COVID-19: What Now, What’s Next?

The United States, with over 11.5 million confirmed cases of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and over 250,000 deaths, currently holds the highest amount of cases and deaths in the world.^1,2

In this new phase of the coronavirus disease 2019 (COVID-19) pandemic, where phase-3 vaccine results are trickling in and clinical practice points are being released to provide guidance on new therapies, a new question arises: What’s next?

We interviewed Dr George Abraham, MD, chair of the Infectious Disease Board at the American Board of Internal Medicine, president-elect of the American College of Physicians, professor of medicine at the University of Massachusetts Medical School, Worchester, Massachusetts, and chief of medicine at Saint Vincent Hospital, Worchester, Massachusetts, to gain insight into where the United States currently stands with regard to the coronavirus disease 2019 (COVID-19) pandemic, vaccine development, barriers to patient care, and the evolving roles of infectious disease specialists.

Some studies have suggested that less than 10% of the population have detectable antibodies against SARS-CoV-2. However, there has been a lot of discussion recently around “organic herd immunity” in the context of epidemic control. Can you provide more insight into this concept?

Dr Abraham: The general prevailing 10% herd immunity³ and [its contributing factors have] been a subject of a bit of a debate. One of our challenges has been the accuracy of determining antibodies in a person using our current antibody testing. If there is a 10% prevalence in the population, we know now, at least based on preliminary data from vaccine trials, that we need approximately between 50% to 70% prevalence to have herd immunity.

If plasma was transfused from someone who had recovered from more serious disease [compared with mild disease], people seemed to have a better response to therapy. 

There might be a subsection of people who might have very mild to asymptomatic disease, conceivably those people who have very low antibody levels, and what we don’t know is if those [levels] will be sufficient. Firstly, it is reasonable to assume [these individuals] will not be protected and may be vulnerable to a second infection.

Secondly, we do not know how long these antibodies last and therefore we do not know how long the period of immunity is conferred, even among those who have detectable or robust antibody levels. Thirdly, putting all of this in perspective, the underlying issue of our testing not being accurate enough to pick up confounding from other coronaviruses, which are non-CoV-2, all play a role in determining the answer to that question.

For physicians working with populations reluctant to acknowledge the severity of the pandemic and disease, what tools or resources may be helpful in communicating the reality of the dangers of this disease?

Dr Abraham: That is such a pertinent question yet a challenging one to respond to because anything that we say would probably appear glib only because how do you convince a person who does not believe in science that there are scientific principles which underlie [COVID-19], and that this is not about an individual or about the source of the infection? Whether [this disease] is laboratory-derived, a natural mutation, a conspiracy to knock down our economy, or a race-based question, or all of these, different challenges which play into that.

I think what we try, often with limited success, is to, at least, push through the argument that [the disease] is based on science and there are no other ideologic differences that drive our decision making in this situation. 

Using just the scientific principles and staying away from the politics, the religious aspects of this, the ethnic aspects of this, or other ideological aspects that might dilute the strength of the conversation would make it much more believable. Forget everything else in the conundrum.  Because unfortunately, [these] other factors have sort of played a role in diluting the conversation and driven it away from the science, which is simply that there is an airborne virus and if we do not cut off the transfer, then person-to-person acquisition of disease does occur and will continue to occur.

There are more than 40 vaccines in clinical trials worldwide, with over 90 preclinical vaccines under investigation. What are some key outcomes, inclusion and exclusion criteria, and results that physicians should be looking for when evaluating preliminary trial data?

Dr Abraham: For any vaccine that we develop, we have a population which has varied characteristics. Of those characteristics, we know clearly that there is a gender difference, with men being more vulnerable to severe disease⁴ and complications compared with women. We know that age is a bigger factor; CD4/CD8 responses in older patients are much lower^5,6 or they have a much more attenuated immune response compared with those who are younger, and therefore, [older individuals] tend to have more severe disease and other complications. We also know that socioeconomics plays a big role. 

The first thing [that physicians should be looking for] is: were [these data] studied in adequate, diverse populations. Secondly, what are the levels of antibody responses? Are they enough to induce the immunity that we expect to obtain as a result of taking the vaccine, so that we can actually fight infection if challenged and never get actually infected? And thirdly, how long do these antibodies last in the system? Therefore, what is the frequency of redosing the vaccine? Is it 2 doses given a month apart or 6 months apart? Or is it a single dose? Is it given annually, biannually, every 5 years, every 10 years? 

