The Long Shadow of the Coronavirus Pandemic

The ongoing public health challenge of Long COVID

Photo by Elena Mozhvilo on Unsplash

In May 2023, the World Health Organization officially ended COVID-19’s designation as a public health emergency of international concern. After three years of pandemic emergency, nearly 800 million confirmed cases, and over 7 million reported deaths (likely an underestimate of the true totals), the global response transitioned from emergency measures to long-term management. Life returned to a strange, new normal.

But even though the global emergency phase of the pandemic ended, millions of people are still feeling the impacts of COVID. Today, three years after the end of the global emergency designation, millions face the long-term effects of a condition colloquially called “Long COVID”.

Long COVID, also called Post-COVID Conditions (PCC), is an infection-associated chronic condition experienced by some people after they become infected with the acute SARS-CoV-2 virus. Symptoms of this condition are present for at least three months and may persist continuously, relapse, or develop after the initial infection. A recent estimate suggests that 1 in 6 of those infected by the acute disease develop PCC, although different estimates vary widely.

Because of Long COVID, we’re facing a new public health challenge. Still reeling from the impact of a major infectious pandemic, the world of epidemiology is racing to understand the long-term impacts the disease may have.

What We Know About Long COVID

Since the onset of the 2020 pandemic, epidemiologists have placed heavy emphasis on uncovering the mystery of coronaviruses and SARS-CoV-2. Because of the unprecedented pace of global focus, we’ve made profound revelations regarding the disease and the virus.

Today, we know that Long COVID can include many different symptoms (200 have been identified so far), but most commonly, affected patients experience brain fog, fatigue, and a worsening of these and other symptoms following exertion. We have also observed that the heart, brain, and respiratory or digestive systems seem to be more commonly impacted, though there are occasionally symptoms related to joints, muscles, reproductive systems, and even the skin.

Because of its variation, scientists are now proposing that Long COVID isn’t really a single condition. Instead, evidence seems to suggest that Long COVID is an umbrella term for multiple clinical outcomes that may emerge as a result of experiencing COVID-19. Some researchers are classifying types by their potential biological mechanisms: persistent viral reservoir (viral material may persist in the tissues), autoimmunity (immune responses triggered by COVID-19 remain in the body and start attacking our own cells), reactivation (something about SARS-CoV-2 reactivates latent chronic infections), and microvascular and endothelial dysfunction (COVID-19 damages the blood vessels, which results in poorer tissue oxygenation). But these are very much still hypotheses and not established or mutually exclusive types of PCC as of writing this article.

According to a 2023 Brief from the CDC’s National Center for Health Statistics, we also know that some groups are more likely to develop Long COVID than others in the U.S. From the National Health Interview Survey, the brief found that women were more likely to have Long COVID than men, that those aged 35–49 were more likely to have it than other age groups, and Hispanic and Latine people were more likely to develop Long COVID than other racial or ethnic groups. Additionally, the report found that those with Long COVID were less common in urban centers and more common among the middle class. Note that belonging to one of these groups is not the cause of higher rates of disease, but these differences point to broader socioeconomic and structural disparities that should be further researched and addressed. In addition, evidence suggests that pre-existing chronic illnesses (particularly respiratory, metabolic, psychological, and connective-tissue related) may lead to a higher risk of developing Long COVID.

It’s difficult to definitively state the total number of cases of PCC since research is underway to determine how to accurately detect it, but we do have rough estimates. Instead of a laboratory measurement, some researchers are following patients over the course of their infection with COVID to track symptoms that emerge following the acute initial period of the illness, adjusting for what chronic conditions they may have already had before the infection. Using this method, it’s suggested that roughly 15 million Americans have PCC. Globally, among those who have tested positive, estimates suggest between 33–40% of COVID-infected individuals developed Long COVID, with significant uncertainty in measurement.

Each time we are infected with COVID-19, we know that we are at risk of developing Long COVID. Though there is some evidence that the risk of new-onset PCC decreases between the first and second infection of acute COVID, each subsequent infection adds to the cumulative risk of developing it. In cases where people already have PCC, there is an additional risk that subsequent acute infections may worsen present chronic conditions.

And unfortunately, we also know that having Long COVID doesn’t protect us from getting infected with SARS-CoV-2. Long COVID is associated with immune system dysregulation, inflammation, and autoimmunity (meaning the body’s immune system mistakenly identifies its own cells as invaders and attacks them) in some studies. Researchers are still investigating whether any of these immune changes affect susceptibility to reinfection or other illnesses.

Finally, we know that to prevent Long COVID, the best available strategy we have is to stay up to date on COVID-19 vaccinations. As we are still uncertain what leads to the development of Long COVID in some and not others, the most effective way we can avoid it is to avoid the initial infection, but even this does not entirely eliminate risk. In addition to vaccination, it can help to regularly wash hands and encourage others to stay home when they’re showing symptoms of respiratory illness.

Current Challenges in Our Understanding of Long COVID

Despite all we’ve learned about COVID and PCC over the past few years (and this moment in history has fundamentally shifted our understanding of the biology of coronaviruses and vaccination), there is still much we don’t know about Long COVID’s prevention, diagnosis, treatment, and cure.

