Author Archives: Eric

About Eric

Immunologist and Infectious Diseases Research Scientist by day, ultra runner and mountain adventurer in my spare time. Blogging about whatever comes up in life.

2022 Hardrock 100; Acceptance

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The best crew and some of the best humans around.

Going into the 2022 Hardrock 100 I had grand aspirations and goals (which included a sub-30h finish). The quick answer is things went about as well as it could have, but not as well a I dreamed it would. I’ve always set big goals for myself, many of them born out of insufficiency and insecurities from past lives; You’re too slow, you’re not strong enough, you’re too short, too awkward, not smart enough…
Every person who steps foot on the line at Hardrock has dealt with their own challenges to get there and most likely still carries some of those challenges through the race and life in general. To claim we are all equal is a lie, we all are unique and none of us will ever have the same experience and that’s perfectly ok. Something I’ve struggled with for a long time is the idea that if I worked hard enough I could achieve some of the lofty aspirations, maybe not Killian level, but pretty high. 16 years after I started ultrarunning, I’m finally accepting that’s just not the case. To be clear, I’m not looking for a pity party, but rather through a recognition of my own weaknesses (and also my strengths), I can become the best version of that self and achieve whatever my personal limits may be.

Pre-race nervous shakeout and relaxation up at Hematite Lake with Jason.

Ok, back to Hardrock. Last year (2021) I went into the race determined to push hard and really find my potential, and a new level of success (time and place). What ended up happening was out running my capabilities early and suffering through the last 1/3 of the experience. 2022 brought a much different approach, listen to my body, be grateful for every experience (good and bad) and to enjoy a much as possible. In the past what’s done me in is running to others expectations, trying to keep up with others (not myself) and not fully listening to my body. The biggest challenge was admitting that my airways and lungs are my weak point and will always limit what I can do, especially at high altitude. This is not new (Nolans, past Hardrocks, 24h 14ers, Elks and others), but it’s been a hard thing to admit that it’s not something I can train past or “overcome”. I’ve found ways to cope and build other strengths; getting faster downhill, increasing overall fitness, running longer and slower, but none of these will ever remove this weak link of mine.

Cresting the Putnam Divide early in the race, mm10.

The infamous Island Lake near Grant Swamp Pass, always a worthwhile visit.

I slept terribly the week before the race (another temporary challenge) and work stresses had me a bit out of sorts, not the best way to start a super hard 100mi race. But I was promised to spend a long weekend running around some is the most beautiful mountains, with a crew of great friends, I was lucky indeed. The first climb went by smoothly, as I focused on just taking in as much of the experience as possible, soon finding myself in the familiar position of leap-frogging with Darcy. Maggie soon caught up to us not too much later and the three of us would spend the next 30miles leap frogging back and forth (them on the ups, me on the downs). Every time I rolled through an Aid Station the friendly faces would provide a boost, finally getting to see my crew in Telluride (mm28). The stoke was high, I was still feeling great and just doing my own thing. As we (Darcy, Maggie and I) left Telluride a big storm dropped in and pummeled us with rain and hail for 45min, but it was fine, we were below treeline and safe, just moist. The ominous skies still threatened as we approached Kroger’s Canteen. A couple of perogies, some coke and off down to Ouray I went. I was finding my own rhythm, playing to my strengths, listening to my body and just letting the miles roll by. Ouray was a wild circus full of energy. Tons of friends, spectators and confused tourist everywhere. For the first time at Hardrock I left an Aid Station without a pacer, focusing just on myself and the mountain experience I was seeking. Darkness fell as I led a group of us up and over Engineer Pass and down into Animas Forks. The aid station was a bit of a mess and I almost ran right by my crew without either of us realizing it. After a quick change into my nighttime gear, Jason and I were off to Handies, my white whale.

Nearing the summit of Virginius Pass, just after one thunderstorm had passed over, right before another one was about to hit.

Crew stop and refeul in Ouray before heading up to Engineer Pass.

As we headed up the Grouse saddle the work stress and lack of sleep were catching up with me and I’d spend the next 5h a walking zombie. My lungs strained in the cold air and I knew if I didn’t slow I was at risk of damaging the rest of my race, so upwards we crawled. After much bitching and moaning on my part (Jason was great) we made it to Burroughs AS where Jesus greeted us with open arms (no I want hallucinating yet). I kept trudging forward at what felt like a slow crawl, picked up Gwen at Sherman, then slowly staggered my sleepy way to sunrise at the pole creek divide. As the sun illuminated the surrounding mountains, my spirits began to lift. Gwen commented that she knew I was back when I made some very juvenile comment that only a 12yo would make, oops. So we ran (some) and walked (a bunch), enjoying what was a mostly lovely day. I probably groaned a bit when we hit the precipitous descent into Cunningham, but that meant only 1 AS left! I did my best to keep things fun at our last crew exchange, but I was just a wee bit tired, so who knows how well that came off. Bailee and I set off at a slow trudge up Dives/Little Giant, trying to keep my breathing in check (and not set off my asthma), but also wanting to get done. As we crested the top, I took one last look back at Green Mt and finally let myself believe I was going to get it done.

Full moon rising as Jason and I make our way over Handies Peak at 14000ft.

Down into Maggie we go, endless wildflowers all around and Day 2 sunshine.

Still kinda smiling and kinda having fun, final climb up and over Dives/Little Giant, almost done!

Whatever pain and fatigue I felt didn’t matter, all I had to do was will my way downhill to the finish. We ran as fast as I could down the technical descent, taking a few walk breaks to catch my breath. We stomped through the river and hit the final few miles into town, running into Jefferson along the way. I ran as hard as my lungs would allow, but with two miles to go I was sent into a coughing fit, diaphragm spasms and promptly threw up. This was the first time that’s ever happened during a race. Once I stopped coughing I felt fine, so we jogged it in. As we cruised through town we were greeted by many familiar faces, including my crew. It felt really good to kiss the rock for the 3rd time, but it felt even better to be in good spirits (despite puking) and to have enjoyed the experience (for the most part).

The rest of the day was spent on a quick nap, cheering on the multitude of friends finishing that afternoon/evening and eating all the food I could find (burrito, 2x burgers, cookies, soup, etc). My training had succeeded, my legs held up (my legs are never my limiting factor at elevation), and other than my 5h sleepy stretch so had my energy levels. I’ve learned that no matter how hard I train, at Hardrock I can’t outrun my lungs, so sub-30h may never be in the cards for me, and I’m ok with that. I had a great run with my good friends, and that is really what I wanted most out of the experience. Sure it would be awesome to run faster, but after 34:38, 33:52 and 33:10 finishes I’ve accepted this is who I am. On to other new adventures, different races and to enjoy crewing my friends at Hardrock in future years, where I get to eat all the food, take a few naps and not run 100miles of that crazy course all at once.
Big thanks to Vfuel for supporting my training and my Hardrock adventure, all the Rocky Mountain Runners for the training miles shared and my friends and crew for dragging my sometimes grumpy ass around the San Juans yet again.

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.

Canyonlands Island in the Sky Ultra, 1/2/21

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Sunrise from the Island in the Sky in Canyonlands, 1/2/21.

Better late than never? It’s been a whirlwind of a year and 8 months later I’m finally catching up on my early year projects. Winter motivation is often a hard thing to inspire, but the desert has definitely been my oasis in this department. Adler, Owen and I headed to Utah for New Years. After a couple of cold days in Central Utah exploring Capitol Reef (the next blog to come!) we made our way back to Moab for the next installment of the National Park Ultra series, Canyonlands Island in the Sky.

Canyonlands is divided into three distinct districts by the Colorado and Green Rivers; Island in the Sky to the North, Needles to the SE and The Maze to the SW. When I started my project to run an ultra in every National Park I decided that some parks just require more than one run, because one really can’t experience each unique landscape without dividing them up, and Canyonlands is a prime example. The Needles consists of a desertscape chopped up by giant rock fins and slickrock canyons, The Maze is just that, a maze of narrow slots and deep chasms that carve up the landscape while The Island in the Sky consists of a high plateau guarded on all sides by imposing walls, dropping thousands of feet down to the rivers below. All three can seem impenetrable at first glance, but improbable breaks in the canyons allow one to move across the complex landscape.

Adler cruising around the White Rim Rd in Canyonlands, 1/2/21.

The most well known feature of the Island in the Sky district is the White Rim Road, this 71mile road follows the White Rim sandstone formation as it circles the Island in the Sky, 1500ft below the plateau and 1000ft above the Green and Colorado Rivers. I started my morning at the Murphy Hogback trailhead at sunrise jogging the paved road North as it traversed it’s way through the park. I passed the jam packed Mesa Arch TH and onward to the Lathrop TH where I met Adler and Owen (7mi in).

Descending down the Lathrop Trail into the depths of Canyonlands.

