PANDEMIC YEAR THREE: A Critical Update – LEO GALLAND, M.D.

January 1, 2022

Containment of Covid-19, either by social and physical restrictions or by mass vaccination, has failed completely. The emergence of the Omicron variant and its lightning spread through the world is proof that a much broader (and deeper) strategy is needed to allow us to live with this virus. I strongly support both physical measures and vaccination, but the expectations placed on both have been misguided and unrealistic.

Specifically, the hope that vaccination (or prior infection) would yield neutralizing antibodies that prevent infection has not been fulfilled. Omicron is unfazed by pre-existing neutralizing antibodies, so that people with prior infection and triple vaccination are getting symptomatic infection at high rates when exposed. What vaccination or prior infection does accomplish is stimulation of immune memory for the virus, which substantially limits the severity of infection and which does not appear to fade rapidly over time.

  • We need greater attention to boosting immune memory, rather than relying on multiple doses of booster vaccines given in a desperate attempt to chase the specter of herd immunity and the prevention of infection.
  • As for physical separation, masks and distancing are not enough and compliance with them is low. There is strong evidence that nasal sprays can dramatically reduce the incidence of infection in animals and humans, yet governments, health authorities and big pharma have shown no interest in promoting their development and use, with tragic results.

There are two characteristics of Covid-19 that have brought us to the place where we are now:

  1. The escalating rate of mutation of its viral cause, SARS-CoV-2. Every time a person is infected and this virus multiplies, a mutation will occur about once a week[1]. The longer the duration of active infection, the greater the opportunity for mutation. This process has occurred in hundreds of millions of people over the past 2 years and has yielded over 40,000 separate mutations. Most are inconsequential or harmful to the virus, but so many people have been infected that we have seen an alphabet of variants with combinations of mutations that increase the ease of transmission or the ability of the virus to avoid antibodies created by vaccines or previous infection.It took about 6 months for the original Wuhan strain to be overtaken by an unnamed variant with a single mutation called D614G, which became the  dominant worldwide form of the virus in the summer of 2020. Over the subsequent 9 months, 5 major variants appeared, each with several functional mutations, competing with one another for regional dominance. By mid-summer of 2021, the Delta variant had conquered the world, to be replaced 4 months later by Omicron, which has 3 times as many mutations and a facile ability to escape existing antibodies[2]. There is no reason to expect this pattern to end. If anything, it may accelerate, until the virus runs out of mutations.  SARS-CoV-2 consists of only 20 different proteins, so its options are limited. But no one can predict how long that will take[3].As I’ve said in every version of my Coronavirus Guide, first posted online in February 2020, a strategy based on limiting social interactions and attempting to induce herd immunity with vaccination or natural infection cannot succeed.
  2. Factor 2: the remarkable variability in human responses to SARS-CoV-2. Since the beginning of the pandemic, over 80% of infected people have been asymptomatic or experienced a trivial illness, but roughly 3% became severely ill and required hospital care. Between 10 and 50% experience a post-viral syndrome, which takes several forms. There may be lingering symptoms of the acute infection that last for months or longer. Or there may be apparent recovery, followed by a new illness over the next several months.Recent studies indicate that about 25% of people have persisting symptoms up to 7 months after the initial infection[4]. This includes people whose initial infection was mild or asymptomatic[5]. Vaccines do not appear to significantly reduce the incidence of longhaul covid[6]. In addition, people who have recovered from Covid-19 are about twice as likely as matched controls to develop neurologic or psychiatric disorders, diabetes or high blood pressure during the 6 months after becoming infected.[7]  Large, carefully controlled studies from the U.K. find that people who have recovered from Covid-19 showed loss of brain cells on brain MRI and impairment in higher cognitive functions that match the MRI abnormalities[8]. Most of these people had not been sick enough to need hospitalization. The potential burden of long covid or post-covid syndromes is enormous[9] [10] [11] and may eventually have a greater impact on human health than the pandemic itself.

