COVIDOLOGY 2

I had in the earlier blog on Covidology mentioned that I would take a topical approach to the whole problem. In this second blog I would like to put my views on the preventive aspects of infection with SARS-CoV-2, the dreaded corona virus which has really turned the world upside down taking a heavy toll of the healthcare system , the tourism and travel industry and economic and financial activities. As I communicate with you after a gap of more than a fortnight,India’s tally of the Covid-19 cases has crossed the 5.3 million mark, more than 2 million additional cases, since then.

Prevention of Covid-19 is a serious subject, but the whole aspect of prevention has been taken over by Whatsapp university, YouTube, Twitter, and more such internet sites and certain TV channels. Here I try to examine the preventive aspects of Covid-19: vaccines , drugs, immunity boosters, physical therapies such as steam and others.which are being discussed fervently. But universal wearing of a mask properly, frequent hand sanitisation and physical distancing which was intially very keenly enforced has been put on the backburner both by the authorities and the populace at large. My drive down the crowded streets of Thane on my way to my hospital, gives me a sinking feeling as I see many of the young and the old, the shoddily dressed and the well-healed, males(more than females), merrily saunter around , knock into each other with gay abandon, not wearing a mask or a mask covering the mouth and not the nose or masking the chin alone.

VACCINES : By definition a vaccine is a substance used to stimulate the production of antibodies and provide immunity against one or several diseases prepared from the causative agent, which is either weakened or killed, its products, or a synthetic substitute, treated to act as an antigen without inducing the disease. Researchers world-wide are working round the clock to find a vaccine against SARS-CoV-2. But the earliest that experts expect a thoroughly phase 3 trialled vaccine for public use is atleast one year away.

To date, just one corona virus vaccine has been approved. Sputnik-V(Gam-Covid vac) developed by the Gamaleya Research Institute in Moscow was approved by Russia’s Ministry of Health on Aug 11. Worldwide, experts have expressed considerable concern about the vaccine’s safety and efficacy, given the fact that it has not entered Phase 3 Clinical Trials. The Oxford Vaccine(Astrazeneca) is in Phase 3 trials in UK, India(Serum Institute) and other countries. The recent incidence of a strong adverse reaction in one of the volunteers has been sorted out and the trial is once more on course. A Chinese vaccine( Ad5-nCoV) sponsored by Cansino Biologics is in Phase 3 in Wuhan,China. Moderna’s mRNA-1273 is also in phase 3. Two Indian vaccines are in Phase 2: Covaxin( Bharat Biotech; NIV) and ZyCoV-D (Zydus Cadila).More than 30 other vaccines are in various stages of development.

Older vaccines are being repurposed. Both the measles and the BCG(TB) vaccine are being tried as covid-19 vaccines. BCG vaccine for example is a strong candidate, as it has reduced incidences of viral respiratory tract infections in both children and adults.Whether it will do so against SARS-CoV-2, is being studied.

But still with all the above and 35 or more other vaccines in development, are we near any early date of the launch of a vaccine? Nope. The earliest we can expect is by April-May 2021 and that too based on a surrogate marker rise( antibodies against SARS-CoV-2) and not clinical data, as that would require the trialists to show atleast 50% protection by the vaccine as compared to a placebo,certainly a tall order in this short period of time. The picture gets murkier, with possible political interference; the launch of Sputnik-V by Russia, with President Putin mentioning that his younger daughter too had received the vaccine,Trumph hinting at a date of launch in October before the Nov 3 presidential elections and the inscrutable Chinese not to be left behind mentioning vaguely about a November 2020 launch of a Chinese vaccine. The ICMR too had reportedly mentioned about Aug 15 as the date of launch of Covaxin, enjoining the trial sites to speed up the studies but then quickly withdrew this and at present there is nothing further from the Indian side.

DRUGS : Can drugs prevent infection with covid-19? A number of medicines, most notably hydroxychloroquine(HCQ), chloroquine(CL), Ivermectin have made their claims. Many doctors have taken HCQ as prophylaxis against the virus. This claim is due to the fact that in vitro (outside the body in the labs) HCQ is a strong inhibitor of coronavirus growth. Additionally, since it has a very long half life, the medicine can be taken at less frequent intervals ( presently advocated weekly) for its proposed action of prevention. HCQ was made famous by American President Donald Trump who swore by its preventive powers and forced India to export the drug to the US.

Another drug on the horizon is Ivermectin. This is a cheap drug easily available in pharmacies across India on prescription. It has shown very good SARS-CoV-2 inhibitory properties in vitro carried out in Australia. Studies in Bangladesh and elsewhere have claimed efficacy of Ivermectin in combination with doxycycline. But to note that these are treatments when the virus had already established itself in the body and patients had either mild/moderate/severe symptoms. But the topic we are discussing is prevention. There is no controlled study which can claim that it has prevented the infection with SARS-CoV-2. Proper studies are required before it can be advocated in general populations as a prophylactic. There are NO ICMR guidelines recommending the use of Ivermectin as a prophylactic, as was wrongly reported on WAU/other internet sources.

Steam inhalation : This is in vogue all over. Traditionally, on advice of doctors or on their own people take hot steam as mitigation against the common cold or other upper respiratory viral infections. But now it has been propounded as the ultimate tool to prevent the coronavirus SARS-CoV-2 from infecting us. No data to date about its efficacy in covid -19, but several media claims swearing its efficacy have surfaced. The use of this method could be dangerous,especially in unattended children,as reported in the Lancet. In the Burns Centre, Birmingham Children’s Hospital, there was a 30-fold increase in scalds/burns related to steam inhalations during this period of the pandemic. In a strongly worded advisory authors Colin T. Brewster, Jia Choong et al have asked “clinicians to actively discourage steam inhalation and educate parents about alternative treatments for their child”.

