Exploring the Interplay of Vitamin D, Tuberculosis, and COVID-19 Severity in Mongolia

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Mongolia, a landlocked country in Central Asia, nestled between China and Russia, boasts a unique geographical and demographic landscape.

With a population of approximately 3.4 million people, it has the distinction of being one of the least densely populated countries globally.

The capital city, Ulaanbaatar, is home to around 1.2 million inhabitants, constituting a significant proportion of the country’s population. However, beneath the vast, picturesque landscapes and nomadic traditions lies a pressing health concern – the high prevalence of vitamin D deficiency.

Mongolia’s geographical location, characterized by its high latitude and extreme cold weather, presents a formidable challenge when it comes to vitamin D synthesis through sunlight exposure. Additionally, the scarcity of vitamin D-rich foods in the local diet further exacerbates the deficiency.

A nationwide survey conducted in urban and rural areas of Mongolia has revealed alarming statistics: during winter, 100% of the adult population had deficient or inadequate serum 25(OH)D concentrations, defined as less than 20 ng/mL. Even during summer, the deficiency still afflicted a significant 42% of the population [1].

The significance of Vitamin D in Immunity

Emerging research suggests that vitamin D plays a crucial role in modulating both innate and acquired immune responses, particularly in the context of respiratory infections caused by viruses and bacteria [2][3]. This has profound implications for two major health concerns in Mongolia: tuberculosis (TB) and COVID-19.

Both TB and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infections are intimately linked with innate and acquired immunity. Vitamin D, especially in its active form, calcitriol, demonstrates potent immunomodulatory effects in various studies involving humans and animals [4].

Clinical evidence has indicated that COVID-19 may predispose individuals to TB infection or reactivate latent TB [5]. Likewise, underlying TB infection can exacerbate the severity of COVID-19 [6].

Given the limited direct treatment options for COVID-19, there is a growing interest in exploring immunomodulatory approaches like vitamin D supplementation. Reports have indicated that COVID-19 patients with concomitant TB exhibit increased inflammatory markers, elevated mortality rates, and a higher prevalence of vitamin D deficiency [7][8].

Epidemiological studies have also hinted at vitamin D deficiency as a potential risk factor for severe COVID-19 and TB [9][10]. With the dual burden of these diseases, there is a compelling case to investigate whether vitamin D supplementation can mitigate the severity and mortality associated with SARS-CoV-2 and COVID-19 in Mongolia.

The Mongolian Context

In Mongolia, the coexistence of high rates of vitamin D deficiency and TB is a grave concern [8]. Since the outbreak of COVID-19, there has been a notable surge in vitamin D supplementation among the general population. However, despite this widespread practice, no research studies have explored the intricate relationship between vitamin D status, TB, and COVID-19 in Mongolia.

Thus, the aim of our study was to elucidate potential risk factors for COVID-19 severity, including serum vitamin D levels and latent TB infection, among Mongolian inpatients diagnosed with COVID-19. We also sought to unravel how these factors relate to disease complications and treatment outcomes.

Discussion

Our study has unveiled several key findings regarding the interplay between vitamin D, TB, and COVID-19 severity in the Mongolian population.

  • Active TB and COPD as Modifiable Risk Factors: Our analysis revealed that certain comorbidities, notably active TB and chronic obstructive pulmonary disease (COPD), along with factors such as being male and of older age, significantly influenced the severity of COVID-19. Among the 270 participants, 11% had active TB, while 14% had a household pulmonary TB contact. Patients with active TB displayed a more severe clinical course compared to those without TB. Surprisingly, individuals with latent TB infection (LTBI), as determined by QuantiFERON testing, were less likely to develop severe COVID-19, although this difference did not attain statistical significance. These findings align with a growing body of research indicating that LTBI may confer a protective immunological response against COVID-19 [16][17][18][19][20]. Conversely, COVID-19 patients with active TB exhibited a higher risk of severe disease and poorer outcomes [12][13][14][21][22].
  • The Protective Role of BCG Vaccination: Interestingly, our study identified a strong protective effect associated with the presence of a Bacille Calmette-Guérin (BCG) vaccination scar against COVID-19 severity. BCG, primarily employed as a tuberculosis vaccine, has been the subject of ongoing debate regarding its effectiveness. Nevertheless, BCG vaccination has been shown to modulate both innate and acquired immunity, potentially enhancing resistance against viral and bacterial infections [23][24].
  • Serum Vitamin D Levels and COVID-19 Severity: Surprisingly, our study did not establish a significant association between serum vitamin D levels and the severity of COVID-19. It’s essential to consider that our study was conducted during Mongolia’s coldest and darkest months, a period when vitamin D levels naturally tend to be at their lowest. Additionally, 69% of our participants were already taking vitamin D supplementation. Moreover, acute systemic inflammatory conditions like COVID-19 can reduce serum 25(OH)D concentrations, potentially influencing the observed relationship [25]. Furthermore, the cold climate in Mongolia can independently contribute to the severity of COVID-19, affecting the size and duration of SARS-CoV-2-laden aerosols and inducing cold-related physiological responses that increase infection susceptibility [26][27][28][29]. Nevertheless, prior research has suggested that vitamin D supplementation may reduce the risk of respiratory infections, including TB, particularly in individuals with vitamin D deficiency [30][31][32]. Some studies have even reported that COVID-19 patients receiving vitamin D supplementation experienced reduced mortality, decreased pro-inflammatory cytokines, and increased anti-inflammatory cytokines [33][34].

Strengths and Limitations of the Study

Our study benefits from several strengths, including the use of the QuantiFERON test to detect Mycobacterium tuberculosis (MTB) infection, which eliminates confounding factors associated with BCG sensitization or environmental mycobacteria. We also employed an objective assessment of BCG status through the presence or absence of a BCG scar. The laboratory responsible for QuantiFERON testing participated in an External Quality Assurance scheme conducted by an ISO 9001-accredited laboratory.

However, the study is not without limitations. As an observational study, there remains the possibility of residual and unmeasured confounding factors influencing the associations observed. Additionally, we did not screen for HIV infection, although the prevalence of HIV in Mongolia is exceptionally low [35].

Conclusion

In conclusion, our study underscores the importance of active TB and Chronic obstructive pulmonary disease (COPD) as potentially modifiable risk factors for COVID-19 severity in Mongolian inpatients with vitamin D deficiency.

These findings suggest the necessity of early TB evaluation in susceptible populations with COVID-19, potentially mitigating severe complications and the impact of acute respiratory distress syndrome (ARDS) in hospitalized patients.

The complex interplay of vitamin D, TB, and COVID-19 in Mongolia highlights the need for further research to elucidate the underlying mechanisms and potential interventions that could alleviate the burden of these diseases on the population.


reference link : https://www.mdpi.com/2072-6643/15/18/3979

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