 

The high range of inter-personal variability of Covid-19 can be explained by two factors:

  1. Variations in the immune response to this virus. The immunology of Covid-19 is extremely complex. Some immune responses are beneficial, some are harmful, and their timing is critical. As explained in the section on IMMUNITY in the Coronavirus Guide, too much attention has been given to virus-specific antibodies and not enough to cellular immunity. Within that lie two key parts:
    • Cellular production of the anti-viral proteins called Type 1 Interferons
    • Viral killing by a group of white blood cells called TEMs (T-effector memory cells, a sub-group of cytolytic T-lymphocytes,also known as killer T-cells).These two separate parts are related, in that type 1 interferons enhance the development of TEMs. The action of TEMs requires a memory of the microbe being attacked. Fortunately, vaccination and prior infection create this memory. Covid-specific TEMs are the main reason that the Omicron surge is not more deadly.
      But the activity of TEMs varies greatly from person to person, declines with age, and is strongly impacted by each person’s health. The body’s normal bacteria, the microbiome, have a significant effect in this area.  Probiotic supplements taken as pills or yogurt or fermented foods increase that activity.[12] [13] A microbiome metabolite called butyrate appears crucial for supporting TEMs function[14].
  2. Factor two: variations in nutritional and metabolic health. A single study shows this effect with great clarity:

Scientists at John Hopkins, Stanford, Harvard and Columbia examined the impact of pre-covid dietary patterns on the severity of Covid-19 in health workers from 6 countries. They controlled for multiple variables and contrasted people with mild or very mild Covid-19 to those with moderate or severe disease. Diet had no impact on who got infected, but a 40% increase in vegetable consumption produced a 72% decrease in the likelihood of severe or moderately severe infection.

People eating more vegetables were eating more beans and nuts and happened to be eating less sugar, but sugar is not what made the difference. A group of health-care workers eating a low carbohydrate high protein diet, which had no added sugar but fewer vegetables and more red meat and poultry, had a risk of being sicker that was almost 4 times as high as people whose diet was described as plant-based[15]The plant-based diet was not a true vegan diet. It included fish, eggs and dairy products, even a little meat and poultry. It just had more vegetables, about 4- 5 additional servings a week, with beans, nuts and seeds replacing meat and poultry.

There are many reasons why diets high in vegetables may limit severity of Covid-19. They are naturally anti-inflammatory, as I discuss in my book, The Fat Resistance Diet. They are high in fiber and in polyphenols, natural plant-derived anti-oxidants.  As a result, they help to create a healthier population of gut bacteria (see THE GUT MICROBIOME AND COVID-19). The polyphenols found in vegetables, herbs and spices also increase activity of a vital enzyme called ACE-2, which is depleted by Covid-19 (more in the Coronavirus Guide: ACE-2 ENHANCEMENT).

Since the first publication of the Coronavirus Guide in February of 2020, I have advocated diverse strategies for reducing severity and transmission of Covid-19 by analyzing the unique biology of the virus and how that interacts with human physiology.  My major goal has been to empower people by providing scientific evidence for nutritional and hygienic measures that mitigate the severity of the infection, helping with rapid recovery and avoidance of serious illness. Bioflavonoids in food and as supplements have been an important part of that strategy. Validation of these measures is supplied in 3 recent publications:

    1. In a recent study from Italy, the bioflavonoid quercetin (in liposomal form for increased bioavailability) at a dose of 200 mg 3 times a day dramatically reduced symptoms and viral load in outpatients with early Covid-19.[16] Reduction of viral load not only decreases illness, it reduces the likelihood of transmission to others and the occurrence of mutation. An earlier study from Iran (cited in the Coronavirus Guide) found that health care workers taking quercetin were much less likely to test positive for Covid-19 than their co-workers, suggesting benefits in prevention.
      Aside from its broad ant-inflammatory effects, quercetin has two actions that make it promising in prevention and treatment of Covid-19: it can interfere with the ability of SARS-CoV-2 to attach to human cells[17] and it can block enzymes that the virus needs to replicate itself[18]. This last action is the mechanism of action of Pfizer’s new anti-covid drug, Paxlovid.
    2. Two recent randomized controlled clinical trials demonstrate the effectiveness of the bioflavovoid curcumin, a polyphenol that is a staple of my covid control protocol, in reversing Covid-19 (There’s more on curcumin in ACE-2 ENHANCEMENT and in THERAPEUTIC PROFILES in the Coronavirus Guide):
      1. In a study from India, patients with mild, moderate or severe Covid-19 were treated with curcumin 525 mg twice a day (plus 2.5 mg of piperine, a component of black pepper, to enhance curcumin absorption). There were 11 deaths in the control group (1 person had presented with mild infection and 5 each had presented with moderate or severe infection) and only 2 deaths in the curcumin group (both patients had presented with severe disease to begin with). Aside from an 82% reduction in mortality, curcumin produced faster recovery from fever, cough, sore throat, and breathlessness and less need for supplemental oxygen; it also shortened hospital stay.[19]
      2. Iranian researchers administered curcumin as a nano-particle preparartion 80 mg twice a day to patients with mild to moderate Covid-19. At 2 weeks there was faster resolution of most symptoms, especially chills, cough, and loss of smell or taste, along with faster return to normal of the lymphocyte count, a key laboratory marker of severity of illness[20] (more on the importance of the lymphocyte count in STAGES OF INFECTION and IMMUNITY in the Coronavirus Guide).

