- A new systematic review reports that individuals with more than five symptoms during the first week of a SARS-CoV-2 infection were at increased risk of developing persistent symptoms or long COVID.
- Age, sex, comorbidities, and hospitalization during the initial phase of illness also predicted the development of this form of the disease.
- Individuals with long COVID were at increased risk of cardiovascular and respiratory abnormalities.
- Multidisciplinary care, including physical rehabilitation, social support, and mental health services, may be necessary for managing this condition.
According to the World Health Organization (WHO), the total number of COVID-19 cases has surpassed 190 million globally, with the death toll crossing 4 million.
As the COVID-19 pandemic has progressed, it has become evident that besides the potential of developing severe or fatal illness during the first few weeks, a SARS-CoV-2 infection may also result in prolonged illness in some people.
Most individuals with COVID-19 develop mild-to-moderate symptoms and recover within 2–3 weeks after symptom onset.
However, a small but significant number of individuals tend to experience persistent symptoms beyond 4 weeks after developing COVID-19. The symptoms that people experienced after this acute phase are collectively known as long COVID or “post-acute COVID-19.”
Individuals with this condition may experience prolonged illness, regardless of the severity of symptoms during the acute phase of the infection. Although the presentation of symptoms varies among those with this form of the disease, the common symptoms of long COVID include fatigue, muscle pain, headache, and depression.
Around 1 in 5 individuals tend to experience COVID-19 symptoms after 5 weeks. Additionally, these symptoms persist beyond 12 weeks in about 10% of all people with a SARS-CoV-2 infection.
The Therapies for long COVID (TLC) study group, at the University of Birmingham in the United Kingdom, analyzed 27 previously published studies on long COVID to delineate the most common symptoms and gain insights about the predictors of prolonged illness.
The researchers also reviewed the literature to identify complications associated with long COVID and management practices for the care of individuals with prolonged illness.
Speaking to Medical News Today, Dr. Shamil Haroon, study co-author and co-lead of the TLC group, noted: “One of the challenges of assessing someone with long COVID is the sheer breadth of symptoms that people have reported and that have been published in the literature.”
“Our systematic review enabled us to combine the results of previous studies on long COVID to produce estimates of the prevalence of the most common symptoms. We [have] used this to develop a symptom burden questionnaire for long COVID that holistically assesses the wide range of potentially related symptoms while providing an objective measure of symptom burden as well as the impact on people’s lives.”
The study appears in the Journal of the Royal Society of Medicine.
To identify the most common symptoms and predictors of long COVID, the researchers first conducted a literature search to find studies involving individuals with the condition.
The researchers analyzed the pooled data on the prevalence of various long COVID symptoms from 27 studies to derive a more robust estimate of the most common symptoms.
They found that fatigue, difficulty breathing, muscle pain, joint pain, headaches, and altered sense of smell and taste were among the most prevalent symptoms during the illness. Researchers also frequently observed sleep disorders and cognitive symptoms, such as memory and concentration problems, in individuals with this condition.
Interestingly, having only mild COVID during the acute phase did not preclude the occurrence of prolonged illness, although being hospitalized at symptom onset or needing oxygen had associations with an increased risk of long COVID. One study also found that individuals exhibiting more than five symptoms during the first week of the illness had an increased likelihood of developing it.
Other factors associated with an increased risk of developing long COVID included older age, being female, and having preexisting health conditions.
Age and preexisting health conditions also influenced the number of symptoms that persisted during long COVID.
The researchers also found that long COVID negatively affected subjective quality of life, mental health, and employment in a significant number of participants. A majority of participants in the studies self-reported a decline in quality of life, even months after COVID-19 onset.
Among the reviewed articles, one study reported that nearly 1 in 4 individuals hospitalized for acute COVID-19 had symptoms of anxiety or depression at 6 months after symptom onset.
A separate study found that individuals hospitalized for acute COVID-19 were at increased risk of post-traumatic stress disorder (PTSD). Inadequate social support, stigmatization, female gender, and the number of protracted symptoms were associated with severe PTSD symptoms.
Complications involving multiple organ systems, including the respiratory, gastrointestinal, cardiovascular, and nervous systems, are known to occur during the acute phase of COVID-19.
Similar to acute infection, the researchers found that a significant number of individuals with COVID-19 had heart inflammation, impaired lung function, other lung-related abnormalities, diminished kidney function, and neurological abnormalities at 2–3 months following symptom onset or hospital discharge.
