Long COVID May Manifest Itself in 4 Major Ways, Research Shows

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Key Takeaways

  • Researchers from Weill Cornell Medical College have identified four distinct subtypes of long COVID using a machine learning algorithm.
  • The subtypes are marked by different ranges of symptoms: cardiac and renal issues; respiratory problems, sleep problems, and anxiety; musculoskeletal and nervous system issues; digestive and respiratory system issues.
  • Experts say that having medical professionals understand the different long COVID subtypes can help ensure that patients receive better treatment. 

A recent study published in the journal Nature Medicine outlines four major subtypes of long COVID, each defined by a different range of symptoms.

The largest subtype is defined by cardiac and renal issues, and largely attributable to the early days of the pandemic. The smallest and most mild subtype, on the other hand, is marked by gastrointestinal symptoms.

While being able to cluster together the broad range of long COVD symptoms—and who is most likely to experience them—is a major step for research, experts say people living with the condition shouldn’t necessarily try to identify with one group or another. Rather, this classification system will help experts improve diagnosis and treatment approaches.

The hope is that the study’s findings “can inform future research on the disease mechanism of long COVID, treatment development, and public health policymaking,” Fei Wang, PhD, a corresponding author of the study and an associate professor of population health sciences at Weill Cornell Medical College in New York, told Verywell.

What Is Long COVID?

Long COVID is currently defined as the continuation or development of new symptoms (such as fatigue, shortness of breath, and cognitive dysfunction) that develop three months or more after contracting an initial infection. Long COVID symptoms can also last for at least two months with no other explanation, according to the World Health Organization (WHO).

The Centers for Disease Control and Prevention (CDC) estimates that roughly 1 in 13 adults in the U.S. (7.5%) have long COVID symptoms, which is more than 19 million Americans.

4 Subtypes of Long COVID

For their study, Wang and colleagues analyzed the health records of nearly 35,000 patients in the United States who tested positive for a SARS-CoV-2 infection and later developed symptoms of long COVID.

Each patient had at least one lingering COVID symptom that lasted between 30 and 180 days after their initial COVID-19 infection.≠

Using a machine-learning algorithm to sort through all the health records, the researchers identified more than 137 lingering long COVID-type symptoms. Then, they grouped the symptoms into four main subtypes or categories.

Other studies have also classified long COVID symptoms into groups, but Wang said that their new study is the “largest of its kind” to look at the condition.

Here’s a breakdown of the four subtypes of long COVID Wang and colleagues identified.

Subtype 1: Cardiac and Renal Conditions 

The first subtype of long COVID consisted of around 34% of patients, making it the most prevalent long COVID symptom group. It was most prominent in people who were infected during the first wave of the pandemic: from March to June 2020.

Compared to other subtypes, people in this group skewed older, with a median age of 65. Out of all the subgroups, it had the highest proportion of males at 49%.

The people in this group presented with:

  • Cardiac-related conditions
  • Renal-related conditions
  • Circulation-related conditions
  • Heart attacks
  • Heart failure
  • High blood pressure
  • Renal/kidney failure
  • Anemia
  • Fluid and electrolyte disorders
  • Irregular heartbeat
  • Cramps
  • Dizziness

Patients in subtype 1 had a higher acute severity of COVID, including the highest rate of hospitalization (61%), use of mechanical ventilation (5%), and critical care services (10%).

Subtype 2: Respiratory, Sleep, and Mood Problems

The second most common long COVID category accounted for about 33% of all patients, most of whom were infected later in the pandemic: between November 2020 and November 2021. 

Unlike subtype 1, Wang said most of the people in subtype 2 were female (63%). Subtype 2 was also associated with more mild acute disease. For example, the hospitalization rate was 31%—only half of the rate of subtype 1.

Some of the most prominent symptoms in people classified as subtype 2 include:

  • Respiratory conditions
  • Sleep disorders or insomnia
  • Anxiety
  • Headache
  • Chest pain

Subtype 3: Musculoskeletal and Nervous System Conditions

Around 23% of patients fell in the third subtype group. The majority of this group were female (61%), and the median age was 57.

Subtype 3 occurred most often in patients with preexisting autoimmune and allergy conditions, such as rheumatoid arthritis and asthma, as well as other musculoskeletal and nervous system conditions, like soft tissue, bone, and sleep disorders. 

