Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study

Vitamin D deficiency/insufficiency was present in majority of hospitalized patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism.

• The majority of patients with COVID-19 had total 25(OH)D concentrations indicative of vitamin D insufficiency (29.3%) or deficiency (44.4%).
• Total 25(OH)D was lower in men than in women and weakly positively correlated with increased age.
• For the subjects with  Influenza A (47.3% were insufficient in vitamin D and 37.6% deficient) and for those who were critical illness survivors (30.2% insufficient and 56.8% deficient).
• In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received invasive mechanical ventilation (IMV).
• In COVID-19, biologically active free 25(OH)D correlated with total 25(OH)D and was lower in patients who received IMV, but was not associated with selected circulating inflammatory mediators.

295 hospitalized people with COVID-19 (International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)/WHO Clinical Characterization Protocol for Severe Emerging Infections UK study), 93 with influenza A (Mechanisms of Severe Acute Influenza Consortium (MOSAIC) study, during the 2009–2010 H1N1 pandemic) and 139 survivors of non-selected critical illness (prior to the COVID-19 pandemic).

The observational design of this study makes it challenging to make any definitive conclusions prevents any conclusions about a causal role of vitamin D status in poor clinical outcome being drawn. There is no comparison to healthy people. It is possible that the vitamin D status was caused by the disease.

“Vitamin D deficiency/insufficiency was present in the majority of hospitalized patients with COVID-19 or influenza A and scaled with severity, highlighting that reduced concentrations of vitamin D are common to these disease states and distinct patient cohorts. For the first time, free and total 25(OH)D were studied in COVID-19, demonstrating consistent results. It is not clear whether vitamin D status led to poor clinical outcome or was a consequence of illness severity. Randomized trials will be necessary to determine whether a causal relationship exists between vitamin D early in the course of the disease and development of critical illness. Since vitamin D deficiency/insufficiency persisted at concentrations expected to disrupt bone metabolism in critical illness survivors, investigation of longer-term bone health outcomes is also warranted”.

• This cross-sectional study, reported measurements of total and free 25(OH)D in hospitalized people with COVID-19 and total 25(OH)D in hospitalized people with influenza A and survivors of critical illness. The authors then used these three data sets to test the hypotheses that vitamin D insufficiency in severe respiratory virus infections scales with severity and persists in survivors of critical illness.
• Plasma was obtained from the patients described above
• Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry.
• Free 25(OH)D was measured by ELISA in COVID-19 samples.
• In classifying vitamin D status: Total 25(OH)D >50 nmol/L is reported as ‘sufficient’, 25–50 nmol/L as ‘insufficient’ and <25 nmol/L as ‘deficient

Hurst EA, Mellanby RJ, Handel I, Griffith DM, Rossi AG, Walsh TS, Shankar-Hari M, Dunning J, Homer NZ, Denham SG, Devine K, Holloway PA, Moore SC, Thwaites RS, Samanta RJ, Summers C, Hardwick HE, Oosthuyzen W, Turtle L, Semple MG, Openshaw PJM, Baillie JK, Russell CD; ISARIC4C Investigators. Vitamin D insufficiency in COVID-19 and influenza A, and critical illness survivors: a cross-sectional study. BMJ Open. 2021 Oct 22;11(10):e055435. doi: 10.1136/bmjopen-2021-055435. PMID: 34686560; PMCID: PMC8728359.