COVID-19 survivors — including those not sick enough to be hospitalised — have an increased risk of death in the six months following diagnosis with the virus, according to the largest comprehensive study of long COVID-19 to date.
The research, published in the journal Nature on Thursday, reveals the massive burden this disease is likely to place on the world's population in the coming years, they said.
The researchers at Washington University School of Medicine in the US also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19.
They confirmed that, despite being initially a respiratory virus, long COVID-19 can affect nearly every organ system in the body.
The study involved more than 87,000 COVID-19 patients and nearly five million control patients.
"Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity," said study senior author Ziyad Al-Aly, an assistant professor of medicine at Washington University School of Medicine.
"Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care," Al-Aly said.
The researchers were able to calculate the potential scale of the problems first glimpsed from anecdotal accounts and smaller studies that hinted at the wide-ranging side effects of surviving COVID-19.
These side effects include breathing problems, irregular heart rhythms, mental health issues and hair loss, they said.
"This study differs from others that have looked at long COVID-19 because, rather than focusing on just the neurologic or cardiovascular complications, for example, we took a broad view and used the vast databases of the Veterans Health Administration (VHA) to comprehensively catalogue all diseases that may be attributable to COVID-19," said Al-Aly.
The researchers showed that, after surviving the initial infection –beyond the first 30 days of illness — COVID-19 survivors had an almost 60 per cent increased risk of death over the following six months compared to the general population.
The researchers noted that at the six-month mark, excess deaths among all COVID-19 survivors were estimated at eight people per 1,000 patients.
Among patients who were ill enough to be hospitalised with COVID-19 and who survived beyond the first 30 days of illness, there were 29 excess deaths per 1,000 patients over the following six months, they said.
"These later deaths due to long-term complications of the infection are not necessarily recorded as deaths due to COVID-19," Al-Aly said.
"As far as total pandemic death toll, these numbers suggest that the deaths we are counting due to the immediate viral infection are only the tip of the iceberg," he added.
The researchers analysed data from the national health-care databases of the US Department of Veterans Affairs.
The dataset included 73,435 VHA patients with confirmed COVID-19 but who were not hospitalised.
For comparison, almost 5 million VHA patients were included who did not have a COVID-19 diagnosis and were not hospitalised during this time frame. The veterans in the study were primarily men — almost 88 per cent — but the large sample size meant that the study still included 8,880 women with confirmed cases.