Patients in subtype 3 were most likely to experience:

  • Symptoms of musculoskeletal and nervous system disorders
  • Nerve pain
  • Headaches
  • Sleep-wake disorders

Subtype 4: Digestive and Respiratory System Problems 

The last subtype was not as common as the other subtypes and was only seen in about 10% of patients.

Compared to the other subtypes, patients in subtype 4 had a lower overall burden of underlying conditions, but had a slightly higher prevalence of digestive system conditions, such as stomach disorders and vomiting blood (hematemesis).

Most of the patients in subtype 4 were female (62%). This group had the lowest rates of mechanical ventilation use (0.8%) and critical care admission (3%) in the acute phase of SARS-CoV-2 infection.

People in subtype 4 experienced conditions like:

  • Gastrointestinal disorders
  • Stomach pain
  • Nausea
  • Other gut symptoms

How Do You Know Which Type of Long COVID You Have?

While the researchers have pointed out four distinct types of long COVID, Wang said that does not mean that people who have long COVID must strictly place themselves into one of the groups.

Instead, this information can be used to help other researchers, clinical professionals and the public better understand the implications of long COVID, such as the different symptoms of the condition and who they might affect.

Linda Yancey, MD

It’s a great start for research but will not mean anything to individual patients at this stage.

— Linda Yancey, MD

“These are common patterns we saw, although it doesn’t mean you must strictly fall into only one subtype. These are just the potential groups,” said Wang. “Instead of thinking of the subtypes one by one, these four subtypes are the group of combinations that tends to occur together rather than independently.”

While the new study is useful for research purposes, Linda Yancey, MD, an infectious disease specialist at Memorial Hermann Health System in Houston, said that it cannot be applied to individual patients yet. 

“There was a huge range of symptoms that were considered and they used coding data from visits—which are notoriously inaccurate,” said Yancey, who was not involved in the study. “It’s a great start for research but will not mean anything to individual patients at this stage.”

This Research Could Benefit Other Conditions, Too

Yancey said that studies like this are important because the findings will improve our understanding of post-infectious fatigue syndromes that don’t have much data, especially since so many Americans have had COVID in the last three years.

“This is an opportunity to gather population-level data in a way that we have never been able to do before,” she said. “Some of these patients have life-changing symptoms.”

Having a better understanding of life-changing symptoms can help guide research on how to treat them.

“This will be helpful to patients with long COVID and other chronic post-infectious syndromes like post-treatment Lyme syndrome,” Yancey said.

Can You Get Help For Long COVID?

Wang said that people who think they could have long COVID should closely monitor their symptoms and talk to their healthcare providers about taking an individualized approach to managing them.

Yancey added that people can look for long COVID studies or therapy centers in their communities that may provide treatments like multi-modal rehabilitation, strength and endurance training, a neurological evaluation, and even “smell training” for people who have lost their sense of smell.

“Right now, there are not a lot of proven treatments for long COVID. However, there is a lot of work going on trying to find them,” said Yancey. “I am confident that with the help of studies like this one, we will have better treatments in years to come.” 

What This Means For You

The proposed subtypes of long COVID may not be useful to individual patients, but they are helping us learn more about the symptoms of the condition.

If you think you’re experiencing long COVID, reach out to your provider and talk to them about how you can manage your symptoms.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

5 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Zhang H, Zang C, Xu Z, et al. Data-driven identification of post-acute SARS-CoV-2 infection subphenotypesNat Med. Published online December 1, 2022. doi:10.1038/s41591-022-02116-3

  2. World Health Organization. Post COVID-19 condition (long COVID).

  3. Centers for Disease Control and Prevention. Nearly one in five American adults who have COVID-19 still have “long COVID.”

  4. Weill Cornell Medicine. Study identifies four major subtypes of long COVID.

  5. Ford E, Parfitt H, McCheyne I, Kiss IZ, Sellers R. Risk factors and symptom clusters for long Covid: analysis of United Kingdom symptom tracker app data. medRxiv. Preprint posted online November 14, 2022. doi:10.1101/2022.11.14.22282285

By Alyssa Hui
Alyssa Hui is a St. Louis-based health and science news writer. She was the 2020 recipient of the Midwest Broadcast Journalists Association Jack Shelley Award.