COVID: The Risks Ahead - Part 2: Long COVID

Written by Ethan Thio '22

Edited by Elizabeth Zhang '23

https://www.pexels.com/photo/shallow-focus-of-clear-hourglass-1095601/

“We always look for everything in the immediate proximity, that is a mistake.”

-Thomas Bernhard

It’s human nature to focus on the short term. Long-term concerns are predicated on short-term survival. Whether or not something bad will happen a year from now is unimportant if your life is in danger today. But I think that tendency is at odds with how a lot of Americans actually think about the future. We do make plans, years in advance. Family planning, careers, education, we make decisions with the understanding that they will have long-term consequences. Given that, long-term risks also must be relevant, as they endanger those very plans, decisions, and dreams.

I know many will disagree, but in my opinion, COVID-19 is a significant, long-term risk for both individuals and society at large. I know this is the last thing people want to hear, if they are even willing to hear about COVID at all at this point. We have understandably placed a lot of focus on the acute risks of COVID. Overflowing hospitals and well over 1 million dead in the US are horrific, acute consequences that deserve our attention. But as we “move on” and have “moved on” from COVID, our ignorance of COVID’s long-term risk unfortunately does not defang the danger it presents.

Let me make an admission. Trying to decrease the spread of COVID, through masks, social distancing, testing, the whole shebang, all of this is not easy. It sucks. Little things, from my dang glasses fogging up thanks to masks, to big things like having missed family gatherings, are terrible. It’s exhausting. It’s anxiety-inducing. It also, for a while now, has seemed pointless. Some pundits say the country is moving on from COVID, but the truth is that most of America moved on a while ago. I understand why people are tired of COVID, it’s been well over two, long years. I also want to be clear — I and this article do not intend to judge people’s decisions, or prescribe some specific way individuals should live their lives. These are profoundly personal decisions, with a host of concerns I can’t even begin to consider, not to mention address. I admit I’m risk-averse and a general outlier when it comes to maintaining some level of COVID precautions.

This series does not intend to shame those who take more COVID “risks,” who live their lives with COVID as a small or no concern at all. I really do understand. I’m exhausted of COVID and taking some “risks” too. The thrust of this series is not to judge or dictate, but rather to help clarify what we know about the risks we face. The overarching theme of this series is that COVID presents a significant, long-term risk that I don’t think we have adequately appreciated. If we can understand the risks ahead, we can work to decrease them as unobtrusively as possible.

If you read the first article, you can skip ahead to the Long COVID heading, but I want to set the stage. This entire series will revolve around a scenario I will pose to you here about the future (or perhaps present) of societal attitudes toward the pandemic. What do I mean? Let me paint a picture for you all. Let’s say that in the near future, all states and the federal government give up on any COVID mitigation. Mask advisories, vaccine drives, subsidized testing and treatments, COVID briefings and public health messaging, and COVID cases in the news, are all gone. Almost everyone stops ever masking or testing because they believe the risk to themselves is nonexistent and they largely have moved on from COVID. People think it’s “just like the flu,” and people coughing at the grocery store no longer elicit side-eyes. Vaccination rates stagnate, and uptake of boosters/new vaccines is limited. People go back to the pre-pandemic normal of going to school and work when sick. Societies fail to implement systemic mitigation (ventilation, filtration, etc) because of the belief that COVID is/will become “endemic.” Scientific research on new vaccines, treatments, and more stalls as funding and interest in COVID dies out. Honestly, I feel like this scenario is highly likely. Not only that, I think it’s basically the reality in most, if not all of America now.

There are four reasons why I am concerned about the scenario I posed.

1. Reinfections, or the possibility/probability of getting COVID a second, third, etc. time even after vaccination. I covered this in the first article, but briefly, reinfections are likely to become a common occurrence, facilitated in part by waning immunity to SARS-CoV-2. This likely means the virus will continue to circulate at high levels even after vaccinations and infections. The virus, even after vaccination, has caused a significant number of deaths, easily outstripping that of a moderately severe flu season. While data on reinfections supports the idea that they are generally milder, this mildness is not ironclad. Some studies disagree, and crucially, our data is necessarily constrained to a short period of time given the novelty of COVID-19. Our research cannot yet take into account the fact that people become older, sicker, and more vulnerable to COVID with time. These reinfections also may cause additional health consequences to healthy individuals along similar mechanisms to long COVID. That leads to the subject of this article —

2. Long COVID, or the significant long-term suffering endured by many who are infected by SARS-CoV-2 (the virus that causes COVID-19), linked to multi-system organ damage and other complex factors not fully understood by science (yet!). If that wasn’t enough, there is a wild card that threatens to exacerbate both aforementioned factors —

3. Variants, or the simple fact that viral mutation has already and will likely continue to lead to new variants that may be more transmissible, virulent (cause more severe disease), or evade immunity (vaccines/natural immunity) more effectively, which could interact with long COVID and reinfections in ways we cannot predict. This all does damage to our

4. Shattered healthcare systems, or the fact that the successive COVID waves we have already endured have devastated our healthcare workers, with retiring and resigning meaning our healthcare systems will be weaker in the future if we do not act. The convergence of the above three factors threatens to place even more pressure on both inpatient (hospital) and outpatient (clinic, non-hospital) care.

I’m going to be honest, this sounds really depressing. It is. In many ways, it’s a pessimistic scenario. I also admit that it is far from certain to occur. But here’s the thing — it’s possible, and if we have learned anything over the last 2 years, blind hope doesn’t make COVID or its consequences go away. But I believe that we can avoid these significant potential concerns by first acknowledging their enormity. Then, by understanding the threat we face, we can make decisions about what countermeasures, if any, we should use against it. Let’s get into it.

2: Long COVID

Rather than bury the lede, I’m going to make my thesis/claim upfront, have a ton of analysis, and return to the claims/argument at the end.

This article will cover how COVID infection has been associated with a greater incidence of cardiovascular and neurological disease after recovery. It’s not limited to those two, to be clear, we’ve seen damage to the kidneys, musculoskeletal system, and more, but this article is long enough. Further, COVID infection has also been associated with persistent symptoms months after recovery from acute illness, which can range in severity from mild to debilitating. This has an incidence ranging from 5-30%. Vaccination decreases the odds of persistent symptoms, but the risk reduction is both uncertain and largely limited, with estimates ranging from 15% lower to 50% lower. Paxlovid also doesn’t seem to be a silver bullet for long COVID either. There are other conditions that increase the risk of long COVID, but even if you aren’t in a higher-risk category, operating from a base of 5-30% means that literally any individual, given what we know currently about long COVID, has a non-negligible risk of getting long COVID. For comparison, the odds of getting in a car accident during a 1,000-mile trip is 1 in 366 or a bit under 0.3%. People do recover from long COVID, but it takes time and full recovery is not guaranteed.

The fundamental claim I’m making on the basis of the research analyzed in this article is that despite the concerning conclusions, it’s entirely possible, if not probable, that none of this happens to you if/when you get COVID. If anything, the most likely outcome in most cases is a full recovery. But as stated before in the reinfections article, a small percentage (those who develop long-term health issues from COVID) multiplied by a massive number (like the almost 100 million confirmed and the certainly much greater actual number of infections) yields a significant number. I believe that a significant number of Americans have and will continue to unfortunately develop long COVID, and this will have a serious, likely negative impact on society. Alright. I’ve made my claims, let’s get into it.

