COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not

Silberstein, Morry

doi:10.1016/j.ejphar.2021.174031

Cited by 19 publications

(18 citation statements)

References 29 publications

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“…Our findings support the case for a net negative effect of IL-6 in COVID-19 as we demonstrate that DES, a downstream biomarker of tissue damage, associates with higher circulating IL-6. However, where monoclonal antibodies non-selectively block IL-6 signaling and may consequently be expected to have both favorable and unfavorable effects, we hypothesize that IL-6 modulation by vitamin K may instead be more selectively beneficial ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Vitamin D and K on Interleukin-6 in COVID-19

et al. 2022

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BackgroundPathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.MethodsWe assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.ResultsComparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.ConclusionsDp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Effects of Vitamin D and K on Interleukin-6 in COVID-19

et al. 2022

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“…Vitamin D supplementation in those patients was able to reduce IL-6 levels and to decrease the prevalence of such inflammatory response. Importantly, while tocilizumab non-selectively blocks both anti-inflammatory and pro-inflammatory actions of IL-6, vitamin D does not target IL-6 receptors and thus directly reduces IL-6 production from immune cells avoiding potential deleterious effects related to the complete suppression of the anti-inflammatory actions of IL-6 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy

et al. 2021

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Background Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. Methods We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. Results Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0–56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0–32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0–99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5–45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ − 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98–1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95–0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. Conclusion In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

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“…It is possible that insufficient vitamin D levels contribute to cytokine storms, inadequate protection from epithelial cell apoptosis, and deficient epithelial cell repair, ultimately making the lungs vulnerable to fatal immune system dysregulation. The evidence that vitamin D is a better and more holistic modulator of the immune system than antibody therapy to prevent the action of cytokines like IL-6 is not surprising [ 110 ].…”

Section: Vitamin D and Covid-19: Summary Of The Evidencementioning

confidence: 99%

Vitamin D and COVID-19: An Overview of Recent Evidence

Ghelani

Alesi

Mousa

2021

IJMS

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The novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) has progressed rapidly from an outbreak to a global pandemic, with new variants rapidly emerging. Coronavirus disease 2019 (COVID-19), the disease resulting from SARS-CoV-2 infection, can lead to multiorgan damage. Due to the extremely contagious and fatal nature of the virus, it has been a priority of medical research to find effective means of treatment. Amid this search, the role of vitamin D in modulating various aspects of the innate and adaptive immune system has been discussed. This review aims to consolidate the research surrounding the role of vitamin D in the treatment and prevention of COVID-19. While there are some conflicting results reported, the consensus is that vitamin D has a host of immunomodulatory effects which may be beneficial in the context of COVID-19 and that low levels of vitamin D can result in dysfunction of crucial antimicrobial effects, potentially contributing to poor prognosis. Studies also show that the effects of low vitamin D can be mitigated via supplementation, although the benefits of vitamin D supplementation in the treatment of COVID-19 remain controversial.

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COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not

Cited by 19 publications

References 29 publications

Effects of Vitamin D and K on Interleukin-6 in COVID-19

Effects of Vitamin D and K on Interleukin-6 in COVID-19

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy

Vitamin D and COVID-19: An Overview of Recent Evidence

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