- Initially, scientists considered COVID-19 a respiratory condition, but they are slowly building up a clearer picture of the wide-ranging impacts of the disease.
- Researchers have now shown that COVID-19 can affect many systems in the human body.
- A recent study investigated the longer-term effects of COVID-19 in older adults.
- It found that around one-third of older adults with COVID-19 went on to develop new conditions, compared with roughly one-fifth of older adults who did not have COVID-19.
In its acute phase, COVID-19 mainly involves the respiratory tract. However, researchers have shown that the disease can affect multiple organs in a person’s body.
In addition, there is a growing recognition of long COVID among researchers and clinicians. Long COVID manifests as persistent symptoms in people who have recovered from the acute phase of a SARS-CoV-2 infection.
In the present study, the researchers wanted to better understand the likelihood of older adults developing health conditions following a SARS-CoV-2 infection, which experts generally refer to as sequelae.
The study, which appears in the BMJ, lays the groundwork for further research to understand the long-term effects of COVID-19 on people’s health.
Medical News Today spoke with Dr. Ken Cohen, executive director of translational research at Optum Labs and the corresponding author of the study.
“With over 400 million cases of COVID-19 worldwide, even a modest risk of long-term sequelae will have a major impact on patients and our healthcare systems. Understanding the magnitude of this impact and the specific organ systems that can be affected by the post-acute sequelae of COVID-19 is critically important information.”
To do this, Dr. Cohen and his colleagues looked at the health insurance records of 133,366 older adults in the United States. The participants were 65 years old or older and received a COVID-19 diagnosis before April 1, 2020.
The researchers matched these participants to three other comparison groups: two groups that did not have COVID-19 in 2020 and 2019, and a third group that did not have COVID-19 but had a lower respiratory tract infection.
The researchers then identified new conditions occurring 3 weeks or more after each participant’s COVID-19 diagnosis.
The study authors found that 32% of the participants who had a SARS-CoV-2 infection in 2020 sought medical attention for a new or persistent condition. This was 11% higher than the comparison group from 2020.
Compared with the 2020 comparison group, the new or persistent conditions that showed the greatest risk were respiratory failure, fatigue, high blood pressure, memory issues, kidney injury, mental health-related diagnoses, hypercoagulability — which occurs when the blood clots more easily — and cardiac rhythm disorders. The researchers note similar findings for the 2019 comparison group.
When the authors compared the COVID-19 group with the lower respiratory tract infection group, risk increases only occurred for respiratory failure, dementia, and post-viral fatigue.
“Our lower respiratory infection group included exacerbations of chronic obstructive pulmonary disease and likely included some undiagnosed bacterial pneumonias, and therefore, many of these patients were likely quite ill,” said Dr. Cohen.
“The differences in sequelae between this group and the SARS-CoV-2 group were therefore much less pronounced. We saw a higher risk of respiratory failure, dementia, and post-viral fatigue in the COVID-19 group, compared to the lower respiratory tract infection group, but the other sequelae did not occur with a higher frequency in the COVID-19 group.”
Dr. Irene M. Estores, director of the Integrative Medicine Program at the University of Florida Health, said the findings confirm previous work in this area. Dr. Estores was not involved in the study.
“The data builds nicely on Veterans Affairs data on post-acute sequelae of COVID-19, with the inclusion of a cohort of patients who were admitted to a hospital compared to those who were not, and using a comparison group of patients with other viral lower respiratory tract infection.”
“Notwithstanding the limitations acknowledged by the authors, validation of our observations as clinicians allows us to continue to advocate for measures to protect this population,” said Dr. Estores.
MNT spoke with Dr. Alicia Arbaje, director of Transitional Care Research at Johns Hopkins Medicine and a clinician at the Johns Hopkins Bayview Medical Center in Baltimore. Dr. Arbaje was also not involved in the study.
“I think this work is significant. First, because it focuses on older adults, and this is the population that’s most likely to demonstrate long-term effects from this infection, and so I think it’s important and timely given the phase of the pandemic that we’re in.”
“A year ago, 2 years ago, we were asking, ‘How do we treat this illness? What do we do?’ Those are still questions, but now, we’re asking how we help people recover, how we help them long-term, how we deal with the disability that occurs afterward — and how we restructure our healthcare system to deal with a large number of people coming with all these sequelae that this study is starting to highlight.”
– Dr. Alicia Arbaje
“So I think this study is important, because it can help for planning purposes to help us see longer-term what we may need. This is not a simple pneumonia or an illness that comes and goes. It’s something that we’re starting to learn has longer-term effects beyond the respiratory component.”
Dr. Arbaje said that the study would help doctors pay attention to a patient’s perspective and the “disease journey” they are on.
“This study showed that many of the sequelae were respiratory complications, but there were cardiovascular, hypercoagulable, clotting disorders, and fatigue as well. So I think the study is important, because it helps us begin to think of COVID-19 as having a broader effect than maybe one might have thought of before.”
“[Another] reason this is significant is that it honors the patient’s disease or illness journey. In research, we often limit our studies to one disease and what happens with that one disease. But with older adults, it’s so important to look at the entire picture from the person’s perspective, the person’s journey.”
“A person may be experiencing diabetes and hypertension and stroke and COVID-19 — not just COVID-19 alone. So I think this study begins to shift the frame of how we look at illnesses in older people,” said Dr. Arbaje.
Dr. Arbaje also highlighted some of the limitations of the study.
“There are a couple of caveats in looking at this study. We can’t look at causation, which is fine for this kind of study because they are open about it, and I think this study is meant to lead to other studies.”
