Tag Archives: SARS-CoV-2

Omicron and Endemicity? 1/24/22

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The question I’ve received many times is what does Omicron mean for the end of the pandemic and the future of the vaccinated? The short answer is, anyone who tells you they know what is going to happen, when things will end or what the future holds is lying. While there are definitely signs of what the future of Omicron and the pandemic (maybe turning endemic) hold, Nature does not listen to our whims and there are biologically and epidemiologically still several paths we could travel down. The following blog is a departure from many of my previous writings in that it’s mostly my opinions and thoughts on these topics, lots of hypothesis, many of which are far from proven, but are still none the less backed up by scientific evidence and general biological principles. Welcome to the inner wanderings of my mind…..

Omicron Spread and Vaccines:
I’ll start by diving into why is Omicron spreading so fast, how might it be different and what does it mean for the future of the vaccine programs. The Omicron variant was first detected in South Africa in November 2021 (though the variant could have originate elsewhere), and what made it so unusual and worrisome was it contained 53 (!) mutations from the original founder strain, an extremely high number for a coronavirus. Hypothesis are currently that this virus must have evolved on it’s own in a long term reservoir (either immunocompromised host or animal) separate from Beta or Delta because it doesn’t closely resemble those two variants, but these are just hypothesis at the moment. What makes Omicron so successful is that these mutations appear to allow it to more efficiently bind to and enter human cells of the upper airway. This combined with the evidence that several of the mutations also interfere with the binding of some antibodies created by the vaccines (and previous infections), mean that our barrier to preventing initial infection with Omicron are torn down a bit more, but our protection is not lost!
So while vaccine detractors will point to vaccinated people becoming infected (which is true), there is a lot of real world evidence coming out that if you received a Covid vaccine (booster even better) you’re MUCH less likely to suffer severe disease or be hospitalized, which after all is what worries us the most. Part of the reason for this is that even though your immune defenses can’t prevent the initial infection, there appears to be enough cross-reactivity between existing immunity and Omicron that the body gets a jump start on fighting the infection, and as such has a much easier time controlling the disease. I attribute my current case of Omicron being mild to these advantages (in addition to being young-ish and healthy). We also have the good fortune that Omicron appears to not cause as severe disease (on average) when compared to Delta. A current working hypothesis is that what makes Omicron more infectious, may also mean it doesn’t damage the pulmonary tissue as much. After all, a virus’s main goal is to replicate and spread, and a dead host is not useful for spreading a virus. Successful viruses infect a host efficiently, replicate quickly and allow that host to spread the virus to other hosts. This is exactly what Omicron appears to be doing, and what also brings us to the next topic, Endemicity.

Endemicity?
The hope has always been we get to a place through vaccination, medications and natural immunity where we can live in more of a steady state with SARS-CoV-2. What this would include is the virus being a normal part of life, circulating within the population, not causing massive outbreaks, overflowing hospitals, killing hundreds of thousands and infecting millions each month. Obviously we’re not there yet as we still see massive numbers of new infections each day, a lot of hospitalizations and far too many dying (as of 1/24, >1000/day US). But what people are starting to allow themselves to talk about with Omicron is the potential that with how fast Omicron is spreading and the more widespread availability of vaccines, that maybe moving from the current pandemic to SARS-CoV-2 being endemic is possible.

For this to happen, enough people would have to be immune and/or refractory to severe infection that the virus is no longer a concern for most people (or our hospital system). The current variant, being less severe (on average) and far less severe (on average) in vaccinated individuals does look like it could push us in that direction. The trouble with proclaiming the end of the pandemic pre-maturely is that no one can tell you for certain that as the virus infects hundreds of millions more people in it’s push to endemicity, it won’t mutate again to become more severe/deadly. While the idea that there aren’t direct biological evolutionary pressures pushing the virus to be more effective at killing the host…mutations can be random and don’t always follow that path. But if Omicron continues on it’s current path (BIG IF) and infects much of the population in the coming months then maybe the number of new infections in each outbreak will greatly dwindle, our hospitals won’t overflow with severely ill patients and maybe we can move forward with thinking of SARS-CoV-2 as just another cold virus…..just maybe.
Our work is still not done, hundreds of millions will still get infected in the coming months/year and many will die sadly. Our job right now is to arm ourselves with as many tools to fight the virus as possible (vaccinate the world, stay healthy, wear a mask to reduce exposure, keep researching new medications) and to protect those who are still at the highest risk of severe infection.

