Vaccine or herd immunity?

Canada’s response to the COVID-19 pandemic has been well-articulated for the short term in the form of disease suppression to ensure that our health care system is not overwhelmed. Overall our governments have managed to maintain adequate capacity in our hospitals and clinics to handle COVID-19 and the regular health care load. The major black mark on the way we have handled the disease is in relation to our elderly in long-term care facilities. This now appears not to be specific to COVID-19 but the pandemic has exposed the weaknesses in our long-term care homes. With the publicity our long-term care homes have received it seems possible that these problems will now receive the attention they deserve.

On the other hand, Canada’s full strategy to address COVID-19 has not been well communicated to the populace. Is our way forward dependent on a vaccine or herd immunity? This question must be explored and fully communicated to the Canadian public. For the sake of argument, I would like to suggest that our national strategy should be achievement of herd immunity. The rationale for this is that most authorities warn that the earliest that a vaccine will be available is by the summer of 2021 and it could be much longer than that. Most of us cannot wait that long for our way of life to resume some normalcy. In addition, all governments cannot wait that long; to be blunt- we cannot afford the current path. If we accept this position, our goal should be to attain herd immunity. Now that the world has learned more about COVID-19, I think there is a way forward.

Accordingly, we should relax our procedures so that a sufficient portion of the population is exposed to the SARS-Cov2 virus to allow 50 to 70% of the population to develop immunity. This is where we should use the knowledge that the world has learned about COVID-19 to make the cost of herd immunity acceptable to Canadians. There is a lot of information indicating that a deficiency of vitamin D in the Canadian (and world) population has made COVID-19 about 10 times worse than it should be in terms of morbidity and mortality. https://vitamindcovid.blogspot.com/2020/05/vitamin-d-covid-19-and-me.html I would argue that if we make the Canadian population vitamin D sufficient, the effects of COVID-19 can be mitigated enough to be acceptable to the public. Thus we require a program that creates vitamin D sufficiency in our population by sunlight exposure and/or oral supplementation immediately with step-wise opening of the economy during the summer. The aim should be herd immunity before the onset of seasonal influenza. My concern is that COVID-19 combined with seasonal influenza will be far more deleterious to the health of our population than sequential COVID-19 followed by seasonal influenza. At the same time, we know that the most vulnerable Canadians are those in our nursing homes; we will require special consideration for this population.

This will not be a popular suggestion or solution to the problem facing us as a nation but we need to have this discussion now. I do not think that we should continue without a clear goals.

Vitamin D Absorption and Excretion

Vitamin D comes in two forms, Vit D₂ and Vit D₃ . Most of the information being published now refers to Vit D₃ , which is the form made in the skin of humans; Vit D₂ is obtained from plant sources. Vit D₃ is converted to 25-hydroxy Vit D₃ in the liver, and then to 1,25-dihydroxy Vit D₃ (active form) in the kidney and other tissues. Before I go into perhaps too much detail, I should say that vitamin D activity stays in the body for a long time, and that daily dosing with fatty food is probably best.

Vit D₃ is fat soluble and appears to be absorbed best when it is taken with food containing some fat; I take it with peanut butter at breakfast time. Once it has been absorbed it distributes into fat with a half-life of about 1.5 days, and then is removed by metabolism with a half-life reported be three days to almost a month. There is likely to be considerable variability in the both phases in part because of the varying amounts of fat in the bodies of different people. The original study I read was done on a small number of people in 1969 when obesity was less prevalent. The half-life of 25-hydroxy Vit D₃ and 1,25-dihydroxy Vit D₃ appear to be 15 days and 15 hours, respectively. In practical terms, this means that the blood levels take quite a long time to stabilize fully; some authorities suggest 6-8 weeks (see below). For most of us, taking a consistent dose will get us to a steady state level after 4-5 times the half-life of the longest lived molecule in question (Goodman & Gilman, the Pharmacological Basis of Therapeutics, Chap 1). I think (guess?) that we get some vitamin D benefit almost immediately and then continue to get it full benefits over a period of many days. Using the principles of pharmacokinetics, one might predict that a loading dose followed by a maintenance dose would be best, but the observations seem to support just daily dosing. Maybe the modelling, multiple variables and unknown properties of vitamin D₃ and its metabolites are just complex for me to understand.

