Abstract: www.nature.com/scientificreports OPEN Relationship of anti‑SARS‑CoV‑2 IgG antibodies with Vitamin D and inflammatory markers in COVID‑19 patients Hatixhe Latifi‑Pupovci1,2, Sadie Namani1,2*, Artina Pajaziti1, Blerina Ahmetaj‑Shala3, Lindita Ajazaj2, Afrim Kotori4, Valdete Haxhibeqiri2, Valentin Gegaj2 & Gramoz Bunjaku2 Several studies have found an association of COVID-19 disease severity with Vitamin D deficiency and higher levels of anti-SARS-CoV-2 IgGs. The aim of this study was to determine whether levels of Vitamin D and “inflammatory state” influence the magnitude of anti-SARS-CoV-2 IgGs levels in COVID-19 patients. For this purpose, in 67 patients levels of anti-SARS-CoV-2 IgG were measured in week 4 whereas in 52 patients levels of Vitamin D were measured in week 1 after symptom onset. We found that low Vitamin D levels were significantly associated with age and disease severity whereas there was a trend without significance, towards negative correlation of Vitamin D with antiSARS-CoV-2 IgG. Anti-SARS-CoV-2 IgG were significantly higher in older ages, patients with severe disease, diabetes and those who received corticosteroid and antibiotic therapy. There was a positive correlation of anti-SARS-CoV-2 IgG with IL-6, CRP, LDH, ESR and with percentages of granulocytes. In conclusion, Vitamin D and anti-SARS-CoV-2 IgG share common parameters associated with inflammatory state. However, even though Vitamin D protects against severe forms of COVID-19 it could not directly affect anti-SARS-CoV-2 IgG production. The coronavirus disease 2019 (COVID‑19) is caused by a new coronavirus which in addition to acute respira‑ tory failure is associated with systemic disorders such as hyperinflammation, hypercoagulation and ­vasculitis1. Although many people exhibit mild ‘flu-like’ symptoms, in severe responses systemic changes have been attrib‑ uted to the cytokine storm accompanying severe inflammatory s­ yndrome2–4. Severe forms of COVID-19 have been linked with low levels of circulating 25-hydroxy Vitamin D (25[OH]D) as an expression of Vitamin D (Vit. D)5–10. Vit. D has immunomodulatory activity in response to invasion of bacterial and viral ­pathogens11,12 interacting with its receptor (VDR) in immune c­ ells13–15. In several studies it was shown that severe inflammatory syndrome was accompanied with changes in hematological markers and increased several inflammatory markers such as CRP, LDH, ESR, ferritin etc.2,16–18. A recent study has shown that in the presence of Vit. D, IL-6 induces higher production of IL-10, a known anti-inflammatory cytokine which is expected to lead to the reduction of inflammatory markers such as C ­ RP19. Several studies have shown inverse association between Vit. D and CRP ­levels20–22. Additionally, high levels of CRP were associated with lowering levels of Vit. D ­ 23 indicating that Vit. D is a negative acute phase reactant. Thus, Vit. D insufficiency could be the cause and effect of high CRP levels in COVID-19 patients. Humoral and cellular immune responses, two wings of adaptive immunity, are crucial in clearing a variety of viral ­infections24, and have been implicated in recovered COVID-19 ­patients25,26. In several studies disease sever‑ ity of COVID-19 was associated with higher levels of ­antibodies27–29 whereas asymptomatic patients minimally produced anti-SARS-CoV-2 IgGs which were poorly m ­ aintained28,30. Taking into account that Vit. D affects adaptive immune response, it may have an impact on..