Eric is an Immunologist and Infectious Diseases Scientist based in Boulder, CO. The thoughts in this blog are his own and are by no means proclamations of certainty, but rather musings and hypothesizing.

Sciencing the shit outta stuff, that’s how we do it.

The COVID-19 Workplace

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This past weekend much of the State of Colorado moved from “Stay-at-Home” to “Safer-at-Home” restrictions. This is the first step to us opening up more businesses and moving slowly back towards a state of ‘new’ normal. As part of this a lot of people across the country are preparing to go back to work (or into an office/store) in some capacity in the coming weeks. Some people think this is all BS and a hoax, you can stop reading now, for those who are worried or uncertain exactly what this return to a ‘normal workplace’ might look like, I’ll try to outline a few best practices that my work has been using and also highlight what the State of Colorado has outlined for businesses that are reopening.

Governor Polis’s outlines what Safer-at-Home means for Colorado. Note that individual Counties may enact additional legislation beyond these basic measures. Here in Boulder County masks are required in public settings where you can not maintain 6ft of separation.

To start with for those that don’t know my background, I work in a vaccine and drug development laboratory. So my workplace will definitely look different than many of yours, but there are still many applicable practices that we’ve implemented that all types of work environments can utilize. Much of my experience in mitigating infectious hazards comes from years of working in Biosafety Level 3 facilities (with airborne, highly infectious, incurable pathogens). The stringent types of biosafety measures we implement in the lab aren’t applicable to daily life, except if you’re working in a healthcare setting in close contact with highly infectious patients (ping me separately if this is of interest to you). I’ll divide the topics up into three categories; general work place practices that should be implemented at the management level, engineering controls (equipment) and lastly how many of the common workplace practices can and should change to help you protect yourself during this uncertain time.

General Workplace Policy

While some people can work remotely from home (best practice), many of us require specialized equipment/facilities, customer interactions or other tools that are simply not available at home. If your work place is welcoming employees back into the office/store, the State of Colorado has set out several guidelines for how work place policy should be setup to protect the employees. First, spread out the hours people work; work from home, work shifts, segregate tasks people are working on to different areas, etc. Second, the employer should be providing ample cleaning supplies, hand sanitizer and soap. In our office we also have an employee tasked with daily cleaning of the common areas and commonly touched surfaces (door knobs, time clock, fridge, conference table, etc). In addition to this I clean my personal desk each morning, it only takes a few minutes, but alleviates any concern about contamination of my immediate workspace. Third, the wearing of masks should be made mandatory for all employees (and customers) when you’re interacting with anybody else (even in passing or in the bathrooms) or moving around the office. The reason this needs to be made a company wide policy is, otherwise it’s too easy for a portion of the population to not adhere, making the effectiveness of cloth/surgical masks far less on a company wide scale, everybody needs to protect everybody else. Additionally, signage reminding everybody about the policies on staying home if you’re sick, hand washing, cleaning of common areas and wearing of masks are helpful. Many of these measures are requirements of the State of Colorado for reopening a business, check with your individual state about their requirements.

Mandatory cleaning supplies near our front entry. All offices should have these available for employee use.
Masks, gloves and all the protective equipment. Despite what Trump recommends, injecting bleach and UV irradiating yourself are not a good idea. But these are good tools for cleaning equipment and surfaces (just not your body).

Engineering Controls

Engineering controls is a term used for physical barriers or equipment that is used to reduce the hazards of a workplace. In regards to COVID-19 in the workplace it’s referring to barriers and office setup that can help reduce interactions with coworkers and thus reduce the risk of someone getting sick. One method of limiting the workplace risk is to spread out employees desks/work spaces. Providing all employees with at least 6ft of space as to reduce the likelihood of infectious transmission. Another way is to setup barriers between employees desks/work spaces. This can be done by putting up plexiglass walls (or other materials) to block the direct line of transmission from one person to the next. So the open workspace system that so many tech companies love, is probably going to need to go away for the immediate future. Cubicles (or closed offices) actually provide a fairly safe way for each employee to have their own protected space, where infection risk is low, and you don’t have to wear a mask all the time. Work with your employer to establish these ‘safe zones’, because not only will it reduce the transmission risk, but it makes the employee far less anxious because they have their own personal space (at least in our office it works that way). For those of you working retail, store fronts or other customer based jobs, many of these rules won’t directly apply. My recommendation would be to establish a safe zone for yourself (back room, office, car, outside). Take breaks to get out of the mask for a few minutes (pretend like you’re a smoker) or just to step into the back room/warehouse for a few minutes to relax and breath. Plan and prepare for the long haul.

