A team of researchers led by the Allen Institute for Immunology and the Fred Hutchinson Cancer Center has recently found that an overactive and prolonged inflammatory response could be at the root of many – but not all – long COVID cases.
These findings could be used to distinguish between different types of long COVID and help experts design better therapeutic approaches to this still puzzling condition.
The experts examined blood samples of 55 patients with long COVID and compared them with samples from 25 people who had COVID but fully recovered, and 25 who were never diagnosed with COVID. The participants were part of a larger, ongoing initiative based at Fred Hutchinson, the Seattle COVID Cohort Study, which was launched in the spring of 2020 and was originally designed to follow the immune responses over time in patients with mild or moderate COVID in order to clarify the features of a “successful” immune response, in which patients did not get too sick and recovered.
However, the leaders of the project soon noticed that even among patients who did not get very sick, not everyone managed to fully recover, and continued to experience a variety of symptoms months after the acute infection – a condition later known as “long COVID.” One of the symptoms that these patients experienced was persistent inflammation.
In the current study, the researches focused on a panel of 1,500 proteins circulating in the blood of the participants, to help them distinguish between inflammatory and non-inflammatory long COVID. Out of the 55 patients with long COVID, approximately two-thirds had persistently high levels of certain signals of inflammation, while those without long COVID did not show the same signs of inflammation in their blood.
Moreover, the blood markers uncovered in the subset of patients with “inflammatory long COVID” exhibited similarities with those seen in autoimmune diseases such as rheumatoid arthritis.
These findings suggest that certain kinds of anti-inflammatory drugs – such as an existing class of medicines known as JAK inhibitors and used to treat rheumatoid arthritis – might alleviate symptoms for some long COVID patients. However, physicians need a reliable way of telling which patients might benefit from which treatment – a challenging form of precision medicine for a disease that so far remains highly elusive.
“The big question was, can we define which long COVID patients have persistent inflammation versus those that don’t? That would be useful in terms of clinical trial planning and in terms of helping clinicians figure out targeted treatments for their patients,” said senior author Troy Torgerson, the director of Experimental Immunology at the Allen Institute.
According to Torgerson, patients with non-inflammatory long COVID that exhibit permanent organ or tissue damage would require completely different treatments than those with high levels of inflammation. Thus, in order to find a proper therapeutic pathway, patients should be screened to determine which form of the condition they have.
“The ultimate goal is to treat patients,” said lead author Aarthi Talla, an expert in Bioinformatics at the Allen Institute. “Although we call everything long COVID, what’s come out of this work shows us that we might not be able to give everyone the same kinds of therapies and we shouldn’t put everyone into one group for treatment purposes.”
“We hope these findings provide features of long COVID that may guide potential future therapeutic approaches,” concluded co-author Julie McElrath, the director of the Seattle COVID Cohort Study. The research is published in the journal Nature Communications.
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is a term used to describe a range of symptoms that continue for weeks or months after the acute phase of a COVID-19 infection has resolved.
The condition is characterized by a wide range of symptoms, including but not limited to fatigue, difficulty concentrating, sleep disturbances, headaches, and lingering loss of taste or smell.
Long COVID has been increasingly recognized as a significant public health concern. For some individuals, this condition can significantly impact the quality of life and ability to perform daily activities or work.