[ad_1]
The United States is breaking new records for the number of daily deaths from COVID-19. The breakneck speed with which several vaccines have been developed and deployed is simply breathtaking. Yet we still have to face the grim prediction that our national death toll will surpass 500,000 Americans before widespread immunizations can get us out of this crisis. The response to the pandemic, therefore, should include an effort to aggressively eliminate what is becoming apparent as a risk factor for morbidity and mortality in COVID-19 – vitamin D deficiency.
For any risk factor for COVID-19, such as obesity, hypertension, or diabetes, strong correlative data is sufficient to inform clinical care, as in Surgeon General Luther Terry’s 1964 Tobacco and Health Report. This groundbreaking publication, which saved tens of millions of lives from lung cancer, was based on a causal analysis by an advisory committee. The team looked at the existing data and drew on the work of Sir Austin Bradford Hill and Sir Richard Doll, who had examined the increase in lung cancer cases in UK Hill, later described the standards resulting from their investigation, now known as Hill’s criteria for causation. He hypothesized that correlation data can be used to infer causality by satisfying various criteria such as consistency, specificity, temporality, and dose-reactivity. Vitamin D deficiency, associated with deleterious effects on innate and adaptive immunity, has many small but growing data sets that meet all of Hill’s criteria as a risk factor for severe COVID-19. And unlike other risk factors, it can be drastically changed.
Jain and his colleagues studied 154 patients who presented to a medical center for 6 weeks. When deaths were assessed on the basis of vitamin D deficiency (serum 25-OH-D <20 ng / mL), the death rate was 21%, compared with only 3% for those with levels higher. high. More strikingly, vitamin D deficiency was found in 97% of critically ill patients who required intensive care hospitalization, but in only 33% of asymptomatic cases, suggesting that low levels are a necessary component of COVID- 19 severe. This is one of several studies this year correlating low levels of vitamin D with worsening COVID-19 outcomes, as revealed in a meta-analysis by Pereira and colleagues.
Yet to confirm Hill’s criteria, some experimental evidence is not only recommended but needed, and small randomized trials with aggressive vitamin D reconstitution have shown positive results. Rastogi and his colleagues treated 40 people with mild COVID-19 and vitamin D (25-OH-D <20 ng / mL) deficiency with a placebo or 420,000 IU of cholecalciferol (vitamin D3) in a nanoemulsion at rapid action over seven days, equivalent to 60,000 IU (1,500 μg) per day. The results showed that supplementation helped clear the virus faster - 63% of treated patients tested negative for SARS-CoV-2 on day 14, compared to just 21% of the placebo group. Additionally, the treated group showed decreased fibrinogen levels, which is believed to contribute to the higher risk of thrombotic events in COVID-19.
Castillo’s team in Cordoba, Spain randomized 76 COVID-19 hospital patients in a 2: 1 ratio to receive either open-label calcifediol or no supplementation, in addition to standard care. The intervention group received 1,064 μg of this fast-acting vitamin D analogue in the first week, three times more potent than vitamin D3, followed by 266 μg per week thereafter. Among treated patients, only 2% (1 in 50) required ICU hospitalization, compared to 50% (13 out of 26) in the untreated group. In addition, 8% of untreated patients died, compared to none in the intervention group. Although vitamin D deficiency was not identified on admission, researchers cite a report that 25-OH-D levels in Cordoba in winter are deficient, averaging 16 ng / mL. Using a study population that leans toward vitamin D deficiency makes this a good study to examine the benefits of aggressively correcting this COVID-19 deficiency. To our knowledge, only one intensive care program in the United States has adopted such an aggressive reconstitution protocol in its treatment of COVID-19.
There is more evidence pointing in this direction. Using a quasi-experimental approach, Annweiler and his colleagues examined elderly and frail patients hospitalized for COVID-19 in France. The researchers obtained records for those who received regular bolus supplementation of vitamin D3 – 20,000 to 50,000 IU per month, a common practice in French retirement homes – and those who did not. Only 10% of those who received regular supplementation progressed to severe COVID-19 compared to 31% of the non-supplemented group. In addition, the 14-day mortality rates were only 7% in the supplemented group, compared to the same 31% in the non-supplemented group. The researchers also identified a third group of patients – those who received a single dose of 80,000 IU of cholecalciferol when they were diagnosed with COVID-19. This group performed better than the group that got none, but the result did not reach statistical significance, suggesting that the dose could have been too low or too late.
We discovered a pending peer review study that did not show the benefits of treating vitamin D deficiency in COVID-19. The researchers administered a single dose (200,000 IU of vitamin D3) to patients ten days after the first symptoms of COVID-19 appeared. Unlike calcifediol, it can take a week or more for the body to convert vitamin D3 to its active form. In addition, being fat soluble, the body competes with fatty tissue for the necessary amount, necessitating higher doses in obesity (the average BMI in this study was 31.6). Compare the dose given here to the standard protocol for correcting vitamin D deficiency in healthy ambulatory patients, who routinely receive a total of 600,000 IU over twelve weeks at 50,000 IU per week.
Data like this is not new. A 2014 Austrian study of 475 patients showed that supplementation with 540,000 IU of vitamin D3 followed by 90,000 IU per month halved the inpatient mortality rate in intensive care patients with severe vitamin D deficiency ( 25-OH-D level <12 ng / ml). Patients with higher levels did not show benefit, which pointed to a possible flaw in many vitamin D trials - should they focus only on results for those who are deficient?
It is not yet common to check serum 25-OH-D levels in hospitalized COVID-19 patients, although many practitioners prescribe supplementation at typical (and possibly insufficient) doses. A Canadian study of 22,214 people supplemented found that 1000 IU of cholecalciferol per day increased 25-OH-D levels on average by only 4.8 ng / mL with diminishing returns for each additional increase of 1000 IU per day. Toxicity was not seen in people who reported taking doses as high as 20,000 IU per day, an amount roughly equivalent to what is generated by a sunny summer afternoon on the skin. (Various medical companies claim that doses of up to 4000 IU of vitamin D per day are safe without medical supervision, and that up to 10,000 IU per day have shown no observed side effects.)
It is our responsibility as physicians not to wait for perfect evidence to make life and death decisions. Considering the safety profile of vitamin D, the 40% prevalence of vitamin D deficiency in the United States, and the fact that this season will likely be the deadliest phase of the pandemic to date, we must act now. Identifying and eradicating vitamin D deficiency with early and aggressive COVID-19 supplementation has the potential to save thousands of lives and should be one of our highest public health priorities.
Richard H. Carmona, MD, MPH, was the 17th U.S. Surgeon General and is now a distinguished professor of public health and COVID-19 Incident Commander at the University of Arizona. Vatsal G. Thakkar, MD, is an integrative psychiatrist, a founder of Reimbursify, and can be followed at Twitter. John C. Umhau, MD, MPH, is a retired Commander of the US Public Health Service and has published over forty peer-reviewed research articles.
[ad_2]
Source link