As I continue to provide pandemic-related scientific resources, explanations, and news, please remember to take my interpretations with a grain of salt, as you should with everything you read on the internet. You can find my first batch of updates here and the second batch here.
March 25, 2020 Update
Today’s update is a reminder of the lessons from the 1918 Spanish Flu pandemic which killed 50 million people worldwide and around 675,000 in the U.S.
On Friday, May 30, 1919 an article was published in the esteemed journal Science on “The Lessons of the Pandemic” by a Department of Health sanitary engineer George Soper. I can only hope that each and every person who reads this can take the wisdom from 100 years ago to heart. Tell your friends, call your lawmakers, wash your hands. To summarize the piece…
Three main factors stand in the way of prevention:
a. “People do not appreciate the risk they run”
The character of the preventative measures that must be employed
a. “The kind of preventative measures which must be taken in order to control the respiratory infections devolve upon the persons who are already infected”
b. “It does not lie in human nature for a man who thinks he has only a slight cold to shut himself up in rigid isolation as a means of protecting others on the bare chance that his cold may turn out to be a really dangerous infection”
The highly infectious nature of the respiratory infections adds to the difficulty of their control
a. “The period of incubation varies considerably”
b. “The disease may be transmissible before the patient himself is aware that he is attacked”
“There is one and only one way to absolutely prevent it and that is by establishing absolute isolation.”
I fear a scientist could write this same piece in May of 2021. Don’t give her the opportunity. Cancel your plans now. Limit your contacts to your single household now. Self-isolate for 14 days after potential exposure now. The decisions you make today will have impacts on patient counts in 2-3 weeks. You can calculate your pandemic footprint here.
As national hero Dr. Tony Fauci, who has been on the front lines of every infectious disease response since HIV/AIDS says, “I like it when people are thinking I’m overreacting because that means we’re doing it just right.”
Here’s what the scientists are reading.
State by state stats supplied by Johns Hopkins University. Additional stats by The Covid Tracking Project which also assigns a data quality grade to help you interpret how much you should believe the state’s numbers.
Some good news:
- Italian engineers at Isinnova worked with the company Decathalon to create 3D printable valves that convert snorkeling masks to C-PAP masks for sub-intensive therapy (e.g. not as intensive as ventilation).
- Scientists are testing compounds that may target the spike structure on SARS-CoV-2 to block its ability to infect cells. These potential compounds were identified by supercomputing.
March 24, 2020 Update
Just a quick note today. A story published by many news outlets has headlines that the CDC found coronavirus RNA in the Princess Cruise ship cabins up to 17 days after passengers left. After reading the report from the CDC I would like to emphasize this relevant section:
SARS-CoV-2 RNA was identified on a variety of surfaces in cabins of both symptomatic and asymptomatic infected passengers up to 17 days after cabins were vacated on the Diamond Princess but before disinfection procedures had been conducted (Takuya Yamagishi, National Institute of Infectious Diseases, personal communication, 2020). Although these data cannot be used to determine whether transmission occurred from contaminated surfaces, further study of fomite transmission of SARS-CoV-2 aboard cruise ships is warranted.
Fomite transmission means infection caused by virus or bacteria on a surface. A Harvard epidemiologist has an important Twitter thread regarding the inaccuracy of the headline. Essentially, just because the viral RNA is detectable does not mean the virus is infectious. It is also true that based on this information we can’t completely rule out that the RNA found was in infectious viral particles, so more study is needed.
The study I highlighted in the March 18, 2020 Update looked at fomite transmission, but they actually tested if the viruses could infect cells. They measured the volume of infectious virus present on surfaces and in the air with a metric called TCID50 or 50% tissue culture infectious dose. It quantifies the amount of virus required to infect 50% of tissue culture cells (cells growing in a petri dish). The virus did seem to live as an infectious agent on surfaces like cardboard and plastic from 20-80 hours. Although over time the amount of infectious viral particles exponentially decreased.
Ultimately, we don’t know enough about transmission of the virus from surfaces yet. My advice is that of most public health experts: I would regularly clean surfaces in your home as well as possible, practice good hand hygiene, and not touch your face. If you are in a high risk category, you may consider additional precautions regarding fomite transmission until we know more.
