For most healthy, middle-aged and especially younger people, infection with COVID-19 has been a non-event – a positive PCR test with few, if any symptoms to show for the infection.

But for older folk and those with comorbid conditions, infection was often associated with moderate or even severe symptoms that required hospitalization and even ventilator support.

After that many patients were crippled for many months by shortness of breath, fatigue and difficulties concentrating and forgetfulness, or what some patients called “brain fog.”

For those managed in intensive care units, it was tricky sorting out which symptoms were directly attributable to COVID and which to being on a ventilator, powerful drugs (including corticosteroids), immobilization and extended bouts of disorientation.

However, over the next several months another picture emerged.

Some patients who tested positive and experienced minor initial symptoms such as a dry cough and loss of smell or perhaps no symptoms at all, went on to develop a mysterious constellation of debilitating symptoms lasting many months.

Most long-lasting symptoms improve, although for some, the symptoms continued in some fashion. But whatever the severity of the initial symptoms, most refer to the clinical syndrome as “Long COVID.”

The cause of such long-lasting symptoms isn’t known but because the symptoms are so common (15 to as high as 80 per cent of patients), the National Institutes of Health in the United States committed over a billion dollars, and the U.K., roughly half that amount, toward better understanding and managing lingering post-COVID symptoms.

The similarity to long-lasting symptoms following other viral infections such as the closely related SARS, SARS-CoV-1 and MERS, suggests that persistent viral particles might trigger a smoldering autoimmune response.

Long-COVID symptoms are also similar to those observed in chronic fatigue syndrome (CFS), otherwise known as myalgic encephalomyelitis (ME). The chief difference between the two is the high incidence of abnormalities of smell and taste, and strong evidence of involvement of the lungs in many people suffering from Long-COVID.

The truth is we don’t understand the cause of such protracted symptoms. But in the absence of verifiable evidence, some physicians take the position that what’s unverifiable, doesn’t exist and must be “all in the patient’s head.” Well, they may be right on that one, but not in the way they imagined.

Oxford University and the Imperial College in London recently collaboratively posted online comparative MRI and functional MRI (fMRI) studies of volunteers who a few years earlier were studied as part of the U.K. Biobank program. Some of them later developed COVID and others, who did not, acted as controls.

The authors posited that the SARS-CoV-2 virus gains access to the brain through the olfactory and gustatory systems, which are intimately connected to structures in the temporal lobe and elsewhere in the brain that play major roles in memory, mood and emotion, as well as smell and taste.

Their findings were striking. Abnormalities were found in many of latter regions of the brain, mostly on the left side, and more widespread in the small subgroup of patients, usually older, who were hospitalized.

For me the most important observation was the clear finding of abnormalities in the brains of COVID patients, most of whom were not hospitalized (only 15 of a total of 379 subjects). It was a marveLlous study because it strongly suggests the virus reaches the brain through the olfactory system, as suspected.

Unfortunately, the study made no mention of which subjects developed symptoms and if so, what symptoms? But given the localization of the findings, it wouldn’t be too much of a stretch to suggest that some of the Long-COVID cognitive symptoms might be related, in part at least, to what was observed in this study – and not the imaginations of the patients.

The hypothesis that lesions in the brain might be far more common than we thought and possibly related to Long-COVID symptoms is well worth further study but would need a bevy of psychological and other tests to complement the imaging studies. And that would only be the beginning.

Still, the study was a very good start. But given the prevalence and duration of Long-COVID symptoms, the challenges of COVID will be with us for a very long time – long after the last surge is a memory.

That’s something we’re just beginning to realize.

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the Infohealth series at the Niagara-on-the-Lake Public Library.