Infection, Testing, and the Cure
I find that I can’t keep up with the constantly changing information about this corona virus. Each article I read tackles one variable and leaves another out. Some theories are accepted as fact, taken for granted early on but constantly evolving. Some interpretations of data have turned out to be just that, interpretations or premature. Mixed in between the “facts” are a bunch of theories, conjecture, media hype, and sadly political spin. I spent a sleepless night trying to sift through what I was unclear about and capture it here. The virus is new, we’re collecting data, comparing it to other past experiences and slowly uncovering its differences. My hope is to bring some clarity to what we know now.
Here’s what I am digging into:
Corona Virus Symptoms, Incubation Period, Duration & Contagiousness
Testing methods
South Korea vs. the US
The “Cure”
What was the impact of SARS
What will happen to our medical community
The Virus is Outrageously Contagious
Infection to Symptom: this period is typically 4-8 days, but to capture 95-98% of all cases, the range is more like 3-10 days before any onset of symptoms.
Symptom to Recovery: the disease can last 2 weeks for mild cases and 3-6 weeks for patients with severe cases. Total time each person may have the illness is 2 weeks - 6 weeks
Contagiousness:
After a virus hijacks a cell, it starts using the cell’s manufacturing tools to replicate itself and releases the copies to go find other cells to infect. This is referred to as Viral Shedding.
This process begins immediately after infection and can be found in the nasal passage, mouth or throat of the host.
You can be out infecting people without knowing it. This has been happening here in the US for months.
Viral Shedding can happen from a few days to 3 weeks after symptoms have disappeared. It’s unclear still how infectious it still is at this phase. There are some that have said it is transmittable, but a German study (not peer reviewed yet) suggests its not infectious at this stage.
Adding all of this up, the contagious period for each infected person (whether symptomatic or not) can be from 3-10 weeks.
Covid-19 Tests & Availability
To start, no test is perfect. Tests have what’s called a sensitivity and a specificity . Sensitivity is measuring how well the test identifies people that are virus positive and therefore have the disease. It is unclear what the sensitivity of our tests are. There was an escape rate in Wuhan early in the testing of 30% so they were re-testing every patient with a negative result again to be sure. Specificity is a measure of the true number of negative tests. In other words, does the test do a good job of finding all positives and rejecting the negatives, or does it cast such a wide net that it indicates a bunch of people as positive that don’t actually have the disease.
Now that that’s out of the way, as far as I can tell there are three types of testing on the table.
Lab Based Polymer Chain Reaction (PCR)- this is the test we have as of today. It requires a nasal swab to extract a sample. It must then be packaged and sent to a lab for analysis. The lab then analyzes and send the the test and the results were sent back. People getting tested are sent back home to await the results. It can take 72 hours to get a result. If there’s a negative, they likely have to be tested again because of the sensitivity mentioned above. You could be back and forth for 144 hours and infecting all sorts of people along the way.
Point of Care (POC) based - This allows for immediate results to happen at the place and point of care. When all of this started we had ZERO POC based tests approved by the FDA in the US. A lot of the news we’re hearing now is related to those tests getting approved. I think important to note that these tests, historically have a lower sensitivity than the PCR type of test. That means they miss more positive cases. At least they are fast and you don’t wait 72 hours if they try again, and they can still send you for a PCR test as a backup. Progress, but we still have to ramp up supply chains, manufacturing, distribution and training. It will take some time to proliferate, and is a little too late at this point to make a substantial impact in the areas where it is already wide-spread (but could help communities that haven’t been hit yet).
Antibody - It’s possible that a lot of us have already been infected by Covid-19 but have never had any symptoms. This is especially true with kids. There is currently no way (but as with everything, there are currently attempts to solve this) to test a healthy person for the antibodies that would indicate that they are already immune to the virus. This presents a problem when trying to sample a population to inform the shutdowns and economic halts we’ve seen across the country. We don’t know how many people have already been infected. If we knew, then those who had the antibodies could be the first to go back to work, sign up for the war effort, and rev the engine of our economy back up. This is something we’ll need to correct for and have at the ready in the future.