1. COVID infections can have serious, long-term consequences for a number of organ systems.

When you think of actually catching COVID, what comes to mind? Personally, before going deep down the rabbit hole of COVID research and news, I thought this was strictly a respiratory issue. It’s like a really bad flu. The virus gets into your lungs, you start coughing, having trouble breathing, and if that progresses, you get pneumonia (severe lung infection), and in bad cases, you get hospitalized and/or die. You have to breathe to live, it makes sense that screwing with the lungs is really dangerous. But what’s become clear after 2 years of research is that COVID is much more than a respiratory concern.

Before that though, I want to qualify all of the following by stating that I am not a doctor, biologist, physiologist, or expert of any kind. I have a bachelor’s degree in biology (shameless humblebrag), which has helped me glean some level of understanding from the research articles I’ve read, but I urge you to read the linked research papers, ask your doctor, and consult actual experts. In my defense, I think this article is legit. I’ve spent many, many hours poring over it and the research, but I don’t want to claim any credibility I don’t deserve.

Back on track. Long COVID is a broad term that encapsulates a lot — but in short, it relates to persistent health problems after a COVID infection. I’m going to separate this section into two parts: asymptomatic Long COVID and symptomatic Long COVID. You might be thinking, Ethan, what the heck is asymptomatic long COVID? Does asymptomatic mean no symptoms, meaning, I shouldn’t care about it? Not quite. Asymptomatic long COVID refers to the documented increases in the risk of a variety of health conditions (heart attacks, neurological issues) that occur after COVID infections, often without any signs until the health condition occurs. Symptomatic long COVID refers to the protracted suffering experienced by a sizable portion of people who have been infected with SARS-COV-2. It’s likely that the two are linked, but for this paper, I’ll separate them. Let’s start with asymptomatic long COVID.

Emerging research has shown that people who have recovered from COVID infections have experienced health problems outside the respiratory tract, well after their recovery from acute illness. Let’s start with the heart. In February, researchers published a massive study involving a group of 153,760 individuals who had tested positive for COVID-19 and over 11 million controls (people who did not test positive for COVID-19 and are compared against those who did) to examine whether COVID infections were associated with higher rates of adverse (bad) cardiovascular (heart and heart-related) outcomes. What they did was utilize the Department of Veterans Affairs electronic health record database to compare the incidence (rate of occurrence of a disease) of cardiovascular problems among those who had tested positive for COVID-19 and those who did not after 1 year. Remember, nowadays every time you go to the doctor or hospital, it’s recorded in the computer, which is collated in huge electronic databases. That’s why your doctor (or a lowly scribe) is always typing when you talk to them. The researchers also ensured that the COVID cohort and controls were statistically weighed to ensure similarity. What does this mean? In short, they did some math to weigh different portions of the group differently, so that on average, both groups (those that tested positive and those that didn’t) had comparable BMI, race, age, and other health problems. This way we can isolate the impact of COVID on heart problems and attempt to exclude the impact of BMI, race, age, and other health problems on heart problems.

As a whole, it’s a simple, yet effective strategy. Follow those who tested positive for COVID, see what happened to them after a year, and compare them against people who didn’t test positive for COVID. Science, baby. It’s beautiful. (sheesh I’m a nerd). So enough prelude, Ethan. What did this study find? In short, the study was alarming. For any adverse cardiovascular outcome, ranging from heart attacks to strokes to heart rhythm issues, the COVID cohort experienced higher incidence compared to controls. Even when considering the severity of infection, mild (non-hospitalized) cases of COVID were 1.39 times more likely to experience some kind of cardiovascular event compared to controls, and this risk increases significantly with infection severity. Further, even when whittling down to individuals without any history of cardiovascular problems, those who tested positive for COVID were 1.58 times more likely to experience some kind of cardiovascular event compared to those who did not test positive for COVID. I urge you to read the study and examine the supplementary tables, because, across the board, the risk is elevated for the COVID cohort, regardless of age, gender, race, or pre-existing health conditions.

The study pushed the analysis further, using this risk to calculate the absolute (actual numerical) difference in the incidence of specific cardiovascular problems between people who tested positive and those who didn’t. Let’s focus on one problem, a heart attack. After a year, the researchers calculated that COVID infections are associated with 1.89 more heart attacks per 1,000 people compared to people who did not test positive. This analysis matters. I can tell you that you might be 1.58 times more likely to win the lottery, but if the odds are almost zero to begin with, that increase doesn’t matter that much. But what’s clear is that the odds of heart problems after COVID are not almost zero, and that multiplier is significant. 1.89 more heart attacks per 1,000 people means that if we roughly generalize this out to the population of the US (325.9 million), which is not super scientific but good as a thought experiment, we can expect 6,227 additional heart attacks if everyone in America gets COVID compared to if no one did. That’s a lot of heart attacks, and that’s just heart attacks. The paper surveys over a dozen cardiovascular problems whose incidence rises post-COVID.

I think it’s easy to get lost in the numbers. But the researchers actually step away from them briefly, and rather than water down their words by paraphrasing, I’ve decided to include a direct quote. I think their analysis here is crucial.

“Our study shows that the risk of incident cardiovascular disease extends well beyond the acute phase of COVID-19. First, the findings emphasize the need for continued optimization of strategies for primary prevention of SARS-CoV-2 infections; that is, the best way to prevent Long COVID and its myriad complications, including the risk of serious cardiovascular sequelae, is to prevent SARS-CoV-2 infection in the first place. Second, given the large and growing number of people with COVID-19 (more than 72 million people in the United States, more than 16 million people in the United Kingdom, and more than 355 million people globally), the risks and 12-month burdens of cardiovascular diseases reported here might translate into a large number of potentially affected people around the world. Governments and health systems around the world should be prepared to deal with the likely significant contribution of the COVID-19 pandemic to a rise in the burden of cardiovascular diseases. Because of the chronic nature of these conditions, they will likely have long-lasting consequences for patients and health systems and also have broad implications on economic productivity and life expectancy. Addressing the challenges posed by Long COVID will require a much-needed, but so far lacking, urgent and coordinated long-term global response strategy.”

What are the key takeaways here? First, the risks COVID poses extend past the acute infection. You can recover from COVID, but the damage done by the disease can pose a risk to your health for months, and in the case of this study, at least a year later. Second, the most effective way that we currently know of to prevent this risk is to not get COVID, and that flies in the face of literally all current COVID policy, which tolerates infection as long as hospitals are not overrun. Third, and this is a long-running theme in this series, even if the individual risk of a heart attack is not significant post-COVID, the fact that we are dialing risk up for everyone infected by COVID, which is a huge amount of people, means that the total amount of cardiovascular disease caused by COVID is going to be significant. Finally, cardiovascular disease is not a joke. A heart attack, a stroke, this stuff can royally screw up your life. Treating this in the future will require significant healthcare intervention, something that very few governments or health systems have even acknowledged, not to mention prepared for.

Certainly, this study has significant limitations. It only utilizes data up to January 15, 2021, which is before the widespread adoption of vaccines. Further, the dataset of veterans is generally White, male, and old, which doesn’t render it fully generalizable to the broader population. It’s also entirely possible that confounding variables (some other variable that is actually responsible for heart disease observed) could be masquerading for the effect that the researchers are trying to attribute to COVID, given that this research is being conducted retrospectively (looking backward, rather than making groups and then following them) and observationally (not actually involving an experiment or clinical trial).