From there we began our descent down one of the improbable trails that switchbacked down the cliff bands into the depths of Canyonlands, 1500ft below. Across this ledge, down this seam, over this talus rock fall and finally down the rim of a small slot to the White Rim. The cool winter air was delightful to run in and we had this region of the park all to ourselves. We hit the White Rim Rd (mm13), bid Owen farewell (as he headed back up to the car), and took off CW on our journey. The White Rim is mostly very cruisy jeep road, trapped between the towering Chinle/Wingate/Navajo sandstone walls above and the Cedar Mesa sandstone below. When you run/ride/drive the road you truly get a sense of the immensity that is Canyonlands, and the isolation that one can find in it’s depths. We continued on the road past the Airport Tower, Washer Woman tower and several immense canyons to our left that dropped to the Colorado River, still miles away. At mm24 we intersected the Gooseberry trail, our only easy bail exit (ie trail) from the canyon. We were still feeling great so forged onward with the long looping traverse around Grand View Point at the head of the Island in the Sky.

A dusting of snow coats Canyonlands, Adler and Owen lead the way.

A few snack breaks, one floss break above Monument Basin and lots of photo-ops later we finally turned the corner and began to head back North towards Murphy Wash (mm35). The miles were starting to wear on both Adler and I, so we settled into a mixture of fast hiking and jogging, finally reaching our turn back up to the Rim. This run is what I describe as a ‘Pay Later’ run, as with only 5miles to go we had a long sandy wash and 1400ft to climb back to our finish line. The sand felt like cement to our tired legs, but when we finally reached the steep cliff-bands that marked our final ascent back to the rim the hiking actually felt really good after all the flat runnable miles. As we climbed our way up through the different layers of sandstone the views started to expand and the late afternoon light lit up the walls with a reddish/orange glow. We hit the top of the climb right as the sun started it’s descent below the horizon, what a way to end an amazing day in the canyons.

Looking down from the White Rim towards the Colorado River far far below.

25mi of White Rim Rd done, back up the Murphy Trail we go!

After a quick high five we booked it back to town to eat every single thing we could get our hands on (9h12min and 43.69mi of running makes one hungry!). On the surface the desert may not have the diversity or grandeur of the mountains, but look a little closer and she just might reveal her secrets to you. The Island in the Sky district is a wonderful example of the diversity of Canyonlands; juniper forest on the high plateau, massive sandstone cliffs, arid slicrkrock and two rivers that create an impassable oasis far below. So many sections of this park are nearly inaccessible to all but the most dedicated, and that’s what makes it so special, you earn what you get, and nothing is easily given up. Huge thanks to Adler and Owen for sharing this adventure with me, Vfuel for powering me through yet another 9h unsupported adventure and to being healthy enough to challenge the body in such spectacular ways. Strava Track.

Hiking the way up the Murphy Trail back to the top!

Sunset from Island in the Sky looking towards the Lasals. Winter in the desert is beautiful.

Life in the Vaccine World, 4/26/21

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Well, it’s now been over a year since the US went into it’s first set of shelter in place/stay at home orders at the beginning of the Covid-19 Pandemic. And while there is hope moving forward, there is still a lot of unknown and I’ve received a lot of questions about what this new ‘reality’ means. Specifically about what it means to be vaccinated both now and in the future and what risk does the virus and vaccine pose to those who are still unvaccinated? Note that unlike some of my previous posts this one will contain a lot of opinion and speculation, as it’s dealing with unknown topics. I will try to be clear of when I’m giving my thoughts vs providing evidence from research and data as always, and if you disagree that’s perfectly fine (All I ask is you use evidence to support your claims).

First off, the discussion about the vaccines. Currently in the US there are three vaccines that have been given Emergency Use Authorization, meaning they have been approved for distribution in a regulated manner, pending constant review of safety and efficacy data. As with all medicines, if any issues or uncertainty arise the FDA has the authority to modify their status and reassess the situation. So far the Moderna and Pfizer vaccines have had no major issues with vaccination (that have warranted a pause), just the usual side effects that recipients experience (sore arm, fatigue, headaches, fever, etc). For the Johnson and Johnson and AstraZeneca (not given EUA) adenovirus vaccines this is a different story. As of this writing on 4/23/21 both of these vaccines are being investigated for rare adverse event blood clots (US FDA, see link below). These rare blood clots have occurred both in the US and Europe and at the time of this writing one hypothesis is, in rare cases autoantibodies are created causing platelet aggregation and a medical issue known as Cerebral venous sinus thrombosis. The Johnson and Johnson vaccine has been released from it’s temporary hold in the US (as of 4/23/21), after a thorough review of the cases and data by the FDA and CDC, and is again being distributed. This is sign of the system working, when ANY issue arose the vaccine was paused and investigated, the risk was found to be extremely low and medical providers have been notified how to identify and treat the rare cases of clotting (Yale Medicine 2021). Note that the rare cases of blood clots in the US have occurred in 8 out of nearly 6.8million J&J vaccinated people in the US (I received my J&J on 3/22), making them very very rare (0.00012% of those receiving the vaccine). In fact, the frequency of these cases of vaccine induced blood clots is approximately 10x lower than occurs with natural Covid-19 disease (Taquet et al 2021) and is also a rare adverse event for many other widely utilized medications (like contraceptives, Aleve, Ibuprofen and Viagra), meaning while it’s something to be aware of, it’s not unusual for medicines. So while the vaccine is far safer and less risky than natural Covid-19 disease, for women between the ages of 16-50yo (primary affected group) it’s something to consider and one may opt to receive the Pfizer or Moderna vaccinations instead while these events are being further reviewed and understood. An additional note, that while the blood clots can be life threatening, if the signs/symptoms are identified they are treatable, so if you receive the J&J vaccine keep an eye out for severe headaches, severe abdominal pain, shortness of breath within 6-14days of your vaccination.

With that out of the way, I now wanted to dive into the topic of “I’m vaccinated, now what does that mean for our lives?” From an efficacy standpoint, once you are two weeks out from receiving your vaccination(s) you are much less likely to become infected, but this does not mean it’s impossible. The CDC recently released the first set of data discussing the breakthrough cases, these are cases of Covid-19 in previously vaccinated individuals. The case count as of 4/20/21 was 7,157 individuals over the 4months of vaccination (over 100million people vaccinated) with 498(7%) cases of hospitalization and 88(1%) deaths (CDC Stats). While this is unfortunate, it was NOT unexpected as the vaccines were shown to be 70-95% effective at REDUCING infection in the clinical trials, meaning sadly not everyone is fully immune from potential infections. This is due to insufficient immune building or receiving a viral inoculum that overwhelms the immune system (happy to answer direct PMs about this complicated topic). The good thing is, 7,157 breakthrough cases in the US is actually a fairly small number when you consider that in the month of April >1.2million new people have become infected already and >14,000 people died this month (CDC Covid Data Tracker), so again, the vaccinate have a GREATLY reduces the chance of becoming infected.

Now on to a much more complicated topic, what a vaccine means for our daily lives, interactions and opening up society. First off, a lot of this decision will be based on an individuals risk tolerance and personal decision making, as such I’m going to do my best to refrain from telling you what you should or shouldn’t do, and instead provide each individual things to consider while they go through their daily lives. I’ll first go into what it means to be vaccinated, then speculate on how some of the new mutations might affect the future.

As discussed above, once you are fully vaccinated your risk of becoming infected dramatically drops. Meaning, you are far less likely to both carry the virus and to become infected (CDC MMWR 4/2/21). The converse of this is there is a small possibility that a vaccinated individual becomes infected (especially from an unvaccinated person) and can spread the virus. Now this doesn’t mean you have to keep yourself shut inside forever, but it does mean there is still a low level of risk out there. Situations that would pose the highest risk are any that put you in contact with large numbers of people, indoors in close proximity (yes bars and restaurants), unmasked for extended durations. Thus there are plenty of things that create much less risk in your life but still allow you to connect with others and socialize. Just consider who and how long you’re interacting with people, hopefully from known social circles. So just remember, each person you interact with and are in close contact with, whether you know them or not, becomes part of your social circle, and connects to others in your social circle (think of a giant spiderweb). Based on my personal risk tolerance I won’t be going to any bars, clubs, indoor concerts and will be minimizing indoor restaurant dining for now.

As of this writing the strains discovered in Italy 2020 and UK 2020 are the predominant strains circulating in the US, but there are newer strains discovered in South Africa, Brazil and India containing mutations that reduce the vaccines effectiveness (note they DO NOT render vaccines ineffective). Even with that, the vaccines appear to reduce severity and symptoms of the new viral strains, thus offering some protection. No one can predict the exact future, but here are a few things to watch for as the pandemic moves forward. While the virus still spreads at an uncontrolled rate worldwide, mutations will continue to accumulate, many unproductive, though some will lead to changes that are beneficial for the virus. As such I expect there to be a new vaccine booster shot that becomes available in 2021/2022 to address some of these changes, scientist from Moderna are already testing one of these (NIH 2021). So while it is fantastic news that the US is nearing half the population having received at least 1 shot, until we can vaccinate a large proportion of the world this virus will continue to spread and mutate. Locally, vaccines will dramatically slow the spread, reduce the hospital burden and save tens of thousands (or maybe hundreds of thousands) of lives but vaccinating the US alone won’t bring things fully back to normal. Since SARS-CoV-2 has a proof-reading enzyme the virus doesn’t mutate as fast as others (thankfully), so once the viral spread no longer becomes globally uncontrolled the mutations will slow and eventually cease. Again, this is just a hypothesis, but is one of the long-term goals of the global pandemic response. Combined with the potential of discovering additional live saving therapeutics, these are the tools that will help us move into a healthier future. Again, this last paragraph is all speculation and there are innumerable factors that could easily swing us off this trajectory or dramatically change the course of the pandemic response. No one knows the future, all we can do as Scientists and society as a whole is be aware of the most likely future directions and plan as best we can to deal with those challenges.

