The Covid pandemic has cast a long and bewildering shadow that continues to confound scientists – long Covid – an all-encompassing term used to describe more than 200 different symptoms suffered by people long after they were first infected by the coronavirus. The scientific community is unsure why certain conditions persist, who will be affected, and for how long. The World Health Organization (WHO) has given it a name – post-Covid condition – and is focusing more resources on refining the diagnosis. Hospitals continue to improvise their treatment approaches, while patients and physicians struggle with all the uncertainty. The most in-depth research study to date on long Covid was recently published in The Lancet. It found that one in eight adults (13%) infected with coronavirus suffered post-Covid symptoms, but experts are calling for more research and specialized healthcare facilities for this “urgent health problem.”
Vicky Béjar caught Covid in March 2020, at the beginning of the pandemic. The disease affected her digestive system, and she had fever, headaches, fatigue, and more. Months went by and the symptoms persisted. Some days were better than others, but she was never the same, and her post-Covid conditions have stayed with her ever since. “I still have fevers above 100.4°F (38°C), tachycardia, bradycardia (slow heart rate), fatigue, and mild cognitive impairment,” said the 47-year-old woman from Barcelona (Spain). “I’m an accountant and manage a family business, but I still can’t work. I’m trying to relearn the multiplication tables, but struggle with numbers and organization. I have this mental fog that makes it hard to concentrate.”
Scientists are trying to identify the distinct sequelae (the consequences of a previous illness or injury) of severe disease, such as respiratory failure following severe pneumonia, from the nonspecific symptoms that often persist in people who had mild cases of Covid. The latter usually don’t have any physical signs or affected organs, which complicates the diagnosis. Béjar says she is lucky that a specialized medical unit is monitoring her health, but complains of “institutional mistreatment” by Spain’s public health system and says, “They don’t listen to us.”
It’s not easy to measure the pervasiveness of a clinical condition that displays such variability and lacks specific symptoms
Lorenzo Armenteros, a spokesperson for the Spanish Society of General Practitioners (Sociedad Española de Médicos Generales), also claims that some colleagues “still do not believe that this condition exists.” Armenteros said, “It’s a public need and a significant epidemiological challenge – it must be treated.” The WHO’s clinical case definition of post-Covid condition states that it occurs in individuals, “… usually three months from the onset of Covid-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis.”
But it’s hard to get a fix on the scope of long Covid. The WHO’s European Observatory on Health Systems and Policies noted in 2021 that 25% of people with Covid had symptoms up to a month after diagnosis, and 10% still had symptoms 12 weeks later. One study found that only 2.3% had post-Covid conditions, while another found at least one recurring symptom in 73% of those infected. A June 2022 survey by the US Centers for Disease Control and Prevention (CDC) reported that one in five adults who had Covid suffered from persistent symptoms.
It’s not easy to measure the pervasiveness of a clinical condition that displays such variability and lacks specific symptoms. The time period measured, the study population, and the symptoms used to define long Covid all influence this variability, notes one of the authors of The Lancet study, Aranka Ballering (Department of Psychiatry, University of Groningen, Netherlands). “Many studies only assessed whether people’s symptoms were present at a certain point in time after their Covid diagnosis. However, some post-Covid-related symptoms such as headaches and fatigue are very common, and people experience them regularly, even if they are not ill. In addition, some symptoms may also be caused by a change in season. For example, a runny nose or sneezing may be caused by allergic rhinitis rather than by Covid. This means that proper control populations are needed to accurately estimate the prevalence of post-Covid.”
The research by Ballering and her colleagues used regular questionnaires to monitor over 76,000 people from March 2020 to August 2021. During that time, 4,231 study participants became infected with Covid, and were matched to a group of 8,462 people of similar ages and gender who were never diagnosed with Covid. “This control group of Covid-negative people enabled us to account for the effects of public health measures (such as confinement, home schooling, etc.) on somatic symptoms, and also allowed us to account for symptoms caused by seasonal changes,” said Ballering. “Second, because our study used a general population cohort, we had information on their health even before they were diagnosed with Covid. This allowed us to assess whether people had an increase in symptom severity after the Covid diagnosis compared to before.” Thus, the study participants functioned as their own control mechanism. “It enabled us to see whether any symptoms experienced three to five months after their Covid diagnosis were more severe than before, or whether they represented a continuation of pre-existing symptoms.”
The study found that one in eight adults (12.7%) in the general population experienced long-term symptoms due to coronavirus infection. The main symptoms reported were loss of smell and/or taste (anosmia and ageusia) and muscle pain, although chest pain, shortness of breath, tingling, and fatigue were also common.