In April, 2020, I began research on nasal sprays for preventing transmission of the SARS-CoV-2 virus. My reasoning is described in the Guide’s section called THE KEY ROLE OF THE NOSE. In July, 2020, I formulated an anti-viral spray based on the use of the anticoagulant heparin, which can block the attachment of the virus to the cells lining the nose. It’s been used by hundreds of people. A research team in Australia is testing a similar spray for prevention of Covid-19 transmission[21].  I have compiled a list of nasal sprays available in various countries that are likely to prevent Covid-19 or limit its severity by reducing the initial viral load. (Described in THERAPEUTIC PROFILES: NASAL SPRAYS in the Coronavirus Guide). New research has confirmed the importance of nasal entry for determining severity of Covid-19. People with naturally high levels of anti-viral factors in the nose usually develop mild illness when they have Covid-19. People lacking those protective factors go on to develop more severe illness[22].

I continue to recommended anti-viral nasal sprays for all my patients, regardless of vaccine status, when in situations that present a risk of exposure to Covid-19. It has become clear to me that in the age of Omicron, these sprays lose their effect after about 4 hours, so I recommend using them regularly, before and after a brief social encounter and every 4 hours during more prolonged encounters (these include living with someone who is not as careful as you are).

I continue to advocate an anti-inflammatory diet and specific supplements (like curcumin) that target ACE-2, the enzyme destroyed during viral cell entry (see ACE-2 ENHANCEMENT). Widespread acceptance of these measures would, I believe, provide major personal and community protection against the burden of the pandemic.

I also believe nutritional measures will help prevent or reverse long covid. I describe their use in several presentations available online at no charge:

Healing Long Covid, video presentation
https://www.youtube.com/watch?v=DSqhsci6uj8

Your Brain After Covid-19, Power Point Presentation
https://youtu.be/HSgT_A38Q20

Interviews with the Long Covid Charity (U.K.) about the brain after Covid-19 and the gut and oral microbiome in long covid
https://youtu.be/HU8QjMBCxMA
https://www.youtube.com/watch?v=8ugebwwv1AI
https://www.youtube.com/watch?v=-pLViwVaMC8&feature=youtu.be

Understanding Long Covid: a comprehensive presentation for health professionals
https://vimeo.com/577817133

Although the published incidence of post-covid illness is typically in the range of 25-30 %, my experience with people following my protocols at the onset of acute covid finds prolonged symptoms in under 2%. I believe that the strategies that I present in the Coronavirus Guide are effective in preventing long covid. My goal for 2022 is to seek wider application of those methods in the U.S. and other countries.

1. https://phys.org/news/2021-08-mutation-covid-virus-percent-higher.html

2. https://www.washingtonpost.com/health/2021/12/16/omicron-variant-mutations-covid/

3. https://www.sfchronicle.com/bayarea/article/Scientists-didn-t-see-omicron-coming-And-no-16711301.php

4. https://www.medrxiv.org/content/10.1101/2021.03.03.21252086v1?mc_source=MTEyNjQxNzM4NjMzNDg2MjM3NzEwOjo6YzVjN2E5OGQzNWQxNDllYWE2MDdjMzgyNmNkOTJlYWQ6OnY0OjoxNjE1MTMwNjcwOjox