On an optimistic note, a scientist volunteer form has been circulating: “Our plan is to create a national database of scientists located in the United States who are ready and willing to deploy their advanced skills, expertise, and access to reagents/equipment towards the fight against COVID-19 in their local communities.” If you’re a decision maker who wants access to the list, a scientist who wants to sign up, a lab interested in helping, etc. more info is here. As of this morning 6,400 scientists from 49 states, Puerto Rico, and Guam have signed up!
March 22, 2020 Update
Today’s explainer is a Q&A on COVID-19 testing.
Q: What is the classic COVID-19 test looking for?
A: Every virus has RNA (ribonucleic acid) which allows it to replicate in a host’s cells. A swab is used to sample from your nose/throat and this must be transported to a lab. In the lab, technicians isolate the RNA out of the sample. Then a process called reverse transcription quantitative polymerase chain reaction (RT-qPCR) begins. This 1) turns the viral RNA into complementary DNA (cDNA) 2) amplifies the cDNA. Specifically designed primers that match the viral RNA are used to ensure we are amplifying SARS-CoV-2. You can think of this as two legos that lock together and we can use one lego (the primer) to basically go fishing in a bucket of toys for the matching lego (the virus). Then we use fluorescent dye that binds to DNA and a special sensor in the PCR machine to quantify how much light is emitted—the more DNA, the more light. So a bright fluorescent pattern means DNA matching the virus has been identified and the sample comes from a patient with SARS-CoV-2. A nice explanation of the RT-PCR testing process is here, and it also discusses some of the blunders that have occurred with U.S. testing.
Q: Speaking of testing blunders, what has been going on with U.S. testing?
A: This is more bureaucracy than I would like to go into, but I will point you to some non-scientific sources which contain interviews with scientists that I would consider trustworthy. The NY Times reported on testing blunders here and here. The New Yorker reported on U.S. testing blunders over a week ago. A March 21, 2020 piece by journalists at The Atlantic outlines the testing debacle in the U.S. This article presents a sobering fact about the timeline: “If someone is infected with the coronavirus on Monday, she may start being contagious and infecting other people by Wednesday. But she may not start showing symptoms until Friday—meaning that she was spreading the virus before she even knew she had it. And in some cases, infected people take 14 days to start showing symptoms. The onset of symptoms starts another awful clock. Many people will recover in a few weeks. But if someone’s case is severe, he may not recover for a month. And even if someone’s case is fatal, she may still survive for three weeks. This means that, first, cases discovered now may not become deaths for weeks; second, some people who will die in early April may only start showing symptoms today.”
Q: Is the same test method being used around the world?
A: No! The process I described above is generally the same for each test, but there are different protocols (like a scientific recipe) that can vary slightly but ultimately have the same outcomes. You can think of this as there are many recipes for making an oatmeal cookie. The World Health Organization (WHO) released a test kit using RT-qPCR early on, and is maintaining technical guidance for laboratory testing. Originally the Food and Drug Adminsitration (FDA) only approved the Center for Disease Control (CDC) protocol, but the test kits shipped with a faulty reagent (like an ingredient in a recipe). On February 29, the FDA changed it’s regulations so that any testing lab certified for high-complexity testing could run its own COVID-19 test and bypass the CDC kits.
Starting on page 33 you can see WHO’s February 24, 2020 report on testing in China. They mention serological tests. These are currently being used in Singapore, China, and potentially elsewhere. These tests look for antibodies that a human’s immune system has created to fight the viral infection. So in our metaphor, this is like making a muffin instead of an oatmeal cookie—-completely different receipe but you still get a treat at the end. Read more about Singapore and China. Several U.S. institutions are also working on antibody tests.
Q: Why does testing take up to 48 hours?
A: See the steps involved in the first answer above. The protocol to perform these reactions could take a full day. In addition, technicians may do this at scale by performing the same chemical reaction on hundreds of samples at once using something like a 384 well plate. Waiting for hundreds of samples to be transported from a hospital to a lab environment may be a time-limiting factor. The article from WIRED says “As more labs come online, nearly every step in the RT-PCR test has the potential to run into bottlenecks.” The testing laboratories need PCR instruments that are approved by the CDC and reagent kits from suppliers, lke Qiagen, and some of these are now on backorder.
Q: What is the rapid test we are hearing about?