One of the most challenging aspects of Long COVID is diagnosing it. We don’t currently have any single test that lets us know whether it’s the culprit of a patient’s symptoms definitively. To diagnose the condition, clinicians consider infection history and symptoms, perform physical examinations, and run targeted tests to evaluate for alternative or co-occurring conditions. Depending on what patients can afford and how long it takes to schedule healthcare appointments, this manner of diagnosing Long COVID can be agonizingly lengthy.

Because so little is known about PCC and how to diagnose it, it’s highly likely that we are underdiagnosing it, too. There may be people who are experiencing newfound chronic pains, discomforts, and mood shifts that have yet to be connected to the condition, and others who are having their symptoms dismissed. With a range of severity of symptom presentation and a wide variety of symptoms, it’s likely some folks are living with PCC without realizing it, too.

We also aren’t aware of any universal cure for PCC. For now, the current strategy is to treat the symptoms that emerge to minimize patient discomfort and improve quality of life. For some, treatments include medications that ease pain, suppress coughs, and combat newfound mood disorders. For others, treatment may look closer to physical therapy and treatments that have the patient practice retraining specific organs and senses. For even others, treatments may include talk therapy to help patients work through the feelings they may have about their long-term illness. Because cases can vary widely between patients, patient-centered care (in other words, opting for custom care over the cookie-cutter) is crucial.

And, though we’ve begun to scratch the surface of identifying and treating Long COVID, there is still much about the condition that we have yet to uncover. The core biological mechanisms that lead to Long COVID, for example, are still a major medical mystery. There are hypotheses present in research communities, but we’ve yet to determine a unified understanding of why the condition triggers in some and not others following an acute infection.

Clearly, we are in dire need of additional research. Beyond determining core mechanisms, we are also uncertain if different subtypes of the condition may benefit from certain treatments differently, if Long COVID behaves differently among children compared to adults, and how the disease progresses over the long term (and if it stabilizes or resolves). With major gaps in our understanding, our greatest challenge is to discover more, and quickly enough to maximize how many people we can help.

The Public Health Implications of COVID Long-Haulers

With such high estimates of chronic COVID prevalence, we must consider the ways our societies may be impacted, and the ways in which we must alter policy and infrastructure to accommodate this group of individuals.

For some, Long COVID can take a major toll on how much work they’re able to accomplish in a day. With a symptoms list that includes chronic fatigue, mental health problems, chronic pain, brain fog, and inflammation, it can become incredibly difficult to maintain the level of productivity they were able to achieve before contracting the illness. In the most severe of cases, these symptoms can result in disability.

A recent estimate suggests that 1.5% of U.S. adults (3.8 million people) are experiencing Long COVID in such severity that it qualifies as disabling. Some long-haulers experience newfound difficulty performing basic tasks like dressing and bathing, while others suffer brain fog and memory loss, or develop new mobility limitations.

This increase in disability may have profound impacts on who is capable of entering the workforce, particularly in the highly competitive job market we’re seeing today. Though those with particularly severe Long COVID may qualify for disability pay in the United States and other high-income nations, those who do not meet specific thresholds for disability in these countries may be left behind, even though they may find it more difficult to find or maintain a job. And globally, only about a third of people with severe disabilities receive pay benefits, particularly because many countries don’t have the money or infrastructure to provide this service. An unexpected increase in disability from COVID may result in both shifts in expected workforces and significant individual financial strain.

As I mentioned above, PCC can cause a wide variety of symptoms and complications. Because of the condition, those affected may see an impact on their routine healthcare needs. Some with PCC may require additional visits, diagnostics, medications, treatments, and other services. With increased hospital visits, particularly in countries without universal healthcare, there is a risk of increased direct and indirect costs to patients. And additional visits by a subsection of a society place an additional burden on the healthcare system, requiring more beds, a greater cost, and a larger workforce of health professionals.

And, as a result of all this, Long COVID may deepen existing health inequities by increasing medical costs and making it harder to sustain employment among groups already faced with structural disadvantages tied to social position. Essentially, long COVID could amplify extant inequity.

This decade has been defined by COVID: its emergence, public response, its research, and the profound revelations we’ve uncovered as a result of investigating it. We’ve made incredible progress, but we still have a way to go to demystify all of its impacts. To successfully uncover what we don’t yet know about Long COVID, we need additional resources and funding to research it.

The stepping stones ahead we must traverse are numerous. We must standardize subtypes of Long COVID cases into meaningful categories, as there isn’t yet a consensus on these categories. We must continue exploring potential biomarkers of Long COVID, so that we have a more objective way to determine when someone truly has Long COVID. We must find methods to make predictions of how long-haulers will respond to particular treatments, too. To manage these advancements, we need additional research: long-term and large-scale studies that take into account how patients are experiencing their symptoms, how the disease progresses over time, and what causes it to develop in some and not others. To accomplish this, we need better surveillance and more cooperative information sharing between countries to improve the efficiency of our research.

While we work towards prevention, better treatments and, hopefully, an eventual cure, we need better accommodations for those who are afflicted with Post-COVID conditions today. The first step is spreading awareness, so these long-haulers are no longer invisible in our society. Our friends, our family, and our neighbors may be experiencing these ill effects without a diagnosis. They may be commenting on a newfound set of symptoms that can’t be diagnosed despite the tests they’ve endured, unaware that it’s Long COVID. Others may already know. Either way, with profound implications for the long-term impacts of COVID, we must consider how to create a world that works for the Long COVID long-haulers. Post-pandemic, we must consider long-term adaptations that will minimize the negative COVID outcomes we now face.