- Researchers analyzed primary care data from the United Kingdom to identify symptoms and risk factors for long COVID.
- They found 62 symptoms of long COVID, including hair loss, and reduced libido, as well as several risk factors such as smoking or being socially deprived.
- They concluded that SARS-CoV-2 infection is linked to various symptoms associated with sociodemographic and clinical risk factors.
After contracting SARS-CoV-2, around 10% of people develop long COVID, or persistent and relapsing symptoms 4-12 weeks after infection. These symptoms typically last for at least two months and cannot be explained by alternative diagnoses.
Systematic reviews have shown the most common symptoms to include:
- fatigue
- shortness of breath
- muscle pain
- joint pain
- headache
- cough
- chest pain
- altered smell
- altered taste
- diarrhea
As many of these studies were based on self-reported symptoms or lacked a control group, inferences drawn from them on long COVID symptoms may be limited.
Recently, researchers conducted a large-scale analysis of primary care data from the U.K. to investigate a comprehensive range of long COVID symptoms.
They identified 62 symptoms as being significantly associated with a history of SARS-CoV-2.
The study was published in Nature Medicine.
62 long COVID symptoms
For the study, the researchers examined primary care data collected between January 31, 2020 and April 15, 2021 from 486,149 adults with a confirmed COVID-19 diagnosis and 1,944,580 controls with no history of SARS-CoV-2 infection.
The participants were matched for sociodemographic characteristics, including smoking status, body mass index (BMI), and comorbidities at baseline.
Their mean age was 43.8 years old, and 55.3% were female. Altogether, 64.7% of participants were white, 12.2% were Asian, 4% were Black Afro-Caribbean, and 16.2% lacked ethnicity data.
After adjusting for demographic factors, the researchers found that 62 symptoms were linked to a history of SARS-CoV-2 infection.
The most common symptoms, including new additions, were:
- anosmia (loss of smell)
- hair loss
- sneezing
- ejaculation difficulty
- reduced libido
- shortness of breath at rest
- fatigue
- pleuritic chest pain
- hoarse voice
- fever
The researchers were further able to cluster these symptoms into three main groups:
- A broad spectrum of symptoms, including pain, fatigue, and rash— 80%
- Respiratory symptoms, including cough, shortness of breath, and phlegm— 5.8%
- Mental health and cognitive symptoms including anxiety, depression, insomnia, and brain fog— 14.2%
They also found that long COVID symptoms were more pronounced during the second wave than in the first wave.
Whereas COVID-19 diagnosis was linked to a 28% relative increase in reporting cough after 12 weeks during the first wave, it was linked to a 77% relative increase during the second wave.
Who is more at risk?
The researchers also conducted a risk factor analysis for long COVID involving 384, 137 individuals who contracted SARS-CoV-2. Overall, they found that women were at an increased risk than men for long COVID.
Meanwhile, those ages 30–39 years old and over 70 were 6% and 25% less likely than 18–30-year-olds to develop long COVID.
They further found that people of Black Afro-Caribbean descent, mixed ethnicity, native American, Middle Eastern, or Polynesian origin were more likely to develop long COVID than white ethnic groups.
Social deprivation also played a role; those with the highest levels of socioeconomic deprivation were 11% more likely to develop long COVID than the least deprived.
Other risk factors included:
- being a smoker or former smoker
- having overweight or obesity
- comorbidities such as chronic obstructive pulmonary disease (COPD), fibromyalgia, and depression.
What causes long COVID?
When asked about what might underlie long COVID’s long symptom list, Dr. Shamil Haroon, clinical senior lecturer at the University of Birmingham’s Institute of Applied Health Research, one of the study’s authors, told Medical News Today:
“The mechanisms that cause long COVID are not well understood, and the list of hypotheses are quite diverse, including organ damage (e.g. lung scarring) from the acute infection, chronic inflammation, viral persistence, endothelial dysfunction, and blood clots, autoimmunity, mast cell activation, and many others.”
“Long COVID is unlikely to be a single condition but rather several overlapping conditions that occur following SARS CoV-2 infection.”
— Dr. Shamil Haroon
Dr. PJ Utz, professor of immunology and rheumatology at Stanford University, who was not involved in the study, told MNT:
“Almost certainly, multiple mechanisms underlie long COVID and in part explain the incredible heterogeneity. For example, intense inflammation during the initial illness can damage tissue, leading to long-term signs and symptoms. This may underlie some findings such as anosmia and pulmonary symptoms.”
“Endothelial dysfunction and microclotting [have] been observed in acute illness. Activation of the immune system leading to inflammation and the development of autoantibodies is also likely to be important. NIH’s large RECOVER study is actively pursuing all of these mechanisms,” he noted.
The researchers concluded that SARS-CoV-2 is linked to various symptoms related to sociodemographic and clinical risk factors.
An autoimmune link?
When asked about limitations to the research, Dr. Haroon said more data was needed for the complete picture.
“The limitations of our research include that we only considered symptoms that were reported to primary care services. We, therefore, cannot comment on the overall prevalence of these symptoms in the general population, since many people with long Covid may not necessarily report their symptoms to their general practitioners,” he said.
“We also used coded data from health records. Many symptoms will be recorded by clinicians as free text, which we did not have access to analyze,” he added.
Dr. Utz agreed with Dr. Haroon and suggested that this research opens avenues for future research.
“A very important question that has not been addressed yet is whether an increase in incident classifiable autoimmune diseases are observed—if so, this would suggest that a severe acute viral infection can directly trigger autoimmunity,” he said.
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