Thursday, September 10, 2020

Vitamin D and COVID-19 Update

It's been months since my initial entry on COVID-19 and vitamin D.  In that period there have been a number of further publications related to the value of vitamin D in the prevention or mitigation of this viral disease.  The findings of four reports are summarized below; all are consistent with the notion that vitamin D status affects the COVID-19 response.  

One study entitled "Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results" by Meltzer et al can be found at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770157 and was released on 2020 Sep 03.  They looked at the records of 4314 patients at a Chicago medical facility and identified 489 who had their vitamin D status measured before the arrival of COVID-19.  Then they tested those with some COVID symptoms and found 71 who tested positive.  Among patients who were determined to have COVID, those who were considered to have low vitamin D levels had a 77% higher chance of getting the disease, i.e relative risk of 1.77.  Moreover, non-White (mostly Black) people were 154% more likely to contract COVID, relative risk 2.54. 

In a similar study conducted by Merzon et al in Israel, 7807 patients whose vitamin D status had been determined were followed for the development of COVID between Feb 1 and Apr 30.  When tested 782 were positive and 7085 were negative. The authors concluded that those who were deemed to have low plasma vitamin D were 45% more likely to contract the virus, and also more likely to be hospitalized. https://febs.onlinelibrary.wiley.com/doi/epdf/10.1111/febs.15495 

In another Israeli study each of 52,405 COVID-infected patients were compared with 10 well matched control individuals, thus, a total of 524,050 controls, https://www.medrxiv.org/content/10.1101/2020.09.04.20188268v1.full.pdf.  They found a significant association between low vitamin D levels and COVID occurrence, and the risk of developing the disease was higher for those with severe deficiency (<20 nmol/L) than for those with milder deficiency (<50 nmol/L).

The study entitled "Effect of Calcifediol Treatment and best Available Therapy versus best Available Therapy on Intensive Care Unit Admission and Mortality Among Patients Hospitalized for COVID-19: A Pilot Randomized Clinical study" by Castillo et al was released on August 29 in the Journal of Steroid Biochemistry and Molecular Biology.  This study involved 76 consecutive patients hospitalized with COVID-19 infection in Cordoba, Spain.  Of these 50 were randomly treated with high dose calcifediol and 26 were maintained as controls; both groups were given the best available treatment at the time.  Calcifediol is the molecule that vitamin D is converted to by the liver, and would act faster than vitamin D.  In the treated group, one patient out of 50 had to be placed in ICU, while in the control group 13 out of 26 went to ICU.  No deaths occurred in the treated group but two died in the control group. https://www-sciencedirect-com.proxy.queensu.ca/science/article/pii/S0960076020302764

This latter study is the closest that I have seen to the gold standard large-scale, prospective double-blind study.  Nevertheless, I think that all four recent reports strongly support the widespread use of vitamin D to reduce the burden on our health care system.  

Canada's Policy on COVID-19.  Now that there is considerable evidence that is consistent with idea that vitamin D status matters with respect to the possibility of individuals contracting COVID-19 and the severity of the disease after contracting it, Health Canada should advocate the widespread taking of vitamin D for our population.  If Health Canada takes the position that they require information from a large-scale, prospective, double-blind trial before making such recommendations, then my question becomes "why haven't you done these experiments?"

This leads me to suggest that Canada should have a serious discussion about our approach to this disease.  The national objective to this point appears to be suppression of COVID-19 followed by widespread vaccination of the populace once an acceptable vaccine becomes available. This assumes that a vaccine will become available in a timely manner.   Now that the world knows more about this disease, its treatment and current damage to society inflicted by its indirect effects, we should discuss other possible approaches. One potential approach could be to encourage vitamin D sufficiency in our population and institute appropriate preventive measures for vulnerable populations, and then open up the economy significantly faster.

Let's start by examining the indirect damage being done by this disease; to date I have not observed a federal or provincial analysis of the these adverse effects.  We know the economy has suffered and continues to suffer; how is this affecting the health and quality of life for Canadians?  Workers and business owners in the hospitality industries are hurting.  The travel industry is still a mere shadow of its former self.  How are our isolation policies affecting students and instructors right from kindergarten to post-secondary education?  How has the mental health of our population been affected?  Various reports indicate that mental health problems have resulted in increased domestic violent.  How has physical health been affected?  Many people have reported developments ranging from the trivial (weight gain) to the serious (lack of health services including cancer diagnosis and treatment).  Personally, I have a minor example of delayed treatment; it is about a year since I was diagnosed with a full thickness tear of my left supraspinatus tendon.  COVID has resulted in me not even been interviewed by a surgeon yet.  Many others have serious conditions that have gone untreated.

Let's also consider other ways in which we might try to resume close-to-normal activities.  How badly would COVID-19 affect our collective health if we made the population vitamin D sufficient, used anti-inflammatory steroids, and protected identified populations?  Early in the current pandemic the case fatality ratio (number of deaths divided by the number of confirmed cases, CFR) was estimated to be in the order 5%- i.e. 5 people died for every 100 who tested positive for the disease.  As testing has become more available, and information about vulnerable individuals has accrued, the estimates of the CFR have fallen substantially.  By June, it had decreased to less than 2% in Canada.  By late summer, we began to appreciate that the number of COVID-infected people was substantially greater than the number who had tested positive for the disease; this was due to the use of tests for COVID-19 antibodies.  This had the effect of giving us an Infection Fatality Ratio (number of deaths divided by the number of infections, IFR)  somewhere in the range of 0.2 - 0.6%.  If we consider that these statistics were gathered in the absence of knowledge about the beneficial effects of anti-inflammatory steroids and vitamin D, it may be possible to reduce the IFR estimate by a further order of magnitude to the range of 0.02 to 0.06%.  These numbers put the risk of dying due to COVID-19 close to that of seasonal influenza, and we have not imposed lockdowns for the flu.  What I've not taken into consideration is the relative contagiousness of COVID-19 compared with influenza.  Even if the IFR is considered low, the number of vulnerable people contracting the disease could be sufficient to overwhelm our hospitals. The operative words herein are "number" and "vulnerable", and the former is substantially under our control.  For the most vulnerable, such as those in long-term care homes, the necessary precautions are quite well known now, and these people can be protected.  Control of the numbers of people contracting COVID is largely behavioural.  Perhaps the key question, is how careful or draconian (the word used depends on your point of view) we should be in our efforts to control the overall rate of infection.  The studies cited above and others suggest that we have the tools that can be used to open our society and economy more quickly.