The dreaded cube farm, a great way for every employee to have their own protected safe space and to minimize COVID-19 transmission risk.

Common Workplace Practices

While the previous two sections mostly addressed changes that can/should be broadly implemented in the workplace, this section is going to address how the actions of individuals/groups should change. I have a feeling for many people this is going to be the hardest section to incorporate into our daily lives, but these changes are equally as important as those above. The first one is simply an extension of the general social distancing policy that pervades our lives, but applied to the workplace. No group lunches, standing around the coffee/espresso machine, office parties, etc (yes, sad face, I know). It doesn’t mean you can’t chat with coworkers or socialize, but it does mean it has to be done at a safe distance apart and while wearing your masks. If/when you need to use common office equipment (printers, coffee makers, fridge, cash register, etc) either make sure the equipment is well cleaned off or sanitizer/wash your hands afterwards as a precaution. This mitigation measure may be slightly less important for some workplaces, and more important for others (depending on how many people you’re sharing space with). On the far end of the spectrum are people whose jobs require direct contact with others (massage therapist, physical therapist, hair stylist, acupuncturist). For these professions it’s even more important to sanitize all surfaces after each client, wear masks (tough for hair salons), make sure both client and provider clean their hands before interacting, and of course pre-screen your clients to make sure they are not sick or symptomatic.

The last one is probably fairly obvious for many people, but meetings are going to look quite a bit different (if they happen at all). The easiest way to mitigate the risk is to do virtual meetings (Zoom, Skype, Teams, etc) whenever possible. Of course sometimes it’s much faster and more efficient to meet in person, which can definitely be done very safely. The smaller the better to start with, but as meetings grow, ensure there is at least one seat between everybody in the room, and everybody continues to wear their masks when in the same room.

Workplace meetings in the COVID-19 era. Join virtually, space out, masks for all those who attend in person.

Final Thoughts

My office/lab implemented most of these procedures the first week of Colorado’s Stay at Home order and shutdown. We have our own cubicles/workspaces that are our own private areas when we’re not working in the common lab spaces. We wear gloves (because it’s a lab) and masks whenever working in close proximity to others, common surfaces are regularly cleaned, our employees with COVID-19 risk factors spend much of their time working from home, or working off shifts, our meetings are done half virtual half in person (with masks). Using all these measures we’ve had no issues with viral transmission and also minimal issues slowing down our workflow. If you or your employer are hesitant to implement many of these actions, just look at the extreme cases of the meat packing plants all over the country. They stayed open but didn’t implement any infection risk mitigation (employees working in close quarters), and ended up suffering large outbreaks forcing their businesses to shutdown. So it’s really in everybody’s best interest to protect themselves and those around them, to stay healthy and keep the business running without the major setbacks that an outbreak would cause.

While company wide policy is up to the employer, you are your own strongest advocate. So it’s important to assess your work place (and how it operates) and how best to mitigate risks. If an employer isn’t providing you at least the minimum levels of protection outlined above, then speak with your local public health department, as they will come in and further assess what more can and should be done. Going back to work in and of itself isn’t a problem, it’s doing so in a responsible and controlled manner that allows your workplace to implement and test out these new policies. For all businesses there will be a trial period of adjustment to the new way of functioning, just be flexible and understand most of these changes really don’t dramatically affect our lives (and definitely don’t impinge our our civil liberties), we’re all going to get through this.

State of Colorado general Guidelines
State of Colorado Guidelines for Protecting Workers and Customers
Definition of Lab Biosafety Levels
CDC Guidelines for Businesses (far less specific than individual states)

COVID-19 and Masks, 4/5/20

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There’s been a lot of debate and misinformation floating around about the use of masks for the general public as a measure to prevent the spread of infectious diseases, specifically Covid-19 in the United States. Do they help, do they not? Is an N95 really better than a surgical mask, is this better than a cloth mask? How and when should they be used? On 4/3/20 the CDC in the United States finally came out with a blanket recommendation that ALL citizens of the United States wear some sort of face covering whenever in public. This was a dramatic change of direction from the previous recommendation that masks were completely unnecessary, except for front line hospital workers and for the infected. In this rendition of Eric’s Science Corner I’ll do my best to present some of the data and studies that have looked at the questions above, in an attempt to clarify the misunderstandings and the mixed messages. The topics I’ll try and cover are; what are the different types of masks and what are they designed to do? How useful are the different types of masks for the general public? And finally, a few best practices on how to wear and use a mask or face covering. Rule #1, just ignore anything Donald Trump says, now on with the info.

