During the COVID-19 pandemic, it became clear to scientists that in a significant part of people who have overcome the infection, some symptoms of the disease still persist.

This phenomenon is called long-term COVID and means a condition in which symptoms last three months or more after the onset of the disease. These symptoms include fatigue, trouble concentrating, muscle and joint pain, shortness of breath, headaches, sleep disturbances, and cognitive disturbances such as "brain fog."

This condition can affect people of all age groups, regardless of the severity of the infection, and it is estimated that 5-10% of those infected develop it. In fact, the data shows that even children are not spared from long-term COVID, where in the US alone, about 5.8 million children are sick with long-term COVID. Its global prevalence is estimated in the hundreds of millions.

Until recently, it was not clear what causes these prolonged symptoms. Scientists have proposed several biological mechanisms that include immune and inflammatory dysfunctions, microbial dysbiosis, autoimmunity, endothelial dysfunction, abnormal neurological signaling, reactivation of endogenous herpesviruses, and persistence of coronaviruses.

However, in an article published in the latest edition of the Medical Journal of Australia (MJA), a team of scientists concluded, based on multiple studies, that most, if not all, long-term COVID cases are caused by viruses that have remained hidden in the body.

Relatively early in the pandemic, it was realized that in some people the SARS-CoV-2 virus, or at least the remnants of the virus, can remain in various tissues and organs for a long time. This phenomenon is known as "viral persistence".

Although the long-term presence of remnants of viral fragments in the bodies of some people is now well established, it remains less clear whether there are still live viruses in the bodies of those who have recovered, and not just their remnants, and whether they exist , regardless of whether they are the real cause of long-term COVID.

The authors of the new paper from MJA point out that this difference is crucial because a live virus can be targeted by specific antiviral approaches in ways that "dead" virus fragments cannot.

Viral persistence has two important implications:

When it appears in some extremely immunocompromised people, it can become the source of new and distinctly different variants, such as JN.1. It has the potential to continue to cause symptoms in many people long after the acute illness.

While there is no research that directly and irrefutably confirms that a persistent virus is the cause of long-term COVID, a number of recent studies strongly point to such a conclusion.

A study published in February in the journal Nature showed that a large number of people with mild COVID-19 symptoms experience a prolonged period of shedding the virus's genetic material, so-called viral RNA, from the respiratory tract. Those with viral RNA, which almost certainly means the presence of live virus, had a 50% higher risk of developing long-term COVID.

Some other research has found replication of viral RNA and protein in patients' bloodstreams years after the initial infection, a sign that the virus is likely to replicate for longer periods in some hidden reservoirs in the body, which can include blood cells.

One study, published in the Lancet Infectious Diseases journal, detected viral RNA at ten different sites in tissue and blood samples one to four months after acute infection. It found that the risk of long-term COVID four months after infection was higher in those with persistently positive viral RNA.

The same research also provided clues as to where in the body the virus may be harboring. The gastrointestinal tract turned out to be one of the main areas.

Finally, a study published in the journal Clinical Microbiology and Infection also confirmed that the continued presence of the virus increases the likelihood of long-term COVID.

Australian scientists, authors of a new study published in AMJ, in the journal Conversation, pointed out that there is still no official evidence that the SARS-CoV-2 virus can stay in the body for years, able to reproduce. They explain that it is technically challenging to isolate the live virus from the reservoir inside the body where the virus "hides".

However, they believe there is now enough convincing evidence that live viruses cause long-term COVID to warrant action.

The team believes that based on existing knowledge, trials of known antiviral drugs should accelerate the prevention and treatment of long-term COVID and the search for new ones. One such potential diabetes drug could be metformin, which has been shown to have a dual positive effect on long-term COVID.

According to the Australian team, the risk of long-term COVID is not only carried by the first infection, but also by each subsequent one. They remind us that long-term COVID is common and that it is not limited to those at high risk of severe acute illness, but affects all age groups.

It is interesting here that a study published in MJA showed that the greatest long-term impact of COVID was recorded among people aged 30-49.

A new study published in the journal Lancet eClinical Medicine showed that vaccination was associated with a lower risk of long-term COVID after 3 to 12 months in older children, as well as a lower risk of re- infection.

The authors presented several key recommendations. For now, they point out, we should all reduce our exposure to the virus by using the tools available:

- ensuring clean air indoors by ventilating the rooms

- the use of quality masks in situations when we are not sure about the quality of the air indoors or in crowds

- testing and treatment in case of a positive test, and patients should take care to protect others by wearing masks, staying at home and ventilating the area.