But I don’t think those weaknesses are enough to discredit the risk that the study presents. Vaccination clearly reduces the risk of severe disease and hospitalization, which is a great thing, given that the highest risk of long-term heart problems comes from severe cases of COVID. But as the study mentions, even non-hospitalized cases of COVID were associated with a statistically significant risk of heart problems. I do believe that a mild vaccinated case of COVID is likely less damaging than a mild case of COVID in someone who is unvaccinated. My limited knowledge of immunology tells me that our immune systems, primed to deal with the threat of COVID thanks to vaccines, could clear the virus faster and therefore diminish the damage done. But at the end of the day, the vaccine is insufficient to prevent infection, especially when it comes to Omicron. People still get pretty darn sick and get hospitalized, despite their vaccine, especially vulnerable groups. Also, studies that document persistent symptoms after COVID infection (which I will cover later), show that vaccinated individuals still have issues months after their infection. Given that, it’s hard for me to believe that vaccines eliminate the risk of long-term damage. I will delve deep into the impact of vaccines in the next section, but in short — the risk is likely diminished, but unlikely to be eliminated. Given that the risk shown is already significant (1.39 times more likely to have cardiovascular problems in non-hospitalized infections), diminishing this risk still likely means that statistically significant risk remains.

And in regards to the other concern of representation, while the group studied is not completely representative, breaking the group down into subgroups of race, gender, and age shows similar increases in risk.

Finally, when considering the observational, retrospective nature of the study, I must admit that we can’t draw unassailable causal conclusions. Other factors may very well be at play here. But what I think we can say with some level of certainty is that while other factors were likely at play, COVID probably was one of the factors at play too. The researchers did control for many factors, such as BMI, race, gender, age, etc. These controls obviously were and cannot be perfect, but this diminishes the chance that the conclusions drawn are completely unsound. In short, I think all of this is sufficient, for me at least, to believe that COVID plays a role in heart disease risk.

I also think the study’s limitations may actually understate the impacts at play here. The study was conducted over a year, which is a decent amount of time, but in terms of a person’s life, it’s a small fraction. Cardiovascular damage doesn’t always immediately translate into serious problems. A poor diet, heavy in cholesterol, slowly leads to the accumulation of plaques in arteries that could cause problems years, if not decades later. I find it plausible to believe that some members of the COVID cohort who did not experience cardiovascular issues over the one year examined in this study sustained subclinical (not severe enough to present symptoms) cardiovascular damage that could rear its ugly head 2, 5, or 10 years later. As such, the actual cardiovascular burden of COVID could be even higher. Reinfections also play a role. Over 1 year, it’s unlikely that a large portion of the COVID cohort got infected more than once. I explored this in my last article, but researchers estimate that we will all get reinfected with COVID once every year or two. If one infection does this damage, what kind of damage could two, three, four, or five COVID infections do? Unfortunately, new research published in Nature in November by the same team confirms that additional infections do confer additional damage. Taken directly from the abstract, the study notes that “Compared to no reinfection, reinfection contributed additional risks of death … hospitalization … and sequelae including pulmonary, cardiovascular, hematological, diabetes, gastrointestinal, kidney, mental health, musculoskeletal and neurological disorders” (Bowe). Further, to address the former knock against the earlier study for lacking data involving patients who had been vaccinated, this study in November noted that “The risks were evident regardless of vaccination status. The risks were most pronounced in the acute phase but persisted in the post-acute phase at 6 months” (Bowe).

Another thing we have to consider is that the cardiovascular study clearly shows that the likelihood of long-term heart problems increases with the severity of the COVID infection. What is associated with more severe COVID infections? Increased age and other health problems. America is getting older, with estimates stating that people over 65 will outnumber children by 2035. 1.4 million Americans are diagnosed with diabetes each year. As more people get older and sicker, not only are they at risk for more severe acute COVID, I’d imagine that their risk of long-term issues from COVID rises as well given the results of the study, only increasing the incidence of these problems with time.

Finally, there’s the issue of infections that didn’t lead to positive results. It was notoriously hard to get tested for COVID early in 2020. That means that it’s likely that there are people in the control group who actually got COVID but never got tested. This only reinforces the significance of the findings, because there are likely people in the control group who likely got COVID and theoretically would experience similar cardiovascular problems as the COVID cohort, which would “water down” the differences observed between the COVID and control cohorts. Nonetheless, the COVID cohort still showed statistically significant increases in cardiovascular problems. As such, it’s possible that if we actually took everyone who truly got infected with COVID and compared them against people who actually never got infected, the difference in risk could be even starker.

Yeesh. That was like 2,000 words for just one organ system! And COVID affects more. I don’t have the energy, (and I doubt you have the patience) to bear with me through all of the organ systems that COVID has been documented to affect over prolonged time periods, but I do want to cover one more. The brain.

In a highly-touted study published in Nature in March, 785 study participants had their brains scanned. 401 of these participants later tested positive for COVID and had their brains scanned an average of 141 days post-infection. Controls who were not documented to have tested positive also received a second brain scan. Both groups were matched for sex ethnicity, age, location/date of where the imaging was conducted, socioeconomic status, and pre-COVID health, and most of the patients who tested positive for COVID experienced mild symptoms. At face value, this is a really beautiful study design. Let’s think about why. What if the study just involved scanning patients who tested positive for COVID and comparing those who did not? What if this hypothetical study found more neurological abnormalities in the group who tested positive? The role of COVID in causing these abnormalities would be really tough to ascertain because it would be entirely possible that the patients who tested positive for COVID had some other underlying neurological problems unrelated to COVID that were simply exposed in that scan. But by having a scan before COVID infection and after, for both those who tested positive and those who didn’t, it’s possible to not only compare the cohort who tested positive against those who didn’t, but also to assess the changes in the brain after a COVID infection. So what did the study find?

Patients who tested positive were noted to have decreased “whole brain volume,” which is what it sounds like, even when controlling for head size. Tissue damage was also observed, most notable in regions connected to the primary olfactory cortex, the part of the brain associated with smell detection. This sorta makes sense — remember that one of the common symptoms of COVID is that it causes loss of smell. Damage was also observed in the parahippocampal gyrus, anterior cingulate cortex, temporal pole, left orbitofrontal cortex, insula, and supramarginal gyrus. These differences were still observed when excluding patients who were hospitalized. Comparing these results against uninfected controls showed significant differences between the two, with many of the longitudinal changes (differences between the two scans) not observed in the control group.

Let’s be honest though. Do I really know what the heck the anterior cingulate cortex is? No. And I’m not going to act as if I do. But the key here is that damage was observed, and this was recorded an average of 141 days post-infection. This isn’t some kind of short-term thing that heals in the 5 days it’s supposed to take some/most people to recover from a COVID infection. While it’s entirely possible that this damage is mitigated over time, the fact that it was significant and observable, even when compared against controls, is concerning. But you might be thinking, heck, we make jokes all the time about how bumping our heads leads us to “lose brain cells.” Who cares if my darn anterior cingulate cortex is a little smaller?

The researchers also conducted cognitive tests on study participants to assess whether these observed brain changes were associated with perceptible changes in cognitive functioning. They noted that while the COVID cohort did not display differences in memory, they did show a statistically significant “worsening of executive function,” and inattention, even when cases that were hospitalized were excluded. If you’re like me, you know what inattention means. I personally experience it several times an hour. But what about that executive function thing? Executive function refers to planning, focus, and the ability to juggle multiple tasks simultaneously. If you ask me, that’s pretty darn important. Any job you do, heck, any life being lived isn’t made better by decreasing attention spans, or the ability to focus, plan, or multitask. As an extremely unathletic nerd whose life mainly revolves around mental exercises (studying, video games, reading), losing cognitive function is certainly alarming.

If this study didn’t do enough already, it also conducted a similar comparison for 5 patients who were infected by the flu. This is huge, after all, a common refrain is that we need to treat COVID like the flu. In these patients, no statistically significant differences between the pre-and-post-flu scans were observed.

