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

Objectives: The steroid hormone vitamin D has roles in immunomodulation and bone health. Insufficiency is associated with susceptibility to respiratory infections. We report 25-hydroxy vitamin D (25(OH)D) measurements in hospitalised people with COVID-19 and influenza A and in survivors of critical illness to test the hypotheses that vitamin D insufficiency scales with illness severity and persists in survivors. Design: Cross-sectional study. Setting and participants: Plasma was obtained from 295 hospitalised 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). Total 25(OH)D was measured by liquid chromatography-tandem mass spectrometry. Free 25(OH)D was measured by ELISA in COVID-19 samples. Outcome measures: Receipt of invasive mechanical ventilation (IMV) and in-hospital mortality. Results: Vitamin D insufficiency (total 25(OH)D 25–50 nmol/L) and deficiency (<25 nmol/L) were prevalent in COVID-19 (29.3% and 44.4%, respectively), influenza A (47.3% and 37.6%) and critical illness survivors (30.2% and 56.8%). In COVID-19 and influenza A, total 25(OH)D measured early in illness was lower in patients who received IMV (19.6 vs 31.9 nmol/L (p<0.0001) and 22.9 vs 31.1 nmol/L (p=0.0009), respectively). 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. Conclusions: Vitamin D deficiency/insufficiency was present in majority of hospitalised patients with COVID-19 or influenza A and correlated with severity and persisted in critical illness survivors at concentrations expected to disrupt bone metabolism. These findings support early supplementation trials to determine if insufficiency is causal in progression to severe disease, and investigation of longer-term bone health outcomes

The percentage of persons by household telephone status and percentage of persons tested for HIV by telephone status, NHIS, United States, 2003–2013^a.

<p>Note. 95% CI = 95% Confidence Interval; HIV = human immunodeficiency virus; NHIS = National Health Interview Survey</p><p>^a Persons in cellphone-only households are respondents living in a household with only a working cellphone. Persons in landline households are respondents living in a household with a working telephone that is not a cellphone. Data not shown for respondents living in a household with no cellphone or landline telephone, which remained relatively stable and <2% of respondents in all years.</p><p>^b From 2003 to 2013, there was a 42.0% increase in the percentage of persons aged 18–64 years living in cellphone-only households. Linear regression modelling found this change was statistically significant (<i>p</i> < 0.001).</p><p>^c From 2003 to 2013, there was a 42.2% decrease in the percentage of persons aged 18–64 years living in landline households. Linear regression modelling found this change was statistically significant (<i>p</i> < 0.001).</p><p>^d From 2003 to 2010, the percentage of persons in cellphone-only households who had ever been tested remained stable; linear regression modelling found this change was not statistically significant (<i>p</i> = 0.6147).</p><p>^e From 2003 to 2010, there was a 3.1% increase in the percentage of persons in landline households who had ever been tested. Linear regression modelling found this change was statistically significant (<i>p</i> < 0.001).</p><p>The percentage of persons by household telephone status and percentage of persons tested for HIV by telephone status, NHIS, United States, 2003–2013<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0125637#t002fn002" target="_blank">^a</a>.</p

The percentage of persons tested for HIV, NHIS and BRFSS, United States, 2003–2013.

<p>Note. N = Unweighted sample size; 95% CI = 95% Confidence Interval; BRFSS = Behavioral Risk Factor Surveillance System; HIV = human immunodeficiency virus; NHIS = National Health Interview Survey</p><p>^a Linear regression modeling was used to assess for statistically significant changes in the percentage of persons aged 18–64 years ever tested for HIV in NHIS during 2003–2013. From 2003 to 2010, there was a statistically significant 4.8% increase in the percentage ever tested for HIV (<i>p</i> < 0.001). From 2010 to 2011, there was a statistically significant 4.4% decrease in the percentage ever tested for HIV (<i>p</i> < 0.001). From 2011 to 2012, the percentage ever tested for HIV did not change significantly (<i>p</i> = 0.101). From 2012 to 2013, there was a statistically significant 2.5% increase in the percentage ever tested for HIV (<i>p</i> < 0.001).</p><p>^b Linear regression modeling was used to assess for statistically significant changes in the percentage of persons aged 18–64 years ever tested for HIV in BRFSS during 2003–2013. From 2003 to 2010, there was a statistically significant 5.7% decrease in the percentage ever tested for HIV (<i>p</i> < 0.001). From 2010 to 2011, there was a statistically significant 2.7% increase in the percentage ever tested for HIV (<i>p</i> < 0.001). From 2011 to 2013, there was a statistically significant 0.6% increase in the percentage ever tested for HIV (<i>p</i> = 0.016).</p><p>The percentage of persons tested for HIV, NHIS and BRFSS, United States, 2003–2013.</p

The percentage of persons aged 18–64 years by household telephone status and select characteristics, NHIS, United States, 2003 and 2013.

<p>Note. 95% CI = 95% Confidence Interval; HIV = human immunodeficiency virus; NHIS = National Health Interview Survey</p><p>^a Persons in cellphone-only households are respondents living in a household with only a working cellphone. Persons in landline households are respondents living in a household with a working telephone that is not a cellphone. Data not shown for respondents living in a household with no cellphone or landline telephone, which remained relatively stable and <2% of respondents in all years.</p><p>The percentage of persons aged 18–64 years by household telephone status and select characteristics, NHIS, United States, 2003 and 2013.</p

HIV Testing among Outpatients with Medicaid and Commercial Insurance.

To assess HIV testing and factors associated with receipt of testing among persons with Medicaid and commercial insurance during 2012.Outpatient and laboratory claims were analyzed from two databases: all Medicaid claims from six states and all claims from Medicaid health plans from four other states and a large national convenience sample of patients with commercial insurance in the United States. We excluded those aged 64 years, enrolled <9 of the 12 months, pregnant females, and previously diagnosed with HIV. We identified patients with new HIV diagnoses that followed (did not precede) the HIV test, using HIV ICD-9 codes. HIV testing percentages were assessed by patient demographics and other tests or diagnoses that occurred during the same visit.During 2012, 89,242 of 2,069,536 patients (4.3%) with Medicaid had at least one HIV test, and 850 (1.0%) of those tested received a new HIV diagnosis. Among 27,206,804 patients with commercial insurance, 757,646 (2.8%) had at least one HIV test, and 5,884 (0.8%) of those tested received a new HIV diagnosis. During visits that included an HIV test, 80.2% of Medicaid and 83.0% of commercial insurance claims also included a test or diagnosis for a sexually transmitted infection (STI), and/or Hepatitis B or C virus at the same visit.HIV testing primarily took place concurrently with screening or diagnoses for STIs or Hepatitis B or C. We found little evidence to suggest routine screening for HIV infection was widespread