Defining Mask Types

To start there are three main categories of face masks that I’ll be discussing; fitted N95 respirators, professional grade surgical masks and cloth masks (variety of materials). There are numerous sub-categories for each and also other types of protective face wear I won’t discuss because they aren’t really relevant to the general population, only to those in the hospitals and those of us who work in laboratories. The first type is the fitted N95 respirator, these are face fitted respirator masks that have been certified to filter out approximately 95% of aerosols and particulate matter (when worn properly). You breath through either a small filtration unit in the front of the mask or directly through the filtering material of the mask, NOT around the sides (as it should be sealed). The professional grade surgical masks that many of us have seen in the hospitals are loose fitting non-sealed masks that are designed to block the wearer from inhaling large droplets/splashes and to block their respiratory emissions (protecting others around them). They are not designed to prevent the wearer from inhaling aerosolized particles as they are not sealed around the edges (cdc.gov, crosstex.com). The final group are the cloth masks which can be made from various materials. Their main purpose is to allow more comfortable widespread facial covering for the general public; to reduce the inhalation of larger droplets and to reduce one’s own exhalation and aerosol creation. These types of masks are not specifically certified in any way, though I will discuss the research that has been done looking at filtration, efficacy and utility of the different materials.

On the left is a standard N95 Respirator mask, on the right is a surgical mask.

So now on to how well do these different types filter out microparticles, specifically in regards to viral transmission (because that’s what’s on everyone’s mind). Numerous studies that compare N95s and surgical masks and how they prevent infection in hospital settings have shown both to be similarly effective when dealing with droplet based respiratory viruses like influenza (Randanovich 2016, Smith 2016). Laboratory testing of these two types of masks does confirm that the smaller the particle size, the better an N95 performs compared to a surgical mask (van der Sande 2008, Shakya 2016), thus they are more effective for those dealing with high level risk of aerosolized viral exposure. These two types of masks are certified, so it’s no surprise they perform fairly well, but what about the cloth and homemade masks? The first thing to consider is the type and thickness of material being use for the mask. Things that allow easy breathing or light to penetrate aren’t going to filter the air as efficiently, but if it’s too thick that you can’t breathe through it then it becomes extremely hot, uncomfortable and unwearable (and you breath around the sides, rather than through the material). One study comparing the filtration efficiency (of masks in a lab test, not on a person) of different materials found that items such as tea towels and cotton mixed fabrics did the best job of filtering particulate matter (up to 70% mean filtration) out of the air, while silk, scarves (like buffs), pillow cases and normal cotton T-shirts did not perform as well (45-60% mean filtration efficiency), with surgical masks being their standard (90-96% mean filtration)  (Davies 2013). When commercially available cloth masks were compared to surgical masks on humans (again in a lab) filtration efficiency was more variable; with cloth filtering out 30-50% of microparticles while surgical masks filtering out 60-90% of microparticles and N95s consistently filtering out 80-95% (Shakya 2016). The efficiency of filtration directly correlated to the size of the particle, with cloth masks performing the poorest on particles small than 1µm in size. So that’s a little background about how the masks are INTENDED to be used and how they function in a laboratory, how about in real life?

Use in the General Public

By now you’ve probably heard many times that the public should not hoard or use N95s because we need them for our frontline workers (very true) and they don’t work for the public (partially true). The first piece is that because of the size of this pandemic we don’t have sufficient supplies of N95s for highly trained hospital workers who are coming into direct contact with the virus on a daily basis, thus need this heightened level of protection, first (and most important) reason not to stock up or hoard them. The second is that for an N95 to be at it’s most useful and functional you have to have it fit tested, you need to be trained in proper techniques to don/doff a mask and you have to actually use it correctly (you can’t be taking it off to talk, to eat, to drink, basically you can’t break the seal unless in a clean contained environment). They are also designed to be disposable, meaning you can’t wash them, though sadly our healthcare workers are being forced into extreme measures to try and sterilize/reuse them for lack of options. For the general public a surgical mask would be a descent option because they are designed to reduce droplet transmissions and to block one’s exhalations (protecting those around you), but sadly our hospitals are also short on these too, so for now they need to be saved for the frontline works (and patients) where they’ll do the most good. Also remember that both of these are designed to be disposable, so can’t be washed and aren’t designed to be reused for weeks on end (like the public would need).