References:
CDC Stats. COVID-19 Breakthrough Case Investigations and Reporting. 4/20/21. https://www.cdc.gov/vaccines/covid-19/health-departments/breakthrough-cases.html
CDC Covid Data Tracker. 4/23/21. https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases
CDC MMWR 4/2/21. Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers. CDC MMWR 4/2/21. 70(13):495-500.
FDA. FDA and CDC Lift Recommended Pause on Johnson & Johnson (Janssen) COVID-19 Vaccine Use Following Thorough Safety Review. https://www.fda.gov/news-events/press-announcements/fda-and-cdc-lift-recommended-pause-johnson-johnson-janssen-covid-19-vaccine-use-following-thorough
NIH. NIH clinical trial evaluating Moderna COVID-19 variant vaccine begins. 3/31/21, https://www.nih.gov/news-events/news-releases/nih-clinical-trial-evaluating-moderna-covid-19-variant-vaccine-begins’
Taquet M et al. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine. Oxford University, 2021.
Yale Medicine. The Johnson & Johnson Vaccine and Blood Clots: What You Need to Know. 4/23/21. https://www.yalemedicine.org/news/the-covid-vaccine-blood-clots

Catching Up with Covid, 11/12/20

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Topics:
Vaccines
Therapeutics
Reinfection and Immunity
Children and Schools
Looking Forward

Well, a lot has happened since I last wrote a Covid related piece, and a lot of important things have come to light very recently. In the past six months those of us in the United States have endured several waves of outbreak, and currently as of this writing we’re in the middle of the worst outbreak since the initial outbreak in April/May (Nov 11^th, 2020; 144,000 New Cases, 65,000 hospitalized patients and 1400 New Deaths, John’s Hopkins data). There are many possible reasons for this proliferation in infections, but it’s not specific to a political party, demographic or portion of the country. Rather than argue about that, I’ll simply say, it doesn’t seem like people are acting responsibly and we’re going to pay the price, as death rates always lag a few weeks behind infections.

In the following paragraphs I’ll outline a lot of what has happened with the development of the SARS-CoV-2 Vaccines (including immunity, data, side effects, and timelines), what we’ve learned about the virus and how we’re treating it with new therapeutics, what the data tells us about how safe schools are and lastly some additional important notes about transmission. Note that this write-up is based on the information known as of 11/11/20, and I’m sure in the weeks following a lot of new information will come out. So let’s dive right in to the topic on almost everybody’s mind….are the vaccines going to work, when will they be approved and how long before ‘I’ can be vaccinated?

SARS-CoV-2 Vaccine Development and Trials:

The big headline on 11/9/20 was that interim data on the Pfizer/BioNTech’s vaccine “BNT162b2” shows 90% efficacy in preventing SARS-CoV-2 infection. Before we jump to too many conclusions, let’s take a step back and talk about how we got where we are and what we know. Since the release of the first genetic sequences of SARS-CoV-2 way back in January 2020 (10 months ago!) the scientific community has been working at a feverish pace to learn everything we possibly can about the novel coronavirus, turning out a mountain of research that would normally take a decade, in just a year’s time. A search for scientific articles containing “Covid” on pubmed.ncbi.nlm.nih.gov/ returns 68,494 hits! On top of this, many of the biggest Biotech companies in the world have dedicated huge proportions of their of their staff (often working lots of overtime) to the single task of solving this public health crisis, so believe me when I say this has been a truly unprecedented time for Science.

Vaccines against SARS-CoV-2 have progressed along timelines never seen before, partially because of this massive effort by the scientific community to execute multiple steps in the pipeline simultaneously, building off previous research on SARS-CoV and utilizing advances in vaccine development discovered in recent years. But questions remain, will the vaccine work, what kind of immunity is possible against SARS-CoV-2 and how long will it last? A lot of research has focused on assessing two major pieces of the human memory immune response to viruses; Bcells/Antibodies and Tcells. Most people have heard of antibodies (and the Bcells that produce them), and while most of the literature has shown that moderate to severe cases of Covid-19 lead to strong neutralizing antibody responses (Long April 2020), the durability (how long they last) is still open for debate and seems to depend on the severity of the disease experienced (Long June 2020). Thankfully the other arm of the memory immune response (CD4+ and CD8+ Tcells) seems to be far more robust and durable, and many studies have shown strong levels of anti-viral activity in a wide array of Covid-19 patients, even those who become seronegative (negative for antibodies) (Sekine June 2020, Le Bert July 2020, Grifoni June 2020). So this brings us back to vaccines, and a growing mountain of evidence that a well designed vaccine that leads to a robust immune response can subsequently lead to immunity against Covid-19.

There are currently 10 vaccines in Phase 3 clinical trials (raps.org), this is the final Phase of testing in which a large number of patients are vaccinated with the aim of looking at how effective the test vaccine is at preventing SARS-CoV-2 infection compared to a placebo control. Each trial is set to vaccinate upwards of 60,000 of people and won’t close down until a certain number of people become infected (doesn’t matter if they’re placebo or test vaccine). The threshold for the Pfizer trial is set at 164 infections, and the trial currently sits at 94 positive Covid cases, meaning they’re targeting another 70 positive Covid infections in the study before they close down and analyze all the data (though this could happen sooner). Early data from Phase 1&2 Trials of the successful vaccine candidates have shown a strong and consistent induction of the immune system, with SARS-CoV-2 specific antibody titers and SARS-CoV-2 reactive CD4+ Tcell levels being as high or better than those found in patients who have recovered from natural Covid-19 disease (Folegatti July 2020, Anderson Sept 2020, Sahin Sept 2020, Walsh Oct 2020). While the long term efficacy (>1year) of these responses is not known at this time, these trials are set to follow patients out for 2 years post-vaccination, and so far early returns (3-4months post-vaccination) are all promising that the vaccines create durable responses that will last for at least some time (TBD).

So we might have an approved vaccine before the end of the year (maybe even several), what next? Well thankfully for the general public many of these companies have already started building production capacity and scaling up production, banking on a successful Phase 3 trial (a big gamble). This means that if/when their vaccine is approved they are ready to start shipping vials almost immediately. Both the Pfizer/BioNTech and Moderna vaccines are mRNA vaccines, a relatively new technology that is MUCH faster to produce than traditional protein based vaccines. Problem is, there are some 7.5billion people to vaccinate, and initial estimates from Pfizer are to have enough vaccine for 50million doses (25million people) this year, that’s not a lot when distributed around the world. The WHO has a plan to evenly distribute the vaccine across all countries, but it remains to be seen if wealthier nations allow this to happen (WHO.INT/). Here in the US a team led by the Army have already worked out a supply chain and distribution plan to the different states, and then it’s up to each state to create a prioritization plan on who gets vaccinated first. Here in Colorado a rough draft of this plan has already been submitted to the CDC for approval, check this link for the full draft.
Skip to page 22-23 if you want to see the tiered priority list of who will be vaccinated first. In short the higher risk professions and people will be given first priority, even then estimates are that Colorado will receive 100,000 doses in the first shipment, enough to vaccinate 50,000 people, only a portion of those in Tier 1A. For those of you in the healthy general public, expect to wait until next Spring/Summer to get vaccinated (these timelines are still very fuzzy).

So whenever your turn comes up, there is a big question of what to expect from this vaccine. First off, there might be several choices available, and it remains to be seen if they all have similar efficacy and longevity. Second, there are different kinds of vaccines (mRNA, whole inactivated, subunit vaccines, hybrid vectors, etc) (Krammer Sept 2020). We don’t yet know how they stack up against each other, so I won’t elaborate any more at this time on them, but welcome questions about the different types if anybody has them. None of these vaccines are using live replication competent virus, so they do NOT cause infection. Two things to note about the vaccines in full disclosure, it’s not going to be as convenient or as comfortable as other vaccines we’re given in a more routine manner. This is part of what was sacrificed to make these timelines possible. Note, this DOES NOT in any way mean safety corners were cut or that regulatory steps were skipped, but rather it means that the comfort and patient experience isn’t quite as clean or easy. Many patients receiving the two dose vaccine regimen (Oxford, Moderna, Pfizer) report mild to moderate flu like symptoms within 24hours of administration; fever, fatigue, headache, etc. The symptoms are reported to go away within 24hours and are indicative of the body mounting a very strong immune response against a very strong vaccine, a good thing! Just be prepared to take a day off after receiving the vaccine, because there’s a good chance it’ll knock you on your ass (very short term).