More questions than answers
Pere Domingo, the Covid coordinator at Sant Pau Hospital in Barcelona (Spain) says the study published in The Lancet is “very solid… because it has a Covid-negative control group that helps us determine whether Covid caused their symptoms.” But Domingo also cautions that “This study used old [coronavirus] strains. We don’t know whether [its conclusions] can be applied to the delta or omicron variants. There are probably some differences because we don’t see as much anosmia with omicron.” Widespread vaccination began after this study was already underway, which could also have a tempering effect on long Covid, said Domingo. One of the limitations of the study noted by its authors is that the incidence of Covid may be underestimated because of unidentified asymptomatic cases in the supposedly Covid-negative control group, highlighting the difficulty and need for accurate diagnosis.
Aside from the number of people affected, there are more questions than answers about long Covid, said Domingo, starting with its origin. “One hypothesis is that bits of virus may remain in the body and generate a pathological and immunological response. It seems plausible,” he said. Joan B. Soriano, an epidemiologist with La Princesa Hospital in Madrid (Spain) and a member of the WHO working group that defined the post-Covid condition, says that up to seven different mechanisms are being studied. “Persistent inflammation, immune dysregulation, coagulation disorders, viral persistence, autonomic dysfunction, endocrine and metabolic mechanisms, and maladaptation of the ACE2 pathway [the receptor through which the virus enters the cells].” Soriano points out that it’s likely that “… many of these mechanisms interact synergistically in some patients.” What we do know, said Soriano, “is that revaccination reduces the frequency and severity of long Covid.”
The main symptoms reported were loss of smell and/or taste (anosmia and ageusia) and muscle pain, although chest pain, shortness of breath, tingling, and fatigue were also common
One of the most common symptoms are neurocognitive disorders, said Domingo. People report having “… a kind of brain fog… they have trouble concentrating and can’t remember things.” He has also observed respiratory problems. “We saw a study of a group of patients with air trapping in the lungs, which is when the smallest airways remain inflamed, like asthma.” Vicky Béjar says that the most debilitating problem for her is the neurological deterioration and fatigue. “There are days when I just can’t get my body going and I can’t leave the house.”
Deciding on the right treatment for long Covid is difficult without knowing its cause. Specialists recommend mental exercises to overcome neurocognitive problems, physical exercise for motor damage, and training methods to recover the sense of smell. But all the experts agree that long Covid has a high impact on quality of life. It has “many social and personal implications,” said Armenteros. “Some patients don’t fully recover by the time they run out of sick leave from work, and their employers don’t offer any options for a gradual return to the workplace.” Other patients are still struggling to recover from long Covid. Armenteros says that it’s not clear what type of person is predisposed to long Covid. Some studies indicate that it affects women more than men, but he says “… we need more research to evaluate whether the female gender is a risk factor.”
It’s also unknown how long post-Covid conditions can persist. The study conducted by Ballering and her colleagues only collected data for five months after infection, so Domingo says that only time will tell the real duration of long Covid. “The most important consideration is the impact on quality of life. If 13% of the millions of people who had Covid are suffering from post-Covid conditions, then the impact of long Covid is stratospheric.”
Impacts to healthcare systems
Healthcare systems, already under pressure from staffing shortages that were exacerbated by the pandemic, are worried about the impacts of long Covid. Some hospitals have created multidisciplinary units to respond to this new demand, but patients complain about the lack of resources and focus on the problem as they bounce from one doctor’s office to another searching for answers.
Domingo says, “… we’re doing what we can” with the resources available, but “… it would be ideal to have specialized units to address the different health problems. This is not being done enough.” Armenteros agrees that patients become desperate wandering from doctor to doctor without getting any answers. “The primary care settings and hospitals are unprepared. The system is already stretched to the limit, and a new crisis will exceed capacity. And without people and facilities specializing in long Covid, we’re just going around in circles.” There is an urgent need for more resources for long-term Covid research and patient care, warns Domingo. “We need to understand the natural evolution of this condition. If it is self-regulating, the impact will be manageable. But if it persists over time, then it will require higher levels of research and care.”
Experts say that symptoms usually disappear or at least diminish in most cases. A study published in JAMA Otolaryngology-Head & Neck Surgery found that 88% of the people studied who had olfactory or taste dysfunction after Covid fully recovered after two years. “A significant number have fewer symptoms over time, but others still need support – they don’t heal on their own. Some people recover and then relapse again,” said Armenteros.
One thing experts share is a concern about the uncertainty that surrounds long Covid and its impacts. Ballering warns that it is “an urgent health problem, with a growing number of victims.” US Assistant Secretary for Health Rachel Levine agreed in a recent JAMA article, “It is important to focus a new lens on the pandemic and direct much-needed attention to long Covid. Taking care of affected patients presents challenges given the incompleteness of research, the lack of sufficient diagnostics support, and pervasive problems with access to services.”