Study sheds new light on long-term COVID illness

Most people who get COVID-19 recover within a few weeks. But some people — even those who had mild cases of the disease — continue to have symptoms weeks or months after initial exposure to COVID. These persistent health problems, called post-COVID conditions (PCC), post-COVID-19 syndrome, prolonged COVID-19, and post-acute SARS COV-2 (PASC), can reduce patients’ quality of life and increase the burden of disease on health care systems health. As more patients suffer from prolonged COVID, it becomes increasingly important to identify symptoms associated with prolonged COVID for effective diagnosis and treatment of the disease.

New research by doctors and researchers at Kaiser Permanente, Mid-Atlantic Permanente Research Institute (MAPRI) and Johns Hopkins University has identified 17 long-term COVID-related illnesses to better diagnose and treat the disease. The study “Post-acute effects of SARS-CoV-2 with clinical disease definition and comparison in a matched cohort” was published on October 12, 2022 in Communications of nature.

“Although considerable research has been done to determine the clinical definition of long-term COVID, the reality is that the disease can look very different from patient to patient,” said lead study author Michael Horberg, MD, a physician- infectious disease specialist and associate medical director of Kaiser Permanente, Mid-Atlantic Permanente Medical Group. “Our study aimed to identify conditions that were most likely to be associated with prolonged COVID.”

The study reviewed the medical records of more than 100,000 Kaiser Permanente Mid-Atlantic States adult patients — more than 30,000 who tested positive for COVID-19 and more than 70,000 who tested negative for COVID-19 — in 2020. 17 diseases were identified:

• Other diseases of the lower respiratory tract
• Diabetes mellitus
• Gastrointestinal diseases
• Dizziness or vertigo
• Abdominal pain
• Nonspecific chest pains
• Mental health disorders
• Anxiety disorders
• Genitourinary symptoms
• Fatigue and malaise
• Heart rhythm disorders
• Disorders of the nervous system
• Respiratory failure
• Anosmia (loss of smell)
• Nausea and vomiting
• Fluid and electrolyte disorders
• Nutritional disorders, endocrine and metabolic processes

The researchers were most interested in diseases that developed in patients within 30 days of a positive test for COVID-19 and persisted for almost four months after the date of analysis, as well as diseases that developed between 30 and 120 days after a positive test. Major illnesses included loss of smell, cardiac arrhythmia, diabetes, genitourinary disorders, fatigue, and chest pain.

The researchers used reliable Kaiser Permanente electronics medical documentation to classify illnesses into three different time intervals based on when the patient tested positive for COVID-19. By organizing the conditions by the date of the patient’s positive test, the researchers were able to effectively assess whether the symptoms that occurred were related to prolonged COVID rather than due to an existing health condition.

In addition, comparing patients with COVID-19 with negative patients (the control group), the researchers were able to find out which symptoms appeared more often in the COVID-positive group, which symptoms appeared more often in the COVID-negative group, and which symptoms appeared at the same rate in both groups.

“One of the reasons that COVID has been difficult to identify for a long time is that many of its symptoms are similar to those of other diseases and conditions,” said Dr. Horberg. “Some pre-existing conditions may have been present or worsened at the time of contracting COVID-19, but this does not mean that it should be defined as ongoing COVID.”

“When we compared the population that tested positive for COVID and the population that tested negative, especially during and after the first 30 days after the positive test date, some predicted symptoms and conditions appeared to be less significant than we expected,” said Eric Watson, MAPRI. director of research analytics and co-author of the study.

Overall, 16.5% of patients with a positive COVID test developed at least one long-term COVID-related condition within 120 days of the positive test. This finding is below the national average, which is indicative of this nearly 20% of American adults with COVID-19 report having ongoing symptoms of COVID after an acute infectious period.

Diabetes and long-term COVID

The researchers found that some patients may have developed diabetes after contracting COVID-19. More than 780 patients were newly diagnosed with diabetes between 30 and 120 days after testing positive for COVID-19. Dr. Horberg said it is too early to determine whether diabetes should be considered a long-term COVID-related condition.

“Maybe some patients were simply undiagnosed until they sought medical care for their COVID-19 infection, which is why we’ve seen such a spike in new diabetes diagnoses,” said Dr. Horberg. “More research is needed on the relationship between diabetes and COVID-19 before than we can say for sure that this is a prolonged COVID condition.”

Future research

Dr. Horberg and researchers are expanding the study of conditions associated with long-term COVID in another study. The next phase of research will look at data from 2021-2022 and look more closely at the relationship between diabetes and COVID-19, the impact of delta and omicron variants, the impact of vaccines and boosters, and the impact of widespread at-home testing.

“Unlike 2020, 2021 saw mass public vaccination in the US, so we’re very interested to see if vaccines have reduced the incidence of prolonged COVID. We’re also interested in seeing if the new variants have an effect on long-term COVID symptoms,” Watson said.

“This list will likely evolve as more research is done,” Dr. Horberg said. “We really want to continue to study COVID long-term to better diagnose and treat those who may be suffering months after contracting COVID-19.”

According to the Centers for Disease Control and Prevention (CDC), prolonged COVID most often affects people who have not been vaccinated against COVID-19. Boosters are recommended for everyone 12 years of age and older and for children 5 years of age and older who have received the Pfizer vaccine.

Courtesy of Mid-Atlantic Permanente Medical Group