So this brings us to cloth masks and their use in the general public. Mistakenly the US government (CDC) originally came out saying that cloth masks don’t work and that they aren’t necessary. By now most people have realized this isn’t exactly true, because why else would they change their minds and recommend people wear them? Yes, cloth masks are NOT designed to stop all tiny viral particles (and aerosols) from passing through, and yes they are not highly efficacious, but that doesn’t mean they don’t help. While a cloth mask won’t fully stop one from inhaling aerosols and microparticles, they do filter out some of the smaller aerosols (30nm-1µm) but more importantly block larger droplet transmission both inward and outward (Davies 2013, Shakya 2016). So while they do filter some of the air you’re inhaling, the major benefit of a mask is to protect those around you by minimizing the amount of aerosols you create. This is especially true with the knowledge that those infected with COVID-19 can be asymptomatic but still capable of spreading the infection. For masks to be most beneficial we all should wear them in any public setting where we’ll be interacting with others (even if we’re socially distancing).

Best Practices for Masks

Now on to a few personal suggestions for best practices when using a face mask. Note that much of this stems from my own personal training having worked in Biosafety Level 3 laboratories (blood and aerosol transmitted infectious diseases) and in hospitals, but some additional guidance can be found on the CDC website (CDC.gov). First off, once you’ve made/acquired your mask, put it on at home and work on the fit, comfort, breathability. A mask that doesn’t stay on or that you can’t semi-comfortably wear (to the point you’ll touch it a lot or take it off) isn’t very useful. Look to make sure it fully covers your nose and mouth, has a pretty good fit around the bridge of your nose and the sides, and that it won’t slip down when you turn/move your head.

Once you’ve established it works, wear it around for 20-30min inside your house to get used to the idea of breathing through a mask. It’s probably going to be a bit awkward at first, as for most people they’ve never had to do it before. This exercise will make it easier to wear in public without thinking about it too much. Now on to that more critical step, wearing it out. The main times the mask should be worn is whenever you’re going into a public area where you might have close contact with others. If you’re just sitting in your car and driving around, no need to wear a mask, but if you go to the grocery store, pharmacy, liquor store, gas station, work, or even walk around your neighborhood it’s best to wear the mask to protect those around you, even if you don’t think you’re sick.

To put on the mask, do so BEFORE entering that public space, meaning your home entry if you’re walking around the neighborhood or inside your car before you walk into a shop. Then clean your hands off so that you are less likely to contaminate other surfaces (hand sanitizer or washing). When you’re wearing you mask you SHOULD NOT be taking it off or moving it off your nose/mouth until you’re back in your non-public safe area. Wearing it half the time, pulling it down half the time, taking a break to eat or drink in public negates some of the benefits and protection and also adds to the chance that anything you pickup on your hands will be transferred to your face. When you’ve exited the public space, wash/clean your hands then grab the strings/band of the mask and remove it (do not grab the front of the mask itself). If you have a washable reusable mask proceed to wash it with soap and water. Disposable masks are supposed to be discarded into the trash (hence why not ideal for daily use in public). While your mask is your barrier of protection, remember it’s not foolproof, and is merely a way to further reduce your risk of becoming infected and infecting others. IT DOES NOT change the fact we should be social distancing and providing each other space or that we should be staying at/near home and avoiding any unnecessary travel/errands. Wearing a mask is just another tool in our arsenal to help slow the spread of the virus and reduce transmission rates.

One last note about gloves. Wearing gloves for most people in a public setting is useless (yes I said useless). Gloves are a very effective piece of PPE for trained healthcare and lab workers, but in our daily lives most people treat gloves just like their normal hands. They touch common surfaces, pick up food items, open doors, text on their cell phone, touch their mask, etc. All of these practices together make the use of gloves just as bad as dirty naked hands. You’re better off just considering your hands as dirty whenever you’re in public and not touching any of your personal belongings (including that cell phone) until you’ve cleaned them. If you have to touch your phone or food items while in public, there are many ways to also clean these surfaces as well. Don’t waste gloves and don’t touch your face.

