A pair of US studies has better characterized persistent COVID-19 symptoms, with one suggesting a higher likelihood of small blood-vessel heart dysfunction among hospitalized patients, and the other concluding that long COVID is a range of conditions rather than a single one.
Proportion with impaired blood flow fell over time
Researchers from Houston Methodist in Texas used positron emission tomography (PET) to compare myocardial flow reserve (MFR) between 271 symptomatic patients who tested positive for COVID-19 less than 3 months or more than 9 months earlier and 815 uninfected matched control patients during the Beta, Delta, and Omicron variant waves. The research was published last week in European Heart Journal Cardiovascular Imaging.
MFR is a prognostic indicator that shows how much the heart can increase blood flow under an increased need for oxygen.
The most common reasons for PET were chest pain (73% vs 67% in cases vs controls) and shortness of breath (42% vs 36%). Average patient age was 65 years, and 52% were men. The median number of days from COVID-19 infection to PET imaging was 174 days.
Most long-COVID patients (165 of 271; 61%) had mild symptoms, while 92 (34%) were hospitalized, and 14 (5%) were admitted to an intensive care unit (ICU). Average length of stay was 7.6 days for hospitalization and 24.4 for ICU stay.
A higher proportion of long-COVID patients than controls had an impaired MFR (50% vs 27%), mainly because of significant difference in MFR of less than 2 under stress (58% vs 49%) and a slight difference in a myocardial blood flow of less than 1 at rest (66% vs 72% in cases vs controls).
Long-COVID patients had a significantly higher likelihood of having an MFR of less than 2 (adjusted odds ratio [aOR], 3.1). The percentage of patients with this MFR peaked 6 to 9 months after imaging, decreasing thereafter. Impaired MFR rates were similar across variants.
The odds of impaired MFR rose with increasing COVID-19 severity (no symptoms aOR, 2.6; hospitalized aOR, 3.8; and ICU aOR, 8.5). After a median follow-up of 285 days, 41 patients died of any cause, and 46 were hospitalized for heart failure exacerbation, 10 for heart attack, 21 for a percutaneous coronary intervention, and 6 for coronary artery bypass grafting (CABG) 90 days after PET.
Event rates were higher, and event-free survival was lower, in long-COVID patients than controls and in those with a MFR lower than 2 in all analyses and subgroups.
Patients with lingering symptoms such as chest pain or shortness of breath following a severe infection may want to have a PET scan with blood flow assessment to check for microvascular dysfunction.
The study authors noted that COVID-related cardiac damage could be caused by the rupture of inflammatory plaques (vessel blockages), blood clots, low blood-oxygen levels, cardiac output-related stress, or systemic inflammation of the lining of blood vessels.
"Patients with lingering symptoms such as chest pain or shortness of breath following a severe infection may want to have a PET scan with blood flow assessment to check for microvascular dysfunction," senior author Mouaz Al-Mallah, MD, said in a Houston Methodist news release.
The authors called for future prospective studies to assess the small blood vessels of COVID-19 survivors and to identify the implications for long-COVID management.
Four distinct symptom profiles
The latest data from the ongoing, multisite INSPIRE study suggest that long COVID is dynamic and can be grouped into four clinically distinct symptom profiles, or phenotypes.
In a prospective study published last week in Open Forum Infectious Diseases, a team led by Rush University researchers used statistical modeling to identify symptomatically similar groups among adult COVID-19 survivors infected 3 and 6 months earlier and uninfected controls with COVID-like symptoms from December 2020 to September 2022. Participants completed symptom questionnaires every 3 months.
Among 5,963 baseline participants (4,504 COVID survivors and 1,459 controls), 4,056 had 3-month and 2,856 had 6-month data at analysis. Four clinically distinct phenotypes of long COVID emerged for both general and fatigue-related symptoms:
- Minimal or no symptoms
- Fatigue, headache, and muscle or joint aches without loss of smell or taste
- Fatigue, headache, and muscle or joint aches with loss of smell or taste
- Multiple miscellaneous symptoms
Most participants (70%) had minimal symptoms at 3 and 6 months. Relative to the COVID-negative group, COVID-positive participants experienced more loss of taste and smell and brain fog, which the researchers said could mean that these symptoms are more distinctly related to SARS-CoV-2.
Every patient is unique, and these findings can move us towards developing the answers and therapies that address their post-COVID reality.
Many participants changed phenotypes over time, with those in one symptom class at 3 months equally likely to remain or switch to a new phenotype at 6 months, which the authors said suggests that symptoms during the acute illness may differ from prolonged symptoms and that long COVID may have a more dynamic nature than previously recognized.
"While it is becoming increasingly clear that Long COVID is not a singular condition, having data showing several distinct, symptom-defined phenotypes is a strong step towards developing evidence-driven approaches to treat the millions of people who continue to experience lingering symptoms," lead author Michael Gottlieb, MD, said in a Rush University news release.
"Every patient is unique, and these findings can move us towards developing the answers and therapies that address their post-COVID reality," he added.