Therapeutics

Other big news that came out this week was that Eli Lilly’s monoclonal antibody therapy against Covid-19 was given Emergency Use Authorization, though it is only being prescribed to elderly and high-risk patients, but at no charge (per US Government). Thankfully this is one of several therapeutics that have been shown to be efficacious in reducing the severity of Covid-19. Therapeutics can be divided up into those that act during the early stages of infection aimed at reducing the viral load and those acting during the later stages of infection that aim to minimize the damage caused by the immune response. In the former are anti-viral drugs such as Remdesivir (Gilead) (Spinner Aug 2020), monoclonal antibodies like Bamlanivimab (Eli Lilly) and REGN-COV2 (Regeneron, still in Phase 3) and a host of other anti-virals and biotherapeutics progressing through clinical trials. Convalescent plasma, while initially promising and helpful for some patients, is becoming less commonly used due to the inconsistent levels of neutralizing antibodies in donor patients (Agarwal Oct 2020). All of these treatments have been shown to be most efficacious when administered during the early stages of infection, before the disease reaches critical levels. Once the infection becomes more severe, requiring hospitalization, most of the therapeutics above have been shown to have minimal impact on the cytokine storm induced pathology, but this is when dexamethasone comes into play. A corticosteroid first approve in 1958, it acts as an immunosuppressant to help control the body’s over-reactive immune response to the virus that causes much of the late stage disease pathology, keeping many patients off ventilators (Tomazini Sept 2020). While none of these therapies are cures they have been instrumental in helping save some patients and in reducing the overall mortality rate. THIS is what the lockdowns did, they bought the Medical and Scientific community time to catch-up so that we could save more lives, though we still have a long way to go.

Reinfection and Immunity (Update)

Another big question that has arisen recently is about the potential for long term immunity and reinfection, the latter was recently proven by several case studies in Nevada, Hong Kong, Belgium and Ecuador (Iwasaki Nov 2020). First let’s start with what’s been learned about the immune response (for a more details on the immunology/virology, see my previous post). SARS-CoV-2 is a fairly sinister virus, in addition to asymptomatic/pre-symptomatic spread, the immune responses caused by it are quite variable. In many asymptomatic and mild cases the levels of neutralizing antibodies and length of seropositivity were shown to wane quite rapidly (Long June 2020), while those who had more severe disease had longer lasting humoral responses. Thankfully as I briefly introduced above, Tcell immunity seems to be more consistent across all infected patients (Sekine June 2020) and plays a major role in the memory response to the virus. Research has also shown that some people who have been previously infected by other coronaviruses have cross reactive memory responses to SARS-CoV-2 (Sette Aug 2020, Mateus Aug 2020), and that children may harbor higher levels of these cross reactive antibodies, a potential reason they are more resistant to Covid-19 (Ng Nov 2020). Preliminary data from one paper also showed that immune priming using the seasonal influenza vaccine can help promote immune responses to SARS-CoV-2. This is very preliminary lab data, and IS NOT inducing specific responses, but rather just an immune priming effect, similar to an adjuvant (Debisarun Oct 2020). This cross reactivity from other coronaviruses and immune priming from the flu shot DO NOT confer immunity, but may be part of the reason some people have more mild disease than others, though these hypothesis are still under investigation.

But if the body creates all these immune responses (some durable), how are people getting reinfected? Unfortunately for the handful of confirmed case studies we (Scientist) don’t know the exact answer. It’s possible the individual immune response was incomplete and thus proper memory cells were not created or maybe they were infected with such a high dose the memory response was overwhelmed? Thankfully, while viral sequencing of the Nevada case showed two separate viruses during the first and second infection, the mutations in their genomes did not appear to affect the antigenic sites the body recognizes; in short, mutation does not seem to be the reason for reinfection. Now, before you spin yourself into a frenzy, we’re talking about less than a dozen confirmed cases worldwide. If reinfection were a major issue (right now) we’d be seeing thousands of cases, not a handful, and these outliers were inevitable. So for now there is no need to panic about this topic, though it remains to be seen how long (beyond 1 year) immunity lasts and how stable the virus will be long term. So far due to proof-reading enzymes in the virus, and lack of selective pressures the virus seems to be fairly stable (Romano May 2020). Research on both these topics is ongoing, and as we get further out from the initial outbreak more will come to light.

Children and Schools

Now on to something a little more contentious, what role do children and schools play in the spread of the virus and is it safe to open up schools? I’ve spoken with many parents and teachers about this, and have heard stories on both sides; inability to work when kids are home, forcing a 6yo to do 5h/day of zoom (horrible), trying to educate one’s kids while working from home, teachers being given inadequate PPE to setup safe environments, teachers being guilted into working because if they don’t they’re responsible for our kids failing and on and on. It’s a terrible situation all around, so rather than focus on the politics, I’ll try to focus more on the research about how infectious are children and whether or not schools cause outbreaks.

By now most people are aware that children (0-19) rarely get severe disease and their risk of dying is very low. But the role of those under the age of 19 in spreading the virus is not so simple. Younger children (<4 or <6 in some papers) do not seem to be very strong vectors for Covid-19, meaning they are less likely to be infected and to transmit the infection to others. Older children (6-13) on the other hand were far more likely to become infected and transmit the virus, while young adults (14-19) experienced similar disease progression to people in their 20s (Goldstein July 2020). Though one study out of Duke did find that children of all ages (0-19) had similar nasopharyngeal viral loads (Hurst Sept 2020), but did not relate this back to infectious spread. So for children the story is more complicated because there does seem to be age related variability in regards to symptoms, though they can still become infected and transmit the virus in many instances.

Now the big question, what do the case studies from schools that have reopened show about the potential for Covid-19 outbreaks in schools? Unfortunately the answer again isn’t completely clear, partially because schools are reopening with a variety of mitigation measures, different levels of community spread and with different plans for testing, isolating and tracking outbreaks. Case studies out of Germany and Australia concluded that transmission within schools was fairly low IF community spread of the virus remained low AND rapid testing and contact tracing protocols were followed (Ehrhardt Aug 2020, Macartney Aug 2020). In both of these case the schools were running at reduced capacity, and following rigorous cleaning protocols, physical distancing and mask policies in some instances. Another case study out of Luxembourg found that during a community outbreak, secondary infections were transmitted throughout schools, though no large super-spreader events occurred in the schools (due to tracking and tracing programs) (Mossong Oct 2020). Overall the literature seems to agree that school related outbreaks are far more common in secondary and University level facilities (Goldstein July 2020), and while outbreaks do happen in younger children they do not seem to spread as rapidly. Measures such as reduced class sizes, physical distancing, rigorous cleaning, hand washing, mask wearing and testing and contact tracing will help limit any potential outbreaks. Though all of this is also contingent upon the level of community spread, and no study has tested or recommended reopening schools during larger and uncontrolled community outbreaks (like what’s happening in the US right now). The State of Colorado tracks all our larger outbreaks that are associated with a single facility/school, and if you look at the data you’ll notice many schools listed, but also many other businesses, events and gatherings.

Final Notes and Looking Forward

While there is a ton of promising data about vaccines, therapeutics, mitigation measures that help us control the spread, we are far from done with the pandemic. With cases, hospitalizations and deaths spiking all across the United States things are promising to get worse before they get better. Winter will bring the confounding issues of people being stuck indoors more often, influenza returning to the Northern Hemisphere (get your flu shot!) and the holidays (which promise to see lots of people traveling). If you have to travel I’d highly recommend you read my earlier post about navigating airlines, and be aware of the risks you are taking (United has fully booked flights right now, every seat). While airlines have been shown to not be high risk by themselves (Freedman Sept 2020), several outbreaks, including a large one on an Irish airline (59 cases), should be stark reminders of what can happen when people let their guard down (Murphy Oct 2020). Pandemic responses are not just about each person protecting themselves, but about all of us protecting those around us as well. Boulder County just went back into ‘Safer at Home: Level Orange‘, heavily restricting gatherings (2 households/10 people max) and further restricting other events and businesses. While we in the Scientific/Medical community are Catching up with Covid, it appears Covid is catching up with the general public….it’ll be a race to see who comes out on top.

