Evidence for possible association of vitamin D status with cytokine storm and unregulated inflammation in COVID-19 patients

Abstract

Objectives We present evidence for a possible role of Vitamin D (VitD) deficiency in unregulated cytokine production and inflammation leading to complications in COVID-19 patients. Design The time-adjusted case mortality ratio (T-CMR) was estimated as the ratio of deceased patients on day N to the confirmed cases on day N-8. The adaptive average of T-CMR (A-CMR) was calculated as a metric of COVID-19 associated mortality. A model based on positivity change (PC) and an estimated prevalence of COVID-19 was used to determine countries with similar screening strategies. A possible association of A-CMR with the mean concentration of 25-hydroxyvitamin D (25(OH)D) in elderly individuals in countries with similar screening strategy was investigated. We considered high C-reactive protein (CRP) in severe COVID-19 patients (CRP ≥ 1 mg/dL) as a surrogate of a cytokine storm. We considered high-sensitivity CRP (hs-CRP) in healthy subjects as hs-CRP ≥ 0.2 mg/dL. Results A link between 25(OH)D and A-CMR in countries with similar screening strategy is evidence for VitD’s possible role in reducing unregulated cytokine production and inflammation among patients with severe COVID-19. We observed an odds ratio (OR) of 1.8 with 95% confidence interval (95% CI) (1.2 to 2.6) and an OR of 1.9 with 95% CI (1.4 to 2.7) for hs-CRP in VitD deficient elderly from low-income families and high-income families, respectively. COVID-19 patient-level data show an OR of 3.4 with 95% CI (2.15 to 5.4) for high CRP in severe COVID-19 patients. Conclusion We conclude that future studies on VitD’s role in reducing cytokine storm and COVID-19 mortality are warranted.

Deep Phenotyping of Headache in Hospitalized COVID-19 Patients via Principal Component Analysis

“…Severe COVID-19 has been found in patients with high CRP and PCT levels (21), and high CRP levels have been identified in patients with migraine with relative high frequency (seven or more days with headache per month) and chronic migraine (28), and migraine with aura (28,29). High CRP levels have been identified to be correlated with a cytokine storm, showing high CRP levels in patients with severe COVID-19 (30). Increased circulating pro-inflammatory cytokines have been suggested to be related to headache attributed to COVID-19, triggering perivascular trigeminal nerve endings (4).…”

Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study

“…Thanks to its pleiotropic actions, vitamin D has recently emerged as one such hopeful candidate through its established ability to decrease the cytokine/chemokine storm [ 14 ] via immunomodulatory [ 37 ] and anti-inflammatory effects [ 15 ] that could well result in a clinically important benefit in COVID-19 patients with ARDS [ 13 , 38 ].…”

“…In this regard, the activation of the vitamin D receptor (VDR) signaling pathway may generate beneficial effects in ARDS [ 13 ] by decreasing the cytokine/chemokine storm [ 14 ], thus having an important immunomodulatory and anti-inflammatory role [ 15 ].…”

SARS‐COV‐2 (COVID‐19): Cellular and biochemical properties and pharmacological insights into new therapeutic developments

“…The mortality rate was also found as increased in northern countries, where vitamin D deficiency rates are generally high 185 . Based on this relationship, several studies have reported an association between vitamin D deficiency and the incidence of severe COVID‐19 186‐189 …”