Researchers are using slightly different methodologies, all with the end result of the attempt to raise enough antibodies in the person who is being injected with vaccine so that when [these individuals] are actually challenged with disease, they mount enough of a response to never get the disease.

Some pharmaceutical companies have recently made public detailed information on their trial protocols, including conditions under which trials could be terminated early and how participants are being monitored. How can clinicians better navigate these data when it is made available?

Dr Abraham: I suspect most of these [companies] will have studies published in medical literature, which will give succinct information that you pointed out as being relevant, which would help to tease out the issue. Otherwise I’m sure we will see analyses by scientific personnel who will compare and contrast these parameters. First, the transparency by the companies are in response to the scientific community asking for all companies to make that information transparent and public, because it is critically important that we know or understand which population it is being tested in, what are the results so far, or their challenges and any complications. 

But complications, if any, would be extremely important because if the person receiving the vaccine is relatively healthy at the time of vaccination, do we actually induce disease or do we make them more susceptible to the disease? Do we, in any way, protect them from the disease? All of [these] will be questions that a patient is going to ask us before they receive the vaccine.  

So I suspect we will see medical publications, which will synthesize this information. I think looking through some of those publications to be able to tease out that information and synthesize it in some sort of a tabular format [along with comparisons with] different vaccines would probably be the best way to quickly assimilate information and then be able to have some talking points to address with their patients.

For infectious disease specialists, how do you see their roles evolving after the pandemic has eased?

Dr Abraham: Excellent question, and I think this is one that we’re grappling with. Traditionally, one of the criticisms of our country’s response to any pandemic has been that we are so entrenched in acute care medicine that we have really not invested in public health and preparedness, because we sort of see that something that could happen, but as a distant dream. I think this pandemic has taught us that this is not a distant dream, it could be a reality, and it could have devastating effects when we are not prepared.

The role of the infectious disease physician has not been only treating acute problems, but, in most institutions, in infection control, which is monitoring for infectious diseases, the prevalence of those in the community, and the prevalence in the institution. How would you mitigate outbreaks within the institution and keep people safe? And when a pandemic like this occurs, how does the institution continue to be able to deliver care safely to people who may be looking for elective or routine care, and also, providing care to people who are ill? And so these [questions do not have] high economic value associated with it, based on the way our reimbursement system works. Therefore, hospitals have been reluctant to invest in infection control, infection control practitioners, and infectious disease physicians from that standpoint [to prepare] for that sort of eventuality.

In the future, I suspect, based on this pandemic, that hospitals will wake up to the fact that this is no longer a distant reality. The question is not will we, but when will we have the next pandemic. Hopefully this was a wakeup call to which hospitals and the healthcare system will invest in developing and maintaining an infectious disease practitioner and/or an infectious disease service in every institution that provides care so as to be able to deliver safe care.

Editor’s Note: This interview has been edited for length and clarity. 

References

1. CDC COVID data tracker. Centers for Disease Control and Prevention website. https://covid.cdc.gov/covid-data-tracker/#cases_casesper100klast7days. Updated November 20, 2020. Accessed November 20, 2020.

2. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Coronavirus Resource Center at Johns Hopkins University of Medicine. https://coronavirus.jhu.edu/map.html. Updated November 20, 2020. Accessed November 20, 2020.

3. World Health Organization. Coronavirus disease (COVID-19): herd immunity, lockdowns, and COVID-19. https://www.who.int/news-room/q-a-detail/herd-immunity-lockdowns-and-covid-19. Updated October 15, 2020. Accessed November 20, 2020.

4. Griffith DM, Sharma G, Holliday CS, et al. Men and COVID-19: a biopsychosocial approach to understanding sex differences in mortality and recommendations for practice and policy interventions. Prev Chronic Dis. 2020;17:E63. doi: 10.5888/pcd17.200247

5. Chen Z, Wherry JE. T cell responses in patients with COVID-19. Nat Rev Immunol. 2020;20:529-536. doi: 10.1038/s41577-020-0402-6

6. Westmeier J, Paniskaki K, Karaköse Z, et al. Impaired cytotoxic CD8⁺ T cell response in elderly COVID-19 patients. mBIO. 2020;11(5):e02243-20. doi: 10.1128/mBio.02243-20