Symptoms a Year After a COVID-Like Illness: Similar Whether the Test Was Positive or Not

Post-COVID conditions, or long COVID, are symptoms that persist or develop 4 weeks or more after infection. Estimates of how common they are vary, many studies lack a comparison group, and few follow people over time to separate symptoms that persist from those that appear later.

The Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a study run in eight major health care systems, followed adults with a COVID-like illness who had a polymerase chain reaction or antigen test — some positive, some negative — and surveyed their symptoms every 3 months for a year, from December 2020 to March 2023.

Who was studied

• Of 6,075 people enrolled, 1,741 completed every survey through 12 months.
• Those who reported a new infection during follow-up — 271 who had first tested positive and 174 who had tested negative — were set aside, leaving 1,296.
• Compared with those who tested negative, people who tested positive were less often female (65.2% vs 75.2%), more often married or partnered (60.3% vs 48.9%) and more often hospitalized for the illness (5.6% vs 0.4%); they less often had asthma (11.6% vs 18.3%) or kidney disease (0.6% vs 2.5%).

Symptoms were grouped into categories: head, eyes, ears, nose and throat; constitutional; pulmonary; musculoskeletal; gastrointestinal; cardiovascular; cognitive difficulties; and extreme fatigue.

What happened to symptoms

• At the start, people who tested positive had more symptoms in every category except extreme fatigue.
• Symptoms fell sharply by 3 months and kept declining gradually through 12 months.
• Persistent symptoms through 12 months ranged by category from 0.3% (gastrointestinal) to 5.9% (head, eyes, ears, nose and throat) among those who tested positive, and from 1.1% (cardiovascular or pulmonary) to 6.8% (extreme fatigue) among those who tested negative.
• The only significant difference at 12 months: extreme fatigue persisted more in those who tested negative (6.8% vs 3.5%), and was more common in that group at 9 and 12 months.
• About half of each group had some symptom at 12 months.

Symptom prevalence over 12 months after a COVID-like illness, by test result. CDC

Symptoms come and go

New or returning symptoms were reported in every category at every follow-up, in both groups. Those who tested negative reported more emerging symptoms at 6 and 12 months in each category except fatigue. Cognitive difficulties and extreme fatigue were common among symptoms emerging after 6 months. Including people with later infections gave a similar pattern.

What it means

• Not unique to COVID-19. Lingering and new symptoms after a COVID-like illness occurred whether or not the test was positive.
• One snapshot misleads. Counting symptoms at a single time mixes persistent ones with new ones, and can underestimate or mischaracterize the effects of illness.
• A large burden. If many people have symptoms for up to a year, post-COVID–like conditions could weigh heavily on health and the health care system. Clinicians should know symptoms can persist, emerge, re-emerge or resolve.

Limits

Nothing is known about what caused the illness in people who tested negative; later infections weren't tested systematically; other infections or medical problems could explain some symptoms; the survey didn't cover every symptom; and severity and effects on daily life weren't measured.

Sources

Based on Montoy JCC, Ford J, Yu H, et al., "Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID-19 Testing Status Among Adults — United States, December 2020–March 2023," MMWR volume 72, number 32, Centers for Disease Control and Prevention; a work of the United States government in the public domain. The report's summary puts persistent symptoms at "approximately 16%" of participants, which its own group figures of 18.3% and 16.1% do not produce overall, and speaks of both eight and nine symptom categories; the group figures and the eight categories listed in its methods are used here.