Another variable that complicates predictions about body content of vitamin D is exposure to sunlight. The rate at which a person’s skin makes vitamin D depends on-

(a) duration of exposure- longer exposure results in more synthesis

(b) skin colour- darker skin contains more melanin and decreases synthesis; tanning reduces synthesis

(c) area of skin exposed- more area results in more synthesis

(d) time of year- summer months produce the most and winter months the least

(e) latitude- closer to the equator is best, all of Canada is in a low synthesis zone

(f) time of day- maximum vitamin D synthesis coincides with the time of maximum sunburn risk

(g) altitude- there is less atmosphere to block UV radiation at higher altitudes

(h) age- older people tend to make less vitamin D

To put this into context, a light skinned person with full body exposure to sunlight at mid-day may start to turn pink in 15-20 minutes and make 10000 IU of vitamin D.

The American Association of Clinical Endocrinologists has a nice set of slides on vitamin D requirements and dosing at https://www.aace.com/sites/default/files/2019-02/Vitamin_D_Deficiency_formatted.pdf

Slide 3 shows how the definitions of deficiency vary in comparison with other academic parties; nevertheless there is a trend toward recommending higher intakes of vitamin D. Slide 10 describes using a loading strategy to address frank vitamin D deficiency; this would be done under medical supervision for individuals whose blood level of 25-hydroxy Vit D₃ has been determined.

I think that the now known properties of vitamin D, where we live and how we live are consistent with a number of health issues facing contemporary Canadian society. For example, we know that the “flu” season occurs in winter; this would be about the time that our bodies become quite depleted in vitamin D. Before the advent of effective drugs, tuberculosis used to be treated by putting patients in the sun. We have seen an unexplained increase in the prevalence of asthma, since about 1970 and this coincides with kids spending less time outdoors, partially because of computer toys and partially because of overprotective parents who are hesitant to chase their kids out to play. Obesity is a stated risk factor for death in COVID-19; is this due to the larger vitamin D sink or the generation of inflammatory cytokines by adipocytes? Too many questions, not enough answers.

Walking Paths in Kingston

Exercise during COVID isolation.

Susie and I have isolated ourselves since the middle of March so we are a few days over two months since we had to change our social habits.  I don't know about anyone else but the first month seemed like three months, and the days seem to go by faster now.  I suppose that it has been accepting the social restrictions that has made the last few weeks less onerous than the initial weeks.  Here is how my life has changed.  There are just the two of us in our household, and that has meant that we are each other's company for the duration.  Isolating ourselves from others has not meant staying indoors all day, every day. In normal circumstances, we got our exercise in social settings- Susie in YMCA exercise classes and me playing hockey or ball hockey.  With imposed isolation our exercise had to be solitary or preferably something that we could do together. While the weather was still cold, our daily exercise was walking and with the onset of warmer weather, we have been able to ride our bicycles as an alternative. 

Our initial walking routes were those that we used frequently over the past several years.  A favourite has been to leave our house and walk through Polson Park and the St Lawrence College area into Lake Ontario Park, then to follow the shore of Lake Ontario past Providence Hospital and Portsmouth Olympic Harbour.  From there we returned through Queen's West Campus, then up by Calvin Park Public Library and then home via the walk-throughs of Calvin Park.  This loop is about 8 km.  While this walk is really pleasant, it got a bit boring so we explored every interesting walk within a reasonable distance of home.  If you look at a map and place our home at 10 Holland Crescent in the middle of a clock face and Portsmouth Olympic Harbour at 5 o'clock you can follow the routes that we have discovered. 

At ~7 o'clock is King Street West, which we have used to access LeMoines Point Conservation Area to the west and then the start of the Rideau Trail at the west end of Lake Ontario Park.  We have walked Rideau Trail per se up to Bath Road, but have also found a number of side paths toward the wetlands to the west that are interesting alternatives.  From ~10 o'clock on Bath Road we have gone westward as well as northward.  To the west is Arbour Ridge Park.  You can take it from Tanner Drive all along the creek and under Centennial Drive and into the wetlands north of Meadowbrook Park.  It is also possible to cross the train tracks over to Taylor-Kidd Boulevard.  From there it's a sidewalk stroll to the Via Rail Station, which is ~11 o'clock from our house.  From the Via Station there are numerous ways to get back home.  The one we never use is the Princess Street Overpass because of all the traffic noise.  Just beside Princess Street to the northeast is a section of the Rideau Trail along an abandoned road that takes you back to Princess at Parkway.  From that intersection the Rideau Trail runs south to Bath Road.  This is an interesting path because there are many side trails into the the wetland to the west, and toward Balsam Grove and Grenville Park to the east.  There is even a connection in Balsam Grove toward Grenville Park via the south end of Hawthorne Avenue.  Another way to get from the Via Station to Princess Street is to cross the railway on John Counter Blvd then go across Little Cataraqui Creek.  As soon as you come to William Hackett Park there is a paved path along the creek and through a wooded area to Princess Street and Parkway.

