WASHINGTON: Severe COVID-19 may trigger the reactivation of viruses that have remained inactive in the body, with some of this viral activity linked to prolonged health problems, according to a new study.
Researchers found evidence of at least one reactivated virus in nearly half of the hospitalised COVID-19 patients included in their research. The findings, published Wednesday in the journal Nature, showed that viral reactivation was associated with more severe illness, greater inflammation and poorer outcomes.
However, the researchers stressed that the study does not establish that the reactivated viruses directly cause severe COVID-19 or long COVID.
The research involved 1,154 adults who were hospitalised with COVID-19 at 20 hospitals across the United States between May 2020 and March 2021. All participants were unvaccinated and had contracted the virus before newer coronavirus variants became widespread.
Scientists examined blood samples, nasal swabs and respiratory samples collected from patients who required ventilation. The participants were monitored throughout their hospital stays and for as long as 12 months afterwards.
Of the 1,148 patients for whom sufficient data were available, 550 showed evidence of at least one reactivated virus, representing 47.9% of the group. Most of these patients had evidence of only one additional virus during the acute phase of their illness.
The viruses detected included members of the herpesvirus family, such as Epstein-Barr virus, cytomegalovirus and herpes simplex virus, along with anelloviruses. These viruses commonly infect people earlier in life and can remain in the body in an inactive state while being controlled by the immune system.
The timing of reactivation varied between viruses. Epstein-Barr virus activity was most frequently detected around the time patients were admitted to hospital, with viral material found in 24% of participants during the first eight days before declining.
Anellovirus activity was also more common during the early stages of hospitalisation and remained relatively stable until around the 20th day. Cytomegalovirus and herpes simplex virus generally appeared later, reaching their highest levels around three weeks after hospitalisation and being detected mainly in respiratory samples.
The researchers found links between more severe COVID-19 and the reactivation of Epstein-Barr virus, cytomegalovirus, herpes simplex virus and anelloviruses. Patients with evidence of viral reactivation also had higher levels of inflammatory molecules and changes in certain immune cells, indicating a broader immune response.
Importantly, viral reactivation was not limited to patients receiving medicines that suppress the immune system. It was also observed in people whose immune systems were otherwise functioning normally.
Anelloviruses attracted particular attention because their activity after hospitalisation was associated with physical problems reported by some long COVID patients, including fatigue and reduced physical functioning. The association remained even after researchers accounted for factors such as age, medication-related immune suppression and the severity of the initial infection.
Anelloviruses are considered generally harmless and are estimated to be present in around 80% to 90% of people.
The study did not, however, find that Epstein-Barr virus activity during the initial COVID-19 illness was more common among patients who later developed long COVID.
Researchers said the findings could eventually help scientists develop ways to identify patients at greater risk of severe COVID-19 or prolonged illness. Monitoring the reactivation of dormant viruses could potentially become part of future approaches to treatment, although further clinical research would be needed.
Existing antiviral medicines may already provide possible treatment options for some herpesviruses, but researchers said clinical trials would be necessary to determine whether treating viral reactivation actually improves patient outcomes.
The scientists also cautioned that the findings may not necessarily apply to people with mild COVID-19, vaccinated individuals or those infected with more recent coronavirus variants.
Further research is needed to determine whether viral reactivation plays a direct role in severe COVID-19 and long COVID, or whether it is mainly a consequence of the inflammation and physiological stress caused by the infection.
