My Wife and I Are Both Fighting SARS-CoV-2 in the Lab — We May Win This Battle But I Am Afraid We May Not Win the War
Author’s note: Items in italics throughout represent newer segments of the story that were added after completing the main body of the text. In order to protect our employer’s identities, aspects of the story, including the timing of events have been modified. Additionally, certain key pieces of information have been changed or redacted. Hopefully, it goes without saying that the viewpoints expressed in this piece are my own. They should not be taken as having any endorsement, official or otherwise, from my wife personally or from either of our employers.
Just back from another trip to one of the labs in an undisclosed location in COVID19 shell shocked [redacted] and I am drained, mentally and physically. Exhaustion has my eyelids heavy and brain working at two thirds normal function, and that’s being generous. Traveling these days is a surreal experience. I’ve been in three different hotels in the past two weeks, was the only guest in two of them, and one of two in the third. Spending any time by yourself in a hotel built to accommodate hundreds is eerie, made more so by the strange insistence on the appearance of normalcy by the staff. At each hotel I was treated like any other guest, on any other day, like the situation was nothing at all out of the ordinary. Bizarre to say the least, but we all cope in our own ways it seems. Before heading home I would stop by my home lab to pick up some supplies we were running short on in [redacted]. In the past the need for this sort of transfer would be so rare as to be almost unheard of, these days, with supply shortages of all types affecting many academic, government, and industry labs across the country and around the world, it has become much more common.
Technically I was not supposed to be doing this, travel out of state means 14 days of self-isolation upon return according to the state in which I live, but, it couldn’t be helped, we would need the supplies for next week when I am set to return. I did don a surgical mask which my own workplace requires of anyone traveling out of state in order to return to work. I had hoped I could sneak in and out unnoticed, but within minutes of leaving the building I got a phone call from a manager off site. She had received some communications from technicians who had seen me there, and were anxious about it. She asked if I could send a quick email explaining my reasoning, and why they should not have any particular extra concerns about an exposure because of my presence. Tensions and anxiety were running very high she explained, “I know you would not be there if there were any risk, but they need to know that too.” Fuck, there goes an hour of my day, is what I thought, but I said I would, and after returning my rental car to the airport spent the next 45 minutes crafting an email which listed no less than 10 reasons why their fear was unfounded. The last was perhaps the most convincing, at least to me, and it was the fact that I had been tested for the virus just last week and had a negative result. It would be naive of me to say the technicians’ fears were totally unfounded. Traveling is inherently risky from an exposure perspective, no matter the precautions taken, and where I had been is a hotspot. I would be concerned if I were in their shoes given the circumstances, and they were not even aware of the “false alarm” exposure at the lab up north from the previous week. That debacle had resulted in me spending last weekend not at home with my wife as intended, but instead miles away self isolated in a room in a local [Redacted] until I could be tested.
The Nature Medicine paper from April 15 landed like a hand grenade and it shook me. A large part of our countermeasures in this fight are/were based on the notion of isolating persons showing symptoms of disease from those who are not. But researchers in China showed that out of a pool of 77 infector-infectee pairs they “… observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset.” They go on to estimate that “…..44% (95% confidence interval, 25–69%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering…” (bolding mine). Damn, that sucks, and suggests that all the bulwarks against disease transmission we have constructed and had thought would provide some measure of protection may be completely worthless, or at the very least far less effective than anticipated. I commend the author’s reserve when they conclude the abstract with this classic example of putting it mildly “Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.” Disease control measures should be adjusted? Try completely reworked, totally rethought, or scrapped completely and built from scratch. In any case, some serious work to do to reconcile all the current recommendations with these important and scary findings.
My wife, or her job actually, is partly the reason for my lab’s anxiety about my presence and most of the reason I stayed away last weekend. She spends much of her time in level three biocontainment handling the virus as she and her colleagues work to identify treatment options and develop vaccines. For the last two months, she has worked 12–16 hour days, taking only 2 full days off I can remember that entire time. To those politicians who say we (scientists) are not working hard enough, I say fuck you. Her lab is under pressure from an entire planet full of people desperate for a cure, to come up with something, anything, to change the game, to fix this thing. Rarely does she complain, but I see the physical and emotional toll that working every waking moment is taking. On top of that is layered the monumental guilt she feels every time she takes even a few moments for herself. That guilt is hard to deal with even in the absence of political blowhards taking potshots from the cheap seats about the work ethic of your chosen profession and lifelong passion. There are only a few labs working on vaccine development and screening in the country. It’s a real shame but the economics of vaccines are not good which makes industry loathe to invest in them. In this case, you have the added complication of needing a biosafety level 3 (BSL-3) lab to do the work and those are not exactly a dime a dozen either.
The biosafety level system is a way of classifying microorganisms based on the dangers inherent in working with them. The number is derived from an assessment of the potential severity of disease caused by the microbe in question, along with the relative ease of disease acquisition/transmission. In other words how sick could you get and how easy is it to get sick. Those organisms classified as BSL-1 are completely safe to work with and handle with no special precautions taken. They do not cause disease in healthy humans and you could drink gallons of cultures containing them with no ill effects. A good example would be the vast majority of microbes that make up the normal flora of your skin. In contrast those at BSL-4 require incredibly complex and sophisticated laboratories and apparatus, along with specialized protocols and personal protective equipment to work with, cause almost always fatal disease and are transmitted easily through the air or person to person or both. A good example here would be Ebola. It sounds very straightforward, but there is much room for debate, particularly when it comes to the question of disease transmissibility. Is an organism with an infectious dose of 1 (only a single organism can initiate disease) that is not capable of being aerosolized and thus cannot normally be spread through the air, more or less dangerous than a different microorganism with an infectious dose of 10,000 that can? The biosafety level classification of any given microbe has major implications for who can work with it. Ultimately, this translates into how many people can work with it, and where that work can happen. There are many, many more laboratories certified for use of BSL-2 microorganisms then those capable of working with BSL-3 or 4. These days there is an added complication in that some particularly nasty microbes are considered so called “select agents” by the department of homeland security. These are deemed to have higher than average potential for misuse as agents of bioterror. Working with any microorganism that resides on this list brings additional security and handling requirements and any lab that does must be registered with the department. In the very early days of the SARS-CoV2 pandemic designating the virus a select agent was seriously considered. Fortunately, after much outcry from public health officials this decision was not taken. The implications from a public health perspective would have been grave indeed as the number of persons who could do any work with the virus would have been significantly reduced greatly hampering efforts toward a possible vaccine and treatments.
