MODULATION OF IMMUNE SYSTEM
TO PROTECT AGAINST COVID-19
It has become a dangerously new normal on a daily basis that we exchange news about the fallen: a colleague, coworker, acquaintances, a luminary and so on. The stats are very telling however: in urban areas, neighborhood with high concentration of Blacks are disproportionately affected and idem for mortality rate, more males than females regardless of ethnic group, more complications among those with preexisting cardiovascular conditions. Although old age is a risk factor, there have been enough casualties among the not so young to make this tiny RNA particle protected by a fatty but spikes-protected carapace to cause havoc to all comers.
No one has publicly stated the obvious but the policy in place is an undeniable departure of the binary approach of high tech versus low tech but rather a dual intervention emphasizing prevention on one hand and reliance on the big guns as needed. In fact, the dearth of protective devices in a society accustomed to disposable supplies in huge quantity has led to a recalibration of assumptions, practices and has even led to the mushrooming of a cottage industry of home-made face masks, reuse of once-before-quickly-discarded N95 masks. Along the way, we are discovering that the rush to intubate may not be so wise1. Simpler methods like keeping a patient in the prone or lateral decubitus position may make all the difference, even among intubated patients. Basic but time-tested methods like hand washing is being promulgated with the zeal of a convert with a new discovery.
Analysis of the stats leads one to ask several questions: why the gender discrepancy? Why the racial difference? Last but not least, what else can one add to the list of preventive behavior such as social distancing, confinement, frequent hand washing and wearing a mask when going outside?
There are fortunately some good ideas to explain the above questions. In a book published at the beginning of this month, The better half: on the genetic superiority of women, the author, Dr. Moalem2 makes the case of the better genetic predisposition of genetic females (XX) to deal with diseases by possessing 1000 genes per X chromosome and the genetic male (XY) having only 70 genes on the Y chromosome. This, he claims, explains genetic females’ tendency to outlive genetic males, to better handle pathologic stresses and have a better outcome to serious illnesses, including infections. This is an interesting concept and reading of this book is highly recommended to help us become better clinicians and find out about gender-specific disease profiles. Just in passing the price that genetic females pay for a stronger immune system is a disproportionate rate of autoimmune maladies.
The gender disparity is not cast in stone in the mortality rate of Covid-19. In some other countries, the difference is far less striking and like so many instances of genetic predisposition and disease manifestation, the concept of nature versus nurture tells us that epigenetic factors, aka behavior or lifestyle, can make a difference. Hence cigarette smoking, alcohol use, lack of exercise, unhealthy diet, obesity are all additional factors that can accelerate, worsen disease manifestation and predispose to complications. Timing of seeking medical care is always a determining factor and genetic males tend to lag behind genetic females and this adds another layer to the data.
It follows from the above that minority populations in this country that have always suffered disproportionately from cardiovascular complications will be at higher risk of complications when afflicted by Covid-19.
Along the line of a dual approach to counter this pandemic, is there anything one can do in addition to, not instead of, the basic measures being touted daily or in addition to classic therapeutic interventions? The answer is yes with the understanding that there is no panacea. The best and most one can do is to take measures to minimize risk; we can’t eliminate risk at 100%.
The pathogenesis of the disease tells us that the virus is sneaky. It penetrates our cells and imposes its will so it uses our replication process for its own’s, while devising all clever ways to evade our immune system. So long as it remains undetected, it replicates as it deems fit in an exponential fashion. By the time it reaches a sizable number and our immune system reacts, it goes into overdrive and this is what creates the major problems with dead cells accumulating in the airways and interfering with normal gas exchange; this opens a domino effect and other major organs begin to fail. By the time this happens, we are in serious danger zone and the best that can be done is damage control. Being in the danger zone as we well know is associated with high morbidity and mortality. Obviously and fortunately only about 5 to 10% at the most of infected persons reach the danger zone. The vast majority either have no symptoms or mild illness. It would seem then that to the extent the immune system is able to prevent significant replication of the virus, then the likelihood of disease is low. We need to always remember that unfortunately not being symptomatic is a double-edged sword as it allows propagation of the virus from the vector to others. This is the reason why wearing a mask and practicing the basic measures becomes so important. The low hanging fruit seems to point toward having a solid immune system. So, what are some means of improving one’s immune system?
- First and foremost is good gut health. The microbiome of the gut determines our overall health status3. The use of high fiber is a sine qua non. Prebiotics (leeks, onions, honey, to name a few), probiotics (yogurt, kefir, cottage cheese, etc..) are a good starting point. Antioxidants are also very good. Obviously, some are already high in fiber such as fruits like berries, beans, vegetables; dark chocolate (pleasure and health such a combination!), nuts and so on. A simple amino acid, L-glutamine is preferentially used by the enterocytes, colonocytes and even lymphocytes as respiratory fuel. [After a bout of diarrhea, it’s a good idea to take prebiotics, probiotics to replenish the balance of the gut microflora and also take L-glutamine for a period of up to 3 weeks]4,5.
Healthy eating, exercise are good habits to develop and maintain
- Vitamin D. More of a hormone than a vitamin, the level of vitamin D does matter for the immune system. Studies have shown an increased risk of URI (Upper Respiratory Infection), including the flu, with low level of vitamin D. The prevalence of low level of vitamin D is significantly high among darker-skinned individuals. Although the controversy about the value of Vitamin D in good health has somewhat abated, unfortunately not many of afflicted patients and physicians among our midst heed to the evidence. A simple search on the website of Harvard Chan School of Public Health6 can be useful to delve into this matter. The use of vitamin D as adjuvant during an episode of Covid-19 especially among groups known to have a high prevalence of deficiency or anybody deficient for that matter is basically part of standard practice7. The dose used during an infection can be increased over maintenance dose to increase blood level. One can safely use 5000-10,000 IU/day for a few weeks and then obtain a blood level.