As such, this study tells us a couple of key things. One — COVID infections, even mild ones, are associated with observable brain damage after 5 months. It’s unclear whether this damage will resolve after more time, I really hope it does, but nonetheless, the damage is there. This damage is associated with observable shifts in cognitive performance, not in memory, but in stuff like planning, attention, and focus. These changes also can’t really be chalked up to normal baseline shifts in aging, as the study had controls that were matched for the litany of characteristics I mentioned earlier. As such, while the study authors admit that some other external factor unrecognized in the study could have caused the changes, there’s a pretty dang good chance that COVID is a, if not the culprit.

This study raises similar concerns as the cardiac (heart) study did. Since we are tolerating COVID infections for basically all, we are subjecting everyone to the risk of neurological damage and decreases in cognitive performance. Even if this risk is low and the damage minimal, when you expand to the entire population, the cumulative burden is huge. It’s also crucial to understand how important these things are to our daily lives. Knowledge-based work, and heck, all work depends on planning, attention, and focus, all things documented to be affected by COVID infections. Even if it only lasts for several months, which isn’t known to be the case, having less focus for several months isn’t harmless. Ask any surgeon or pilot how important focus is, heck, ask yourself! There’s a litany of articles and self-help books on the topic, it’s clear that people care about their ability to focus. It’s also unclear whether this damage is worsened by the reinfections we are also all planning to tolerate. I’d wager, given the reinfections study I referenced earlier, it’s certainly possible. Worst case, this damage compounds with time, and our attention spans and focus deteriorate even further as the number of infections we endure mounts. I want to be clear — I’m not saying this is definitely going to be the case. Most people do recover well from COVID. I just mean to say that this risk exists, and I don’t think many are paying attention or are aware.

Identification of neurological issues post-COVID isn’t something limited to this study. Research in the Lancet published in October studied over 1.4 million individuals with a recorded COVID diagnosis and matched them with controls who were infected with another respiratory infection. Quoting directly from the study, for the cohort that tested positive for COVID “risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period.”

What I hope these studies indicate is that beyond any subjective reporting of long-term symptoms (which I’m about to get into), we have serious research that shows how COVID is associated with measurably increased rates of poor health outcomes/changes across two major organ systems. This is something that can have a tremendous impact, both at a personal level and at a societal one.

2. COVID also poses the risk of prolonged symptoms and suffering, even in mild infections and in those who are vaccinated

So now that we’ve covered the heart and the brain, I want to talk about symptomatic long COVID, or the long COVID that people who talk about long COVID generally refer to. Long COVID refers to “new, returning, or ongoing health problems people may experience more than four weeks after being first infected with SARS-CoV-2.” Long COVID is a huge umbrella term under which many symptoms lie, and I want to first make one distinction between the long-term symptoms suffered by those who have severe cases of COVID and comparatively mild cases.

For instances where COVID patients experience severe illness, are hospitalized, and are admitted to the ICU, persistent symptoms after recovery likely fall under the umbrella of PICS, or post-intensive care syndrome. Critical illness has been shown to cause long-term physical, cognitive, and psychiatric impairment, and it makes sense that a severe case of COVID would do the same. What makes long COVID somewhat unique is its ability to cause persistent symptoms, even in mild infections.

To be clear, post-infectious disease syndromes are not some new idea. Whether it be long-term effects from mononucleosis or syphilis, physicians and scientists have observed how infections can cause long-term health consequences. Increasingly, researchers are drawing links between a condition known as chronic fatigue syndrome and long COVID, with striking similarities between the two. I’m not going to dive into these topics, but to say that long COVID, while novel in some respects, is not entirely unheard of.

So what am I getting at then? In patients with COVID-19, including those with “mild” cases, which can range from cold-like symptoms to being sick as a dog but not requiring hospitalization, a proportion ranging from 5% - 30% exhibit symptoms that persist for more than a month after contracting COVID. These symptoms range from extreme fatigue to breathlessness to anosmia (loss of smell) to reduced libido. A study I will continue to reference in this part of the article studied nearly 500,000 people from the UK who tested positive for COVID and were never hospitalized against nearly 2 million who didn’t test positive. The research found 62 symptoms that were significantly associated with COVID infections after 12 weeks. You might think, how the heck is this virus linked to 62 dang symptoms? This goes back to what I talked about earlier — COVID is not solely a respiratory disease. Even back in 2020, researchers noted how the virus affected the vasculature and was linked to kidney, liver, intestinal, and brain disease. SARS-CoV-2 virus has been found in organs ranging from the eyes to the testes. Once the virus enters through the respiratory tract, the virus interacts with capillaries in the lungs and enters the vasculature, thereby allowing it to spread to other organs. As such, it makes sense that a virus that traverses the body can cause wide-ranging symptoms.

These symptoms can persist for months, and given the fact that COVID has only existed for a couple of years, we don’t know whether some patients may have permanent changes to their health. Even in the absence of detectable virus within the body, patients report these persistent symptoms, with no meaningful treatments for them. Take the story of Elizabeth Mitchell, a once energetic, vaccinated-and-boosted patient who contracted COVID during the massive Omicron wave during Christmas 2021. She was pretty sick for about 10 days, but wasn’t hospitalized for her infection, and somewhat recovered, but never fully. She now experiences persistent exhaustion, memory troubles, and general brain fog, which compelled her to visit a long COVID clinic. These stories are spread widely over the Internet, if you want to read more, here are some. I think it’s easy to take our brains and health for granted (if you’re healthy of course), and having this sort of brain fog or persistent symptoms, even if they aren’t completely debilitating, is a significant drag on one’s quality of life and ability to conduct daily activities.

Thankfully, many long COVID patients do report recovery, but the duration and completeness of said recovery vary. A study from 2021 followed long-haulers (a term for people with long COVID) in online support groups for six months and used surveys to assess their health, symptoms, productivity, etc. It found statistically significant improvements in health status, work productivity, and functional status after 6 months, however, 94.6% of patients still experienced one or more symptoms after 6 months, and 83% still reported moderate-to-poor health after six months. This study is not perfect — there certainly may be issues with recall bias (inaccurate recollection of past health), non-response bias (who is deciding to answer these surveys and who isn’t?), and a plethora of other critiques many can make. However, I do trust the general picture that this study paints — yes, recovery from long COVID is likely, but that recovery isn’t guaranteed or even likely to be quick and complete.

With this in mind, I’m going to approach this from the perspective of someone who isn’t as concerned as myself, which truthfully, is most people. The first, and most common reason why I believe people don’t think much about long COVID is simply that it is rarely ever covered. For example, when President Joe Biden tested positive for COVID, and his physicians gave daily updates, long COVID was never mentioned. When you watch news reports about COVID, you hear about cases, symptoms during acute illness, hospitalizations, and deaths, but rarely ever long COVID. To be clear, those things (cases, hospitalizations, deaths, etc.) matter, but I genuinely believe there is a dearth of effective messaging on the topic of long COVID.

Another reason why I think long COVID doesn’t stand as a major concern to people is because they deny the risks at play, especially estimates of risk from 5-30%. I think a lot of people believe that due to vaccines and treatments, we’ll be fine. And when I started reading long COVID research, those estimates of prevalence truthfully shocked me. To be fair, I admit I come from a privileged background, with friends who are mostly young, healthy, and vaccinated. And in all fairness, vaccines have shown at least some degree of protection in preventing long COVID. This reduction had been estimated to be 50%, but recent research conducted at the VA Saint Louis Health Care System found only a 15% reduction in risk, which truthfully, is not much.

