A large U.S. study uncovers a wide range of complications linked to long COVID

Many survivors of COVID-19 have long-term complications that are commonly called long COVID. Some studies that have been done with these people were not able to dig deeper into the data collected to explore the difference in the manifestations of long COVID between genders or between younger and older people.

Now, a research team in the U.S. has conducted a study comparing health-related information from 266,000 people who became infected with SARS-CoV-2 with about 9 million people who did not. The researchers also reviewed data from other years to compare health and use of medical resources in another group of people.

The researchers found more than 50 different manifestations of long COVID occurring in 14% of participants. Common persisting health issues included the following:

• problems breathing
• abnormal heart rhythms
• excessive formation of blood clots
• brain inflammation
• injured nerves
• memory problems
• diabetes
• liver inflammation
• heart inflammation
• anxiety
• fatigue

The researchers found that the greatest risk for developing long COVID was in people with the following factors:

• older than 50
• having underlying health conditions
• hospitalization for acute COVID-19

Though people outside these groups were at risk for developing long COVID, their risk was lower than that of people with the above-listed factors. Furthermore, the researchers found differences in the distribution of manifestations of long COVID between men and women.

Study details

Researchers reviewed several databases with a health insurance plan called UnitedHealth Group. Using data from 9,247,505 people, the researchers created two main groups for comparison:

• number of people who tested positive for SARS-CoV-2, some of whom developed COVID-19 – 266,586
• number of people who were not diagnosed with SARS-CoV-2 infection – 8,980,919

The main focus of the study was data collected over the period of January through October 2020. For purposes of comparison, the researchers assessed health-related information collected in 2019 and 2017 from people who developed lung infections due to influenza and other causes.

All participants were between 18 and 65 years (average age was 42) and the proportions of men and women were the same.

Results

Among the people with SARS-CoV-2, 8.2% were hospitalized and 1% were admitted to an intensive care unit.

Focus on long COVID

The vast majority of participants (86%) who became infected with SARS-COV-2 did not develop long COVID 21 days after their positive test result (14% did develop long COVID). This figure of 14% is similar to that found by the Office of National Statistics in the UK.

Among the 14% of participants who did develop long COVID, the distribution of symptoms was as follows:

• 10% – one symptom of disease
• 4% – more than one symptom of disease

All 14% required medical care for these symptoms.

Time

Although the risk for developing a serious complication was greatest one month after having a positive test result for SARS-CoV-2, the researchers found that even up to six months after infection, people were at heightened risk for the following:

• high blood pressure
• diabetes
• sleep apnea
• fatigue

Although the risk of symptoms of long COVID was greatest in people over the age of 50, researchers found that people between the ages of 18 to 34 had a modestly elevated risk for at least the following conditions:

• high blood pressure
• abnormal heart rhythms
• excessive blood clots
• memory problems
• diabetes
• fatigue

Mental health

The risk for developing a mental health condition was increased among all people regardless of age or presence of underlying conditions.

Gender

In general, the researchers did not find many differences in the symptoms of long COVID by gender, except for the following:

• women were more likely to have fatigue and loss of sense of smell
• men were more likely to have heart inflammation, excess blood clots, kidney injury and sleep apnea

Bear in mind

Viral illness, including severe bouts of the flu, can cause medium- and long-term problems. However, the depth of issues faced by people with long COVID seems much greater than the consequences of many other acute viral infections. For instance, the researchers analyzed data from people diagnosed with influenza in 2019, when COVID-19 was largely unknown. They found that people who were diagnosed with COVID-19 in 2020 generally had two times as many long-term complications as people who had influenza and other respiratory viral infections in 2019.

Imperfections and strengths

The present study reviewed data for one purpose (an administrative database) and reanalyzed it for another purpose—to find out more about COVID-19 and long COVID. Such a study design may inadvertently cause biased interpretation of the data.

It is possible that the full breadth of long COVID symptoms was not captured by the study. The researchers cautioned that some patients may not have reported all of their symptoms and some doctors may not have recorded all of the reported symptoms.

There was a lack of individual level data on race/ethnicity.

Despite its imperfections, the present study’s findings align with those of other studies. Another study from the British Office of National Statistics found that about 14% of people who survived acute COVID-19 developed long COVID. This is strikingly similar to what the current study has found. The present study also echoed findings from other studies that suggest that long COVID affects women more than men as well as people with low income.

Unpredictability

Commenting on the present U.S. study in the journal BMJ Open, scientific advisor Elaine Maxwell stated in an editorial:

“It is too early to predict how long the [symptoms of long COVID will persist] but the symptoms clearly create a major personal burden for many people, with some individuals experiencing difficulty returning to work and [being] unable to care for dependents.”

She added: “One of the peculiarities of long COVID is its non-linear progression, hampering attempts to predict who will develop particular symptoms and when. Risk factors differ for different new diagnoses of [long COVID symptoms], suggesting that a variety of mechanisms could be subdivided into more specific phenotypes.”

—Sean R. Hosein

 REFERENCES:

1. Daugherty SE, Guo Y, Heath K, et al. Risk of clinical sequelae after the acute phase of SARS-CoV-2 infection: retrospective cohort study. BMJ. 2021; in press.
2. Maxwell E. Unpacking post-covid symptoms. BMJ. 2021; in press.