Citations
Balazy et al. Do N95s respirators provide 95% protection level against airborne viruses, and how adequate are surgical masks. American Journal of Infectious Control, 2006.
cdc.gov/hai/pdfs/ppe/ppeslides6-29-04.pdf . CDC Guidelines for Selection of PPE in Healthcare.
cdc.gov/niosh/npptl/pdfs/UnderstandDifferenceInfographic-508.pdf . Understanding the Differences, Surgical Masks, N95 Repsirators.
crosstex.com/sites/default/files/public/educational-resources/products-literature/guide20to20face20mask20selection20and20use20-202017.pdf . Guide to Face Mask Selection.
Davies et al. Testing the Efficacy of Homemade Masks: Would They Protect in an Influenza Pandemic. Disaster Medicine and Public Health Awareness, 2013.
osha.gov/Publications/osha3079.pdf . OSHA Respiratory Protection Guidelines.
Randanonvich et al. N95 Respirators vs Surgical Masks for Preventing Influenza amount Healthcare Personnel. JAMA, 2019.
Sande et al. Professional and Home-Made Face Masks Reduce Exposure to Respiratory Infections among the General Population. PLOS One, 2008.
Shakya et al. Evaluating the Efficacy of Facemasks in Reducing Particulate Matter Exposure. Journal of Exposure Science and Environmental Epidemiology, 2016.
Smith et al. Effectiveness of N95 Respirators vs Surgical Masks in protecting healthcare workers from acute respiratory infection: a systematic review and meta analysis. CMAJ, 2016.

Covid-19; Testing, Drugs, Vaccines and Seasonality 3/25/20

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It’s been a week since my first Covid-19 blog on 3/18/20, and I will have to admit how amazed I am at the feedback and attention it got. A LOT has happened since that day, and not all of it has not been so positive. Here in Colorado Governor Jared Polis officially announced today (3/25/20) that ALL residents of Colorado are under a ‘Stay at Home’ order. Meaning we’re supposed to stay in our place of residence with the exception of essential trips (medical, food, work for us exempt jobs) and exercise, all the while maintaining social distancing from anyone not in our immediate household (which is just me and my cat). For many of us this isn’t too much of a change, but for those who didn’t think this was serious it’s probably a bit of a rude awakening. Since my post LAST WEEK (now 3/26/20) the number of worldwide confirmed cases has more than doubled to 530,000 (from 219,243), the number of deaths has increased to over 24,000 (from 8,968) and on 3/26/20 the United States confirmed over 17,000 NEW cases, making us the country with the most confirmed cases in the world (go us?) (worldometers.com, washingtonpost.com).

I’m hoping by now that most people realize how serious this is, and that there is definite need to slow the spread; both to allow our medical care teams to keep up and to allow scientist to keep working (please no arguments on the political actions or economic impact, yes it’s going to be bad). My goal in this blog write up is to outline the things that help us bring this pandemic to an end (or at least slow it down). I’ll be focusing on the status of testing in the US (what those tests are), the current drug pipeline and what is being tested, the process and timeline for a vaccine and whether there’s anything to the claim of seasonality with the infection. So here we go, Round 2, diving back into the Science!

Testing

So in my last post I wrote about how much of a mess the Covid-19 testing and surveillance were in the United States, well sadly that has not improved a whole lot. While we’ve definitely tested a lot more people, I’ve been hearing from providers and hospitals all over the country that they’re only testing people who are in high risk populations or have advanced/severe cases of disease. Very recently a rash of new tests have become available to providers and hospitals, meaning the surveillance is starting to grow and hopefully this will continue. There is definitely hope as we are soon to have two different types of tests available, the PCR based tests that we’re currently using for diagnosing active disease and an Antibody based test.

The PCR based test is the one I spoke about previously where labs are able to look for pieces of the viral genome in human samples (usually a nasopharyngeal swab). This test can be quite sensitive and is used to identify infected patients even during the early stage of disease. Though, being such a sensitive test it is more prone to errors and false positives (though they are still very well validated), hence why the original CDC test failed. The other issue right now is that because there’s not a lot of top down coordination in the United States we have dozens of different labs who have created PCR based tests that are being used in different parts of the country. Here are a few of the companies/hospitals who have created PCR based tests; ThermoFisher, Roche, Cepheid, Mayo Clinic, Stanford University, University of Pittsburgh, Atrium Health and the list goes on and on. The CDC even setup a website to allow researchers to develop their own tests and to provide some general guidelines. While on the surface this seems smart, it also means we don’t have any national coordination in our Covid-19 testing on the ground.

The second type of test that is just now being release is a test to look for IgM and IgG antibodies in the blood of patients. You might remember in the previous post where I talked about us building immunity to the virus? Well, antibodies are one of the hallmarks of immunity, and we can test for them, even after we’re no longer infected. A simple prick of the finger (a little blood) on a indicator strip and we have a positive or negative for SARS-CoV-2 antibodies in minutes rather than hours or days, think of it like a pregnancy test for Coronavirus (United Biomedical, Aytu Bioscience). The problem with these tests is that SARS antibodies may not be detectable until 7-14 days after onset of symptoms (Chan et al 2005), so there’s a good chance they won’t identify people who are in the early stages of disease. They WILL help us dramatically as we attend to understand the true prevalence of the disease and how many people are now immune. Once a person is immune and recovered you’re very unlikely to pickup or spread the disease.