South Korea was ready to act, we were not
I’ve heard a lot of my friends suggest that the South Korea & China curves have flattened and we shouldn’t worry because we’ll follow a similar trajectory. However, I don’t think many of the Asian infections curves are easily comparable to ours. There are significant differences with respect to the actions taken by the different governments, the compliance of the population, and the subsequent effect they’ve had. Nor do I think they are in the clear just because their curves are sloping downwards. The rest of the world is still incubating and infecting and when they open their borders back up, they are likely to start the process all over. As I type this, we’re hearing of reports in Singapore and Taiwan of a second wave beginning.
A good example of different evaluations of the risk, and subsquent actions is exemplified by how differently the US and South Korea reacted to the World Health Organization’s (WHO) published “recipe” for testing for Covid-19 in January. Asian countries had previous experience and scars from both SARS and MERS. They remembered, so they acted.
South Korea took the WHO recipe and went to work immediately making tests and gearing up to deploy widespread testing across the country. You see, they have had experience with this before. They went through civil shut downs when they had an outbreak of MERS (Middle Eastern Respiratory Syndrome).
In 2015, patient zero had traveled home from a trip to the Middle East and went from hospital to hospital trying to get a test for the disease, in the process infecting a large number of people. With MERS in South Korea, 50% of infections originated in medical facilities during that epidemic! They had recent memories from shut downs and economic distress after that outbreak. They learned from the experience, passed legislation and put processes in place so they would react more expeditiously if an epidemic occurred again. They would not be caught without a plan. Their government had the power to pass immediate funding and green light their attack plan the moment the next epidemic presented.
A huge contributing factor with their response to MERS was their slow testing, both availability and deployment. So they focused their new process on maximizing test coverage the moment it was suspected that something was a threat. They took the WHO recipe for testing and went to work manufacturing a ton of test kits, setting up mobile testing stations, and putting tracking in place. If a patient tested positive, they published every known location that person went, down to the movie theater row & seat number. They collected credit card receipts, cellphone records and other private data they were pre-authorized to collect in a health emergency. Other Asian countries, democracies like Singapore, and even Hong Kong, have taken similar Orwellian steps for the sake of public health. China of course took extremely draconian measures immediately. Most of all, they highly encouraged testing and were ready for it.
US - our CDC did not believe in the efficacy of the WHO test and found it complicated; remember, while the US was doing this, South Korea went to work. The CDC created our own test, which had problems and a specificity that found too many false positives. We were also mired in a bureaucracy that required tests to go only to the CDC in the beginning, slowing down response times. As the tests were getting better, there were various approvals required through our bureaucracy, before the CDC approved tests could get out for distribution. Some of this was caused by controls that were counterproductive but enacted by our being in a public health state of emergency. A lack of bureaucratic alignment, process, and planning in addition to leadership is likely to have resulted in the long time it took for us to get tests out there. We have done this well in the past, it should be noted with H1N1, but it seems like our people, process, and systems were victims of neglect.
Risk assessments and subsequent preparation, planning and action US vs. South Korea
In the early stages of the pandemic in the US, as we started realizing it had escaped China and would be at our doorstep, we didn’t have the right risk assessment of the situation. We had so few tests, and there were very narrow guidelines on who could get tested, allowing people who didn’t fall into that range, to escape testing and thereby infecting our entire populace. Compare this to South Korea who knew how to assess the risk, had mitigation plans in place, and were mission focused. Mass produce tests immediately. Set up testing stations everywhere. Test everyone. Focus and speed made all the difference..
The Cure and the Impact
So now we’re stuck in shutdown mode because we failed to keep this virus contained early and let it spread unabated. We’re waiting for a cure and there are two types I’ve heard of as of the date of this article.
Serum - People who have the virus and survive generate antibodies. These antibodies can be extracted from the blood and given to other people. Each person with the antibodies could create enough serum to “dose” 1-10 people (unclear yet how many). This is temporary. Think of this as fishing for your immune system. This “serum” could last for 2 weeks or so before requiring another infusion. Anyone who recovers on their own should instantly be signed up to donate their antibodies to the cause. We should probably be looking at this for our healthcare workers to keep them safe. They are at greatest risk, on the front lines and deserve the assistance required to keep them in the fight.
RNA based Vaccine - This provides the immune system the instructions on how to create the antibodies on its own. The vaccine development cycle is long often taking 10-15 years to work out all of the various kinks. We are all different with different health conditions, genetics, and environmental factors. There are a variety of adverse effects of vaccines that need to be worked out. The good news is that there was work already underway for an RNA vaccine so we’re not starting from year 0 but are somewhere along the way. That said, the timeframes being suggested are unlikely as RNA vaccines have had adverse reactions to humans in the past and take time to make sure the end result doesn’t create more damage and strain an already strained healthcare system. In the same way I don’t think my kids are going back to school in three weeks, I don’t think a safe and effective vaccine will be ready in 12-18 months.