Given my extremely limited knowledge of COVID pathogenesis (how a disease develops), vaccines’ inability to eliminate the risk of long COVID sort of makes sense. The key determinant of whether one gets long COVID appears to be whether one is infected or not. This seems obvious and dumb, but stay with me. Remember, we’ve seen that “mild” infections in unvaccinated individuals can cause long-term health issues. Although severe cases are more likely to cause long COVID, any infection seems to hold some level of risk of long COVID. With more transmissible variants like Omicron more capable of evading our immune responses, the current vaccines seem ill-suited to prevent infection, even though they remain very effective at preventing hospitalization and severe illness. So, at the point at which vaccines are no longer highly effective at preventing SARS-CoV-2 from infecting and gaining root inside the body, it makes sense, at least to this amateur COVID-studier, that the risk of long-term complications will persist, although at a reduced level.

There’s also the question of Paxlovid and the new antiviral drugs, which have shown effectiveness in decreasing the odds of hospitalization in high-risk patients. Paxlovid works by disrupting the replication of the SARS-CoV-2 virus. In my mind, it would make intuitive sense that disrupting viral replication could decrease the ability of the virus to multiply, invade more organs, and cause more long-term damage, but again, this is purely hypothetical. The only research I am aware of is a preprint that found that individuals prescribed Paxlovid were about 26% less likely to report long COVID symptoms or associated cardiovascular issues. There are certainly confounding factors at play, after all, while the study’s authors do create a control group that has at least one risk factor for severe disease, we have to think about who can get a Paxlovid prescription nowadays. I’d wager that the Paxlovid has not been distributed equitably, and the research available tends to agree. I’d believe that those who got the drug were likely wealthier, had better health insurance, etc., which could lead to better outcomes. But the research is at least something. Apart from that, a case study of three patients noted one patient who took Paxlovid 24 hours after symptom onset and still developed long COVID. That’s a single case study, so we shouldn’t generalize, but it certainly isn’t promising.

Further, concerns about the virus developing resistance (being able to circumvent the drug) and patients experiencing rebound (resumption of symptoms and testing positive after being symptom-free and testing negative) are genuine concerns here that in my mind, diminish the chances that Paxlovid is a silver bullet for long COVID.

But I’m getting off course here. My point is simply to say: our vaccines and treatments are likely not sufficient, and we shouldn’t reflexively dismiss the seemingly humongous percentages that studies on long COVID often arrive at. Even for me, some of these numbers can seem extreme. I know a ton of people who have had COVID and very few, certainly nowhere near 30%, have told me the sort of debilitating and truthfully heartbreaking symptomatology that many long COVID patients report. To be clear though, that is unscientific and completely anecdotal, and I’d believe many understandably don’t want to discuss any long-term symptoms they may face.

As a result of all of this, I think many may consider dismissing long COVID outright, calling it psychogenic (psychologically driven, rather than physically), because of this. I believe this is a grave mistake. Researchers have identified specific biomarkers (biological molecules associated with a disease) likely indicative of long COVID such as reservoirs of persistent virus/viral RNA. Studies from researchers out of UCSF have similarly noted the presence of specific viral proteins in long COVID patients experiencing neuropsychiatric symptoms. Other research points to microclots, or tiny blood clots, that scientists have identified in the lungs of those who suffer from long COVID. Scientists also hypothesize that inflammation linked to a COVID infection can damage small nerve fibers, thereby causing persistent symptoms. An August preprint from researchers at Yale and Mt. Sinai noted a number of measurable changes among 215 long COVID patients, notably decreased cortisol levels and perturbations in the amount of specific circulating immune cells. The research is certainly still evolving, and I’m going to be honest — I don’t fully understand it. But what seems crystal clear is that this is not a wholly psychological phenomenon and almost certainly has a serious physiological component.

So with this in mind, I think it’s important to not view long COVID myopically as a debilitating long-term condition, even though certainly it has manifested that way for a large number of people. The deeper truth about long COVID is that it likely does affect the 5% - 30% that research has identified, but it doesn’t affect all of those people in the same way. Similar to how acute COVID can kill one person while being asymptomatic in another, long COVID can manifest in a number of ways, and just because it’s more “mild” doesn’t mean it doesn’t exist. As Dr. David Putrino, a physiotherapist, notes, there is significant heterogeneity in long COVID symptoms. They can be mild, not requiring medical care, or significantly affecting quality of life, and they can range in severity all the way to absolutely disabling. And unlike severe COVID, which is relatively rare in young, healthy, and vaccinated people, those populations can and do get long COVID. Anyone can get long COVID. To be fair, researchers have identified risk factors such as female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity, and a wide range of comorbidities. However, if you dig into the numbers, the increased relative risk isn’t humongous. For example, people who smoke have a 1.12 times greater relative risk of reporting long COVID symptoms. While that is statistically significant, when you’re operating off a base average of 5-30%, it’s not large enough, at least in my opinion, to say that nonsmokers or those in lower-risk categories experience “low” risk in an absolute sense.

So with those two somewhat covered, I also want to address another reason why I think people don’t want to think much about long COVID — it’s pure cognitive dissonance. As a society, we have more or less decided to go back to “normal.” Acknowledging that potentially disastrous risk remains is inherently uncomfortable, and therefore we are naturally predisposed to ignore, discount, and find the silver lining in any bad news or heartbreaking anecdotes about long COVID. Any new research or analysis must contend with this brick wall of ingrained opposition towards any attempt to change the current trajectory of the COVID response. I don’t mean to criticize anyone here — I’m as guilty as anyone in preferring the uplifting news and I want to go “back to normal” too. But I think it’s important to ask ourselves — are we ignoring the risks here?

Additionally, somewhat related to this — as I mentioned at the top of this (extremely long) article, I don’t think humans are naturally suited to assessing long-term risks effectively. It’s hard for us to conceptualize how impactful even a minor-to-moderate, long-term impairment could be to our quality of life. Thinking about having moderate brain fog that affects our ability to think sporadically throughout the day doesn’t seem great, but we figure we could deal with it, failing to realize that the sum total of lost function and suffering experienced over time can be astonishing. On the other hand, acute illness like being hospitalized with pneumonia is emotionally charged and visceral. We can imagine how horrific that would be, so when we see data that shows that hospitalization if vaccinated and boosted is relatively low, we feel relieved.

As such, for all of these reasons, I think long COVID is a severely discounted risk for anyone currently living in the United States where COVID transmission remains elevated and COVID mitigation is essentially nonexistent. Catching COVID doesn’t just risk acute illness, which I admit will most likely be generally mild in healthy, vaccinated populations. It risks long-term suffering of indeterminate duration and severity, which is something I personally would like to avoid if possible. However, for the reasons I outlined at the top of this article, outside of hermetically sealing yourself in your home, COVID is increasingly, if not nearly impossible, to completely avoid now. This reality leads to my final point.

3. Long COVID, both the “asymptomatic” and “symptomatic” variants, could have a significant, negative impact on American society.

I know what you’re thinking (if you’re even still with me after this gargantuan article). Goodness Ethan, this is a real downer. Believe me, I get it. When I wrote this, I constantly asked myself, is my natural pessimism/alarmism getting the better of me? Certainly, it may have at some points, so for this final part, where I intend to expand the conclusions of the first two to society at large, I will start with what I consider the “best case” scenario, and try to work from that. Hopefully, from this, you can see why I remain pessimistic despite my desire to be optimistic.

