Most patients who survive the severe form of covid-19 tend to have prolonged symptoms or sequelae of the disease, a condition that has been called long or subacute covid. This is what preliminary data from studies that are monitoring factors such as mental health, quality of life, physical, financial and cognitive rehabilitation of these people point out.
“For more than a year we have been suffering the consequences of the covid-19 pandemic and, over time, we have realized that, in addition to problems related to transmission, infection and death, covid-19 can also bring long-term consequences for patients. As these implications are not yet fully understood by scientists, it is very important to encourage the exchange of knowledge and experiences among researchers from all over the world.”, said Luiz Eugênio Mello, FAPESP’s scientific director, at the opening of the online seminar “Long and post-acute covid-19”, held in early June. The event is part of the FAPESP Covid-19 Research Webinars series, organized with support from the Global Research Council.
At the event, scientists from Brazil and the United States presented preliminary results of studies that are being carried out regarding the prolonged impact of covid-19.
In Brazil, 882 patients who were hospitalized at HC-FM-USP (Hospital das Clínicas, Faculty of Medicine, University of São Paulo) are having aspects of their post-covid life monitored by researchers in order to deepen their understanding of the presence of symptoms of the disease six months after hospital discharge. All study participants had the severe form of the disease, and two thirds needed care in the ICU (Intensive Care Unit).
After six months of analysis, the researchers observed that the occurrence of symptoms after hospital discharge is high. Of the total number of respondents, 89.3% had persistent symptoms such as tiredness, body aches and dyspnea. In addition, 58.7% reported at least one emotional or cognitive symptom, such as memory loss (42%), insomnia (33%), impaired concentration (31%), anxiety (28%) and depression (22%).
“These symptoms are all interrelated. In other words, what we find is that a person who complains of memory loss also reports insomnia, anxiety and depression. It is important to highlight that these results were adjusted for symptoms presented before people had covid-19″, said Geraldo Busatto, coordinator of the Laboratory of Neuroimaging in Psychiatry at HC-FM-USP and coordinator of the study.
Busatto explains that, during the study, structured interviews were conducted with patients, which allowed researchers to categorize diagnoses of psychiatric disorders. “There is a variety of disorders among these patients and a similar rate of post-traumatic stress disorder (13.65%) relative to the data available for the general population. However, we found high rates of hallucinations (8.71%) and delusions (6.35%)”, he pointed out.
Participants were also asked to perform cognitive tasks. “Compared to the Brazilian average, these patients had a worse result, especially among those aged between 60 and 75 years. In the tests that analyzed verbal fluency, there was no difference between the patients and the Brazilian population in general. This shows that the deficit caused by covid-19 is probably not uniform, some areas of cognition must have more deficits than others”, said Busatto.
Post-covid quality of life
Another study that is also being carried out in Brazil and that involves more than 55 research centers intends to investigate the long-term consequences of covid-19 on the quality of life of about a thousand adult individuals who were hospitalized.
“Preliminary data show that six months after hospital discharge, mortality is high (6.9%), and re-hospitalization common (16%). Among patients who used mechanical ventilation, these data are higher: 24% died six months after hospital discharge, against 2% of those who did not need mechanical ventilation. In relation to re-hospitalization, it was 40% against 10% in relation to mechanical ventilation. These are statistically significant differences, even after adjusting for covariates such as age and comorbidities”, said Regis Goulart Rosa, an intensive care physician at the Hospital Moinho de Vento in Porto Alegre (RS) and one of the study coordinators.
Loss of important physical functions for performing daily activities was also observed. “There was a marked worsening in the first three months, showing a relative improvement until the sixth. However, among patients who used mechanical ventilation, even after six months of discharge, they had not yet reached the same levels as before covid-19″said Rose.
A similar study, carried out with North American patients, will monitor 1,500 survivors of covid-19 for six months. The aim is to monitor variations in cardiopulmonary and mental health, as well as socioeconomic issues.
Data from 253 patients collected one month after hospital discharge show that 54.9% had some cardiopulmonary symptom. Among those surveyed, 15.9% continued to need oxygen supplementation in their homes. Also according to the survey, patients also had symptoms such as cough (23%), shortness of breath before bed (13.4%), irregular or fast heartbeats (19.1%) and chest pain, tiredness or angina (11.3%).
“A disturbing finding is that many of the patients who experience any of these difficulties return to their homes without any help to deal with these new problems. This adds to the aspect highlighted in the survey that 53% of respondents had their finances drained after hospitalization. In addition, 38% had to ask for help with relatives to take care of them and 20% had to change jobs. There is a socioeconomic impact of covid-19 and also of long covid”, said Catherine Hough, who coordinates the study at Oregon Health & Science University.
Recovery from covid-19 can be slow for many patients. The study carried out in the United States showed that 85% of patients had not fully recovered one month after hospital discharge. Of the total, 65% had some disability and 63% had some significant cognitive problem. “By analyzing the same data three months after the patients’ discharge, we observed little change in relation to these symptoms: 75% of the patients had not yet fully recovered, 60% had some disability and 54% had some significant cognitive problem.”
Hough noted that studies of long covid need to consider diseases and other health problems that were already present before infection with SARS-CoV-2, the covid virus. According to the researcher, “it can be an amplifier of previous problems”.
The immunological mechanisms that lead to this variation in symptoms and post-covid sequelae are also being researched. “There is great variation in how the human immune system mounts a defense against the coronavirus, so we have this multiplicity of prognoses: asymptomatic, mild, moderate, or severe covid-19. Likewise, we know that, while some people will have only the acute version of the disease, others will have a more prolonged version, with symptoms and sequelae that may last for months.” explained Carolina Lucas, a researcher at the Akiko Iwasaki laboratory at the Yale School of Medicine in the United States.
In a study published in Nature magazine, Lucas identified four predictive immunological signatures that would be able to distinguish and predict the course of the disease in each patient by investigating immunological and clinical parameters of 113 patients, between moderate cases (outside the ICU) and severe cases (in the ICU), throughout up to 53 days after the onset of symptoms.
The group of researchers noted that among patients with moderate illness who recovered, there was an even greater abundance of the proteins involved in tissue healing and repair. However, in those with the aggravated form of the disease, cytokines were more mixed, appearing in combinations that are uncommon for viral infection. More people died in this group.
There is still a question of timing. The results of the analyzes indicated that critically ill patients failed to control their viral load over time and had higher levels of interferon, a class of proteins produced by defense cells to fight pathogens.
Another aspect identified by the researchers is the correlation between viral load and the amounts of cytokines involved in antiviral functions, regardless of disease severity.
With information from FAPESP Agency