SARS-Cov-2 Inoculation Could Reduce Mortality and Save the Economy
By Jim Olsen, Chief Engineer, Implantable Medical Device Industry
Recent articles about the dose-response characteristics of Covid 19 by Mukherjee and Rabinowitz/Bartman (New Yorker and NYT) make a strong case that a higher infectious doses of virus leads to a more severe illness and lower infectious doses lead to milder illness. This explains the large number of severe illnesses amongst otherwise young healthy ICU workers in the US, Italy and China, and also the abundance of mild or asymptomatic cases. It seems logical that getting a high dose of virus into the lungs during infection can lead to more severe illness, as the lungs get overwhelmed before the body mounts a strong immune response. Both articles talk about the history of vaccination and discuss the practice of inoculation that was used for smallpox from the 12th century through till the 19th and 20th centuries. Inoculation consisted of taking smallpox corpuscles, grinding them to dust, and then pricking the skin with a needle dipped in the dust. Subjects were then quarantined while they experienced an abbreviated low severity illness, after which they had lifelong immunity. Quarantine was necessary to prevent the unintended spread of disease. The overall mortality rate from inoculation was 1–2%, whereas the overall mortality rate for smallpox was 30%. Experienced inoculation practitioners achieved better results. A long forgotten point of history is that George Washington inoculated the whole continental army for smallpox, in spite of the opposition of his medical advisors.
The authors of the aforementioned articles use inoculation as an example of dose-response, along with modern studies of viral infections. None of the authors suggested inoculation should be seriously considered as a strategy today. Why? I think inoculation is so outside our current way of thinking about disease treatment, that it is hard for most to fathom as a strategy, but the unique features of the current pandemic make inoculation very attractive.
Most leading epidemiologists say that Covid 19 pandemic will continue until we reach herd immunity, which happens when roughly 60% of the population is either vaccinated or infected. For the US, 60% of the population is roughly 200 million people. With today’s estimate of a 0.5% case fatality rate (CFR), this equates to 1 million deaths. These CFR estimates depends on the healthcare system not being overwhelmed, otherwise the CFR can go much higher. Addditionally, these mortality rates do not include the other preventable deaths while the health care system is strained. Anyway, this is why we are currently practicing social distancing and other restrictive measures to “flatten the curve”. What happens when we relax those measures? The rate of infection will rise again. The only way to prevent this inevitable rise would be to adopt the strict strategies used in S. Korea, Taiwan, Singapore and China. Basically, their approach is to identify the infected via extensive temperature and/or PCR testing, trace contacts, then isolate and treat before they can infect others. Each of the steps is necessary, and it is much easier said than done. Asian countries experienced SARS and MERS, so they were better prepared to take extreme measures.
While we are practicing social distancing, the economy is crashing. Restaurants, stores, sporting events, churches, schools, airfare, subways and all other activities with more than a few people have been shut down. Huge numbers of people have lost their jobs. Can we keep this up until a traditional vaccine is ready in 18 or more months? Some people think a vaccine can be fast tracked. Unfortunately the history of trying to develop vaccines for SARS and MERS is not encouraging. Vaccine development is difficult because you are trying to find a surrogate protein or virus that will create a full immune response to the intended virus, and body is not easily fooled. Several very promising vaccine programs were discontinued when they exhibited antibody-dependent enhancement (ADE). ADE resulted in worse outcomes for many vaccinated patients. There are still no vaccines for SARS or MERS. Inoculation avoids the typical problems with vaccines, since SARS-Cov2 is used instead of a surrogate. The downside is the risk of full infection, but relaxed social distancing has an even greater risk, because of the potentially higher infectious doses, and the resultant severe illnesses.
Covid 19 is unique relative to other lethal viral infections, because it is highly infectious but only lethal for the old and unhealthy. The young typically get mild or asymptomatic cases. People under the age of 60 who get serious illness have comorbidities like obesity, hypertension, diabetes and cardiovascular disease. The young and healthy are less concerned about being infected, except for the prospect of transmitting the disease to those who might suffer. If there is a significant dose-response, the severity for all ages could be reduced if a low dose method of infection could be orchestrated, and large doses were kept out of the lungs. After all, 30–40% of the population does not need to be infected before herd immunity occurs, so those at greatest risk could decline inoculation and stay isolated until a traditional vaccine is ready. Those who are inoculated could easily be quarantined to prevent the uncontrolled spread of the disease.
So how would this voluntary inoculation work logistically? It could be done a number of different ways. First, it would be helpful to have infectious disease experts recommend the best route and dosage (assuming we could find some experts that don’t dismiss the whole idea out of hand). Some tissues have high amounts ACE2 receptors (lungs), and others do not (muscle). Other tissues have higher immune response capabilities, like the skin. If big Pharma were involved, they could probably make a “live virus” vaccine with the actual SARS Cov2 virus in a known quantity. It could be injected into the shoulder or wherever the experts recommend. If this was to be done at the local or grass roots level, nasal swabs could be taken from recovering cases, and then touched to the mouth or a scratch in the skin, just like was done in the 15th century. Obviously, this needs more debate, but time is running out. Simpler approaches could be very attractive in developing countries.
After inoculation, patients could be quarantined together with medical supervision in empty hotels, college dorms or field hospitals. The program would be voluntary and would start with the youngest and healthiest, e.g. ages 18–30 without comorbidities. Over time, the ages and health restrictions could be slowly loosened. During quarantine, important scientific questions could be answered about the amount of asymptomatic transmission, viral loads and so on.
In summary, this inoculation proposal would accomplish two important objectives. It could reduce the dose of virus at infection and the subsequent severity of illness, and second, it would provide a way to isolate newly infected patients without resorting to the more draconian measures used in Asia. Achieving these objectives could lead to a reduction in mortality, with a simultaneous improvement in the economy.