I’m going to start by re-summarizing the individual clinical ramifications of long COVID that we’ve gone over thus far. COVID infection has been associated with a greater incidence of cardiovascular and neurological disease after recovery. It’s not limited to those two, to be clear, we’ve seen damage to the kidneys, musculoskeletal system, and more, but this article was long enough. Further, COVID infection has also been associated with persistent symptoms months after recovery from acute illness, which can range in severity from mild to debilitating. This has an incidence ranging from 5-30%. Vaccination decreases the odds of persistent symptoms, but the risk reduction is both uncertain and largely limited, with estimates ranging from 15% lower to 50% lower. Paxlovid also doesn’t seem to be a silver bullet for long COVID either. There are other conditions that increase the risk of long COVID, but even if you aren’t in a higher-risk category, operating from a base of 5-30% means that literally any individual, given what we know currently about long COVID, has a non-negligible risk of long COVID. For comparison, the odds of getting in a car accident during a 1,000-mile trip is 1 in 366, or a bit under 0.3%. People do recover from long COVID, but it takes time and full recovery is not guaranteed.

With these facts in mind, let’s try to take the most optimistic case possible. Let’s assume that the entire American population (yes this article and series will be US-centric) is very healthy, vaccinated, and has access to Paxlovid (all 100% untrue at the moment). Taking the lowest bound prevalence estimate of 5% for a vaccinated person experiencing persistent symptoms, let’s divide that by 5 to be as extremely and unscientifically optimistic as possible, assuming that Paxlovid and being young and healthy make a massive difference (even though the St. Louis study I referenced would beg to differ on the youth part and no existing research I’ve seen shows that Paxlovid decreases odds of long COVID by that much). That leaves us at 1% of the population experiencing persistent symptoms for months.

Let’s also assume that everyone recovers within, say, six months. The US population is about 333 million. Assuming that 95% of the country gets COVID, supported by this preprint which estimated 94% as of November 2022 (which makes sense given the general lack of attention given to COVID basically nationwide), we’re talking about 3 million people having symptoms lasting for six months. That’s a lot of people, but you might argue, well, Ethan, a good chunk of those people are just going to have a lingering cough or some fatigue. Fair enough, fair enough, but hundreds of thousands or a million people with some lingering fatigue means a massive cumulative loss in productivity and quality of life. Further, let’s unscientifically say just 1 in 20 of those people have debilitating, disabling symptoms, the type experienced by Suki Newman, who had to quit her job due to brain fog, debilitating headaches, fatigue, and heart palpitations. That means 150,000 Americans are going to be dealing with severe, disabling symptoms that will radically diminish their quality of life and take them out of the workforce, with knock-down effects on their families, friends, colleagues, etc.

I know I might seem callous by bringing up productivity and the workforce, but I do that for a reason, the financial impact of this condition on a personal level can be catastrophic. 56% of Americans cannot cover a $1,000 emergency expense with savings, and 54% of all Americans get health insurance through their work. We’re talking about hundreds of thousands, if not a million or more Americans potentially losing their jobs, going into serious financial hardship, and losing health insurance coverage, while they deal with a significant, disabling, long-term health condition. This also assumes a pretty serious deal of privilege as well — people who are uninsured (8.6% of the country), unemployed (3.5% of the country), below the poverty line (11.4% of the country), deal with at least one chronic health condition (51.8% of the country), or experience any of the systemic marginalization or other hardships rampant in this country are in an even worse position. Further, this doesn’t even take into account the increased incidence of cardiovascular disease and neurological issues mentioned earlier, which will further increase the number of Americans experiencing mild, moderate, and severe health complications from COVID-19 months, if not years after infection.

If this wasn’t depressing enough, consider the first article in this series — reinfections. As mentioned previously, new research from Nature published in November shows that reinfections are not harmless. People infected with COVID twice have a statistically significant increase in their risk for developing long-term fatigue, pulmonary, cardiovascular, hematologic, nephrologic, and other problems, compared to those who were infected once. This raises the possibility/probability that long COVID is not a static risk, meaning that even if you get COVID and don’t get long COVID, you could get long COVID after a reinfection. This means that even in my aforementioned best-case scenario where only 1% of the population gets long COVID and recovers, more individuals who get reinfected also develop long COVID, meaning that a significant portion of the population will be dealing with persistent symptoms as long as COVID circulates at high levels, even if recovery is guaranteed.

You might think, well, Ethan, what a depressing hypothetical, but it’s just that, a hypothetical. Unfortunately, it isn’t really. Certainly, while the precise estimates and specific predictions made above are hypothetical, long COVID’s presence and impact on society can be ascertained in existing data. The Washington Post references a Census Bureau survey that estimated that “the number of 16-and-older Americans with a disability is up by about two million since early 2020.” Some might argue that this isn’t related to long COVID, and that’s 100% valid. The same article addresses this concern by referencing another Census Bureau survey called the Household Pulse Survey, which according to the Census, “data on the social and economic effects of coronavirus on American households.” The article’s author examines a portion of the Pulse Survey that assessed the health status of Americans who tested positive for COVID versus those who didn’t.

I personally dug into this survey data, and what follows is an admittedly amateur attempt to assess the existence and prevalence of long COVID through this survey data. The survey is taken frequently, and the first time that the survey included questions relating to long COVID (whether individuals experience difficulty remembering or walking) was on April 14, 2021. That survey estimated that about 1.65 million Americans who had at some point tested positive for COVID either had a lot of difficulties concentrating or couldn’t remember/concentrate at all at the time of the survey. That’s a shockingly high number, and I don’t mean to draw a completely causative link between COVID and serious difficulty concentrating. It’s entirely plausible that someone could have recovered from COVID but had severe difficulty concentrating due to another health issue, personal crisis, etc. These lurking variables (unstudied variables that actually cause the perceived association between independent and dependent variables) are a serious concern. This is emphasized by the fact that the same survey estimated that around 8.77 million Americans had comparable concentration issues, but did not report testing positive for COVID at any point. It’s important to understand that there are other significant causes of concentration difficulties in this nation, obviously.

Sidebar – you might dismiss long COVID from these numbers, as the number of people with concentration difficulties who never reported a positive test outnumber those who did report a positive test and had difficulties. That brings us to a key step in analyzing this data — we can’t compare raw numbers because the number of people who tested positive is different from the number who didn’t. As such, it’s not an apples-to-apples comparison, and percentages are what matter more.

So let’s work with percentages. Using survey estimates of the number of people who tested positive for COVID as of April 2021, my calculations found that around 4.70% of those who reported testing positive for COVID also reported serious concentration issues, compared to 4.16% who had serious concentration issues and didn’t report testing positive. That sounds like a small amount, probably close to the margins of error of the survey, sure. But again, small percentages multiplied on the entire US population, which is what we are working with here, yield answers that affect hundreds of thousands or millions of people. But I admit, the numbers don’t seem too shocking. Let's move to the most recent survey.

Taken on June 29, 2022, this survey asked the same question about concentration difficulties, but was more granular, asking whether one tested positive a month ago, more than a month ago, tested positive twice, or never. I added up the first three categories that all correspond to testing positive at any point, and found that the survey estimated around 6.81 million Americans who had reported testing positive at some point had serious concentration issues. On the other hand, the survey estimated that 6.77 million Americans who never reported testing positive had similar, serious concentration issues. But we need to compare percentages. Now, compared to before, only 140 million Americans report never testing positive for COVID, compared to 210 million in April 2021, and when dividing by those numbers, you get 6.43% of the COVID-positive cohort with serious concentration issues compared to 4.82% in the never tested positive cohort.

This is a major increase from April 2021, both in numerical and percentage terms, but it’s reasonable to think there could be lurking variables at play. For one, the world sure seems worse off now than it did then, and that could cause innumerable effects on concentration. But the difference is starker now, and it’s harder to say that lurking variables can explain all of that.