- Vitamin C. No other vitamin has been the scorn of scientists more than vitamin C. It all started when Linus Pauling of double Nobel Prize fame in the early seventies fawned over it and promoted a daily megadose8. Intentional or not it took the allure of promotion of a panacea. This issue was elegantly litigated elsewhere and there is no need to rehash it9. Nonetheless, history will retain that he did take it daily and lived to the golden age of 93 but died of prostate cancer. It’s universally agreed that no panacea exists and vitamin C is no exception, but painstakingly completed studies over the years have proven that it has a great role to play in inflammatory illnesses (pancreatitis, wound healing), and especially in infectious diseases6,9,10,11. I gave several references in the previous issue of the AMHE Bulletin about the therapeutic role it plays in patients with URI, and in Covid-19. The basic science behind the role of vitamin C resides in the fact that it acts as a modulator of white cells, especially neutrophils, lymphocytes, phagocytes12. In summary, during an infection, the serum level of vitamin C drops as the above cells quickly accumulate vitamin C as protection against oxidative damage while at the same time releasing reactive oxygen species to kill the pathogens and cells containing them, like snuffing them out in the bud. The dose needed in an acute infection is not standardized in the literature. Suffice it to say that one can take up to 9 grams/day orally so long as it doesn’t cause diarrhea. To enhance the absorption of vitamin C from the gut, a clever delivery is used. There’s now the liposomal form that results in higher serum level through enhanced bioavailability. Liposomal vitamin C comes in concentration of 1gm-3 gm; because of a rush on it, lately its availability has been spotty at times. Based on available scientific evidence, it behooves one to take vitamin C during an acute episode of Covid-19 or for that matter in any URI including bacterial pneumonia. The IV form for hospitalized patients can be used but the liposomal form is next best. The dose of the IV is also not yet standardized. It ranges from 1.5gm TID to as much as 50 gm/per day (this much higher dose is primarily used in China). A caution: for patients known to have G6PD deficiency or renal insufficiency, one should use the lower dose; diarrhea is a limiting factor (when caused by vitamin C).
- Zinc. It’s normally found in legumes, nuts, whole grains. It does help the immune system prevent replication of coronavirus in vitro13. It had gained its fame initially against the common cold. It’s now one more an option in the face of Covid-19. It should be noted that zinc deficiency is associated with dysgeusia and hypo or anosmia. Interestingly these two complaints are being found in Covid-19 patients. It’s not, to my knowledge, known if such patients are deficient in zinc but it would be curious to check their level and find this out. A typical dose is 220mg daily or BID during the period of treatment. One caveat: don’t take the nasal formulation as it can temporarily or permanently impair sense of taste.3,6
- Selenium. It’s readily found in nuts, grains, seafood. It plays an important role in the immune response and optimal function of both B and T cells. As such it’s used as adjunctive therapy in HIV cases because of its known antiretroviral activity. It also helps to regenerate vitamin C from its oxidized form and in helping in antioxidant protection. Caution: some people can’t tolerate exogenous selenium pills because of insomnia. Dose ranges from 25 to 100 micrograms, as tolerated14,15,16.
We are learning as we go along with this pandemic. Trying to stay healthy is a daily commitment. Even when we do everything that we are supposed to do, there’s still no guarantee of the outcome. However, enhancing the immune system is another layer of security that we can count on as we are trying to stay safe.
Reynald Altéma, MD
References:
1. https://www.nytimes.com/2020/04/20/opinion/coronavirus-testing-pneumonia.html?referringSource=articleShare
2. Moalem, Sharon, MD, PhD, The better half. On the genetic superiority of women. Farrar, Strauss, Giroux. NY, 2020.
3. http://webmd.com
4. Kim MH, Kim H. The Roles of Glutamine in the Intestine and Its Implication in Intestinal Diseases. Int J Mol Sci. 2017;18(5):1051. Published 2017 May 12.
5. Perna S, Alalwan TA, Alaali Z, et al. The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review. Int J Mol Sci. 2019;20(20):5232. Published 2019 Oct 22. doi:10.3390/ijms20205232
6. http://www.hsph.harvard.edu
7. Ginde, AA,. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Archives of Internal Medicine. 2009 Feb 23;169(4):384-90.
8. Pauling L. The significance of the evidence about ascorbic acid and the common cold. ProcNatAcadSci, Vol 68, 11, 2678-2681, November1997.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=4941984
9. Hemilä, H. Vitamin c and the common cold. Br J Nutr. 1992 Jan;67(1):3-16.
10. Scott, P. et al. Vitamin C status in patients with acute pancreatitis. BJS, Vol 80, 6, June 1993.
11. Hemilä, H. Vitamin C and Infections. Nutrients. 2017;9(4):339. Published 2017 Mar 29.
12. Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors. 2009;35(1):5–13. doi:10.1002/biof.7
13. te Velthuis AJW, et al. (2010) Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathog 6(11): e1001176. doi:10.1371/journal.ppat.1001176
14. http://www.lpi.oregonstate.edu
15. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012;16(7):705-743.
16. Mattmiller SA, Carlson BA, Sordillo LM. Regulation of inflammation by selenium and selenoproteins: impact on eicosanoid biosynthesis. J Nutr Sci. 2013;2:e28