SARS1 had lasting effects, especially on medical workers
We have some prior experiences with the coronavirus, and we can look specifically at SARS 1 which also originated in China. The main area of concern when looking back at SARS1 was its impact on healthcare workers. Globally, healthcare workers represented 20% of the infected during the SARS 1 outbreak. In Toronto, where the virus had the largest impact in North America, 43% of the cases were infected healthcare workers.
Now we’re hearing constant tales of supply shortages. Healthcare workers are lacking commonplace items such as masks, gloves, hand sanitizer, and other medical supplies that are critical to their confidence and safety. We’d be horrified if we stripped our soldiers of their armor and shipped them off to fight the enemy. This is no different and ultimately it will come back to bite us.
Whether we continue our shutdowns or not, the virus is “out of the bag” so to speak. Our hospitals in each of the current hotspots are going to be full of Covid-19 victims. Our healthcare workers taking care of them are going to get sick too. This represents a double problem for both throughput and capacity. We can build more ventilators, but we’ll need more people to replace those that fall from infection to operate them and take care of the inbound patients who need them. As we call up retired workers to pitch in, we must remember that they represent some of the most at risk segments effected by the disease. If and when we return to work, traffic will begin again, as will car accidents. High risk jobs will commence again, leading to work injuries. People will still have heart attacks. There are still medical procedures that need hospital care. These will all now be bottlenecked into a health system with two stress points. One on capacity, and one on the labor to do the work.
So what have we learned? As a matter of national security, we need to have a plan in place for future pandemics; this will not be the last. When the next one strikes, we cannot be caught on our heels again.
What should we be doing now? Prioritize protecting our healthcare workers by manufacturing as many of the in-demand medical supplies as we can. And just as importantly, we not only need to manufacture mass quantities of tests, but must in parallel develop and implement a consistent national policy for using them aggressively and early. We might be doing damage control in the current hot spots, but we can get ahead of future hot spots. Our country is vast, and we can still protect much of it if we can get aligned and focused. Then we can get on with our lives.
If we don’t do this, we are fighting blind and there is no end in sight.
Sources:
The Tip of the Iceberg: Virologist David Ho (BS ‘74) Speaks about Covid-19 https://www.caltech.edu/about/news/tip-iceberg-virologist-david-ho-bs-74-speaks-about-covid-19?from=timeline&isappinstalled=0
Report of the WHO-China Joint Mission on Coronavirus Disease 2019 https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
Coronavirus Testing shouldn’t be this complicated
https://www.theverge.com/2020/3/17/21184015/coronavirus-testing-pcr-diagnostic-point-of-care-cdc-techonologyNew blood tests for antibodies could show the true scale of coronavirus pandemic https://www.sciencemag.org/news/2020/03/new-blood-tests-antibodies-could-show-true-scale-coronavirus-pandemic
COVID-19’s Stop-Gap Solution Until Vaccines and Antivirals Are Ready
https://www.globalhealthnow.org/2020-03/covid-19s-stop-gap-solution-until-vaccines-and-antivirals-are-readyVaccine Development Testing, and Regulation
https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulationHow South Korea Scaled Coronavirus Testing While the U.S. Fell Dangerously Behind. https://www.propublica.org/article/how-south-korea-scaled-coronavirus-testing-while-the-us-fell-dangerously-behind
South Korea; MERS virus outbreak is over:
https://www.theguardian.com/world/2015/jul/28/south-korea-mers-virus-outbreak-is-overWhy the Coronavirus has been so successful https://www.theatlantic.com/science/archive/2020/03/biography-new-coronavirus/608338/
Dr WenHong Zhang - Fudan University, Shanghai, CHINA http://himalayacapital.com/2020.3.13%20Dr.%20Wenhong%20ZHANG.pdf
SARS 10 Years later https://www.theglobeandmail.com/life/health-and-fitness/health/ten-years-later-sars-still-haunts-survivors-and-health-care-workers/article9363178/
German Study on Shedding - https://www.statnews.com/2020/03/09/people-shed-high-levels-of-coronavirus-study-finds-but-most-are-likely-not-infectious-after-recovery-begins/