For one, the quantity of people who experience cognitive issues after COVID is significantly greater now than over a year ago, which corresponds to a significantly higher amount of infections that have transpired over that period. To be fair though, this doesn’t necessarily mean that COVID is having an outsized effect — individuals who had preexisting cognitive issues before testing positive could have those very issues persist post-infection, thereby increasing the number of people who report having cognitive issues and having tested positive. That’s why the percentages are so significant. Not only are the raw numbers of individuals with cognitive issues and positive tests increasing, the difference in the percentage of individuals who reported serious cognitive issues between COVID + and COVID - cohorts increased over that same period. Recall — in April 2021, 4.70% of those who reported testing positive for COVID also reported serious concentration issues, compared to 4.16% who had serious concentration issues and didn’t report testing positive. This compares to the data from late June 2022, which found 6.43% of the COVID positive cohort also reported serious concentration issues compared to 4.82% in the never tested positive cohort. Individuals who had pre-existing cognitive issues and then tested positive shouldn’t lead to such a significant difference in percentages, as they should be proportionately represented in both groups.

In all fairness, there are other potential explanations for this than long COVID. Reverse causality (when Y causes X instead of the assumed X causing Y) is possible. Theoretically, if individuals with pre-existing cognitive issues are disproportionately vulnerable to contracting COVID, then we’d see a difference in the data here as well. I’m not going to completely write that off, I think it’s plausible, the CDC does list some neurological conditions as risk factors.

But I don’t really buy this argument. While other medical issues, life events, etc. can and do cause cognitive issues, I think it’s reasonable to assume that all or even most of them don’t have a massive impact on one’s susceptibility to COVID infection, which is the key metric here. The CDC’s listing of risk factors like neurological issues corresponds to severe illness, not infection itself. While I admit some conditions increase the risk of infection, (immunodeficiency, etc.), generally these CDC risk factors are related to the severity of said infection. In a world where COVID is rampant and restrictions are over, it’s personal behaviors, community prevalence, and the level of exposure we tolerate/are forced to tolerate in society that generally determine the odds of infection. As such, I don’t really believe that cognitive issues are a massive risk factor for contracting COVID, therefore I think it’s much more likely that COVID is causing cognitive issues, especially given the research I’ve talked about in this article.

But, let’s say you don’t agree with that argument. It’s important to realize that believing COVID is causing cognitive issues is not mutually exclusive to believing that cognitive issues could be risk factors for COVID infection, or other variables cause cognitive issues, etc. My argument is simply that given the effect size, observed through the raw and percentage change in cognitive issues in COVID + and COVID - cohorts, it’s more likely than not that COVID infection is playing a role here. I admit, we have to consider bias and inaccuracy in this survey — it’s self-reported and subject to non-response bias (perhaps those with cognitive problems post-COVID are more motivated to respond to the survey, skewing results), and a host of other biases inherent to these types of surveys.

But I don’t think these uncertainties disqualify the effect observed, if anything, the uncertainties could swing in the other direction and downplay the actual effect here. Similar to my analysis of the study on COVID’s cardiovascular ramifications, false negatives may be obscuring the effect size here. I think it’s basically a given that hundreds of thousands, if not millions of people who never tested positive for COVID did in fact contract COVID. Some studies estimate that during the spring 2022 Omicron surge in New York, case counts undercounted actual infections by a factor of 30. This means that the cohort of individuals that never reported testing positive likely included a significant number of individuals who did in fact get infected. As such, the fact that there is such a significant observable difference between the COVID + and COVID - cohorts, even when the COVID - cohort was “diluted” with individuals who were infected, indicates that the potential cognitive impact of COVID could likely be greater than what we observe here. If that doesn’t make sense, consider that someone with cognitive issues caused by a mild COVID infection they never tested for would fall under the COVID - cohort in this survey, thereby decreasing the number and percentage of reported COVID + patients with cognitive issues. This would thereby diminish the percentage difference in the prevalence of cognitive issues between the COVID + and COVID - cohorts.

On the other hand, the false positive rate of COVID tests is extremely low, estimated at 0.05% in this study. It’s very unlikely that someone mistakenly tested positive and reported cognitive issues without actually being infected with COVID. This means that there is a reasonable possibility that COVID’s impact on cognition is understated here.

Further, while survey data could very well over-report cognitive issues, I think it’s entirely possible that people under-report their cognitive issues post-COVID. Many people don’t know that cognitive issues post-COVID even exist. Further, studies have argued that older adults have consistently underreported their cognitive impairments. In a country where stigma against people with disabilities continues to be a problem, and where many are scraping by just to survive, admitting cognitive issues opens one up to potential discrimination and questions of fitness to do their jobs. I think there’s definitely pressure to avoid admitting cognitive issues on a survey conducted by the government for goodness' sake. Further, these cognitive impairments may also be subtle — too small to notice easily but nonetheless affecting performance.

In short — I think we can observe, not hypothesize, about the impact of COVID on this one barometer — cognition. This doesn’t even go into the other symptoms of long COVID (exhaustion, shortness of breath, etc.) or assorted health problems (cardiovascular issues, etc.) that cumulatively will likely have a tremendous impact on society and our nation’s health. You might not trust my analysis, after all, I’m not an expert in epidemiology, statistics, or anything for that matter. But that article from the Post comes to the same conclusion — millions are likely suffering from long COVID, which the article notes will affect our labor force and economy. This isn’t just the Washington Post, either. The Wall Street Journal and other economic experts agree. The Brookings Institution recently released a report estimating that 4 million Americans are out of work due to long COVID. These aren’t institutions and people with a vested interest in fear-mongering about COVID, if anything, their focus on the economy arguably makes them less likely to care about COVID. After all, some business leaders played an outsized role in arguing against COVID precautions. I’m not trying to say they are completely right. They may be wrong on the exact number of long COVID patients, long COVID’s precise quantitative impact on the economy. But I do believe that broadly, they are correct. Long COVID has and will continue to have a macro-level impact, and as time passes, I think that will only become clearer.

The broader ramifications are scary to think about. Americans are relentlessly optimistic. We generally believe the future will be better than the past. Long COVID threatens to upend that dynamic for many. A chronic illness, with uncertain pathology, no scientifically-proven, available treatments, and wide-ranging, sometimes debilitating symptoms, will change many lives for the worse. The tragic impacts of severe cases of disability are clear, but even the milder forms can be transformative. Consider a brilliant computer programmer, who experiences some mild brain fog after her second COVID infection. While she can continue to work, the flashes of insight and deep focus she once took for granted are much harder to come by, and her performance suffers. She misses out on promotions and pay raises. Her confidence drops. Maybe she even gets demoted, or decides to take on a less demanding job.

Or think about a high school cross-country runner, who experiences persistent shortness of breath after COVID. He loves being on the team, and maybe was even considering running in college. But his doctor advises him to take it easy on the running, and months later, when he tries to run again, he still can’t do so without feeling faint. He misses out on the season, finds it hard to stay friends with his teammates, and feels terrible.

Or maybe think about a recent retiree, who catches COVID, but thanks to vaccinations and antiviral treatments, is able to stay out of the hospital. He’s eager to enjoy his golden years, golfing, going to the beach, and spending time with his wife. But a year after that infection, he unfortunately has a heart attack that lands him in the hospital. While this was likely a result of many factors, perhaps in this case COVID contributed to it. He survives, but never recovers completely.

These are all examples of long COVID, with impacts that are hard, if not impossible to quantify in a research study. But ask any of these hypothetical three, and I’m sure they would consider the impact significant.

Cumulatively, our nation’s health will suffer dearly. As Dr. Benjamin Mazer notes in the Atlantic, “That form of epidemic—one that degrades quality of life, incrementally, for millions—is likely unfolding, even as a much smaller group of patients … see their lives utterly transformed by chronic illness.” I’m focused here on societal impact, but I bring up those three hypothetical anecdotes for a reason — the individual human cost on individuals who develop even comparatively mild cases of long COVID will be significant. As much as I have delved and will continue to delve into numbers, statistics, projections, etc., I never want to lose sight of that.