Citations:
Agarwal et al, Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicenter randomized controlled trial (PLACID Trial). BMJ, Oct 22, 2020.
Anderson et al, Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. NEJM, September 29, 2020.
Eli Lilly, Lilly’s neutralizing antibody bamlanivimab (LY-CoV555) receives FDA emergency use. Press Release, 11/11/20.
Debisarun et al, The effect of influenza vaccination on trained immunity: impact on COVID-19. medRxiv pre-print. October 16, 2020.
Ehrhardt et al, Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Germany. Eurosurveillance, September 10, 2020.
Folegatti et al, Safety and immunogenicity o ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single blind, randomized controlled trial. Lancet, Vol 396: 467-478. July 20, 2020.
Freedman et al, In-Flight transmission of SARS-CoV-2: a review of the attack rates and available data on the efficacy of face masks. Journal of Travel Medicine, 1-7. September 18, 2020.
Goldstein et al, On the effect of age on the transmission of SARS-CoV-2 in households, schools and the community. medRxiv pre-print, July 26, 2020.
Grifoni et al, Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell, 181; 1489-1501. June 25, 2020.
Guo et al, Long-Term Persistance of IgG Antibodies in SARS-CoV Infected Healthcare Workers. MedRxiv preprint, Feb 2020.
¬Han et al, Clinical Characteristics and Viral RNA Detection in Children with Coronavirus Disease 2019 in the Republic of Korea. JAMA Pediatric, August 28, 2020.
Hurst et al, SARS-CoV-2 Infections Among Children in the Biospecimen from Respiratory Virus-Exposed Kids. medRxiv pre-print, September 1, 2020.
Iwasaki et al, What Reinfections mean for COVID-19. Lancet Infectious Diseases, November 6, 2020.
Kaur et al, COVID-19 Vaccine: A comprehensive status report. Virus Research, Vol 288. August 13, 2020.
Krammer et al, SARS-CoV-2 vaccines in development. Nature, September 23, 2020.
Le Bert et al, SARS-CoV-2 specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature, Vol 584, August 20, 2020.
Long et al, Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature Medicine. June, 18 2020.
Macartney et al, Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study. Lancet Child Adolescent Health, August 3, 2020.
Mateus et al, Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science, August 4, 2020.
Mossong et al, SARS-CoV-2 transmission in educational settings an early summer epidemic wave in Luxembourg. Pre-print, October 2020.
Murphy et al, A Large National Outbreak of COVID-19 Linked to air travel, Ireland, Summer 2020. Eurosurveillance, Oct 6, 2020.
Ng et al, Preexisting and de novo humoral immunity to SARS-CoV-2 in humans. Science, November 6, 2020.
Romano et al, A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping. Cells, Vol 9(5): 1267. May 20, 2020.
Sahin et al, COVID-19 vaccine BN162b1 elicits human antibody and Th1 T cell responses. Nature, Vol 586. October 22, 2020.
Sekine et al, Robust T cell immunity in convalescent individuals with asymptomatic or mild Covid-19. bioRxi preprint. June 29, 2020.
Sette et al, Pre-existing immunity to SARS-CoV-2: the knows and unknowns. Nature Reviews, Vol 20: 457-458. August 2020.
Spinner et al, Effects of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients with Moderate COVID-19. JAMA, August 21, 2020.
Tomazini et al, Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients with Moderate or Severe SARS Distress Syndrome and COVID-19. JAMA, September 2, 2020.
Walsh et al, Safety and Immunogenicity of Two RNA-Based COVID-19 vaccine candidates. NEJM, October 14, 2020.
Willyard, Ageing and COVID Vaccines. Nature, October 15, 2020.

24hours of 14ers; Revisiting the Past

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Seven years ago a crazy idea was hatched out of an online discussion on 14ers.com, how many 14,000ft peaks was it possible to climb in 24hours, and what would be the optimal linkup? I love 14ers, and I love logistical challenges, so I set out working some variations and timing, scouted a few lines and put some wheels in motion. I made my first go at the linkup in July 2013 as a training run leading up to UTMB, ultimately bowing out after tagging Sherman in 18h37min, for a total of 9 summits. At the time it was a good first effort, but I felt that I had a left a lot more potential out there and that 12 was feasible on a good day. Since 2013 several others have improved upon my original 9 summits, pushing the number to 11 summits in 22h, though still no one had crossed the 12 peak threshold.

Smokey views from the Mt Evans Rd, 9/18/20.

After a summer of running around the mountains, I was searching for a little inspiration, something to cap the summer and add a little extra motivation to the weird race-less Covid year it’s been. The opportunity presented itself, so I worked the schedules, lined up a driver and was set to go. Friday morning at 430a my friend Misti picked me up and we headed out for the Mt Evans Rd, the starting point for the journey. At 6:11am on 9/18/20 I clicked the watch and started jogging up the Rd to Mt Evans. It was cool and breezy, smoke hanging in the air from all the wildfires, but on I ran. I hit summit lake at 1:10 and busted up the NE slope to the summit (1:43). For some reason I thought I was behind schedule so I cranked my way across the Sawtooth, gasping as I scampered around the snow on Bierstadt, hitting the summit in 2:38. Even though it was a Friday it was a bit of a cluster, so I wasted no time and hammered down the trail, passing dozens upon dozens of onlookers, not even registering their comments or questions, reaching the Guanella Pass Rd, and eventually 11000ft at 3:25 (10min ahead of schedule).

Headed across the Sawtooth to Mt Bierstadt.

Finally a bit of downhill after dodging the crowds atop Mt Bierstadt.

I jumped in the car, and Misti promptly took off for Stevens Gulch as I packed my water, food and gear for the next leg of the journey. The word of the day was ‘efficient’. We pulled up to the Stevens Gulch TH, I jumped out, poles in hand and headed straight onto the trail for Torreys Peak. I dug into the trail, and found a steady rhythm up and over Torreys (5:31) and over to Grays (5:55). Thankfully the trail wasn’t too busy and CFI has done some great work, allowing me to cruise at a quick pace back down to the car where Misti had a cup o’noodle waiting and off we bounced down the Stevens Gulch Rd, next stop Quandary!

We had a good rhythm going, I’d stuff my pack with food, water and gear, eat something solid and do some recovery work on my legs while we drove. After a short nap we navigated our way onto the Blue Lakes Rd on the South side of Quandary Peak, where I again hopped out of the car at 11200ft, intent on making quick work out of the dirt road section. I soon crested the dam at Blue Lake, and struck off on the climbers trail headed for Cristo Couloir. My semi-secret shortcut and little known fact that it’s only 2mi from 11200ft to the summit of Quandary via Cristo (1mi gaining 2300ft!). I’ve always been good at digging my poles in and just grinding out slow vert, so that’s what I did. Reaching the summit of Quandary Peak at 9:06 (1:24 from the car) to cloudy cool skies with only one other person in site. I made quick work of the steep loose descent, getting back to the car in 37min (9:43)! Then began the frantic recovery and repacking effort before we hit the Kite Lake Rd, this would be the shortest turn around, and with a long loop of the DeCaLiBron to come.

Looking down Cristo Couloir on my way up Quandary.

Misti dropped me at 11100ft on the Kite Lake Rd at 10:07 (4:45pm) and I began the long slog up to Kite Lake and Mt Democrat. After 10hours I wasn’t feeling as spry but I just kept grinding away, for the first time starting to struggle a bit on the uphills, reaching the summit of Mt Democrat at 11:52 (1:45 from the car), slower than I’d hoped for, but still on pace overall. I made decent time over to Mt Lincoln (12:48), spurred on by a bitter cold wind that froze my fingertips. Soon after I crested Mt Bross as the evening light faded into blackness, I paused long enough to take in the fact that I’d had the entire DeCaLiBron to myself, a rare occurrence. The darkness made the rocky descent far tougher than I’d expected, and I rolled back to the car at 14:13. For the first time all day I was a bit beat up, and was looking forward to the long drive over to Missouri Gulch, a chance to rest and recharge before the long night ahead. I refueled and napped as Misti drove, and before I knew it we were bumping down the Winfield Rd, screeching to a halt because we’d flow right by the trailhead!

Cold and windy sunset run up Mt Lincoln, all by my lonesome.

After a quick double check of my gear and food stores I bid Misti farewell and set off into the darkness. I put on some music and just focused on strong and solid movement upwards. I was hitting my splits as I neared treeline, but I could feel the strain in my breathing. As I began to climb the endless switchbacks to Mt Belford I knew I was in for a challenging night. My lungs felt congested and I couldn’t seem to get a full breath, forcing me to take breaks far more often that I wanted just to catch my breath. The switchbacks seemed to drag on forever, made worse by the lingering snow and ice that further slowed progress. At this point I was feeling very demoralized, moving as fast as I could muster, reaching the summit of Belford in 2:31 from the trailhead (18:16). It was dark, cold and I was struggling mentally to stay motivated.

Final bit of light fading away on the Rocky Mountains.

I pushed on to Oxford, once again forced to dodge a bunch of awkward snow and ice blocking the trail, reaching Oxford in 0:47 (19:03), far slower than what I know I’m capable of. On the summit of Oxford I did some fuzzy math, realizing that at my current pace it was gonna be tough to break the current FKT of 11 summits in 22h. When I’d started up from the trailhead 11 summits seemed almost a certainty and 12 seemed very reasonable, but now I was struggling to fathom climbing 11 in the allotted time. As I descended back to Elkhead Pass I was able to talk myself out of the funk….you know these routes, there’s still time on the clock, so keep pushing forward until you run out of time, nothing is certain.

