Saturday, November 21, 2020

Not only the vaccines are making progress this week. New studies are beginning to give us a better understanding of how COVID-19 spreads and how long our immunity lasts. Many of these studies are of the “meta-analysis” type. That is, they search the literature for studies related to an issue like masks or asymptomatic transmission or how long immunity lasts and they pool the information to see what we can learn about the big picture.

This process, even facilitated by databases and digital searches, involves painstaking analysis of thousands of papers to find data that are similar enough to compare. Even studies that ask the same questions vary in the criteria such as age of the participants or how long they were followed. Still, by selecting studies carefully and taking variables into account, a careful meta-analysis can produce valuable information.

Here are some recent examples. Links to all source articles are listed below.

Masks. As you can imagine, masks have been intensively studied in the last 10 months and it is important to look at the most recent data and analysis. One example was published in Travel Medicine and Infectious Disease (Vol. 36, July-August 2020, 101751). This meta-analysis of 21 studies demonstrates the efficacy of wearing masks in preventing transmission of respiratory virus. The following flow chart shows the process of selecting relevant studies to compile.

Selection of articles for a meta-analysis. See source below.

The resulting analysis finds that masks provide significant protection for both healthcare workers and non-healthcare workers. (For specific data, see article link below).

As a meta-analysis, it was incorporated with others into a much larger meta-analysis called “Modeling COVID-19 scenarios for the United States,” published in Nature Medicine in October 2020. This large-scope study modeled the efficacy of non-pharmaceutical interventions (i.e. distancing and masks) to project outcomes of different levels of use on a state-by-state level. The results have been widely published, for example in the Los Angeles Times as “New forecasts show why masks are the easiest — and cheapest — way to save U.S. lives.”

Asymptomatic transmission. (“What the data say about asymptomatic COVID infections,” Nature, 11/18) True asymptomatic carriers, people who test positive yet never have a symptom, appear to be less common than was once thought. And maybe less infectious as well. This comes from a meta-analysis based on 13 articles that followed 663 positive cases (by PCR) for at least 7 days. Overall 17% were asymptomatic. However, the range went from 4% to 41%. Still, this is a lower rate of asymptomatic cases than they thought existed earlier in the pandemic.

Asymptomatic individuals were found to be 42 % less likely overall to transmit the virus. Why this is so remains to be determined (difference in immune competence, viral load, the fact that they are not coughing?) However, people who are about to come down with COVID are infectious before showing symptoms. So a person who is feeling fine may be asymptomatic or pre-symptomatic. If you have been exposed to someone who feels ill a day or two later, you were exposed to them at a highly infectious stage. In turn, you may not feel sick for four or five days, but you will be infectious 1-2 days before that. See: “If You’ve been exposed to the coronavirus,” at https://www.health.harvard.edu/diseases-and-conditions/if-youve-been-exposed-to-the-coronavirus

Transmission timing: Lancet (11/19) reports a meta-analysis of viral shedding in studies of COVID, SARS, and MERS. Although traces of the virus can be detected in the respiratory tract and stool for weeks, they found that no live virus was shed past the 9th day of illness. Shedding of live COVID virus peaked in the first week after symptoms began.

These findings lead to two conclusions about transmission. First, the disease is most infectious in the first week, a few days before and about 5 days after symptoms begin. So early isolation is very important even with very mild symptoms. Second, a positive test for virus after 9 days of onset does not mean that the person is still infectious. The test can be detecting fragments of virus that are not viable.

Immunity: An article in Nature (11/20) reports that immune response to COVID lasts longer than 6 months. This is based on symptomatic cases, NOT on vaccine trials, but it bodes well for the vaccine studies (which don’t have 6 months of data yet). The research evaluated 185 people with symptoms and followed 41 of these for at least 6 months. They all had both T-cell and B-cell immune responses for this entire period. This good news will be even better when we have a larger sample size.

Fortunately we will have a larger sample size coming in the vaccine trials which will be following their immunized population for at least two years. And some where along the line, this study may be incorporated into a meta-analysis.

Ten months after the pandemic was declared we are beginning to accumulate a lot of data and this is fast becoming information we can use. My countdown shows that we have 110 days until the Pandemic Anniversary. Now I’m not saying it’s time to break out the champagne yet. If anything, it’s time to hunker down (see hunker in Pandemic Day 247) and make informed decisions while we wait a few more months for vaccines and improved therapeutics to be available to everyone.

Today’s Notable Headlines

“Modeling COVID-19 scenarios for the United States,” Nature Medicine, Oct. 23, 2020. https://www.nature.com/articles/s41591-020-1132-9#Sec7

“New forecasts show why masks are the easiest — and cheapest — way to save U.S. lives.” Los Angeles Times, Oct. 23, 2020. https://www.latimes.com/science/story/2020-10-23/if-americans-would-just-wear-masks-we-could-save-more-than-671-000-lives

“What the data say about asymptomatic COVID infections,” Nature, 11/18/20 corrected on 11/20/20, https://www.nature.com/articles/d41586-020-03141-3

“If you’ve been exposed to the coronavirus,” Harvard Health Publishing, Harvard Medical School, Updated Nov. 20, 2020. If you’ve been exposed to the coronavirus – Harvard Health

“COVID research updates: Immune responses to coronavirus persist beyond 6 months, “ Nature, Nov. 20, 2020. https://www.nature.com/articles/d41586-020-00502-w

“SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis,” The Lancet, Nov. 19, 2020. https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30172-5/fulltext

Research Articles:

“Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis,” JAMMI, Oct. 9, 2020. https://jammi.utpjournals.press/doi/10.3138/jammi-2020-0030

“Immunological memory to SARS-CoV-2 assessed for greater than six months after infection,” bioRxiv (preprint, not peer-reviewed), Nov. 16, 2020. https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1

Why am I doing this?

The coronavirus pandemic will be indelibly written on our memories just as the Great Depression or the Battle of Britain left their mark on past generations. It is my intention to journal the pandemic experience from three perspectives: as a retired medical technologist, a historian (Ph.D., 2014), and an ordinary person living through an extraordinary crisis.

You are on History’s Edge.

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