What increases the risk of long Covid symptoms?

long Covid symptoms
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A Japanese research team at Hiroshima University have identified what characteristics make a person more likely to develop long Covid symptoms.

Long Covid symptoms are prevalent in many patients that recover from the initial SARS-CoV-2 infection, but what makes some people more likely to develop these lingering symptoms of COVID-19? A study performed at Hiroshima University suggests that having a mild case of COVID-19, smoking status, comorbidities, and sex do not significantly increase the risk of long Covid symptoms, but age does.

Professor Junko Takaka, the leader of the research and Executive Vice President at the University, said: “The prevalence of long-term symptoms did not significantly differ by sex, the severity of COVID-19, place of medical care, smoking status, or comorbidities.”

The team’s observational study was performed between August 2020 and March 2021 and included 127 participants who recovered from COVID-19 at two hospitals in the Hiroshima Prefecture. The investigation analysed four key areas that impact COVID-19 survivors: long term persistence of symptoms, psychological distress, impairments in work performance, and experience of stigma and discrimination.

Predictors of long Covid symptoms

Infection severity

The researchers identified long Covid symptoms in over 50% of the study participants at a median of 29 days following initial infection, with half of those with mild cases experiencing lingering symptoms. The most common symptoms reported included disorders in their sense of smell (15%), taste (14.2%), cough (14.2%), and fatigue (11%).

Aya Sugiyama, assistant professor at Hiroshima University’s Graduate School of Biomedical and Health Sciences, commented: “The most important finding is that the percentage of patients with some long-term symptoms after approximately one month from the onset of COVID-19 was as high as 52%, and even among those with mild disease, the rate was as high as 49.5%.”

The findings reinforce previous studies that between 53% and 55% of non-hospitalised COVID-19 patients develop lingering symptoms.

The researchers said: “Several reports have pointed out that COVID-19 severity is not associated with long-term symptoms. These findings suggest that COVID-19 patients should be followed up for persistent symptoms regardless of the severity of COVID-19.”


The results illustrated that sex is not a risk factor for long Covid symptoms, challenging prior research that suggested women were more likely than men to develop persistent symptoms.

However, there were disparities between men and women who had long Covid symptoms with regards to psychological distress, with 45% of women scoring ≥ 5 on the Kessler Psychological Distress Scale (K6) compared to 17.9% of men, meaning psychological distress from long Covid was more common in women.


Age significantly impacted the prevalence of long Covid symptoms. The team identified that older patients are more likely to develop the condition than those under the age of 40 and discovered age-dependent differences in the incidence of symptoms. For example, patients over 60 were more likely than other age groups to report fatigue, palpitations, dry eyes or mouth, dyspnoea, and sputum production.

They also discovered that long Covid symptoms are more likely in organs with high ACE2 expression – which is the major cell entry receptor for the SARS-CoV-2 virus. ACE2 is expressed significantly in organs such as the mouth, liver, and lungs.

The researchers noted: “COVID-19 affects various tissues and organs, such as those in the respiratory, cardiovascular, and neurological systems.”

Future areas of research

The team expressed that although smoking and comorbidities were not found to increase the risk of long Covid symptoms in their study, these factors should be analysed further, as only 18 smokers were included in the analysis, and the only comorbidities were hypertension in 19 participants and diabetes in 13. The researchers are now aiming to conduct a long-term and large-scale study.


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