From the Via station, we have followed Old Mill Road until it ends and then taken unmarked paths northward through the trees up to the K & P Trail.  There is also an unmarked trail north of the K & P where mountain bikers have created some interesting routes. We have taken the K & P Trail westward under the 401 and then as far as the parking area at the corner of Cordukes Road and Burr Brook Road.  Along the K & P just south of the 401 underpass you can access paths that take you through the woods to Venture Drive.  We have also used the K & P Trail east ward as it goes to the industrial park to the parking lot at the west end of Dalton Avenue.  It follows streets to the intersection of Dalton and St Remy Place where it picks up the abandoned railbed again to the north of the CN line to Division St.  From there you have to follow Division and John Counter Blvd to Elliott Avenue where it again follows the old rail line to Railway and Montreal and then runs parallel to Rideau St to River St. At the east end of River St it runs southward along the Cataraqui River to the south end of Doug Fluhrer Park.  From there it becomes part of the Waterfront Trail and takes you to Confederation Park in front of Kingston City Hall.  Waterfront Trail takes you along Lake Ontario in front of Queen's University to Portsmouth Olympic Harbour at the 5 o'clock position from home.  This spring there has been a real visual treat by the yacht club where a family of foxes has taken up residence under a storage building.  They seem to like posing for pictures.  Bruce Payne says that he has seen mink and weasels in the area as well.

At the intersection of Montreal St and Rideau St you can walk eastward on multiple trails to Belle Island as well as northward to the end of John Counter Blvd where they are building the third crossing over to Gore St. At the 2 o'clock position from home we have accessed the new path starting at the north end of MacDonnell St in Third Avenue Park.  It runs northward through a grassy area up to John Counter Blvd.  We have also picked up the CN spur line at the 9 o'clock position and followed it northwestward to point just north of the CN main line behind the Riocan Centre. There is a short path behind the Riocan Centre that runs northeastward into the residential area west of Centennial Dr.  Unfortunately, we can't walk the tracks any more because we were stopped by the railway police, who warned us about a law that were breaking.  Since they now have our names, we are marked.  We have also walked from our house to the Little Cataraqui Conservation Area north of the 401 at the end of Sir John A MacDonald Blvd.  There are several walking paths there that go north to near Burr Brook Rd.  These are really nice as they are entirely in the woods and away from traffic.

Most of the paths that we walked are essentially flat so we have identified three areas that give us some vertical work for our legs.  There is a good set of stairs in Lake Ontario Park and another one on the the bleachers on the north side of the Memorial Centre. In O'Connor Park straight north of us, there is a hill that we use for vertical exercise. Starting about May 20th I started including some pushups on alternate days.  I hadn't been able to do any since before Christmas because of a torn tendon in my left rotator cuff- specifically "a full-thickness tear of the anterodistal supraspinatus tendon". I struggled to do a set of 10; it's going to be a slow grind back to normal.  Theoretically I am supposed to have an appointment with a surgeon to consider a procedure to repair the tendon.  Who knows when that will happen?  I've had physiotherapy until isolation started.

Two more paths.  At the 10 o'clock position from home, we have found a short but pleasant path in Meadowbrook Park off Kingsdale Avenue behind Frontenac Mall.  Then northwest of that is Trillium Ridge Park just off Edgar Street.  You can walk the marked paths through to Waterloo Drive.  There is a green space further east and just north of Grandtrunk Avenue with rough paths though to Grandtrunk where it turns northwest.

Vitamin D, COVID-19 and Me

2020 May 19

    I have decided to start a blog regarding my experiences imposed by the arrival of COVID-19 in Canada. This first entry is a document that I sent to various federal and provincial political leaders and is based on what I have learned over the past several years. While I wound down my career in Pharmacology at Queen's University, I developed an interest in a variety of topics- vitamin D just happens to be one of them. Accordingly, I do not have any special expertise in vitamin D.  I plan to make regular entries in this blog until we return to our normal lives.

COVID-19: the Case for Making the Canadian Population Vitamin D Sufficient and Relaxing Restrictions

1. Vitamin D deficiency/insufficiency is prevalent in the Canadian population.

G.K. Schwalfenberg*, S.J. Genuis, M.N. Hiltz Addressing vitamin D deficiency in Canada: A public health innovation whose time has come public health 124 (2010) 350–359

These authors reviewed 16 studies and found that 70-97% of Canadians were vitamin D insufficient, and 14-60 % were clearly deficient. Herein insufficiency is defined as less than 72-80 nM and deficiency was less than 25-40 nM.

