Long COVID: 3 in 10 COVID-19 patients not fully recovered after 1 year

Aerial view of people queuing at a temporary COVID-19 testing site on December 10, 2021 in Nanjing, China.
Aerial view of people queuing at a temporary COVID-19 testing site on December 10, 2021, in Nanjing, China. Yang Bo/China News Service via Getty Images
  • Individuals hospitalized with acute COVID-19 may continue to experience long COVID symptoms at least 1 year after discharge.
  • There is considerable variation in the persistence and severity of long COVID symptoms among individuals.
  • A recent study characterized traits associated with severe long COVID symptoms at 5 and 12 months after being discharged for hospitalization with acute illness.
  • Fewer than 3 in 10 patients felt they had fully recovered at 12 months following hospital discharge for acute COVID-19.
  • The study found that being female and having obesity, systemic inflammation, and more severe symptoms during initial COVID were associated with increased risk of long COVID-related severe health impairments.

A substantial number of individuals with an acute SARS-CoV-2 infection do not recover fully within the first 3–4 weeks after developing an illness.

These COVID-19 symptoms often persist for weeks and months beyond the initial phase of the infection. Health experts have described these lingering COVID-19 symptoms collectively as “long COVID” and “post-COVID-19 condition.”

According to the World Health Organization (WHO), long COVID “occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis.”

Previously hospitalized patients are more likely to experience persistent symptoms at 10–14 weeks after contracting SARS CoV-2 than nonhospitalized individuals.

Moreover, some previously hospitalized COVID-19 patients show more severe health impairments associated with long COVID than their peers.

A recent study characterized traits associated with differences in severity of health impairments 1 year after discharge in patients previously hospitalized with acute COVID-19.

These findings may help doctors identify individuals with COVID-19 who are at risk of developing persistent, severe health impairments and may facilitate the development of treatments for long COVID.

A preprint version of the study appears on the site Medrxiv.

Traits associated with long COVID

Previous studies have shown that cognitive and physical deficits persist at least 6 months after discharge in people hospitalized with acute COVID-19. Moreover, there is considerable variation in the severity of symptoms and their persistence at 6 months post-discharge in these individuals.

However, there are limited data tracking differences in the recovery of people with the disease over longer durations after discharge.

A recent study from the Post-Hospitalization COVID-19 (PHOSP-COVID) group characterized the physical and mental health impairments at 5 and 12 months after discharge in individuals previously hospitalized with acute COVID-19.

The study found that less than 30% of patients felt that they had fully recovered at 12 months post-discharge. Factors, such as being female, having obesity, and requiring mechanical ventilation, during initial illness with COVID-19 were associated with more severe health impairments after 12 months.

The study’s co-author, Dr. Rachael Evans, a professor at the University of Leicester in the United Kingdom, says:

“The findings that many patients had not fully recovered 1 year after leaving hospital indicate that healthcare professionals will need to proactively continue assessing their patients for some time to come in order to identify their ongoing healthcare needs and provide support.”

The study also investigated the association between whole-body or systemic inflammation and severity of health impairments at 5 months.

An increase in inflammation is associated with more severe illness during the acute phase of a SARS-CoV-2 infection.

Severe inflammation during the acute phase may result in dysregulation of the immune system, leading to a chronic inflammatory state. This chronic increase in inflammation could potentially result in the persistent symptoms that healthcare professionals have seen in long COVID patients.

The study found that individuals with more severe long COVID-19 symptoms 5 months after discharge had higher plasma levels of pro-inflammatory proteins than those with mild symptoms.

“The good news is that we have identified some differences in the blood samples [pro-inflammatory proteins] of those who are still experiencing the long-term physical and cognitive effects of their COVID-19 hospital admission,” explains study co-author Dr. Louise Wain.

“These differences give us clues about the potential underlying mechanisms and suggest that we may be able to use existing medicines that target these mechanisms to help these subgroups of patients.”

Micro B Life spoke with Dr. Ziyad Al-Aly, the chief of the Research and Education Service at the VA Saint Louis Health Care System, MO.

Dr. Al-Aly, who was not involved with the study, said,” The shocking thing is that most people are not recovering; they report that less than a third of patients reported full recovery. This is alarming, but I am not completely surprised. It is consistent with our evolving understanding of long COVID features.”

“I worry that health systems, governments, and the WHO are all knee-deep dealing with the acute situation (Omicron, etc.) that very little attention is being paid to the millions of people with long COVID,” he continued.

“Long COVID will create a tsunami of medical illnesses that our systems are simply unprepared for. People need to pay attention and deal with this now before it is too late.”

– Dr. Al-Aly

Long-term recovery

The PHOSP-COVID study included patients hospitalized for acute COVID who agreed to visit the research site for assessment at 5 and 12 months after discharge.

