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More than one in three people may experience at least one symptom of long COVID, new research suggests. Jasmin Merdan/Getty Images
  • Individuals with long COVID exhibit lingering symptoms, such as fatigue and brain fog, that persist beyond the typical recovery period of 3–4 weeks after the symptom onset.
  • A recent study assessed the incidence of long COVID symptoms using data extracted from de-identified electronic health records.
  • The study found that more than one in three individuals experienced long COVID symptoms 3–6 months after receiving a COVID-19 diagnosis.
  • The study also reports that women, older adults, and individuals with severe illness during the initial phase of a SARS-CoV-2 infection had an increased likelihood of experiencing long COVID symptoms.

A majority of individuals recover from a SARS-CoV-2 infection within a few weeks after the onset of symptoms. However, a substantial number of individuals continue to experience COVID-19 symptoms more than 3–4 weeks after contracting the virus.

Health experts refer to the symptoms that persist beyond this acute phase of a SARS-CoV-2 infection as long COVID.

Multiple studies have investigated the incidence rate of long COVID and its symptoms. However, these studies have certain shortcomings.

For instance, some of the studies have used self-reported data collected using telephone or app-based surveys. Besides the potential biases that accompany self-reports, the data collected as part of these studies were restricted to patients who agreed to participate in the research.

Other studies have used follow-up data collected from individuals hospitalized with COVID-19 during the acute phase, limiting the generalizability of the findings. Moreover, many of these studies have lacked a control group.

To address these shortcomings, a recent study led by a team of researchers at Oxford University in the United Kingdom used de-identified medical records of 273,618 COVID-19 survivors to assess the risk of having long COVID symptoms in the 6 months after the initial diagnosis.

The presence of persistent symptoms following an acute infection, known as the post-viral syndrome, is a common feature of other viral infections. To evaluate the specificity of long COVID symptoms, the researchers compared the incidence rate of long COVID symptoms after COVID-19 with those observed after flu.

The study, which appears in the journal PLOS Medicine, found that more than one-third of the COVID-19 patients had long COVID symptoms 3–6 months after a SARS-CoV-2 infection. Moreover, long COVID symptoms were more common in women, older adults, and individuals with severe symptoms during the acute phase.

The study also showed that long COVID symptoms were more frequent in people with COVID-19 than in those with influenza.

“This is a very important study again showing that long COVID is common in people who had COVID-19. They also did a comparative analysis and show that the risk of post-acute complications is much higher with COVID-19 than [with] seasonal influenza,” said Dr. Ziyad Al-Aly.

“Long COVID affects a lot of people. I worry that there are a lot of people out there that are not being helped and not being diagnosed and not getting the care they need. It is very important that we start taking this more seriously,” Dr. Al-Aly added.

Dr. Al-Aly is the chief of Research and Education Service at Veterans Affairs St. Louis Health Care System in St. Louis, MO, and was not involved in the study.

There is currently a lack of consensus within the scientific community about the definition of long COVID and the time of onset of long COVID symptoms. Therefore, the researchers used previous studies to identify the nine most common symptoms and diagnoses associated with long COVID.

These symptoms are:

The researchers assessed the incidence of these symptoms during the initial 6 months after symptom onset. They also quantified the occurrence of these symptoms during the “long phase” of COVID-19, which was defined as the period between 90 and 180 days after diagnosis.

The authors of the study found that nearly 37% of the individuals had at least one symptom of long COVID 3–6 months after the SARS-CoV-2 infection.

Of the individuals who experienced long COVID symptoms during the long phase, around 60% also exhibited one or more of these symptoms during the initial 90 days.

In other words, the remaining 40% of this group of individuals who experienced persistent COVID-19 symptoms in the long phase did not experience any of these symptoms during the first 3 months.

The researchers found that certain symptoms, such as difficulty breathing, were more common during the initial 3 months. On the other hand, symptoms such as anxiety and depression were more common during the long phase.

Similar to previous reports, the individuals who experienced severe illness during the acute phase of the infection had a higher risk of experiencing long COVID.

The researchers also assessed the incidence of long COVID symptoms according to gender, age, and race.

Long COVID symptoms were more common in women and older adults. There was also a difference in the incidence of long COVID symptoms among the different patient subgroups.

Women and younger individuals were more likely to experience headaches, anxiety or depression, and abdominal symptoms than men and older adults, respectively.

In contrast, cognitive symptoms and breathing difficulties were more frequent in older adults and men. Older adults were also more likely to experience fatigue and pain than younger patients.

Notably, over 46% of the patients aged 10–21 years had at least one long COVID symptom during the 6-month period after the SARS-CoV-2 infection. Similarly, more than half of the nonhospitalized individuals also experienced one or more long COVID symptoms.

The researchers did not observe any significant differences in the occurrence of long COVID symptoms between white and non-white patients. The study’s first author, Dr. Maxime Taquet, NIHR Academic Clinical Fellow at Oxford University, said:

“The results confirm that a significant proportion of people of all ages can be affected by a range of symptoms and difficulties in the 6 months after COVID-19 infection. These data complement findings from self-report surveys and show that clinicians are diagnosing patients with these symptoms. We need appropriately configured services to deal with the current and future clinical needs.”

Symptoms such as fatigue and brain fog observed in long COVID also occur after the acute phase of other viral infections, including influenza. To investigate the specificity of these symptoms to COVID-19, the researchers compared the incidence of the nine long COVID symptoms in COVID-19 with influenza.

The risk of incidence of any of the nine long COVID symptoms during the long phase and the entire 6-month period after symptom onset was higher for COVID-19 than it was for influenza.

In addition, many of the long COVID symptoms were more likely to occur together after COVID-19 than after influenza.

This indicates that the incidence rate and pattern of occurrence of long COVID symptoms after COVID-19 may be distinct from those present after influenza.

One of the strengths of the study is the use of electronic health records over telephone surveys, thus providing access to a larger dataset. Furthermore, electronic health records can also help evaluate the actual impact of long COVID on the healthcare system.

However, the authors acknowledge that the study had some limitations. One of the disadvantages of using electronic health records is the potential underestimation of long COVID cases. This is because some individuals with mild symptoms of long COVID may not have visited a healthcare professional, resulting in the absence of medical records.

Moreover, electronic health records provided information mostly restricted to the occurrence of long COVID symptoms. Thus, the current study was unable to provide insights about the severity and the duration of these symptoms.

The authors also note that their analysis was confined to the most commonly described long COVID symptoms and hence was not comprehensive.

Dr. Al-Aly noted: “The study is well done. One major limitation is that they only focused on nine features of COVID-19. We know that long COVID is a much broader condition and can involve a lot more features than what was examined in this study. For example, they did not look at diabetes, heart disease, and kidney disease — all these are known to be major issues in long COVID.”

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