A: Scientists at Oxford University have created a test that uses RT-qPCR principles but just takes 30 minutes and can be read by the naked eye instead of the PCR machine’s sensor. As of yesterday, a company in the U.S. called Cepheid announced Emergency Use Authorization (EUA) from FDA for a 45 minute test. I can’t find how it works, but it does require an automated GeneXpert System that is already in use around the world. These rapid tests are going to be useful for more widespread surveillance and to solve some of the bottlenecks going on with the classic test in U.S. laboratories.
Q: Should we still be testing?
A: In parts of the country, testing for containment purposes is futile. We can assume the virus is endemic. The strategy is shifting such that testing should be for health care workers and members of high risk populations. I interpret this to mean that if you suspect you could have COVID-19 symptoms but they are mild and you are generally healthy, you should forego the test, assume you have it, and self-quarantine for 14 days. I predict after the initial peak of cases we will move into a testing and containment strategy like we are seeing in countries like South Korea.
Along these lines, Dr. Tony Fauci emphasized the following in the White House Press Briefing on March 21, 2020: Not every single person in the U.S. needs to be tested. Every COVID-19 test requires the use of personal protective equipment (PPE). These materials are high priority for the health care workers who are taking care of people who have COVID-19. Consider this: if you’re going in for testing, you’re taking a gown, mask, and gloves from a health care worker who is trying to save a patient dying in the ICU. My editorialization: You may think this sounds dramatic. It’s not. A hopeful fact: Dr. Fauci expects tests are coming that can be self-administered so a health care worker doesn’t need PPE. When asked about temperature testing instead of viral testing, Dr. Fauci said he doesn’t see a massive distribution of thermometers having an impact on testing.
Q: How accurate are tests?
A: A Michigan Medicine physician at the Town Hall on March 20, 2020 was asked about testing accuracy. She answered that analytically speaking, viral tests are very good at detecting viral particles. The level of detection is down to just a few viral particles. However, it does depend on technique of swab and correct transport. As with any test, false negatives (e.g. test is negative but person is infected) are still possible and they’re treating some patients with negatives but no other explainable cause of disease (e.g. seasonal influenza) as if they have COVID.
News & Views from my rocking chair:
An excellent piece on learning from Singapore and Hong Kong by Dr. Atul Gawande, a trusted author and physician. He says, “The fact that these measures have succeeded in flattening the COVID-19 curve carries some hopeful implications. One is that this coronavirus, even though it appears to be more contagious than the flu, can still be managed by the standard public-health playbook: social distancing, basic hand hygiene and cleaning, targeted isolation and quarantine of the ill and those with high-risk exposure, a surge in health-care capacity (supplies, testing, personnel, wards), and coördinated, unified public communications with clear, transparent, up-to-date guidelines and data.”
A really nice tool to dynamically visualize the classical infectious disease model SEIR (Susceptible–>Exposed–>Infected–>Removed) allows you to estimate your risk exposure on any given day of an epidemic (click the graph to select a day) given the intervention date (click this to slide it) and your close contact with N people. These estimates are based on the reproduction number (number of people the average case infects), incubation period (time between exposure and symptoms), and infectious period (time an infected person can infect someone else). Estimates of these values from the literature are provided in the table.
A back of the envelope calculation by a scientist in my field is here. Some of these numbers may be a little off because it is based on estimated parameters (e.g. 20 days between infection and death, 150x cases that we are missing from too little testing), but it’s the correct concept that mattters. With these parameters, 7,500 new deaths will happen in 20 days from March 20, 2020 no matter what we do because 750,000 new infections already occurred on March 20 and ~1% percent of those will die from COVID-19. In other words, the snowball is already rolling down the hill for a subset of the population. Social distancing helps us create a barrier for the snowball farther down the hill (e.g. ~20 days from the start of mitigation measures). We are going to see case and death counts rise until the impact of social distancing measures kick in. Dr. Kellis says: “The only parameter we control is the doubling rate (param3) which is a function of social isolation…So please stay home, stay isolated…” Dr. Tony Fauci said the dynamics of the outbreak are more “robust” in places like Washington and New York. This is why mitigation has been ratcheted up (e.g. true lockdown). If the option is available to you, I would suggest beginning to act like your city is in true lockdown as well and STAY HOME.