Drugs and Clinical Trials

Much to the chagrin of many of us in the biomedical research sciences and healthcare, Donald Trump touted hydroxychloronquine as a ‘game changer’….wow wow, let’s pump the breaks for a second, back it up, and talk about the process by which drugs are created, rigorously tested and finally produced for mass distribution (if they even make it there). The first step is identifying potential drugs and targets then testing them in a laboratory to see if they actually work like you hoped and they’re not excessively toxic. This usually involves some mix of cell culture and animals models. If a candidate is lucky enough to make it through the lab testing phase (known as pre-clinical trials, only 1 in 1000 do) then the company can apply to the FDA to move it’s drug on to a multi-stage Clinical trial in human subjects. Phase I of the clinical trials process involves taking healthy individuals and dosing them with the new drug (usually starting low and escalating). They have to look for safety, effects on the body, toxicity, side effects, maximum tolerate dose, tissue distribution, half-life and on and on. IF the drug makes it through this initial phase then it’s on to Phase II where the drug is tested in a medium size group of diseased individuals (in this case Covid-19 positive). All of this under careful supervision of doctors who are specially trained to assess dosing and efficacy. If the drug proves efficacious in this Phase II study it will move on to a larger Phase III randomized double blind study where the drug being tested is compared to a placebo control (sugar pill) to ensure that it’s really the drug having an effect. These large studies can include 1000s of people and take many years depending on the nature of the disease being tested. Finally, once a drug survives Phase III; proving safe, efficacious and with the dosing amount and regimen worked out, the company can file for approval from the FDA (1 in 5000 make it this far)(medicine.net). This whole process can take up to 12 years for chronic diseases, but of course right now things are moving much more rapidly, and a lot of the regulations and paperwork are being modified to speed up the process.

So what about all the drugs that are being tested against Covid-19 right now? There are several drugs that were identified as being potential therapeutics, and thankfully they had already passed Pre-clinical testing and Phase I trials, so this dramatically expedites the process of testing. The most promising seem to be Remdesivir (from Gilead), Favipiravir (anti-viral), and the previously mentioned hydroxychloroquine (cdc.gov, Dong et al, Wang et al). Even though all of these drugs have successfully completed varying levels of clinical trials, using them against a new disease requires a new round of efficacy, dosing and safety testing. Patients with different diseases respond to drugs differently, dosing needs to be adjusted for the new disease and of course the drug needs to be thoroughly tested to ensure that the differences seen in early studies weren’t simply because of patient selection, population bias or other factors that were not controlled for with the small sample set. In short, all these drugs, while promising, are many months away from being approved for safe use in a wide array of Covid-19 patients, if they get there at all. See the comment below from my college friend Aileen, who’s a pharmacist in the San Francisco Bay Area in response to the small test of hydroxychloroquine in patients in France (Gautret et al)….


More PSA from a pharmacist….to detail out certain claims Hydroxychloroquine used in this case is in particular HIGH DOSE (usual dose of the drug is 200-400mg daily, in this case…600mg daily and we only use that dose in Q Fever patients). When the hydroxychloroquine in high dose and azithromycin are taken together, there are risks for GI side effects…and most importantly…POTENTIAL ARRHYTHMIA. First azithromycin is a known QT prolonging agent…but also…hydroxychloroquine can either cause direct mycocardial toxicity or exacerbate underlying mycocardial dysfunction. This is a RISK that must be weighed by physicians and healthcare professionals vs. the unproven benefits.
Is there promise? potentially….but we NEED MORE EVIDENCE TO EVALUATE SAFETY AND EFFICACY.
Please…do not demand for it….leave it to healthcare professionals to make that decision and do our jobs….

