Everyone wants a simple answer to this 2020 COVID-19 pandemic. We have politicians forecasting that a vaccine is on its way that will save us. We are told that this is the only answer. But such predictions are misguided and wrong, especially for older people. A vaccine will not end the threat posed by COVID-19 or other viruses following. To appreciate this view, we need to understand how vaccines work.
We have a lot of experience with flu vaccines. The flu is much simpler than a cold virus (COVID-19 is a cold virus.)
Although there are four types of influenza (flu) viruses—A, B, C, and D—influenza A and B viruses are the only ones that cause flu pandemics. A-type viruses have two proteins called H and N. Since there are 18 types of H and 11 types of N there can 198 different A-viruses. B viruses have two types—Victoria and Yamagata—with sub-types. Every year we check what is happening in Asia and then we select a few flu viruses from there and develop vaccines. Vaccines usually include inactive viruses, dead viruses. In some cases, however, attenuated viruses (weakened live viruses) are used.
Vaccines work by pretending to infect the body and then the body reacts in three ways. It is best to see the body's reaction as a war with different types of defense: soldiers, mercenaries, and intelligence units.
The first line of attack are antibodies produced by B cells. Antibodies are soldiers, that either go out into the bloodstream to fight the viruses or stick close to the fort on the B cells. Antibodies have five methods of killing the virus and are therefore effective soldiers. Newly infected people are unlikely to have detectable antibodies during the first few days, but most develop them after one to three weeks. In the meantime, the second cell type that fights infections is T cells. One type of T cell is mercenaries that inject the virus with a lethal poison. Unlike antibodies, these T cells only fight one specific type of virus. They are very specific. Another type of T cell calls for help, especially from antibodies. In the absence of antibodies, T cells can control infection by themselves. What is interesting is that T cell responses are found in most COVID-19 patients that may last longer than antibodies. The third way the body reacts is through Natural Killer (NK) cells. If B-cells are soldiers, and T-cells are mercenaries, then NK-cells are the CIA, the intelligence unit. They kill viruses, cancer and they play an important role in pregnancy by differentiating the fetus as a special foreign body. Aging reduces the number and effectiveness of NK cells. Taken together, with reduced efficiency at generating antibodies due to reduced B- and T-cells, aging brings about a reduced resilience to infections in general and specifically to COVID-19.
Even with an effective vaccine, sometimes the vaccines completely miss the viruses that are around. The U.S. Centers for Disease Control and Prevention found that in 2018-2019 vaccines were effective between 12%-16%. with older adults having the lowest effectiveness despite having the highest vaccination rates. Meaning that on average the vaccines do not work in seven out of eight cases among older adults. Older adults do not produce enough antibodies even if they take the right vaccine. Most older adults are inefficient at producing antibodies. This is why even though older people take a flu vaccine they still get infected and some eventually still die from the flu. Flu deaths are higher among older people. Also, as Asim Biswas just discovered in 2020, because older adults have had many different colds and flu infections, these earlier antibodies may conflict with current vaccination. Our memory of infections reduces our ability to generate new antibodies. As a result, older adults are not only at greater risk of death and sickness from influenza than younger people, but they also have greater difficulty in developing protection when given the vaccine.
What is surprising is that sometimes it looks like the vaccines not only do not help but they might be detrimental. When the Canadian researcher Melissa Andrew and her colleagues in 2017 compared older adults who were vaccinated with those who were not vaccinated, they found that infections were higher among those who were vaccinated. The argument is that those that get vaccinated are more likely to be frail and prone to get infections in the first place. Most of the time there are other viruses that cause similar symptoms, but they are missed by the vaccines for that year. Tom Jefferson and his colleagues looked at many studies and found no evidence of a benefit of influenza vaccination in older adults. Meaning that it does not matter whether you take the vaccine or not. This is because there are many other viruses floating around at any one time, and that older adults, with or without a vaccine, do not cope well with these other viruses.
The complexity of flu is nothing compared to the complexity of the cold viruses. In addition, cold viruses persist in the environment and are resistant to most household disinfectants—which is why washing our hands is so important as we wash the viruses off our skin, but washing does not destroy them. Some cold viruses are lethal, killing more than a third of those infected, such as MERS-CoV, and some are inconvenient but harmless, such as the common cold.
There are two types of cold viruses either Adenovirus or Coronavirus. Each type has many, many subsets with a lot of variabilities. For example, there are 57 Adenovirus types (and hundreds, or maybe thousands, of sub-types). Then there are seven types of human Coronaviruses with many sub-types and mutations. With flu having two proteins in comparison cold viruses have many: COVID-19 for example has 29 proteins.
Because the T-cells are too specific and the COVID-19 mutates quickly—already in three months Los Alamos National labs found 14 strains—it is unlikely that T cells will be effective. Antibodies are still the best attack, except for older people who are not efficient at producing them, even with a vaccine. The Natural Killer cells are still an unknown in this fight and might be another avenue for controlling COVID-19 but we know older adults have fewer of these cells as well. Overall the only sure way we have of combating this disease is through social measures of reducing the probability of infection and reducing the infection load. Both can be achieved through the well-known drill of distancing, hand washing, wearing masks, and most importantly, not to gather. The world is going to be a distinctly different place.
The activity by drug companies is to develop therapies rather than vaccines. Therapies that address some of the effects of the disease, in particular, the lung infections that leave some of the COVID-19 victims scarred for life. But there is another side of the infection that is more worrisome, the infection to the brain. Recent studies showing that COVID-19 causes dementia takes us back to an awareness of how few tools we have to combat this disease. We know how difficult it is to treat the brain, as research on dementia has taught us, so this will be a challenge to address. In the end, we need to rely on preventing rather than attacking. The world has changed for all, but it will be especially different for older adults.
Further Readings
Andrew, M. K., Shinde, V., Ye, L., Hatchette, T., Haguinet, F., Dos Santos, G., ... & Chit, A. (2017). The importance of frailty in the assessment of influenza vaccine effectiveness against influenza-related hospitalization in elderly people. The Journal of infectious diseases, 216(4), 405-414.
Bernstein, E., Kaye, D., Abrutyn, E., Gross, P., Dorfman, M., & Murasko, D. M. (1999). Immune response to influenza vaccination in a large healthy elderly population. Vaccine, 17(1), 82-94.
Biswas, A., Chakrabarti, A. K., & Dutta, S. (2020). Current challenges: from the path of “original antigenic sin” towards the development of universal flu vaccines: Flu vaccine efficacy encounters significant hurdles from pre-existing immunity of the host suggesting assessment of host immunity before vaccination. International Reviews of Immunology, 39(1), 21-36.
Centers for Disease Control and Prevention; Seasonal Influenza (Flu) (2017) Seasonal influenza vaccine effectiveness 2018-2019. Available at https://www.cdc.gov/flu/vaccines-work/2018-2019.html Accessed June 25, 2020
Jefferson, T., Di Pietrantonj, C., Al‐Ansary, L. A., Ferroni, E., Thorning, S., & Thomas, R. E. (2010). Vaccines for preventing influenza in the elderly. Cochrane database of systematic reviews, (2).
Varatharaj, A., Thomas, N., Ellul, M., Davies, N. W., Pollak, T., Tenorio, E. L., ... & Coles, J. P. (2020). UK-wide surveillance of neurological and neuropsychiatric complications of COVID-19: The first 153 patients. The Lancet Psychiatry.
