Critical Knowledge Gaps We Must Define, Fill to Combat COVID-19

Critical Knowledge Gaps We Must Define, Fill to Combat COVID-19 

By Dr. Rob Breiman

As I write this, the country is five months into a pandemic that has claimed the lives of more than 150,000 Americans. The crisis has changed the way we live, the way we interact, the way we work. If forecasting is correct, we still have a long road, and much additional change, ahead of us.

Rapidly changing information, priorities, deliberations, and decisions make this pandemic the most dynamic, ever-changing global health crisis in a century. Every week there are new priority questions appearing via social networks, media, webinars, and scientific meetings. This week, discussions have revolved around:

  1. Considering their cognitive and social development, how can young children be brought back to in-person learning without substantially increasing the risk of serious illness in the students, teachers and school staff, parents, grandparents, and other family members? Likewise, should universities and colleges open their campuses for in-person learning and athletics in the Fall?
  2. If SARS CoV2 vaccines ultimately are shown to be safe and effective, how will they be equitably distributed?
  3. Why is there such a massive disproportionate risk of COVID-19 deaths for people of color, including Blacks, Hispanic/Latinos, and some Native American tribes? And why does the risk appear to vary substantially by location?
  4. What are the best approaches to ensure safe work environments?

Ideally, answers and approaches related to these four questions would follow the data.

In A Surgeon’s Notes on an Imperfect Science, physician/writer Atul Gawande said: “We look for medicine to be an orderly field of knowledge and procedure. But it is not. It is an imperfect science, an enterprise of constantly changing knowledge, uncertain information… The gap between what we know and what we aim for persists. And this gap complicates everything we do.

During the course of this pandemic, while there have been no shortages of strong opinions, it often has felt like we are in a data-free zone, or worse—the data available come from limited surveillance information and sub-optimal studies, so that the interpretation of the results are operator dependent—that is, there is not a unified impression on what the data are telling us and often disparate conclusions are reached without solid bases of evidence. Messy data (or no data), leads to messy assumptions, which, in turn leads to inconsistent policies, inaction, when action is needed, and loss of clarity and confidence in our collective way forward.

What has been consistent in this very fluid environment has been the need for better surveillance data and research to provide evidence to drive public health decision making; that is, evidence for effective and impactful action.

The knowledge gaps are yawning, and the progress towards filling them has been halting. What sort of knowledge gaps are we faced with? While there seems to be new questions every week, the needed information to answer them remains consistent, often underpinning each new decision point.

Consistent knowledge gaps that underpin the questions include:

  • What factors make a SARS-CoV2 infected person likely to transmit to others? Or said more specifically, we know that asymptomatic people can transmit, but how likely is it that they will do so with non-intimate contact, and, how likely is it that infected early school-age children (K-6) will transmit to other people? Are there specific characteristics of their infection (like cough or wheezing) that dramatically increase transmissibility? In short, who are we really worried about with regard to spreading virus? Can we characterize and define the attributes of SARS-CoV spreaders so that we can refine mitigation strategies? And, what are the best, most feasible to make available, masks that everyone should ideally use?
  • What are the key factors associated with becoming infected with SARS-CoV2 and for experiencing severe COVID-19 illness, including death? We know that there are disproportionate risks for people of color, of advanced age, and of certain co-morbidities (like diabetes, chronic heart and lung disease), but given those characteristics, what multiplies the risk? We need to better define the occupational, community and residential factors that could be modified to reduce the likelihood of infection and of severe outcome. Potential physiologic contributions to severe disease could be important. Could, for instance, differential absorption of sunlight by skin color impacting levels of vitamin D, which affects immune function, be a factor in the disproportionate mortality risk for people of color ?

In addition to epidemiologic investigations, attention is also needed for two crucial types of study often neglected during crises: behavioral research and operations research. Behavioral research provides the ingredients for developing a solid plan for communications and community engagement, ultimately leading to uptake of behaviors consistent with public health guidance. The struggle over wearing face coverings demonstrates this need. Perceptions, attitudes and behaviors among people of different races, ethnicities, socio-economic status, and, as has been so painfully obvious in the US, political identity, determines the response to a behavior change recommendation like wearing masks.

It is not enough for people working in public health institutions to make a one size fits all pronouncement like “my mask protects you, your mask protects me.” What is needed are community discussions, focus groups, interviews of key informants, ultimately leading to customized, resonant messaging and community engagement designed to optimize compliance with the recommendation.

Through grinding effort and hard realities, we have made slow progress on broader adherence to face coverings. We cannot revisit the same process with immunizations. As COVID vaccine development moves at “warp speed,” parallel behavioral research and community engagement, beginning now, will be crucial to acceptance and wide use of anticipated safe and effective vaccines.

Operations research involves the field testing of approaches to deliver interventions or implement strategies often through demonstration projects. The findings of what works and doesn’t leads to fine tuning, which then optimizes the efforts that can then be scaled up more widely. So, with efforts to promote safer and healthier workplaces, as well as school environments and houses of worship, demonstration projects can test, evaluate and show the best way to operate in a variety of environments to allow, work, education, and worship to occur without creating undue risks for participants.

As each day passes without refined evidence-based prevention and control approaches, people become ill (with some illnesses leading to long-term impairments or death). We do not have the luxury of time and we cannot allow knowledge acquisition to be accidental. On the contrary, we know enough now about knowledge gaps to be quite intentional about filling them. Data that are collected when people are tested, and when tests return as positive, need to include elements that will help answer key questions. And prioritized, epidemiologic, behavioral and operations research is needed in a variety of settings to provide evidence for action.

The increasing burden of disease we are currently experiencing in the US and in many countries globally, coupled with recognition that most people on the planet have not yet been exposed to the virus, is a stark reminder that SARS-CoV2 and associated covid-19 will remain a threat to human and economic health for the foreseeable future. This makes it all the more essential to establish a prioritized agenda to systematically fill critical public health knowledge gaps, in addition to the ongoing clinical research on diagnostic tests, therapeutics and vaccine development.

Dr. Robert Breiman is professor of Global Health and Infectious Diseases at Emory University and Chief Scientific Officer for the Global Health Crisis Coordination Center. He is a member of the National Academy of Medicine.

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