The net result is a fairly meager overall capability and in circumstances like these that lack of investment and focus is keenly felt. With so few labs doing this type of work, the impact of even one shutting down could be catastrophic. Because of that when I travel there is a new reality. For me, going home to quarantine following a known or even suspected exposure isn’t really an option. Unlike millions of other Americans who have only their own health and household to worry over, if I bring the virus home with me from a work trip, it’s not just my wife or kids or neighbors I run the risk of infecting. I now also have the pressure that comes with the knowledge that not being careful may very well spread the virus to her workplace, which could significantly compromise our state’s testing capacity and regional/national vaccine/drug screening. And with that, all of the people they could have helped. Which is why the ‘false alarm’ from the lab [redacted] wreaked so much havoc. Until it was sorted and I had a negative test result, I simply could not go home for fear of putting far more people than just my family at risk.
Her knowledge and my own has fueled my growing fears about our prospects for a vaccine and the unknown aftereffects of coronavirus infections. ADE, antibody dependent enhancement, is not a term I was at all familiar with until very recently. It has however become just about the only thing work related my wife and I talk about these days. It is the source of much (though not all) of my fears. Usually when a person is exposed to a pathogen and recovers or receives a vaccine there is short and long term protective immunity against re-infection. Neutralizing antibodies develop and the body “remembers” how to make them again so the next time we encounter that same pathogen the immune system reaction is quick, efficient, and effective. The end result is we do not get sick again from exposure to that same pathogen, in many cases this protection is life-long. We can thank evolution, specifically natural selection, for that neat little trick, advantage human. Of course for some pathogens, including some viruses, that is not the case for various reasons and in some, rare cases, re-exposure or exposure to similar but slightly different viruses results in even more harm than the original infection.
In these cases, the ADE phenomenon causes low levels of circulating antibodies to actually enhance viral entry and subsequent replication which leads to a much more severe infection than was observed the first time around. The best known example is dengue fever which is caused by the dengue virus. There are currently fiver recognized strains (serotypes) of dengue virus that can cause disease in humans. The first time someone gets dengue fever from any of the five serotypes, they suffer for a week with a fever and agonizing pain in their limbs, but they recover. If they are subsequently re-infected with one of the other four strains, their own antibodies from the first infection can cause this secondary infection to turn hemorrhagic and quickly fatal. This was discovered many years ago when the first dengue prototype vaccine was taken to clinical trials in a country where all four (only four were known at the time, the 5th was added in 2013) strains are endemic. Why does this matter for the current pandemic? Consider that many of the feline coronavirus vaccines trialed to date have made the disease much worse in cats. This virus is in the same family as SARS and SARS-CoV2 but has been far better studied for a longer period of time as it does not infect humans.
Vaccine trials are underway across the world. There is no shortage of volunteers. I really, truly, hope these people all know the risk they are taking. That they all remember the lessons taught by the dengue fever vaccine.
My worst case scenario, and it does keep me up at night sometimes, goes a little something like this. We beat this thing off, maybe even eradicate it entirely. Perhaps there is a vaccine or even very effective therapeutic drugs are developed. We think we have won, celebrate our genius and good fortune and then go to sleep. We wake up two or three or four or even five years later and suddenly we notice a slight uptick in certain unusual diseases effecting specific organs. Hmm, that’s odd we think. Then the cases start to increase, and they continue to increase until it becomes evident that every single person who was infected with the virus, symptomatic or asymptomatic, who got really sick, or just mildly sick, or not sick at all, each and every one of these people is at a hugely elevated risk for kidney disease or lung disease. The association of the virus with a particular receptor ACE2, which is found in the kidneys among other places in the body, and infection with SARS-CoV2 suggests any organ which has this receptor could be at future risk of disease. We are already seeing evidence of kidney disease and enhanced kidney disease risk in patients who have recovered from covid19 disease. Recent numbers suggest up to 20% of symptomatic persons may end up with permanently impaired kidney function. Even more frightening however is another possibility, and it too is one for which sadly we have seen some evidence. In this nightmare scenario every single person who was infected with SARS-CoV2 is at a hugely elevated risk of developing formerly rare autoimmune disorders like multiple sclerosis (MS) or, even worse, the so called “Kawasaki-like” autoimmune disorder which causes rapid onset multi organ failure and death.
What does my wife think you might be asking yourself? I had originally originally intended to use her own views as a powerful closing statement, to both amplify my own concerns, and add a dramatic flourish to the ending. However, each time I tried to pin her down she deflected. Instead of an answer, I was regaled with some tale of the current status of various ongoing experiments and/or drowned in data and numbers and questions and her own speculation and hypotheses. In the end she did not really answer the question. Not really, not exactly. Maybe it was my own pessimistic take clouding my judgment, but the more I pressed the more I sensed just a little less optimism about the prospects for a happy ending to this ongoing tragedy, and that scares me most of all.