During these visits, the researchers conducted physical tests and tests to measure pulmonary function. They also collected blood samples to evaluate the levels of inflammatory proteins.

During these visits, the team used a questionnaire to assess the participants’ perception of recovery. They also used questionnaires to evaluate the individuals’ health and health-related quality of life.

The researchers found that a majority of patients perceived their recovery from COVID-19 to be incomplete or were not sure whether they had recovered at 12 months after hospital discharge.

Around 25% of the participants reported having recovered fully at 5 months post-discharge. Similarly, a little over 29% of participants felt they had fully recovered at 12 months after discharge.

There were limited improvements in cognitive and physical health during the period between the 5-month and 12-month visits.

Some commonly observed symptoms at 12 months post-discharge included fatigue, difficulty breathing, muscle aches, and poor sleep.

The factors associated with participants reporting a lack of recovery after 12 months included being female, having obesity, and receiving invasive mechanical ventilation.

Recovery clusters

The researchers then classified participants into four groups according to physical and mental health symptoms at 5 months after discharge. The team achieved this using a statistical method called cluster analysis.

According to the cluster analysis, the researchers were able to categorize participants as having “very severe,” “severe,” “moderate,” or “mild” physical and mental health impairments at 5 months after hospital discharge.

The researchers found that being female and having obesity were associated with an increased risk of belonging to the more severe health impairment cluster.

This suggests that weight reduction could potentially help alleviate long COVID symptoms. Moreover, healthcare professionals may need to closely monitor female patients with COVID-19 for the development of severe impairments.

Individuals in the very severe group had an increased likelihood of having lower exercise capacity, a higher number of symptoms, and feeling not fully recovered than the mild group at 12 months post-discharge.

Individuals in the more severe group also had higher plasma levels of C-reactive protein, a protein associated with increased inflammation.

The reduced exercise capacity of patients with severe health impairments may interfere with their participation in physical rehabilitation programs generally recommended to long COVID patients. Therefore, other interventions may be necessary to improve the physical function of these individuals.

The researchers asked the participants to estimate their health-related quality of life before the SARS-CoV-2 infection based on their recollection. The team then compared these pre-COVID-19 estimates with the results of the health-related quality of life assessments conducted during the 5-month and 12-month post-discharge visits.

They found that health-related quality of life at 5 and 12 months post-discharge was inferior to that before the SARS-CoV-2 infection.

The researchers noted a correlation between the severity of physical and mental health impairments and patients with long COVID.

In other words, individuals with severe physical health impairments also simultaneously showed severe cognitive symptoms. These findings suggest that integrative care addressing both physical and mental health may be necessary for the treatment of long COVID.

Dr. Al-Aly said, “We need a multipronged holistic approach to treating these patients. Long COVID is a multifaceted disease and requires multidisciplinary care.”

Inflammatory proteins

The researchers then used the plasma samples collected during the 5-month visit to compare the expression of 296 inflammatory proteins.

The participants in the very severe impairment group had higher levels of 13 proteins associated with systemic inflammation than the mild impairment group.

The moderate impairment group also showed elevated levels of two inflammatory proteins than the mild impairment group.

These inflammatory proteins may be useful markers to identify individuals at high risk of developing severe health impairments.

Moreover, reducing systemic inflammation could be a potential target for the treatment of long COVID. For instance, there was a rise in pro-inflammatory protein interleukin-6 (IL-6) in both the severe and moderate impairment group, so anti-IL-6 treatments could be potential treatments for long COVID.

Identifying different inflammatory proteins associated with specific recovery clusters may also allow the use of anti-inflammatory drugs targeted to a particular cluster.

Limitations of the study

The authors note that the proportion of participants in the study who had received invasive mechanical ventilation was greater than that observed in patients hospitalized with acute COVID-19 in the U.K. Therefore, their results may not be generalizable to the entire population.

Also, the measurements of health-related quality of life before COVID-19 came from participants’ recollections of their health before illness. There is a chance that these measurements could be biased.

Lastly, the authors noted that their results show a correlation between various traits and severity of health impairments due to long COVID. Therefore, further research is necessary to establish causation.

Dr. Claire Steves, a researcher at King’s College London, told MBL, “This study is about people who have been hospitalized and often been very ill, requiring intensive care. Therefore the findings do not apply to people who have not been hospitalized.”

Dr. Steves added, “It’s likely that recovery is quite different in people living with long COVID who have not been hospitalized. [Hence], we need further studies on these groups, which constitute the majority of people living with long COVID.”

“This study cannot separate the long-term effects of being severely ill in general (especially during this traumatic time where they could not be visited) from the effects of COVID-19 itself, as they do not follow up people who have been admitted to hospital for other conditions.”

“Nevertheless, this does show just how many people have long-term symptoms after severe illness — which is important for the delivery of services,” noted Dr. Steves.

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