What I hope is crystal clear is that long COVID is a major threat to individual and societal health. A major tenet of public health is the concept of social determinants of health — that being how structural, environmental, economic, and other broad societal aspects of the community one lives in have a significant impact on one’s health. For example, having accessible, healthy food in nearby grocery stores enhances people’s nutrition, which improves their health. Whether it be safe housing, economic security, or education, there is a multitude of societal factors that play a significant role in an individual's health. Many of these are largely out of any one person’s control. How can any single person ensure that well-stocked grocery stores are in close proximity to their apartment if that’s one of the only apartments they can afford?

These are absolutely fundamental to understanding public health and have a deep linkage to COVID. For example, frontline, essential workers (34.5% of all workers) face higher viral risk than those who can work from home. These inequities and determinants are crucial, and in many ways, they will also be reflected in the ultimate toll of long COVID. For example, a frontline worker is more likely to get infected and reinfected with COVID, increasing their risk of long COVID. Lower-wage workers or those with limited health insurance will likely find it harder to secure diagnosis and treatment for long COVID, as they would for almost any health condition.

Understanding these social determinants of health is crucial. But I also think the inverse is crucial as well — broader health outcomes can have a significant impact on society at large. The potential ramifications are endless. Consider the families of those afflicted by long COVID. Patients with severe cases of long COVID may require caretaking from family members or hired help, imposing a significant emotional, time, and financial burden on people not directly affected by the illness. Or think about the economy and our workforce. Small businesses are already having trouble hiring employees, for countless reasons. Do we really think this will improve as more individuals develop long-term symptoms from COVID infections, causing them to potentially perform worse at their jobs, cut back hours, or quit entirely in the event that they get a severe, disabling case of long COVID? Also, consider the impact of a potential rise in disability claims. Without additional government action, Social Security Trust Funds are estimated to be depleted by 2035. While I assume the government would step in to ensure Social Security doesn’t become insolvent, adding more pressure via long COVID on an already overtaxed and underfunded social safety net doesn’t bode well.

Further, going back to American optimism — what drives much of our improved quality of life, economic growth, etc. is innovation. Whether it be new scientific and technological advancements or just creative and ingenious thinking broadly, innovation is a solid reason to believe that our future will be better than the past. But innovation isn’t easy, and we may need it now more than ever. As we face serious issues such as climate change, resource depletion, global pollution, cyberwarfare, and of course, COVID, we will need to marshall all the human brainpower, labor, knowledge, and ability we can to confront these problems and create innovative solutions. Even if small, I’m concerned that a non-negligible portion of our population will be facing long-term health issues of varying severity that will diminish their abilities when we need them most. How can we innovate and pursue cutting-edge solutions to the many problems that bedevil us if we aren’t healthy?

These are all hypotheticals, I admit, bordering on alarmist if not outrightly so. But the most pressing and currently evident impact that long COVID has on society will be on our already overburdened healthcare system. Currently, one of the primary means by which long COVID patients receive treatment for their condition are specialized long COVID clinics. Dozens of hospitals and health systems have opened these clinics, which is a welcome sight. However, as a poor omen of what is potentially to come, it’s simply not enough. Long COVID clinics are already facing months-long wait times. We need to rapidly expand healthcare capacity to treat long COVID patients, especially because COVID transmission remains elevated. All signs, at least in the research done for this article, point to more COVID cases also leading to more cases of long COVID.

The problem is we don’t have much capacity to spare. The US is already facing a dire physician shortage. Hospitals across the country face nursing shortages. Healthcare worker burnout, especially after over 2 punishing years of COVID-19, is rampant and alarming. About 1 in 5 healthcare workers have quit or retired from their jobs since the pandemic started. I will analyze this more in the final article of this series, but it’s a potentially disastrous state of affairs, with demand on healthcare systems likely to increase, while provider capacity simply fails to keep up. This doesn’t even take into account the “asymptomatic” long COVID I talked about. If the research in this article proves true and COVID infection does lead to a higher incidence of cardiovascular, neurological, and other diseases on a nationwide scale, then we will face additional heart attacks, strokes, psychiatric issues, and more, on top of symptomatic long COVID patients. All of these people will require treatment from a healthcare system arguably in worse shape now than it was a year ago.

I know many of you may disagree with my increasingly shrill, doomerist projections. And that’s completely reasonable. But I want to push back in one respect and reiterate a theme I’ve hammered throughout this article. You may disagree entirely on the rate of prevalence of long COVID. Despite everything I’ve said, perhaps the 5-30% figure doesn’t hit home. That’s understandable. But what I hope is clear is that the exact percentage isn’t what matters most. The fact of the matter is, risk exists, and many people, if not most, don’t even consider long COVID a risk at all. This risk, however small, is significant. When applied to hundreds of millions of people who are generally tolerating infection and reinfection, even an infinitesimal risk will lead to massive cumulative burdens.

So alright. The situation seems dire. But is there any hope?

Despite my pessimism, I believe so. At least 26 different randomized clinical trials are currently in motion, bringing hope that effective, experimentally verified treatments are on the horizon for people with long COVID. The NIH has received over $1 billion in funding to research long COVID. It’s also possible that new nasal vaccines could be en route, helping to stop COVID transmission and infection more effectively than our current intramuscular vaccines, thereby reducing or even eliminating the chance of getting long COVID. You can’t get long COVID if you don’t get COVID, after all. We also understand how COVID spreads — it’s an airborne virus, and by employing ventilation and filtration, we can diminish the number of infections acquired indoors. I realize for many, masking is off the table, and these low-to-no impact interventions could seriously dent the spread of COVID and therefore long COVID incidence. It’s entirely possible that with new treatments, new vaccines, and better ventilation, we can not only decrease the incidence of COVID infections and long COVID, but also diminish the suffering experienced by long COVID patients. But that’s only a possibility — we have to translate that into reality by funding and supporting the research that could yield breakthroughs, and once we get them, mobilize pharmaceutical, political, and public health infrastructure to ensure that these breakthroughs become accessible. It’s a tall task, and my pessimism can’t help but identify potential holes and speed bumps in this optimistic thesis. But I believe it’s definitely within reach.

In conclusion, long COVID is an underappreciated risk. COVID infections are associated with cardiovascular, neurological, and other serious health issues years after infection. Many individuals, even after vaccination, experience long-term suffering after catching COVID. While the exact rate of incidence and mechanisms remain uncertain, we can identify that it has had a tremendous impact on individuals and society at large. I fear that impact will only grow with time.

I admit, it’s weird being someone who writes 10,000+ word screeds about COVID, especially in this day and age when most have moved on from COVID. I have questioned myself a lot. But I keep returning to the research and the stories of those affected by COVID, and I can’t shake my conviction that this remains a concern worthy of my and our attention. To me, the danger of failing to confront COVID extends past the sizable risks of COVID itself. If we continue down our current path and fail to muster the sustained effort necessary to decisively confront the acute and long-term risks of COVID, we will likely just “accept” mounting consequences for increasing numbers of unlucky and underserved people that become seriously affected by COVID. As I mentioned in the reinfections article, I worry that this desensitization and resignation to human suffering and societal deterioration will carry over to the countless significant challenges we face in the future. I also worry that if we don’t have the foresight to counteract a creeping, sustained risk like long COVID, we will respond similarly to other crises. And if that’s the case, we will all pay the price for that.

Yikes. Enough depressing soothsaying. Hope remains, we just have to commit.

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