April 3, 2020

A Selection of COVID-19 Readings

We are two professors (of immunology and of demography/statistics, respectively), and, like all of you, have been reading widely about the COVID-19 pandemic.  Steve Roop suggested that it might be useful to BHV members if we recommended a selection of pieces on the topic for members to read. We were happy to do so, and offer a first pass at that below – a curated and lightly annotated selection of pieces we thought useful and/or edifying.  We have focused on those pieces that we felt addressed fundamental issues, asked important questions, and gave leads to possible solutions.

If the list is helpful to members, we plan to add to it in the coming weeks, and welcome suggestions and comments.

For those of you wishing to refresh your understanding of immunity and immunology, Kim has also written a very brief appendix to this listing, which she entitled: HKB's Immunology 101.

Enjoy.

Kim Bottomly and Wayne Villemez



1. COVID-19:  Why is our Immune System Killing Us?


a. Is the Immune Response to SARS-CoV-2 typical? 

Comments (HKB):  As our understanding of the body’s defense to SARS-CoV-2 increases, there are three major observations that make COVID-19 seem different. Why are older people dying at a surprisingly high rate? Is the virus itself or the host’s immune response to the virus to blame?  Why are children resistant to COVID-19, or are they?  This last observation differs from the responses to influenza in which the very young and very old are most affected.  And why are some individuals asymptomatic and yet contagious?

Reading: This is How Your Immune System Reacts to Coronavirus.

Reading: Possible Biological Explanations for Kids' Escape from COVID-19

Reading: Children and COVID-19

Reading: Covert Coronavirus Infections Could be Seeding New Outbreaks


b. Before a vaccine is developed, how do I know if I’m safe?

Reading: The Importance of Antibody Testing

Reading: Can You Become Immune to the Coronavirus?


2. What do we need tests for?  What kind of tests are there?  What do they tell us?

Comments (HKB and WJV): To get ahead of the coronavirus pandemic, it is necessary to understand the spread of and response to the disease. This knowledge can guide policies for, among other things, reducing the spread, for developing the requirements for patient care, and for creating new vaccines. Two broad types of very different tests are being discussed: those that measure the presence or absence of virus, and those that measure the presence or absence of viral-induced antibodies.

To date, the focus has been on developing tests that reveal the presence of virus in an individual. Because these tests have been in short supply, the necessary information about who is or isn’t currently infected is not available, which is greatly constraining our understanding of the spread. The test for the virus can only be effective during a short period of time, when an infected individual is actually carrying virus. Once an individual has recovered, the virus is no longer detectable. So, even with adequate tests of this type, it will be impossible to distinguish those individuals who haven’t been infected from those who have recovered (i.e., the at-risk from the immune). To do that, we need the second type of test.

Recent work has focused on testing for COVID-19 specific antibodies which are present in recovered individuals. These antibody tests provide information at the individual level about likely immunity, and at the group level about how many in a population have had the disease (and thus can measure our progress toward herd immunity). This second type of test, then, can help us understand the spread of the disease and also can inform individuals that they can return to a normal life. These tests will do little to help with policy-making during the peak of the pandemic. For that, we need the first type of test.

The articles below help us understand where we are in this difficult test-creation enterprise.

Reading: Huge testing discrepancies among states muddles the meaning of results

Reading: We need smart coronavirus testing, not just more testing

Reading: The next frontier in coronavirus testing: Identifying the full scope of the pandemic, not just individual infections


3. Now That We Have COVID-19, how do we fix this? Treatments, Antibody Transfer, and Vaccines

Individual approaches
Comments (HKB): You will read below that many types of treatments are being developed and hyped as the cure-all for COVID-19. The articles below describe more fully the current treatments being considered and the role each treatment plays – some are short-term fixes, some are long-term.

Short-term fixes are treatments given to individuals during the course of their illness: some reduce the level of viral replication, and some reduce the level of inflammation (in the hope of reducing the incidence of mortality).

Anti-viral treatments, if they work, have the added benefit of helping health care workers in high-risk situations by reducing the viral expansion in workers who are exposed to high doses of virus released by extensive contact with COVID-19 patients.
Ideally, short term fixes might include the use of the SARS-CoV-2-specific antibodies from the plasma of individuals who have recovered from COVID-19.

The ultimate long-term fix is the development of a vaccine which can be given to uninfected individuals to create immunity before exposure, or to protect them from re-exposure. A vaccine is simply a way to shortcut nature by creating herd immunity without having the experience of so many deaths.