The grind up Missouri felt like death, but I pushed on as hard as I could. 13000ft…..13200ft….13500ft….. dodging a few more snow patches, and not happy to see that my scree shortcuts down the SW face of Missouri was blocked by drifted snow from the prior week’s storm, so I’d have to go around the long way. At last I crested the summit of Missouri Mt, summit #11 at 21:00, giving me an hour to traverse the ridge and drop 3000ft to Clohesy Lake, a task that felt nearly impossible at the moment, but still off I went.

The glory of sleep deprivation and the excitement of endurance events…nap time.

I pushed across Missouri’s NW ridge as fast as I could move in the dark, the whole things is a blur in my memory. I finally turned West and began to drop, astonished to find that the popularity of Nolans had hacked a real trail into the ridge (when I began scouting 13 years ago, no trail existed). This gave me a fighting chance, because descending 2800ft on a steep rough trail in 40min was definitely within the realm of possibility! I charged downhill as fast as my legs and lungs would allow, sliding out now and again, but losing elevation in a hurry. At last I dropped out of the upper basin and began descending to Clohesy Lake. The final mile of trail seemed to take forever, but as I neared 11200ft I turned my path straight down the tundra to the lake, collapsing on the edge of Clohesy Lake at 10991ft at 4:01am on 9/19/20, 21hours and 50min after starting my journey on the Mt Evans Rd the previous day. There had been so much doubt and uncertainty the previous 4hours that I’d actually make it to this point that I was relieved, excited, exhausted and beat to shit. The only thing left to do was trudge my way out of the mountains and back down to the Winfield Rd.

Since I don’t own a jeep this meant walking/yogging a slow 3mi back down the jeep road in the coldest part of the night. After wading through the river (twice) I walked up to Lana (my Rav4) and woke Misti to give her the good news… I’d done it, though barely. I’d set out the ultimate goal to climb 12 14ers in 24hours, and while I’d fallen short of that goal, I’d still managed to climb 11 summits and just squeeze in under the previous FKT by 10min, covering 22,300ft of gain and 48.7mi. It may not have been a perfect day; with all the physical struggles and the additional challenges added by the smoke and snow, but it had been one hell of a journey through the mountains. I’d over come the persevered despite the mental struggles and uncertainty, trusting in the process rather than giving in to the doubts. Though that 12^th summit still lingers….Mt Huron, I’m coming for you.

Asian Bias During Racial Unrest, 6/2/20

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Hello my name is Eric Lee and I’m an Asian American (technically multi-racial). Recent event have really pushed to the forefront of thought my personal relationship with racial bias, racism and the systemic social issues that plague our country. As an Asian American I’ve been exposed to my share of negative racial commentary throughout life; comments about eyes, color, language, driving ability, eating habits, how we name our children, penis size (yes I’m being serious), disparaging looks and on and on.
Though at the same time I must also admit the privilege I’ve had growing up in a middle class community. Most of these taunts and racial slurs have come from stupid and non-physically threatening sources. Meaning, I never had to fear for my life or feared someone was going to do me physical harm as part of this. Having grown up in an immediate community where violence was not the norm, where law enforcement was not prone to profile individual POC, I was privileged that the abuse was only verbal and emotional, not physical. This may not sound like much of a privilege, but I think we are all realizing (because of recent and ongoing events), that this simple factor IS a privilege.

Which brings me to the much messier question, how have I been a part of them problem for all these years. While Asian Americans have by no means had an easy history in the US, we’ve greatly benefited from the civil rights movements while not being as visible on the front lines. Also, because of the backing of strong Asian economies many have been fortunate to position themselves in more affluent settings. While this doesn’t change the profiling or underlying racial issues, it does ease the reactions/interactions that we’ve endured.
I will never know what it’s like to be an African American living in a lower socioeconomic neighborhood, who fears being arrested/beaten or worse every time they leave their home to go to the store, work or school. I will never truly know the frustration of fighting for equal rights for decades, to seemingly make little headway. One of my first exposures to the unrest associated with racial injustice was watching Los Angeles burn in 1992 during the Rodney King riots (and hearing the rise of gangsta rap). As a 10yo I didn’t fully grasp the situation, but the image is still deeply imprinted in my mind.
Do I like that these protests have turned violent (whether it’s the protesters or other agitators not related, remains to be seen)? No, but it doesn’t surprise me one bit. If I’d been trying to calmly, logically and peacefully protest and make my voice heard only to be brushed aside time and again, I too would have little faith in a system that keeps promising things will change but never delivering that change. Whether you like it or not, you can’t help notice what’s going on, and the protesters and voices screaming for change have your attention. I know they’ve got mine, and while I consider myself an educated and empathetic human, they’ve got me reconsidering my place in perpetuating the racial inequality that continues to persist. We can all be better, we can all do better, and we must.

Flying during the Covid-19 Pandemic, 5/18/20

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By now some of you know that this past weekend I took a very short trip back to see family in California, traveling by plane both directions. I know many people are itching to hop back on a plane, travel and to get away from it all. So to help everyone make a more informed choice I’ll lay out what I did to mitigate much of the risk of flying and how my experience went navigating all the public spaces that come with traveling to a different state. If you want to ask (or scold if you must) me about my personal reasons for doing this you are more than welcome to send me a DM or email and I’ll respond individually with that information, but its personal and thus not suited for a public forum and not the point of this writeup.

Every departing flight from Denver between 6p-11p on a Friday afternoon….. wow!

My Mitigation Plan
For me this whole process was a test of my ability to creation infectious disease mitigation plans, a skill I learned and honed working in tuberculosis and HIV labs for many years. So I did not simply hop on a plane and wait to see what happened, I had a whole step by step plan of all the risks involved with travel, how I would protect myself and how I would act in certain situations. Below is my initial plan that I laid out BEFORE traveling, and it is VERY conservative.

Now on to the reality of the situation and what I observed and found. I’ll lump both my flights together as a way to give the sum of a couple different experiences for each step listed above.

The whole journey for me started in Boulder boarding the RTD AB bus which heads to the airport. Under normal circumstances these buses are packed and can be standing room only, but right now RTD is limiting the number of passengers on each bus to <20, has suspended fare collections and is requiring all drivers/passengers to wear face coverings. When I got on it was apparent it was going to be a quiet trip, just myself and one other person headed to the airport!

The Airport

Needless to say the ride went smoothly, but I still kept my mask on the whole time. Arriving at the airport I unloaded my own bag and headed up the escalators to security. I was astonished to find 1 person (TOTAL) in line in front of me. I walked up to TSA precheck, handed the security office my ID, she didn’t even request I remove my mask (though they did in Oakland), then I passed on through. In Oakland they didn’t even have a precheck lane running, instead they specially escorted me through normal security (shoes on, liquids in the bag). After security I sanitized my hands and ID and headed to the gate. I only passed by a few people, almost all of whom were wearing masks of some variety (they are mandatory in the airport). As I approached the gate I was astonished to see the bar at Timberline Steaks (Denver) was open and seating patrons at the bar/restaurant? I filled my water bottle, washed my hands and headed over to the gate.
At the gate there were only about 20 people heading to Oakland, and 30 people on the return flight, for planes that have a capacity for 140 people. I found a spot at the gate spread out between others, which was easy, and sat down to eat my snacks and grab some water before the flight. This was the first time I removed my mask and it was only for a few minutes in a safely spaced out area. While waiting for my first flight an SWA worker came and sat right behind me, no attempts to space out, and while waiting for my second flight a woman came and stood right in front of me to await boarding. In both instances there was plenty of space to maintain at least 6ft of distancing, but neither person was aware enough to realize the situation.

TSA Checkpoint in Oakland, not a single passenger to be seen. TSA precheck was even closed in Oakland, though it was open (with 1 person) in Denver.

Waiting for the airport train at Denver International, people nicely spaced out, wearing masks.

Walking through Terminal C at Denver International, barely anybody around at 6pm on a Friday evening.

Southwest Airlines boarding process in Oakland, a mad rush to the podium as always (only 10 at a time), not much organization to the boarding process.

