I got around to reading the summer issue of my University of Chicago magazine the other day. In it was a COVID article, of course. This one, entitled “Trials by fire”, describes how U of C docs have dealt with the pandemic, not just dealing with the special needs of all the patients, and figuring out other ways to handle things, but also all the research that’s been done, at bedside, bench and in the field (1). There was even a familiar name in there, former U of M rheumatology fellow Reem Jan, who also went to the same London medical school (St. George’s) where I’d spent a month in January ’79 (https://wordpress.com/post/theviewfromharbal.com/409). She conducted a trial using hydroxychloroquine (Plaquenil) at triple the dose we use in rheumatoid arthritis or lupus, finding the drug could be effective if used early in the infection, before more severe features ensued. Another rheumatologist whom I don’t know (although his Chief, Marcus Clark, was once a resident on my service), Pankti Reid, went after the vigorous host immune response, which does most of the damage, rather than the viral infection itself (just like in the 1918 Spanish flu pandemic (2)), using tocilizumab (Actemra), an inhibitor of interleukin-6 used to treat rheumatoid arthritis and polymyalgia rheumatica. Another doc, liver specialist Michael Millis, dipped into the rheumatologist’s bag to come up with leflunomide (Arava), another agent we use to treat rheumatoid arthritis. To be fair, Dr. Willis had done pioneering work using Arava in organ transplantation (3). It was his work advising the Chinese health ministry as they developed their voluntary organ donation system that he developed the connections he tapped to ask whether they had ever tried Arava for their COVID patients. They had, so Dr. Millis conducted a small trial, finding patients benefitted, with their symptoms typically resolving in a week faster than would be expected among that population. Leflunomide is among a class of drugs that inhibit dihydroorotate dehydrogenase (DODH), which do a number of things that would interfere with what a coronavirus is trying to do to our cells, and looks to become an important, relatively inexpensive, and not very toxic member of the anti-COVID armamentarium (4).
I’d known some of this. Actemra is a mainstay now in treating COVID once it’s in the lung. Arava I didn’t know about (for COVID). And I’d held forth many times on this blog about Plaquenil (5), for which I remain a strong proponent, particularly in early mild disease, maybe with a little azithromycin thrown in for good measure. The jury is still out. A PubMed search of coronavirus AND hydroxychloroquine nets 1,394 hits. I can’t say I read them all, but in the first few pages I didn’t find anything concise, clear and recent enough to list here.
But the most interesting part of the article came toward the end. David Meltzer, chief of Hospital Medicine, came across an article on vitamin D in respiratory tract infections, a meta-analysis that showed among people with vitamin D deficiency, symptoms were reduced 70 % when the deficiency was corrected (6). With half of all Americans (upwards of 80% of Michiganders) and 70% of African Americans deficient in vitamin D, that’s an awful lot of people at a level of risk that could easily be reduced, and substantially. Dr. Meltzer’s own survey of UofC patient records found that vitamin D deficient persons were 77% more likely to test positive for COVID than persons who weren’t vitamin D deficient. This increased risk was abrogated if the person’s deficiency had been treated. This has been borne out by multi-nation surveys in Europe (7). So who should take vitamin D, and how much? The RDA of 600 IU is based on vitamin D’s effects on bone health. Doctors treating vitamin D deficient patients prescribe 50,000 IU weekly for 4 weeks. But before you run to buy supplements or ask your doctor for a prescription, look up to that big free source we all share up in the sky! Half an hour of midday sun provides 10,000 units. If you’re one of those whom pharma and the dermatologists have managed to convince that the rays of the sun are some sort of cancer-causing poison to be avoided at all costs, hear here what researchers from the Karolinska and Lund hospitals in Southern Sweden found following 30,000 women for 20 years: sunbathers lived 0.6 – 2.1 years longer than sun-avoiders, reduced mortality due mainly from a lower risk of cardiovascular disease and noncancer/non-CVD (8). Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group. There was a little more melanoma in the sunbathers, but they were 8 times less likely to die from it than sun-avoiders. You know that lucky old sun ain’t got nuthin’ to do but roll around heaven all day https://www.youtube.com/watch?v=7C0ca55mgFM. And we’re lucky he’s up there doing it. We should go out there and catch some of that controlled thermonuclear activity coming at us from 93 million miles away. Sunshine and fresh air was the most effective treatment regimen in that little pandemic over a century ago involving the flu (9). Sometimes it’s worthwhile to take the lid off old treatments. Maybe we can get to feeling as good as Mr. Deutschendorf https://www.youtube.com/watch?v=gQ9kJa_6cBg
1. Kelly J. Trials by fire. The University of Chicago Magazine. Summer 2020. 112(4):24-29. https://mag.uchicago.edu/science-medicine/trials-fire
2. Barry JM. The Great Influenza: The Story of the Deadliest Pandemic in History. New York: Penguin Random House, 2004.
3. Williams JW, Mital D, Chong A, Kottayil A, Millis M, Longstreth J, Huang W, Brady L, Jensik S. Experiences with leflunomide in solid organ transplantation. Transplantation. 2002 Feb 15;73(3):358-66. https://doi: 10.1097/00007890-200202150-00008
4. Coelho AR, Oliveira PJ. Dihydroorotate dehydrogenase inhibitors in SARS-CoV-2 infection. Eur J Clin Invest. 2020 Oct;50(10):e13366. https://doi: 10.1111/eci.13366.
5. https://wordpress.com/post/theviewfromharbal.com/331, https://wordpress.com/post/theviewfromharbal.com/346, https://wordpress.com/post/theviewfromharbal.com/357, https://wordpress.com/post/theviewfromharbal.com/387, https://wordpress.com/post/theviewfromharbal.com/400,https://wordpress.com/post/theviewfromharbal.com/509, https://wordpress.com/post/theviewfromharbal.com/599
6. Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, Goodall EC, Grant CC, Griffiths CJ, Janssens W, Laaksi I, Manaseki-Holland S, Mauger D, Murdoch DR, Neale R, Rees JR, Simpson S Jr, Stelmach I, Kumar GT, Urashima M, Camargo CA Jr. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017 Feb 15;356:i6583. https://doi: 10.1136/bmj.i6583.
7. Ali N. Role of vitamin D in preventing of COVID-19 infection, progression and severity. J Infect Public Health. 2020 Oct;13(10):1373-1380. https://doi: 10.1016/j.jiph.2020.06.021.
8. Lindqvist PG, Epstein E, Nielsen K, Landin-Olsson M, Ingvar C, Olsson H. Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort. J Intern Med 2016; 280(4): 375–387. https://doi: 10.1111/joim.12496.
9. Hobday R. Coronavirus and the sun: a lesson from the 1918 influenza pandemic. https://medium.com/@ra.hobday/coronavirus-and-the-sun-a-lesson-from-the-1918-influenza-pandemic-509151dc8065
Bob Ike's blog 
Good article with sound info. A big compliment my mom gave me often was, “you smell like fresh air & sunshine!” Little did she know my childhood suntans were healthy. That was before sunscreen of course.Thanks,Mrs.We’re John Denver fans too.Sent from my Verizon, Samsung Galaxy smartphone
LikeLike