The next question is in regards to a vaccine against Covid-19. Unfortunately, the process I outlines above for drugs, also applies to vaccines, but we’re starting from ground zero. Prior to this pandemic there were no coronavirus vaccines available (though plenty of background research), so companies have gone into serious overdrive trying to develop something, and amazingly in just two months Moderna, in collaboration with the NIH, took the first vaccine candidate to Phase I clinical trials this month (March 2020) (nih.gov). A process that usually takes 6-12 months took them 2, let that sink in for a moment. And they’re not the only company working hard on creating a vaccine, as there are numerous others with vaccine designs being tested in Pre-Clinical trials as we speak. But, this bring us back to question of time. Before a vaccine can be deployed to the general public it has many hurdles to pass, and only if it successfully passes those hurdles can it be mass produced and distributed. So, as Dr Fauci has explained many times, we’re looking at best case 12-18months for a vaccine. Guess we’re going to have to hang tight and weather this storm for a bit longer.

Seasonality

Most people have probably heard the claim at one point or another that this thing (Covid-19) is like the flu and it’ll go away when the weather warms up. Even our President claimed “…you know, a lot of people think that (the virus) goes away in April with the heat — as the heat comes in. Typically, that will go away in April.” Is there any logic or scientific evidence to support this claim? The short answer is, no, but it’s definitely more complicated than that.

The idea of seasonality was brought up because the influenza virus does see a very seasonal pattern of spread and retraction. During the cooler winter months in the Northern Hemisphere we see a dramatic rise in influenza infection rates, then a drop as the weather warms in April, as Trump suggested. There are many reasons for this; reduced contact time between people (stuck inside, schools) as weather improves, improvements in immune responses due to people being outside more and increases in Vitamin D, potential increase in duration of infection during winter months, and decreased survival of some pathogens in warmer environments (Fisman et al). While we do have the first three things going for us as they are environmental changes that aren’t pathogen specific, what about the survival time of different viruses? It’s been well documented that influenza viruses survive and transmit best at lower environmental temperatures in the range of 5C and 20C. Though starting at 20C, depending on humidity, influenza virus transmission becomes much more variable, and at 30C a dramatic decrease is seen in viral transmission (Lowen et al). Unfortunately, coronaviruses don’t seem to have the same susceptibility profile. Testing on the original SARS-CoV-1 virus showed that it was fairly stable at environmental temperatures as high as 33C (91F), and only when temperature was increase to 38C (100F) did the virus infectivity begin to dramatically drop (Chan et al 2010). SARS-CoV-2, the causative agent of Covid-19 seems to be more temperature resistant than the influenza viruses that we commonly associate with having seasonal cycles. So with the virus currently spreading in the Southern Hemisphere and in several warm weather countries we shouldn’t expect too much help with the virus from Mother Nature’s change of seasons.

But not all hope is lost! I’ve heard recently that the extreme measures taken by many states have allowed the hospitals in the US a little breathing room. Even if this is short lived it means that staff and supplies can be replenished and that buys more time for widespread testing to come on line. Countries like Germany and South Korea are good case studies for how excellent testing and surveillance can lead to minimizing the number of fatalities (testing large percentages of their populations, and doing so quickly). Even though cases and number of deaths are still increasing, we’re slowly catching up on testing, and keeping our death rate low, but the fact that we have 2,122 serious or critical Covid-19 cases is still a little scary. For now, we’re all going to have to sacrifice a bit, be more compassionate to our fellow humans and just realize that we’re living through unprecedented times, that we will get through, though it’s going to take some time. If you’re interested in reading about some potential scenarios on how the pandemic plays out in the next 3-12months this article from the Atlantic outlines them pretty well in my opinion.

Citations
aytubio.com/covid-19/
cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html
Chan et al. The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus. Advances in Virology, 2011.
Chan et al. Serological response in patients with Severe Acute Respiratory Syndrome Coronavirus infection and Cross-Reactivity with Human Coronavirus 229E, OC43, and NL63. Clinical and Diagnostic Laboratory Immunology, 2005.
Dong et al. Discovering Drugs to treat Coronavirus disease 2019 (Covid-19). Drug Discoveries and Therapeutics, 2020.
Fisman et al. Seasonality of Viral Infections: mechanisms and unknown. European Society of Clinical Microbiology and Infectious Diseases, 2012.
Gautret et al. Hydroxychloroquine and azithromycin as a treatment for Covid-19: results of an open-label non-randomized clinical trial. Journal of Antimicrobial Agents, 2020.
Lowen et al. Roles of Humidity and Temperature in Shaping Influenza Seasonality. Journal of Virology, 2014.
nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins
unitedbiomedical.com/COVID-19/
Vincent et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virology Journal, 2005.
Wang et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCov) in vitro. Cell Research, 2020.
washingtonpost.com/world/2020/03/24/coronavirus-latest-news/
worldometers.info/coronavirus/