The Flight

Now on to the fun chaos of boarding. Southwest is famous for their open seat policy, normally boarding in groups of 30 at a time, all crammed together in small lines. Now they are calling up 10 numbers at a time to allow people to spread out. The problem is, when they call those 10 numbers it’s a free for all, no organization, so of course everyone immediately rushes to the counter and stands right next to each other trying to be the first on. I simply stood back, let them crowd ahead and walked on once my group had thinned out. Boarding the plane you have to walk by/near people, there’s just no fix for this situation (wearing my N95 still). I chose a window seat about halfway through the plane, spread out from other passengers, right now there is plenty of space on many flights. But, of course, on my first flight someone came and sat right in front of me (there was no need), so I moved over two seats to the aisle. As planes begin to fill up more and more the actual seating part is going to become impossible to not have several people within a 6ft radius of you, so that’s a part of travel risk one will just have to accept as being unavoidable.
On the plane almost everyone was wearing masks, including the crew. But not long after take off many people removed their masks for most of the flight (about ½ on my first plane, and 10-20% on my second). I even witnessed one woman call the flight attendant over to ask a question, then promptly pull down her mask to speak directly with her (really???). On the flight I spent most of my time working and reading as I watched the scenery go by. I did sanitize my hands and remove my mask for a brief few seconds to grab a drink of water, but that was the only time in the 2.5h flight my N95 came off. Overall a pretty uneventful flight once we were in the air, no food and beverage service, a few trash collection passes by the friendly flight attendants, but that was it.
Both flights landed early so we had to wait a few extra minutes for our gates. Even though very few flights are running (<30-40/day outbound at DIA and Oakland it looked like) each airport is only operating a fraction of it’s gates. When we finally got to the gate and the captain turned off the seat belt sign, the mad rush to the aisles to be the first off was on. Social distancing be damned, everyone did their normal thing and crammed into the aisle way right next to each other. So I simply stayed in my seat at the window, let most of the people deplaned, then grabbed my bag and headed out. I cleaned off my hands, took off my outer jacket and headed to the curb side. Again both airports were fairly empty for now, and getting through was a breeze.

On board headed to Oakland, most people spread out. After all, there’s only 20 of us. Masks still on.

Headed back to Denver, a few more people, but still everyone has their own row and plenty of space. Imagine this plane 2/3 full, with only middle seats empty. People in front and behind you, people across the aisle from you, etc.

People can’t help their natural tendencies. As soon as we land, it’s a rush to the aisle, everyone lines up nice and close to each other to rush off the plane.

Final Thoughts

Right now the overall take home from my experience is that airports are fairly empty and the airlines are still trying to figure out how to manage travel during the Covid-19 pandemic (which will continue on for many more months ahead). While I was able to protect myself fairly well throughout the entire travel process, it was evident to me that one can not rely on the airline’s good intentions or the unaware strangers around you to protect you. And while right now it’s easy to find some space, once passengers start returning to air travel (and they will) you will be forced into closer quarters/contact with people no matter how hard you try to avoid it.
Lines for buses, security, trains, escalators, seating areas at gates and on planes will all become busier to the point where you’ll have to be within 6ft of people, some will wear masks, some won’t (unless it becomes a Nationally enforceable law, unlikely). So if you choose to travel by plane in the next few months be prepared to accept the risk you are taking and knowing that you will be exposing yourself to people outside your realm of control and to people who might not all be acting very conservatively (or even think the virus is real). Hopefully during this lull in travel the airports and airlines can better test and implement their policies (I’ve written to Southwest), but that remains to be seen. And for those wondering, I’m now on a 14 day quaratine/watch for any symptoms (5/21, Day 3, ending 6/1).

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; Immunology and the Infection Cycle, 4/22/20

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Sorry for the delay, but this one has taken a lot of time and thought to put together (and reading some 80 odd Covid research papers). My goal in this edition of Covid Science Theater 2020 is to talk about what happens when the virus enters our body, infects our cells and subsequently leads to either mild disease or more severe infections. It’s going to be a fairly dense article, but I’ll do my best to keep the science and terminology to something generally understandable and hopefully educational.

For those who don’t want to delve too much into the specifics of all the virology, immunology and pathology I’ll provide a short 1 paragraph set of clifs notes here. The virus most commonly enters the host through mucus membranes (eyes, nose, mouth) and infects vascular endothelial cells and cells of the lungs, kidneys, GI tract and begins to replicate. The body initially responds to the virus through a host of Innate Immune mechanisms; these generic counter measures are deployed against all invading pathogens as a first line defense and are not specific to the invading pathogen. Unfortunately, these initial immune responses aren’t always adequate to contain the virus (the virus sometimes evades destruction, other times the virus just overpowers the immune response) so our body deploys a second type of response known as the Adaptive Immune response. In this phase, T-cells and B-cells are primed to respond to the specific infectious agent (here, SARS-CoV-2). Often this two-pronged approach works to contain the infection, eliminate the virus and build up lasting memory to subsequent infections. Unfortunately in some people the virus spreads too rapidly and the immune response doesn’t respond appropriately, leading to destruction of their organs (notably the lungs) and potentially death. Sometimes this more severe outcome is caused by the virus itself, but more often it seems to be caused by an overzealous immune system trying to play catch-up. So there’s the quick and dirty; in the following paragraphs I’ll go into more detail about Viral Entry/Binding/Replication, Early Cellular Responses, Clinical Symptoms, Adaptive Immune Response and What Happens and Why the Immune System Sometimes Fails.

The information in the following paragraphs comes from a combination of basic immunology principles (Kuby Immunology textbook), observations and early research released about Covid-19 and conclusions drawn from earlier studies of SARS-CoV-1 (a virus that is very similar to the current SARS-CoV-2, but with some caveats of course). As Covid-19 is still a new disease, we are constantly learning new things about the virus, infection cycle and pathology, so while what I outline here is based on a lot of research, there are definitely aspects of this virus that we don’t fully understand, and need further investigation.

Graphic of the structure of a SARS virus, the S, M and E proteins are the most important in regards to host recognition, Li et al 2020.

Viral Entry and Replication

Coronaviruses get their name from the hallmark shape, a circular capsid (or shell) that is spiked with proteins on the outside and sheltering the virus genetic sequence on the inside. The Spike (S), Membrane (M) and Envelope (E) proteins make up the majority of the viruses outer shell, while the Nucleocapsid (N) protein found inside the virus assists in viral replication. This small assortment of proteins, plus a few others, make up the bulk of the very simple viral structure (Weiss 2005, Li 2020). The novel coronavirus 2019 (COVID-19) shares a lot of homology or similarity with the original SARS virus that was discovered in 2002, genetically 80% similar, while being 76-95% similar for the major proteins listed above (Xu 2020). This allows researchers to draw a lot of conclusions from previous research on SARS-CoV-1, though we must be careful when doing so, as there are some known (and unknown) differences between the two viruses. The infection cycle starts with the virus gaining entry to the host, usually through mucus membranes of the eyes, nose and mouth. Once inside the virus often begins it’s infectious cycle by infecting vascular endothelial cells that line vessels throughout the body. While different viruses have different mechanisms by which they enter host cells, SARS-CoV-2 binds to the ACE2 receptor using its spike protein (same as SARS-CoV-1), allowing it to enter the host cell (Jia 2005, Walls 2020). Like most viruses, SARS-CoV-2 then goes through a multi-stage process by which it hijacks some of machinery inside our own cells to in order to replicate, escape and subsequently infect more cells in a continual cycle (Frieman 2008).

Overview of the SARS viral life cycle inside the host, Frieman et al 2008.

Early Cellular Response

Thankfully our body has a whole host of immune mechanisms it utilizes to deal with infectious agents of all types. Almost as soon as an invading pathogen has infected our cells the immune system starts going to work. The Innate Immune response is our constantly active sentinel, whose cells are constantly circulating all over our body just looking for foreign invaders to attack and kill. These innate cells use Pathogen Associated Molecular Patterns (PAMPs), or markers of foreign invaders, as the initial signals something is wrong and that it’s time to go to work (Li 2020). Some cells go to work directly attacking the virus and infected cells in an attempt to destroy the virus, others release signaling molecules known as cytokines and chemokines that recruit other cells to help in the fight (Frieman 2008), and some cells just go ahead and sacrifice themselves in an effort to prevent the virus from hijacking them, a process known as apoptosis (Lim 2016).

Symptoms: What and How They Manifest

While this system works well for many invading pathogens (why we are not sick all the time), allowing our body to control the infection, many viruses (and bacteria) have evolved mechanisms by which to evade, subvert and co-opt the immune response to their advantage. For SARS-CoV-2 it seems to be able to prevent the host immune system from activating one of it’s key anti-viral signaling pathways, the Type 1 Interferon pathway (Lim 2016, Li 2020, Frieman 2008). While it is not known exactly how the virus subverts this system a few hypotheses involve the Nucleocapsid protein (Lim 2016), other non-structural proteins (Lim 2016), and some of the SARS enzymes (Chen 2014). So by reducing the host immune response the virus is able to more effectively replicate and spread, leading to a more systemic infection. This is when we start to experience more of the hallmark symptoms of the infection; fever, sore throat, coughing, fatigue, pulmonary inflammation leading to shortness of breath and possible pneumonia and lymphopenia (a decrease in lymphocytes, more on that later) (Huang 2020, Zhu 2020). Most of these symptoms are a physical outcome of the body’s ongoing fight with the virus, trying to delicately balance destroying the invader, while preserving the host organs and system. The fever is the immune system’s attempt to raise the core temperature enough to burn out the infection. The sore throat/cough is an outcome of our immune system attacking infected cells of the airways and trying to expel the invader (mmm mucus), same for the pulmonary issues (initially, more on this later too). While many of these symptoms may be scary and uncomfortable they are often a normal part of our body’s healing process when dealing with a foreign invader. So under normal circumstances, it’s best to rest and let your body do it’s thing, unfortunately this doesn’t always go as planned, as we’ll find out in the following sections….

