Researchers and doctors of the University of Tartu, Tartu University Hospital and South-Estonian Hospital are studying how COVID-19 affects patients over the course of three years after infection. At the third- and sixth-month follow-up, more than half of the patients reported various health concerns, although their routine analyses were fine. In the third-month follow-up, the main complaint was a decrease in physical exercise capacity. By the sixth month, the number of patients with complaints had increased and problems with joints were added to the decreased exercise capacity. Also, fatigue and a lack of sense of smell were reported.
Since COVID-19 is such a new disease, its long-term effects are not yet well known. Therefore, researchers of the University of Tartu and doctors of Tartu University Hospital and South-Estonian Hospital are conducting a three-year study to monitor the health of corona patients during up to 36 months after the infection. To this end, they invite patients to a follow-up visit three, six, twelve, 24, and 36 months after infection, fill out health questionnaires and collect biological material for immunological, virological and genetic analyses.
So far, 86 corona patients, most of them middle-aged, have been recruited in the study. The recruitment of new patients will continue this year as well as the next.
According to Anne Kallaste, one of the organisers of the study and Head of the Department of Infectious Diseases of the Internal Medicine Clinic of Tartu University Hospital, the majority of subjects have suffered from a severe form of the COVID-19. “63% of them also have underlying diseases – hypertension, ischemic heart disease, diabetes and malignant tumours,” described Kallaste.
The study has shown that while 50-year-olds mostly suffered from a mild to moderate form of the disease, it was rather severe and critical for people ten years older. A comparison of severity also revealed that while 46% of patients suffering from a mild case of COVID-19 had underlying diseases, the figure was 71% among critical cases.
Formation and persistence of antibodies
In cooperation with the research group of Professor of Molecular Immunology Pärt Peterson at the University of Tartu, also the patients’ level of coronavirus antibodies was assessed in the third- and sixth-month follow-up. Almost all patients had antibodies in the third month, and they persisted in the sixth month.
“However, in the group of severe cases, a decrease in the antibody levels could be noticed in the sixth month. We are looking forward to the results of the 12-month follow-up to see what happens to the antibody levels by then,” said Kallaste, adding that unfortunately, the level of antibodies that could protect against repeated infection is still to be known.
In the study, also the patients’ blood, urine and saliva are analysed to see changes in the body over time. For example, the value of C-reactive protein is reviewed. Usually, it does not significantly increase in viral diseases, but COVID-19 is an exception in this respect, especially in the acute phase of the disease among severely and critically ill patients.
However, this does not mean that these patients have bacterial co-infections, as studies have shown that they are rather rare compared to, for example, flu. By the third-month follow-up, the C-reactive protein levels had normalised in all patients.
Also, the change in total ferritin and lymphocyte counts was assessed, which are well known to be abnormal in COVID-19 patients during the acute phase of the disease. These indicators had also reached their normal level by the follow-up.
Health problems three and six months later
Although the patients’ routine analyses were normal, Kallaste said that more than half of the patients reported health concerns during both the third- and sixth-month follow-up: “According to the patients, they did not have these complaints before COVID-19, and the results of routine analyses cannot explain these complaints, either.”
In the third-month follow-up, slightly more than half of the subjects reported reduced physical performance, followed by a loss of sense of smell, fatigue and joint discomfort. In the sixth-month follow-up, even more patients (65%) had complaints – most of them reported reduced physical performance and joint discomfort. Patients still complained of fatigue and a lack of sense of smell. “Physical performance was impaired the most in patients who had suffered from a severe and critical form of the disease,” underlined Kallaste.
The researchers emphasise that the study is only in its early stage and only a small part of the results has been analysed so far. The team includes Anne Kallaste, Head of the Department of Infectious Diseases of the Internal Medicine Clinic of Tartu University Hospital, Agnes Aart, Head of Treatment of Southern Estonian Hospital, Kai Kisand, Research Professor of Cellular Immunology, Kalle Kisand, Professor in Laboratory Medicine, and Margus Lember, Head of the Internal Medicine Clinic of Tartu University Hospital, Head of the Department of Internal Medicine at the University of Tartu, Professor of Propaedeutics of Internal Medicine.
Anne Kallaste made a presentation entitled “Follow-up of COVID-19 patients three and six months after the infection” at the University of Tartu conference “Intelligent adaptation to the coronavirus”.