Significantly, the studies on cardiovascular abnormalities involved nonhospitalized individuals who were asymptomatic or had mild COVID-19 symptoms, highlighting the possibility of long-term complications in nonhospitalized individuals with long COVID.
Although some institutions have issued guidelines for managing long COVID-19, these recommendations are still evolving as more evidence emerges about the illness.
COVID-19 patients admitted to the intensive care unit may experience muscle weakness, muscle disease, neurological damage or dysfunction, and lung-related abnormalities. Therefore, they must undergo physical therapy and respiratory or pulmonary rehabilitation immediately after their condition stabilizes.
The researchers suggest that such therapy may also be beneficial to nonhospitalized individuals with long COVID. However, they may not receive the appropriate care due to their symptoms not being recognized or investigated by clinicians.
Due to the prevalence of mental health symptoms, such as anxiety, depression, and PTSD, in people with long COVID, the authors suggest that those with this condition undergo screening for these symptoms and access mental health services if necessary. People living with this form of the disease may also experience social isolation and stigmatization and may benefit from social services support.
MNT also spoke with Dr. David Putrino, director of rehabilitation innovation for the Mount Sinai Health System, about caring for individuals with long COVID.
Dr. Putrino, who was not involved in the study, while discussing the importance of multidisciplinary care for those with long COVID, noted that the symptoms that healthcare professionals are seeing are highly complex and involve multiple systems that heavily interact with each other.
Care of such patients by multiple experts, each treating a specific symptom in an uncoordinated manner, can worsen the overall condition of the individual, Dr. Putrino noted. The health expert also commented that multidisciplinary care involving a team of medical professionals collectively making decisions about patient management is necessary for the successful rehabilitation of individuals with long COVID.
Moreover, patients with this condition present with complex symptoms that require personalized care, Dr. Putrino added.
Dr. Enya Daynes, a research physiotherapist at the NIHR Leicester Biomedical Research Centre in the U.K., who was not involved with the study, told MNT, “Currently, one of the challenges we face is in those [individuals with long COVID who] do not respond to rehabilitation. There will be some people for whom exercise makes their symptoms worse, and while there are a number of theories as to why this is, we do not have a conclusive answer as to what is driving this response and how best to treat this.”
“We need further research for people who do not respond to exercise to explore what might be causing this response and how we can treat these people. Fortunately, there has been a number of studies that have started or are due to start to explore this gap in knowledge, and hopefully, we will have more answers soon.”
– Dr. Enya Daynes
Long-term monitoring of individuals with COVID-19, with the help of individuals self-reporting and remote patient monitoring, may be necessary to address potential complications in a timely manner.
Remote patient monitoring involves using wearables devices to track patients’ vital signs to help clinicians identify at-risk individuals.
The researchers note that a better understanding of the mechanisms responsible for long COVID is necessary for developing suitable treatments for the condition.
The authors observed, “Clinical trials are urgently needed to evaluate interventions for long COVID that address the wide range of symptoms and complications identified in this review.”
The authors continued: “The wide range of potential symptoms and complications patients with long COVID may experience highlights the need for a deeper understanding of the clinical course of the condition. There is an urgent need for better, more integrated care models to support and manage patients with long COVID-19 to improve clinical outcomes.”
The authors also noted that most studies on long COVID have focused on hospitalized patients, and studies involving nonhospitalized individuals with the condition are urgently needed. Lastly, whether racial differences exist in the incidence rate of long COVID, similar to acute SARS-CoV-2 infection, needs to be investigated.
The researchers are about to start a study to address some of these shortcomings. The researchers intend to track the impact of long COVID-19 on symptoms, work capability, and quality of life in nonhospitalized individuals using remote patient monitoring.
Dr. Haroon noted, “We will use statistical methods to identify clusters of symptoms to define specific syndromes and combine that with clinical data to describe these syndromes in detail.
Furthermore, Dr. Haroon noted that the team plans to use blood and saliva samples to study the immune response in nonhospitalized individuals with long COVID and therefore identify potential drug targets.
“We will also hold workshops to gain consensus on the key therapies to put forward into clinical trials for long COVID and to co-produce with [individuals] and clinicians an intervention to support [people] with long COVID in the community,” Dr. Haroon continued.
“This will be vital as the sheer scale of the numbers of people with long COVID means that the health service will not have the capacity to manage all patients in specialist clinics, and different models of care will be needed to meet this rising patient need.”
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