Reading: WHO launches global megatrial of the four most promising coronavirus treatments.

Reading: Blood from people who recover from coronavirus could provide a treatment.

Podcast: The quest for the coronavirus vaccine.  Ted talk by Epidemiologist Seth Berkley (head of Gavi, the Vaccine Alliance). FYI: an hour long, but worth the time, ultimately.

Reading: The Coronavirus Isn't Mutating Quickly

Reading: Synthetic Biologists Think They Can Develop a Better Coronavirus Vaccine

Group Approaches

Comments (WJV): The first article is the one that initially made the powerful case for social distancing and other ameliorative actions (it is usually referred to as the “Ferguson Report”, and is still worth reading).  The other two are useful elaborations.

In the articles below, and many others, you will see reports of a virus’ “reproduction number” or “R0”.  Here is a brief primer on that.

Epidemiologists use R_0, the Reproduction Number (often written in newspapers as R0 and pronounced as “R-naught”, though reporters are using “R-oh” with increasing frequency), to indicate the number of cases an infected person will cause, on average. It is a measure invented by an eminent demographer (Alfred Lotka) in the 1920s, and notably used on a global scale in the malaria epidemic of the 1950s. It has been employed in all subsequent epidemics. 

“Basic” reproduction number (R_0) is useful for comparing the relative virulence of a disease.  For example, the R_0 for measles is in the teens, while the R_0 for flu is only 2 or 3.  Current estimates for the COVID-19 virus place its R_0 at between 1.5 and 3.0.  See seminal article below for this calculation and international comparisons.

“Effective” reproduction number (usually designated as R_1 or R_t, or some other subscript) is the expected number of cases an infected person will cause in a given population.  Basic R_0 for measles might be theoretically 15.0, say, but in a fully vaccinated population, it is less than 1.0. 

Public health measures are designed to reduce Basic R_0 to an Effective R_t of 1 or less (at that level, an epidemic will die out on its own).

Reading: The Ferguson Report

Reading: What is herd immunity and can it stop the coronavirus?

Reading: When will the coronavirus pandemic and social distancing end?

4. Lessons Learned and Future Preparedness

Comments (HKB and WJV): There are many available critiques to read concerning the handling of this pandemic, and more written every day. While our unpreparedness and leadership vacuum is painfully apparent, most articles reprise the obvious. The two below, we think, are more thoughtful than most, and certainly more forward-looking.

Reading: How the Pandemic Will End

Reading: What We Didn't Learn from Ebola

5.  Data Dump: For those who want to track, project, and play with numbers

Comments (WJV):  For those who like to keep track of data trends, we suggest three sites that are accurate, easy-to-use, and fun (or as fun as charting morbidity and mortality can be, anyway).  With these, you can track the spread of the pandemic yourself, on a broad or granular level, without having to rely on news reports (most of which use one of these three). You can experiment to see which format suits you best (if it matters to you, the first two are built on an ArcGIS platform, not sure what KFF is built on).  FYI: because of inadequate and uneven testing, all of these estimates are likely to be conservative ones.

The World Health Organization’s “Situation Dashboard” is the source authority, most used by researchers and reporters.  It offers interactive maps and bar charts for the world, for individual countries, and for states and provinces within countries. 

The Johns Hopkins University’s “Coronavirus Tracker”, created and maintained by the JHU Center for Systems Science and Engineering, is also a reliable source of these data.  They use a variety of publicly available data (not just WHO, though a lot of that), so their estimates may vary slightly from others. The site offers up-to-date tables, maps, and trend charts in a number of forms, for the world, and for individual countries.  

The Kaiser Family Foundation’s “Coronavirus Tracker” offers data drawn from WHO situation reports, but in a slightly more user-friendly and versatile way, with data on cases and deaths for the world and by individual country, available by map, trend charts, or tables.  (If you don’t know them, KFF is a well-respected non-profit, specializing in health-related data and activities, and their data are regarded as trustworthy). 


Reading: WHO Situation Dashboard

Reading: Johns Hopkins University Coronavirus Tracker

Reading: Kaiser Family Foundation Coronavirus Tracker

 
[BHV Note:  H. Kim Bottomly and Wayne Villemez, members of Beacon Hill Village, are retired academics.  Kim (Ph.D, 1975, University of Washington Medical School), taught immunobiology at Yale before becoming the 13th president of Wellesley College.  Wayne (Ph.D., 1970, University of Texas), taught sociology at the University of Connecticut and was director of its Center for Population Research.]