Co-Epidemic of Obesity and COVID-19 (a co-epidemic of Vitamin D not mentioned) – April 2021

Understanding the Co-Epidemic of Obesity and COVID-19: Current Evidence, Comparison with Previous Epidemics, Mechanisms, and Preventive and Therapeutic Perspectives

Curr Obes Rep. 2021 Apr 28. doi: 10.1007/s13679-021-00436-y
Maria Dalamaga 1, Gerasimos Socrates Christodoulatos 2, Irene Karampela 2 3, Natalia Vallianou 4, Caroline M Apovian 5

 Download the PDF from VitaminDWiki

Purpose of review: A growing body of evidence suggests that obesity and increased visceral adiposity are strongly and independently linked to adverse outcomes and death due to COVID-19. This review summarizes current epidemiologic data, highlights pathogenetic mechanisms on the association between excess body weight and COVID-19, compares data from previous pandemics, discusses why COVID-19 challenges the "obesity paradox," and presents implications in prevention and treatment as well as future perspectives.

Recent findings: Data from meta-analyses based on recent observational studies have indicated that obesity increases the risks of infection from SARS-CoV-2, severe infection and hospitalization, admission to the ICU and need of invasive mechanical ventilation (IMV), and the risk of mortality, particularly in severe obesity. The risks of IMV and mortality associated with obesity are accentuated in younger individuals (age ≤ 50 years old). The meta-inflammation in obesity intersects with and exacerbates underlying pathogenetic mechanisms in COVID-19 through the following mechanisms and factors:

• (i) impaired innate and adaptive immune responses;
• (ii) chronic inflammation and oxidative stress;
• (iii) endothelial dysfunction, hypercoagulability, and aberrant activation of the complement;
• (iv) overactivation of the renin-angiotensin-aldosterone system;
• (v) overexpression of the angiotensin-converting enzyme 2 receptor in the adipose tissue;
• (vi) associated cardiometabolic comorbidities;
• (vii) vitamin D deficiency;
• (viii) gut dysbiosis; and
• (ix) mechanical and psychological issues.

Mechanistic and large epidemiologic studies using big data sources with omics data exploring genetic determinants of risk and disease severity as well as large randomized controlled trials (RCTs) are necessary to shed light on the pathways connecting chronic subclinical inflammation/meta-inflammation with adverse COVID-19 outcomes and establish the ideal preventive and therapeutic approaches for patients with obesity.

Vitamin D Deficiency in Obesity (section in PDF)

Based on a recent meta-analysis of 8176 COVID-19 patients participating in 26 studies, individuals with severe COVID-19 presented 65% (OR: 1.65, 95% CI: 1.30-2.09) more vitamin D deficiency (<50 nmol/L) compared with mild caseso f the infection. Interestingly, a serum vitamin D concentration of less than 75 nmol/L increased hospitalization by 81% (OR: 1.81, 95% CI: 1.41-2.21) and mortality by 82% (OR: 1.82,95%CI: 1.06-2.58) from COVID-19 [156]. However, vitamin D deficiency (OR: 1.35, 95% CI: 0.80-1.88) was not associated with an increased likelihood of COVID-19 infection [156, 157].
At the molecular level, vitamin D and its receptor (VDR), which is expressed on immune (B cells, T cells, and antigen- presenting cells) and pulmonary epithelial cells, plays an important role in both the innate and adaptive immune responses [158]. Vitamin D induces the transcriptional expression of antimicrobial peptides such as cathelicidins and defensins. Cathelicidins act by destructing the bacterial cell membranes and the enveloped viruses such as SARS-CoV-2, while defensins enhance chemotaxis of inflammatory cells through increased capillary permeability [158]. At the same time, vitamin D decreases pro-inflammatory cytokines, such as IL-6 and TNF-a, which are involved in the development of the cytokine storm in COVID-19 that precedes ARDS [159].
Remarkably, obesity is associated with vitamin D deficiency due to the lipophilic nature ofthe adipose tissue which acts as an isolator of vitamin D rather than a depot [160]. Other mechanisms linking higher BMI to lower vitamin D include the lesser skin exposure to sunlight, the diminished outdoor physical activity, the lower vitamin D intake, and the reduced intestinal absorption of vitamin D [161, 162].
Interestingly, vitamin D deficiency has been found to be an independent risk factor for the development of ARDS, its severity, and mortality. Notably, a bulk of recent studies have reported that vitamin D deficiency is associated with severe COVID-19 and a higher risk for progression to ARDS [163]. Interestingly, the biologic pathways involved in the pleiotropic actions of vitamin D intersect with the dysregulated mechanisms during COVID-19-related ARDS, providing some possible explanations behind this association. Vitamin D and its metabolites are implicated in the ACE2 expression, modulate genes associated with thrombotic pathways, particularly those related to angiogenesis, activate the lung-protective cathelicidin, and downregulate pro-inflammatory cytokines blocking the cytokine storm, such as TNF-a, IL-6, IL-8, IL- 12, and IFN-y [163]. Collectively, vitamin D deficiency may be a potential link between obesity and COVID-19-associated ARDS [164]. However, the exact efficacy ofvitamin D supplementation for the prevention of or as a potential adjunct therapeutic option for COVID-19 remains to be determined. Currently, a number of RCTs are actively investigating the potential benefits of vitamin D supplementation.

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