Long-term symptoms of COVID-19 disappear in people who had a mild infection – results of a large-scale study

A study conducted by a group of scientists in Israel provides encouraging news: most symptoms associated with long-term Covid can disappear over time in those who initially had a mild case of COVID-19. The study found that within a few months of infection, people with a mild form of the disease had an increased risk of developing more than a dozen diseases, compared to an uninfected control group. But this increased risk largely disappeared during the year.

The study was led by scientists from the KI Research Institute in Israel in collaboration with Maccabi Healthcare Services, one of the country’s four healthcare organizations.

In Israel, virtually all medical services are provided and covered through these organizations, a universal system that allows researchers to study population health relatively easily through de-identified electronic medical records. Compared to many other countries, Israel has been more vigilant during the pandemic in providing residents with readily available testing for acute cases of COVID-19.

Thanks to the vast amount of data available to these researchers, they have been able to track people’s health after the COVID-19 outbreak to a degree that few others have been able to do.

About 300,000 people who tested positive for COVID-19 but were not hospitalized between March 2020 and October 2021 took part in the study. The team tracked how often these people were later diagnosed with 70 different diseases, possibly related to long-term infection, and compared them to a control group who were matched for age and other factors but never tested positive for COVID-19 during same time period. They deliberately focused on patients with a milder course of the disease, since they make up the majority of cases of COVID-19.

KI researcher Maital Bivas-Benita’s team found that people with mild COVID-19 had, on average, a higher risk of being diagnosed with several different conditions compared to uninfected people within one to six months of infection.

These conditions, 13 in all, included hair loss, chest pain, shortness of breath, and problems with memory or concentration, commonly referred to as “brain fog.” However, this increased risk declined over the next six months, and the risk for almost all outcomes reached or approached the baseline risk observed in uninfected controls. The risk of anosmia and dysgeusia (loss or impairment of smell and taste), confusion, shortness of breath, and general weakness remained elevated at one year, but these conditions also became less common over time.

Other studies have shown that some people actually recover after of prolonged Covid, at least in part. But the authors say their study is one of the most detailed and long-term follow-ups of patients with initially mild COVID-19.

The large data set also meant that Bivas-Benita’s team could make many different comparisons between groups of people.

For example, children appear to have a lower risk of developing any lasting symptoms of Covid than adults, while people aged 41 to 60 may be at the highest risk. The risk of shortness of breath was lower in vaccinated people who developed a breakthrough infection compared with unvaccinated people, although the risk of other conditions appeared to be similar. And interestingly, they found no difference in the long-term risk of Covid from infection with the alpha or delta variant compared to the original strain, even though there were only a few months of data on the delta variant at the time.

However, no study is without caveats. Reliance on electronic medical records and official diagnosis codes means that some cases of prolonged covid may have gone undetected. And it’s possible that some people stopped reporting lingering symptoms to their doctors over time. On the other hand, health care in Israel is free and considered to be of high quality, limiting some of the reasons why sick people avoid or stop seeking medical care. And Bivas-Benita points out that people who have contracted COVID-19 may actually be more likely to see a doctor compared to uninfected people, simply because they pay more attention to their health after being infected, “which leads to more reporting and amplification screening for potential covid-related outcomes in these patients.”

On the other hand, a key strength of the study is the ability to compare these cases with a large group of uninfected individuals, which is important because many of the symptoms often associated with long-term Covid can be caused by other causes. As a consequence, these results may also suggest that only a small proportion of mild cases of COVID-19 develop any disease possibly associated with the infection. At the same time, the obtained data do not mean that people did not experience chronic symptoms caused by COVID-19.

“It seems that as long as SARS-CoV-2 is with us, there will be a small proportion of patients who will experience long-term symptoms of this infection,” Bivas-Benita said.

The authors say more research is needed to understand the specific long-term Covid risks posed by the Omicron variant, which has become dominant worldwide since late 2021.

Another important and still understudied area is the impact of reinfections on the risk of long Covid.