5. https://s3.amazonaws.com/media2.fairhealth.org/whitepaper/asset/A%20Detailed%20Study%20of%20Patients%20with%20Long-Haul%20COVID–An%20Analysis%20of%20Private%20Healthcare%20Claims–A%20FAIR%20Health%20White%20Paper.pdf

6. https://www.nature.com/articles/d41586-021-03495-2?utm_source=Nature+Briefing&utm_campaign=07ae2d7007-briefing-dy-20211123&utm_medium=email&utm_term=0_c9dfd39373-07ae2d7007-46153918

7. US Department of Veterans Affairs databases: Increased use of anti-hypertensive and hypoglycemic drugs  -Aly  et al. High-dimensional characterization of post-acute sequalae of COVID-19. Nature 2021.

United Health Group database: New medical diagnoses occurred in 14.02%, RR 1.35 vs controls .
Hazard ratio for specific diagnoses:
Hypertension 1.81 (1.10 to 2.96)
Diabetes 2.47 (1.14 to 5.38)
Sleep apnea 2.31 (1.23 to 4.32)
Fatigue 2.20 (1.48 to 3.27)
Daugherty SE, et al Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ 2021.

US TriNetX HER network: 34% of SARS-CoV-2 + people had a neurological or psychiatric diagnosis made in the next 6 mo . Taquet et al. 6- neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry 2021

8. Hampshire et al. Cognitive deficits in people who have recovered from COVID-19 relative to controls: An N=84,285 online study. medRxiv 2020.10.20.20215863Douaud et al. Brain imaging before and after COVID-19 in UK Biobank MedRxdiv oi: https://doi.org/10.1101/2021.06.11.21258690

9. https://www.scientificamerican.com/article/a-tsunami-of-disability-is-coming-as-a-result-of-lsquo-long-covid-rsquo/

10. Laura Montefusco et al, Acute and long-term disruption of glycometabolic control after SARS-CoV-2 infection, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00407-6

11. Menges D, Ballouz T, Anagnostopoulos A, Aschmann HE, Domenghino A, Fehr JS, et al. (2021) Burden of post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study. PLoS ONE 16(7): e0254523. https://doi.org/10.1371/journal.pone.0254523

12. https://pubmed.ncbi.nlm.nih.gov/16508257/

13. Ashraf R, Shah NP. Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr. 2014;54(7):938-56. doi: 10.1080/10408398.2011.619671. PMID: 24499072.

14. Luu, M, Weigand, K, Ovedi, F. Regulation of the effector function of CD8+ T cells by gut microbiota-derived metabolite butyrate. Sci Rep. 2018;8:14430.
Kespohl, M, Vachharajani, N, Luu, M. The microbial metabolite butyrate induces expression of Th1-associated factors in CD4+ T cells. Front Immunol. 2017;8:1036.

15. Kim H, Rebholz CM, Hegde S, et al. Plant-based diets, pescatarian diets and COVID-19 severity: a population-based case–control study in six countries.BMJ Nutrition, Prevention & Health 2021;0. doi:10.1136/bmjnph-2021-000272

16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238537/

17. M.S. Smith, J.C., Repurposing therapeutics for COVID-19: Supercomputer-based docking to the SARS-CoV-2 Viral Spike Protein and Viral Spike Protein-Human ACE2 Interface, ChemRxiv http://doi.org/10.26434/chemrxiv.11871402.v4 (2020).

18. Nguyen T.T., Woo H.J., Kang H.K., Nguyen V.D., Kim Y.M., Kim D.W. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol. Lett. 2012;34:831–838.

19. Pawar KS, Mastud RN, Pawar SK, Pawar SS, Bhoite RR, Bhoite RR, Kulkarni MV, Deshpande AR. Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial. Front Pharmacol. 2021 May 28;12:669362. doi: 10.3389/fphar.2021.669362. PMID: 34122090; PMCID: PMC8193734.

20. Reza Ahmadi et al: Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial. Food Science and Nutrition. 19 June 2021. https://doi.org/10.1002/fsn3.2226

21. https://apple.news/AKxMGm5xSR4-7WPhNIkWTlw

22. https://www.cell.com/cell/pdf/S0092-8674(21)00882-5.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867421008825%3Fshowall%3Dtrue