Adaptive Immune Response; Stage 2

In the previous two sections you’ve seen how our well intentioned Innate Immune system can sometimes fail leading to illness, thankfully the body has a backup, the Adaptive Immune response. This secondary wave of the immune response goes into action very soon after the initial infection (several hours to few days, infection dependent) and is mostly comprised of two cell types; T-cells and B-cells. When the levels of virus in the body start to rise, several of the innate immune cells can act as activators of the adaptive immune response, taking pieces of the virus to specialized activation centers know as lymphoid organs. These centers of immune activation are spread all over our body and are the primary site of pathogen specific antigen (virus pieces) presentation. The antigen presenting cells (Dendritic cells are most prominent) present the virus to the T-cells and B-cells as if locks in a door, allowing the T-cells and B-cells to go to work making specific keys (receptors and antibodies) that can attack and destroy the pathogen in a very focused manner. The outer proteins that make up the viral capid (proteins S, M, E) tend to be the most effective as this is what is visible to our body when intact virion are released (Liu 2017). So the body makes a whole army of these specific cells that traffic to the sites of infection; T-cells directly attack the virus and infected cells, while B-cells make antibodies that bind to parts of the virus, preventing them from entering new cells and marking them for destruction (Liu 2017).

These two arms of the Adaptive Immune response are also what comprise our immunological memory. Virus specific T-cells and antibody producing B-cells remain dormant in specialized lymphoid organs (sometimes they also remain in circulation), just waiting for the virus to turn up a second time. This time since they are already primed and ready to go, memory T-cells and B-cells start attacking the virus almost immediately, usually preventing the virus from spreading and preventing us from getting sick. Studies of SARS-CoV-1 have found both memory T-cells and memory B-cells (producing neutralizing antibodies) that are capable of rapidly responding to viral reinfection (Li 2020, Liu 2017, Channappanavar 2014). In human patients who recovered from SARS-CoV-1 infection anti-SARS antibodies and memory T-cells were found in most patients up to 24 months after infection (Liu 2006, Ka fai 2008, Liu 2017). While antibody responses did decline over time in SARS-CoV-1 patients (many undetectable at 6 years), memory T-cell responses were conserved for up to 11 years after infection (Tang 2011, Ng 2016, Liu 2017). Similar high quality neutralizing antibodies have been found in COVID-19 patients, but since the disease is so new the longevity of memory responses to this new virus aren’t exactly known. Encouragingly, since SARS-CoV-2 is so similar to the original SARS virus, and lab testing has even shown that their be might cross-reactive protection between the two diseases (Walls 2020), there is much hope that the long lasting memory responses seen for SARS-CoV-1 would also apply to those who have recovered from COVID-19. All of this evidence, both old and new, does inspire a lot of hope that a functional vaccine would both be likely and very effective in providing some duration of immunity from COVID-19, but how long remains to be seen.

Graphical overview of the many cells and pathways involved in the host immune response to SARS. It’s a complex set of feedback loops and interactions with a lot of variables. Li et al 2020.

When the Immune System Fails, Severe Disease

The reason COVID-19 is such a scary disease, isn’t because our immune system has no problem fighting it off, but because in some percentage of the cases (uncertain, but estimates are as high as 10-20%) patients need to be hospitalized due to severe complications. If our immune system is so complex and so strong, why do patients with COVID-19 get so sick that they need hospital care? It comes down to numerous very subtle things this virus does that are different than coronaviruses that cause the common cold. One is the effect SARS-CoV-2 has on Type 1 Interferons mentioned earlier, reducing the body’s initial response to infection. Another early symptom seen in many severe cases is lymphopenia, or a loss of lymphocytes (notably T-cells) early on in disease (Huang 2020, Schmidt 2005, Weiss 2005). While the exact cause of this loss of T-cells is not known, it is hypothesized that the viral proteins may lead directly to T-cell death as a mechanism of immune evasion (Lim 2016, Li 2020). These mechanisms of avoiding immune detection along with the efficiency of viral replication can lead to an out of control infection very quickly.

But in the end, it’s only partially about the virus, and largely about an overexuberate immune response. In an attempt to catch-up to the wide-spread infection the immune response goes into overdrive, ramping up a lot of the inflammatory cells and signaling molecules that tell the body to attack the infection (Li 2020). This response does in fact kill the infected cells, but it also destroys lung tissue (primary target), vascular tissue, liver tissue and other infected tissues (Tian 2020, Schmidt 2005). This is often when the more obvious signs of pneumonia set in; the lungs fill with fluid, the efficiency of aveoli decreases (oxygen absorption) and breathing becomes very labored and difficult. This is the tricky thing about COVID-19, making our immune response more efficient would help prevent early infection, but later on would lead to increased tissue damage. But if we reduce the immune function of the body to prevent self-inflicted tissue destruction, we run the risk of allowing the virus to run rampant throughout our body. COVID-19 is a tricky disease to treat for these reasons, and because the disease severity has a wide range of outcomes for different people. In some, infection is very mild and asymptomatic, in others, their entire body shuts down as the virus (and immune system) destroys the host from the inside. The reason many comorbidities are important as risk factors for severe disease is that most of them either affect the immune system or lung function. Obesity, diabetes, auto-immune diseases all alter the immune system’s ability to function, making it harder to fight off the virus. COPD and asthma (though less prominent then thought) make the host pulmonary system more sensitive to damage caused by the virus and immune system.

But not all hope is lost! Because of the large body of evidence suggesting that SARS viruses create robust lasting immunity, this means a vaccine might be very effective at protecting most of the population. Also, now that there are many patients who have recovered from COVID-19, tests are underway to examine if using their plasma (containing antibodies) can help patients who are suffering from more severe cases of the disease (works for other viruses like Ebola). We also have several promising anti-viral agents that are already in clinical trials being tested against COVID-19, with hopes that one or more of them will help improve patient outcomes and be ready for use later this year. Unfortunately all of this does take time, meaning we won’t have a cure next month, but by slowing the spread of the virus, not only do we allow hospitals to manage the patient load, but we allow all the scientist out there to catch-up and produce much needed data, therapies and vaccines.

Thanks for reading. If you see any mistakes please bring them to my attention and I will correct them ASAP. If you have additional questions or want to discuss the immune response in more detail (this is a very high level overview) I’d be happy to do so via text or email. Stay safe and stay healthy.

Literature Citations:
Chan et al, Serological Responses in Patients with Severe Acute Respiratory Syndrome Coronavirus Infection and Cross Reactivity with Human Coronaviruses 229E, OC43, NL63. Nov 2005, Clinical and Diagnostic Laboratory Immunology.
Channappanavar et al, T cell-mediated immune response to respiratory coronaviruses. May 2014, Immunology Res.
Chen et al, SARS coronavirus papain-like protease inhibits the type 1 interferon signalling pathway through interaction with the STING-TRAF-3 TBK1 complex. Jan 2014, Protein Cell.
Frieman et al, SARS Coronavirus and innate immunity. 2008, Virus Research.
Huang et al, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Jan 2020, Lancet.
Jia et al, ACE2 Receptor Expression and Severe Acute Respiratory Syndrome Coronavirus Infection Depend on Different Human Airway Epithelia. Dec 2005, Journal of Virology.
Ka-fai Li et al. T cell responses to Whole SARS Coronavirus in Humans. Oct 2008, Journal Immunology.
Li et al. Coronavirus infections and immune responses. Jan 2020, Journal of Medical Virology.
Lim et al. Human Coronaviruses: A Review of Virus-Host Interactions. 2016, Diseases.
Lu et al. Immune responses against severe acute respiratory syndrome coronavirus induced by virus-like particles in mice. June 2007, Immunology.
Ng et al, Memory T cell responses targeting the SARS Coronavirus persist up to 11 years post-infection. March 2016, Vaccine.
Schmidt et al. Coronaviruses with a special emphasis on First Insights Concerning SARS. 2005, Birkhauser Advances in Infectious Diseases.
Tang et al, Lack of Peripheral Memory B cell responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-year Follow-up Study. May 2011, Journal of Immunology.
Tian et al, Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients with Lung Cancer. Feb 2020, Journal of Thoracic Oncology.
Walls et al, Structure, Function and Antigenicity of SARS-CoV-2 Spike Glycoprotein. Apr 2020, Cell.
Weiss et al, Coronavirus Pathogensis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus. Dec 2005, Microbiology and Molecular Biology Reviews.
Xu et al, Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Feb 2020, Viruses.
Zhou et al, Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. March 2020, Lancet.

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Author Archives: Eric

About Eric

2022 Hardrock 100; Acceptance

Omicron and Endemicity? 1/24/22

Canyonlands Island in the Sky Ultra, 1/2/21

Life in the Vaccine World, 4/26/21

Catching Up with Covid, 11/12/20

24hours of 14ers; Revisiting the Past

Asian Bias During Racial Unrest, 6/2/20

Flying during the Covid-19 Pandemic, 5/18/20

The COVID-19 Workplace

COVID-19; Immunology and the Infection Cycle, 4/22/20