Woman lying down suffering from symptoms of long covid after COVID-19
Credit: Westend61/Getty Images

New data from the INSPIRE study that is assessing the long-term symptoms and clinical outcomes of the COVID-19 virus has defined four phenotypes—or distinct symptom presentations—of Long COVID, which adds to the growing body of evidence that it is not a single condition, rather a range of conditions that evolve and usually improve over time. The research was published today in the journal Open Forum Infectious Diseases.

Funded by the Centers for Disease Control and Prevention (CDC), the INSPIRE (Innovative Support For Patients with SARS-CoV-2 Infections) study is a collaboration of eight major academic medical centers designed to better understand the long-term effects of COVID-19. The study comprised nearly 6,000 participants and includes a comparative group of patients who presented with COVID-like symptoms but tested negative for the virus. Participants began self reporting their symptoms in December 2020 and were followed for 18 months. Unlike many Long COVID studies that have been retrospective reviews of electronic health records, INSPIRE provided the ability for interaction with those enrolled to better document their evolving symptoms.

“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,” said lead author Michael Gottlieb, MD, an emergency medicine physician and researcher at RUSH University Medical Center.

The newly released data from the study showed that roughly 70% of participants showed minimal or no symptoms at follow ups three and six months after contracting COVID. While most Long COVID studies have detailed the individual symptoms of a few hundred patients suffering from Long COVID, the INSPIRE study employed latent class analysis, a statistical modeling technique that allows for the identification of clusters of symptoms. Using the large data set from the study, the investigators were able to more clearly differentiate symptom clusters of participants who reported persistent, lingering effects of COVID.

The four distinct clinical symptom presentation groups, or phenotypes of Long COVID identified are:

  • Minimal/no symptoms
  • Tiredness, headache, and muscle/joint aches without loss of taste/smell
  • Tiredness, headache, and muscle/joint aches WITH loss of taste/smell
  • Multiple miscellaneous symptoms

The data also showed that large proportions of those in the study changed symptom groups over time, which pointed to the dynamic, non-singular nature of Long COVID. In addition, the data suggest that the initial symptoms during a patient’s acute illness phase are not predictive of what may develop into persistent symptoms. Another important aspect of the INSPIRE study is the inclusion of a control group of patients who initially presented with COVID-like symptoms, but were found to be negative for the disease. Data from these patients allowed researchers to better understand the degree to which similar symptoms may not be particular to COVID.

As an example, the investigators pointed out that those testing positive for COVID-19 reported much higher rates of cognitive problems and loss of smell and taste at both three and six months post diagnosis, which points to these being more distinctly related to the COVID-19 virus.

The hope is that these data, as well as a wider set of data from INSPIRE, can help clinicians provide more relevant treatments for patients based on the understanding of their Long COVID phenotype.

“Every patient is unique, and these findings can move us towards developing the answers and therapies that address their post-COVID reality,” Gottlieb noted.

Also of Interest