WASHINGTON — About 1 in 6 people who had COVID, influenza, or respiratory syncytial virus (RSV) experienced postacute sequelae symptoms that predominantly included fatigue, cognitive symptoms, and respiratory symptoms, according to a prospective cohort study presented at IDWeek in Washington, DC, on October 22.

The burden of postacute sequelae of respiratory infection was high across all three viral respiratory infections, Avantika Srivastava, MS, research scientist and PhD candidate at City University of New York (CUNY) in New York City, told attendees.

“In general, more in-depth prospective research is needed on the epidemiology of long-term quality of respiratory infections, including shared- versus pathogen-specific risk factors, prevention, and management,” she said.

Srivastava noted that the COVID pandemic has led to an increased recognition of long-term sequelae after respiratory infections, but the criteria for postacute sequelae of COVID, or long COVID, cover a wide range of symptoms, including other diagnoses. Meanwhile, limited research exists on postacute outcomes from influenza and RSV, she said.

The researchers therefore used the definition for postacute sequelae of COVID (PASC) from the National Academies of Science, Engineering, and Medicine to estimate the burden of postacute sequelae of all three respiratory viruses 180 days after symptoms between July 2024 and January 2026.

They analyzed data from the project PROTECTS, a prospective community-based cohort of adults aged 18 years or older who used at-home rapid antigen testing for COVID, flu A, flu B, and RSV. The initial follow-up for participant-reported positive infections lasted up to 29 days after acute symptom onset. The participants then completed monthly questionnaires for the 17-item PASC Patient-Reported Outcome scale and a global health questionnaire for 6 months after symptoms began.

The global health questions asked about the patients’ return to usual health, return to usual activities, and overall severity during worst symptoms, all during the last 30 days. The PASC symptoms used for this analysis included shortness of breath (resting and physical activity), cough, difficulty concentrating, difficulty remembering things, insomnia, tiredness (overall, after physical activity, and after mental activity), muscle or body aches, chest pain, heart palpitations, headache, diarrhea, and nausea. 

The researchers analyzed data from participants who completed at least three postacute questionnaires within a 4-month period, but they excluded those who had infections from multiple pathogens at the same time. They defined postacute sequelae of respiratory infection (PAS-RI) as having at least two nonsensory symptoms of any severity repeated for at least three of four consecutive months through 180 days plus a failure to return to usual preinfection health by months 3 or 4, based on the global health question. 

Among 1316 participants who had a positive test for COVID, flu A or B, or RSV during the study period, 96.3% completed at least three of four consecutive questionnaires, resulting in 1267 participants for analysis. They included 773 who had COVID, 385 who had flu, and 109 who had RSV.

The study population was an average of 50 years old, and most (71%) had at least one high-risk condition. Nearly half (47%) were vaccinated and up to date for COVID and flu, including 40% of those who had COVID and 61% of those who had flu. Another 45% had been vaccinated against flu and COVID but were not up to date, and 8% had never been vaccinated or their vaccination status was unknown.

Among the 120 people who had RSV, 14% had been vaccinated, 37% were eligible for vaccination but had not gotten the vaccine, and half (49%) were not eligible for the vaccine. 

Overall, 16% of participants met the criteria for postacute sequelae of respiratory infection during the 6 months after their infection, including 16% of those who had COVID, 14% of those who had flu, and 17% of those who had RSV.

The most commonly reported symptom among those with PAS-RI was fatigue, reported by 93%-100% of participants depending on what their acute infection had been. Other common symptoms included cognitive symptoms, reported by 69%-73% of participants, and respiratory symptoms, reported by 59%-87%.

“This was especially true for the RSV group, where, at month 6, all of the PAS-RI RSV cases were reporting fatigue, and most of them were reporting respiratory symptoms,” Srivastava said.

More than half of those who met the criteria for PAS-RI (53%-67%) were reporting at least eight symptoms at 180 days. In addition, up to a quarter (17%-23%) of those with PAS-RI reported at least eight symptoms every month after their infection. 

“Even when we restricted ourselves just to the moderate and severe symptoms, 10%-14% of all cases reported eight or more symptoms at month 6, and a third of all cases reported at least one moderate or severe symptom in every month of follow-up,” Srivastava said.

The inclusion of 15 symptoms in the case definition allowed for a wide range of clinical presentations and increased the probability of reporting at least two ongoing symptoms, Srivastava said, but there was an overall high rate of symptoms reported even in non-PAS-RI cases, particularly fatigue.

“We included all severity levels when assessing the presence of symptoms, and this relaxed severity threshold allowed us to identify cases with fluctuating symptom profiles,” Srivastava said. However, they still limited their cases to participants who reported that they had not returned to their preinfection health, which excluded many participants who reported a high burden of symptoms but said they had returned to their usual health.

Bill Werbel, MD, associate professor of medicine in infectious diseases at Johns Hopkins University in Baltimore, was not involved with the research but noted that the results suggest a pretty stable prevalence of postacute conditions hovering around 15%.

“If you attribute it to the original infection in a group of average people seems, it seems higher than one would think,” Werbel said. But he also noted that, while the data were interesting, it’s difficult to attribute those symptoms to the original infection over that length of time.

“I feel like the two possible implications are being cognizant of screening patients and thinking about them in the medium- to long-term context if they had a respiratory infection, and then that dovetails with counseling about vaccines and trying to talk about preparation for high-risk situations,” Werbel said. “I feel like that can be part of the conversation.”

The research was funded by CUNY and Pfizer. Four coauthors are Pfizer employees who may hold stock and/or stock options in the company. Werbel reported consulting, speaking, and/or advisory board fees from AstraZeneca and Novavax.

Tara Haelle has been an independent science/health journalist for over 15 years, with work appearing in over two dozen trade and consumer publications. She is the author of Vaccination Investigation: The History and Science of Vaccines and The Informed Parent: A Science-Based Resource for Your Child’s First Four Years. Haelle is the public health beat leader for the Association of Health Care Journalists, where she develops resources to help other journalists report on medical studies and public health. She is based in Dallas.