Immunity Boosters: Can immunity “boosters” really boost your body’s ability to fight infections, such as Covid-19? The immune system is a complex of various cells that help in fighting infections. It is fine tuned to carry on its job of protecting the body from attack from infectious agents. It is divided into innate and adaptive immunity. Innate immunity is already present and mounts an immediate attack on the infecting microorganisms.The adaptive immune response, on the other hand learns to take care of the present infection based on exposure to similar infecting agents in the past, or it gradually builds its defences as the present microorganisms infect the body. It is thus very difficult to gauge whether any substance really enhances immunity because of the complexity of the total immune system. Health Harvard Education lists the following approach to a healthy immune system: diets high in fruits and vegetables, avoid smoking, exercise regularly, maintain a healthy weight, alcohol in moderation (if one drinks), adequate sleep , steps to avoid infections such as proper hand washing and cooking meals thoroughly, minimize stress. No mention of any specific substances has been done. Of the plethora of immunity boosters advised , I’ll restrict myself to 3: vit C, vit D, zinc.

Vit C, Vit D, Zinc: Vitamin C is used freely by one and all as an immunity booster. Some trials have shown it to be effective in very high doses intravenously of greatly improving the status of serious patients with Covid-19(including patients having ARDS-adult respiratory distress syndome). Basically it works as an antioxidant. But its use as an oral 500 to 1000 mg daily tablet as a prophylactic remains unproven. Vitamin D is one of the most vital vitamins. Low levels of Vit D are associated with increased viral infections especially of the respiratory tract. Vitamin D usage has likewise been associated with improved status of the individual’s response to respiratory tract infections. Again no data is available to suggest its benefits in preventive medicine.But we note that Vitamin D deficiency is almost universal. ZINC: Deficiency of zinc is associated with growth retardation (in children), loss of appetite and impaired immune function.Zinc daily requirements are about 10- 15 mg daily. Zinc picolinate is the best form of oral zinc for absorption. Zinc deficiency can be very common. Hence I often advocate Vitamin C (difficult to measure its levels routinely), zinc and vitamin D as supplements to my patients especially in these covid times. You can discuss these things with your family doctors. But the focus on these supplements should not take your eyes off the most important aspect of prevention which I will now reiterate with reasoning and accompanying data: universal masking.

UNIVERSAL MASKING: The New England Journal Of Medicine, the scientific and medical journal with the highest impact factor in the entire world, has come out with a very welcome and startling hypothesis: Facial Masking for Covid -19, potential for “variolation” as we await a vaccine. Drs. Monica Gandhi and George Rutherford put forth their arguments for universal masking rather succinctly in the NEJM issue of September 8 2020.They argue that universal facial masking may become a form of variolation that would generate immunity and thereby slow the spread of the virus , as we await a vaccine. As early as March this year, reports indicated high rates of viral shedding of SARS-CoV-2 from the noses and mouths of asymptomatic patients equivalent to those among symptomatic patients. Thus universal facial masking seemed to be a possible way to prevent transmission from asymptomatic infected people. Past experience related to other respiratory viruses indicates that facial masking can also protect the wearer from getting infected by blocking viral particles from entering the nose and the mouth. Epidemiologic investigations during the SARS 2003 pandemic have suggested that there is a relationship between public masking and pandemic control.. Recent data from Boston corroborate the reduced incidence of SARS- CoV-2 among health care workers after universal masking.Recent virologic, epidemiologic and ecologic data have led to the hypothesis that facial masking may also reduce the severity of disease among people getting infected. This possibility is consistent with a long standing theory of viral pathogensis, which holds that the severity of disease is proportionate to the viral inoculum received. As proof of concept of viral inocula influencing disease manifestations, higher doses of administered virus led to more severe manifestations of covid-19 in a Syrian hamster model of SARS-CoV-2 infection. If this theory bears out,population-wide masking, might contribute to increasing the proportion of SARS-CoV-2 that are asymptomatic. In the USA, the CDC estimated the asymptomatic rate of infection with the coronavirus to be around 40% by mid July, but the rate was closer to 80% in settings with universal masking, providing observational evidence for the above hypothesis. Countries such as those in South East Asia, for example with almost universal and appropriate masking have fared better in terms of severe Covid related illnesses and death, suggesting a shift from symptomatic to asymptomatic infections. Variolation was a process, whereby people who were susceptible to smallpox were inoculated with material taken from a vesicle of a person with smallpox, with the intent of causing a mild infection and subsequent immunity. Variolation was practiced only until the introduction of the variola vaccine, which ultimately eliminated smallpox. Thus till an effective vaccine is available, noting the strong cell-mediated and humoral response generated in both asymptomatic and symptomatic individuals, and the fact that the recurrence rate after more than eight months is very negligible, this type of ‘variolation’ by universal masking till a vaccine becomes available should be very actively pursued by nations such as India, and not run after exotic immune boosters without any evidence direct or circumstantial of their effectiveness. Population-wide facial masking might reduce both the transmission rates and severity of disease.

MYTAKE : So, as they say, ladies and gentlemen, prevention, prevention, prevention and by the most basic and cheapest method , universal masking should be the mantra for the Government. An ad blitz, and making the people aware of this literally day in and out and strict action against covidiots( as is planned in Pune) should be the order of the day. Can we all spread this message far and wide? Please let me know your reactions to this, honestly.

Dr. Prashant Kulkarni, M.D