“The other caveat that I would say is that this was looking at a Medicare Advantage population, which is not the majority of older adults in this country. Most older adults are under traditional Medicare, which would be more representative if the study had focused in that space. That doesn’t diminish the importance of the study, but I think it needs to be interpreted among this population,” said Dr. Arbaje.
Although the research could not demonstrate causation, Dr. Cohen suggested that the findings may be the result of two different syndromes.
“Broadly, I think about post-acute sequelae of COVID-19 as two syndromes, although there is overlap,” he explained. “The first is seen in seriously ill patients typically in the intensive care unit and often on respiratory support. These patients have a systemic inflammatory response that is quite severe, and many of the post-acute sequelae are a consequence of the organ damage that occurs from this process.”
“The other broad category is those with milder infection not requiring hospitalization, and here, we have fewer answers. We do know, for example, that SARS-CoV-2 can affect the olfactory nerve, causing anosmia [inability to smell], and that the clotting system can be activated, increasing the risk of thrombosis,” Dr. Cohen continued.
“But in other areas, such as sleep and mood alterations, cognitive difficulties, and ongoing fatigue and myalgias, to date, we don’t have the answers.”
Dr. Estores said the findings may be due to the limited knowledge doctors currently have of how to care for patients following the acute phase of COVID-19.
“The authors already mention the effect of increased medical attention that can subsequently increase the reported rates of this condition. However, it is also possible this increased risk of sequelae could be attributed to a lack of information on how to best enhance [COVID-19] recovery in the post-acute phase. For instance, how safely can we start rehabilitation interventions? How much or how little should be done?” asked Dr. Estores.
Dr. Arbaje speculated that the increase in sequelae in the COVID-19 group could be due to the significant effect of a SARS-CoV-2 infection on a person’s immune system, as well as the way COVID-19 can damage many parts of a person’s body.
“In terms of causation, or at least speculating around what might account for it, I think — and again, this is speculation — that there may be two things to keep in mind. What I’m thinking about as a geriatrician is that COVID-19 may be accelerating aging in some way.”
“Maybe someone was going to have a stroke or a heart attack 10 years from now, but COVID-19 — because it’s such a heavy hit to the immune system, it’s a huge stressor to the body — may accelerate what was already coming down the pike,” said Dr. Arbaje.
“Again, this is a theory — because if we think about what protects us from heart attacks, strokes, and cancer and other things, it’s our immune system. It’s protecting against inflammation. And when the immune system receives such a hit, I think it may have less ability, defenses, or physiological reserve to do its other duties, like monitoring for cancer cells, monitoring for the things it normally does.”
“So COVID-19 may accelerate what was already coming if we have tendencies that were coming our way, or it may create new injuries that the body then has to deal with. So we were learning that COVID-19 can lead to problems with coagulation, and it may be that it creates a new, thickened blood that can then lead to cardiovascular disease or other things.”
“So I think it could be one of two things or maybe both: accelerating what was already coming, because the immune system is no longer able to tend to those [issues], because it’s so focused on dealing with COVID-19, or it may create new injuries that then need to be dealt with — again, by an immune system that may already be overburdened.”
– Dr. Alicia Arbaje
Dr. Arbaje said that there are many ways that the healthcare system and broader social and political changes could support people in a post-acute phase of COVID-19.
“The bottom line that we can take from this work is that COVID-19 is leading to new [diseases] or is accelerating other illnesses, which means that we need to be ready as a healthcare system. We weren’t ready as a healthcare system to deal with COVID-19, so now, we need to be ready to deal with the consequences [of COVID-19].”
“[This could include] public health infrastructure, disability, rehabilitation, considering what policies might be put into place to support people who have this illness, or the caregivers who are now needing to take off work or maybe quit to care for people with long-term disability,” suggested Dr. Arbaje.
Dr. Arbaje said one way to develop the research is by ensuring the findings are more generalizable.
“I think replicating this work or broadening the scope of the inclusion criteria could be a nice next step — so let’s look at the general Medicare population, or other older adult populations in other countries to see if that’s something similar.”
Dr. Arbaje mentioned that the study uses claims data, something the authors point out as well. An improvement might be to ask patients about their symptoms rather than basing the study on billing and administrative data.
She also said that future research could look at any possible effect the COVID-19 vaccines have on a person’s likelihood of developing sequelae:
“I think that the vaccines are another potential confounder or effect modifier […] Because I think — and this is not a political statement, it is just an observational statement — that just as COVID-19 is a stressor, the vaccines, because they are so effective at generating an immune response, are also stressors.”
“On some level,” said Dr. Arbaje, “they may act as COVID-19 — not in causing illness per se but in being a stressor. And if we’re going to invoke that theory, then we should also study whether there are any sequelae — do people have exacerbations of their underlying illness shortly after vaccination?”
“So I think keeping an open mind on everything related to COVID-19, including vaccines, I think that needs to be studied. That matches with my own clinical practice — I practice in a hospital setting, and I have noticed both patients coming in with exacerbations of their underlying disease after COVID-19, but also after vaccination. And it’s hard to figure out what that is.”
“This is not to say that people shouldn’t get vaccinated — I just think that we’re still early in this process and that it’s important to look at the long-term effects of anything that we’re doing in medicine,” said Dr. Arbaje.
Dr. Estores said extending the study’s observation time could also be a way to develop the research.
“The group looked at symptoms to 120 days. I see patients who still have sequela past 120 days, who want to know if their symptoms can still improve. The research can be expanded to include a longer time frame, such as 6 months, to help me answer this question.”
Dr. Cohen said he and his colleagues have plans to continue the research.
“We have already published a similar analysis in a cohort of