2. Vitamin D effects go well beyond bone health.

In their 2013 review, Uwe Gröber, ^{1 ,*} Jörg Spitz, ² Jörg Reichrath, ³ Klaus Kisters, ^{1 , 4} and Michael F Holick ⁵ ( Vitamin D: Update 2013: From rickets prophylaxis to general preventive healthcare. Dermatoendocrinol. 5(3): 331–347, 2013) summarized the role of vitamin D in a number of functions beyond bone health. Accordingly, diseases associated with vitamin D deficiency include autoimmune diseases (multiple sclerosis, type 1 diabetes) inflammatory bowel disease (Crohn disease), infections (such as infections of the upper respiratory tract), immune deficiency, cardiovascular diseases (hypertension, heart failure, sudden cardiac death), cancer (colon cancer, breast cancer, non-Hodgkin’s lymphoma) and neurocognitive disorders (Alzheimer disease).

3. Vitamin D is anti-viral.

In the context of COVID-19, the germaine property of vitamin D is its anti-viral action. Vitamin D promotes the activity of both the adaptive immune response and the innate immune response. One mechanism by which the innate anti-viral effect is enhanced is through up regulation of cathelicidin and defensin, which are anti-viral and anti-microbial peptides.

John Campbell a retired academic nurse in the United Kingdom has prepared daily video lessons on COVID-19, and clearly explains the potential of Vitamin D in his video on You Tube. https://www.youtube.com/watch?v=1fxw3nTZYlA. Harvard Medicine’s JoAnn Manson has recently taken a supportive position as well.

https://www.medscape.com/viewarticle/930152 These are just two of a growing number of researchers, physicians and concerned citizens who have marshalled respectable arguments in support of vitamin supplementation to face COVID-19.

4. Vitamin D is effective against COVID-19.

Prabowo Raharusuna*, Sadiah Priambada, Cahni Budiarti, Erdie Agung, and Cipta Budi have released a preprint of their retrospective cohort study of 780 (active and expired) cases with laboratory-confirmed infection of SARS-CoV-2. Cases were divided on the basis of serum 25(OH) vitamin D levels with normal being > 30 ng/ml (75 nM), insufficient being 21-29 ng/ml, and (3) deficient being < 20 ng/ml (45 nM) Individuals whose vitamin D levels were insufficient were ~13 times more likely to die while those who were vitamin D deficient were 19 times more likely to die. There are many more published studies that have implicated vitamin D insufficiency and deficiency with greater risk for viral infections.

5. Current status of vitamin D and COVID-19.

There are abundant data showing an inverse relationship between vitamin D status of individuals and their susceptibility to COVID-19. While it would be desirable to have a randomized, double-blind clinical trial showing that vitamin D supplementation is prophylactic, it can be argued that it is unethical to wait for this. People are getting sick and dying as we wait. It is time to promote supplementary vitamin D (≥2000 IU/day) for the Canadian population.

Effect of supplementary vitamin D.

On the basis of current data from Europe, Asia and USA, it can be estimated that the case fatality rate for COVID-19 exposure is ~0.5% (John Campbell, Friday May 15). Germany’s Hendrik Streeck (Director of the Institute for Virology at the University Hospital Bonn) calculated lower estimates of between 0.24 and 0.37% (https://medicalxpress.com/news/2020-05-team-covid-infection-fatality.html) These values for case fatality rate are based on populations following conventional recommendations for vitamin D intake, which would be based on anti-Rickets dosages. Results of recently released study information suggest that making a population genuinely vitamin D sufficient could reduce this by 10-fold or more- bringing the rate down to the range of 0.05%. This would be similar to influenza, which we have learned to live with.

Economic and social effect.

Undoubtedly, COVID-19 restrictions have had a tremendous economic, mental and social cost. I cannot calculate the economic effect on Canada at large but just one company, Air Canada has stated that it lost over $1 billion in the last quarter. Governments are spending huge sums of money addressing the direct effects of COVID-19, and their tax revenues have diminished. Eventually we will have to pay for this in cash. Another incalculable cost is the future effect on our population health due to reductions in tax revenues. In comparison, the cost of every Canadian taking supplementary vitamin D would be negligible- less than five cents/day.

A recommendation.

In closing, may I suggest that we immediately encourage our citizens to supplement themselves with vitamin D3 (2000 IU/day or more but less than 10,000 IU/day, Michael Holick Boston Univ Sch of Med) or get moderate exposure to sunlight, and then proceed with relaxing our social restrictions and opening our economy as soon as the population can be made vitamin D sufficient.