal of medical virology, 10.1002/jmv.26424. 13 Aug. 2020.

[5] Williamson, Elizabeth J et al. “Factors associated with COVID-19-related death using OpenSAFELY.” Nature vol. 584,7821 (2020): 430-436. 

[6] Ejaz, Hasan et al. “COVID-19 and comorbidities: Deleterious impact on infected patients.” Journal of infection and public health vol. 13,12 (2020): 1833-1839. 

[7] Gallo Marin, Benjamin et al. “Predictors of COVID-19 severity: A literature review.” Reviews in medical virology, e2146. 30 Jul. 2020.

[8] Richardson, David P, and Julie A Lovegrove. “Nutritional status of micronutrients as a possible and modifiable risk factor for COVID-19: a UK perspective.” The British journal of nutrition, 1-7. 20 Aug. 2020.

[9] Wu, X et al. “Air pollution and COVID-19 mortality in the United States: Strengths and limitations of an ecological regression analysis.” Science advances vol. 6,45 eabd4049. 4 Nov. 2020.

[10] Nandy, Kunal et al. “Coronavirus disease (COVID-19): A systematic review and meta-analysis to evaluate the impact of various comorbidities on serious events.” Diabetes & metabolic syndrome vol. 14,5 (2020): 1017-1025.

[11] Albitar, Orwa et al. “Risk factors for mortality among COVID-19 patients.” Diabetes research and clinical practice vol. 166 (2020): 108293. 

[12] Zheng, Zhaohai et al. “Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis.” The Journal of infection vol. 81,2 (2020): e16-e25. 

[13] Hernández-Galdamez, Diego Rolando et al. “Increased Risk of Hospitalization and Death in Patients with COVID-19 and Pre-existing Noncommunicable Diseases and Modifiable Risk Factors in Mexico.” Archives of medical research vol. 51,7 (2020): 683-689.

[14] Matsushita, Kunihiro et al. “The Relationship of COVID-19 Severity with Cardiovascular Disease and Its Traditional Risk Factors: A Systematic Review and Meta-Analysis.” Global heart vol. 15,1 64. 22 Sep. 2020.

[15] Baradaran, Ashkan et al. “Prevalence of Comorbidities in COVID-19 Patients: A Systematic Review and Meta-Analysis.” The archives of bone and joint surgery vol. 8,Suppl 1 (2020): 247-255. 

[16] Cao, Xuetao. “COVID-19: immunopathology and its implications for therapy.” Nature reviews. Immunology vol. 20,5 (2020): 269-270.

[17] HBA1c converter 

[18] Gallo Marin, Benjamin et al. “Predictors of COVID-19 severity: A literature review.” Reviews in medical virology, e2146. 30 Jul. 2020.

[19] Gallo Marin, Benjamin et al. “Predictors of COVID-19 severity: A literature review.” Reviews in medical virology, e2146. 30 Jul. 2020.

[20] Richardson, David P, and Julie A Lovegrove. “Nutritional status of micronutrients as a possible and modifiable risk factor for COVID-19: a UK perspective.” The British journal of nutrition, 1-7. 20 Aug. 2020.

[21] Donati Zeppa, Sabrina et al. “Gut Microbiota Status in COVID-19: An Unrecognized Player?.” Frontiers in cellular and infection microbiology vol. 10 576551. 26 Nov. 2020. 

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