Article 3

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com/scientificreports
OPEN Long COVID prevalence and impact

on quality of life 2 years after acute
COVID‑19
Yoonjung Kim , Sohyun Bae , Hyun‑Ha Chang & Shin‑Woo Kim *
There has been an increasing interest in the long-term impact of long COVID. However, only a few
studies have investigated the clinical manifestations of long COVID 24 months after acute COVID
infection. In this study, prospective online surveys were conducted in adults previously diagnosed
with coronavirus disease 2019 (COVID-19) in South Korea between February 13 and March 13,
2020, at 6, 12, and 24 months after COVID-19. We investigated self-reported symptoms and the
EuroQol-5-dimension index. Among 900 individuals enrolled initially, 150 completed all 3 surveys.
After excluding the cases of COVID-19 reinfection, 132 individuals were included in the final analysis.
Among the 132 participants, 94 (71.2%) experienced symptoms of long COVID. The most frequently
reported symptoms were fatigue (34.8%), amnesia (30.3%), concentration difficulties (24.2%),
insomnia (20.5%), and depression (19.7%). Notably, no significant differences were noted in the
incidence of long COVID at 24 months in terms of the number of vaccinations received. Although
the neuropsychiatric quality of life improved over time, it continued to affect 32.7% of participants.
Symptoms of long COVID, particularly neuropsychiatric symptoms, tend to persist over time,
and COVID-19 vaccination or the number of vaccinations received may not significantly affect the
incidence of long COVID.
The coronavirus disease 2019 (COVID-19) pandemic has been ongoing for more than 2 years, and the number
of cases continues to increase worldwide due to the constant mutation of the virus, evolution of infectivity, and
evasion of immunity. Nevertheless, the proportion of people surviving COVID-19 has substantially increased
compared to the initial outbreak owing to the improvements in treatment methods and preventive vaccination
strategies1.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is often
associated with long-term symptoms known as post-COVID-19 condition or long C OVID2. While COVID-19
primarily affects the respiratory system, evidence from the relevant literature indicates that it also affects the
digestive, cardiovascular, nervous, and reproductive s ystems3,4. According to the World Health Organization
(WHO), long COVID is defined as the continuation or development of new symptoms 3 months after the initial
SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other e xplanation5. Although
the symptoms of long COVID typically resolve in most cases6, neuropsychiatric symptoms can persist for more
than 6–12 months after acute COVID-197–10. This is a significant concern as a previous study suggested similari-
ties between brain changes occurring during and after COVID-19 and those seen in human neurodegenerative
diseases11. Although risk factors for long COVID include old age, female sex, and moderate or severe COVID-
1912, long COVID can develop regardless of disease s everity13. Moreover, long COVID is associated with poor
health-related quality of life, both in patients with moderate or severe COVID-19 and in those with mild or
asymptomatic COVID-1914. Notably, a population-representative survey in the United States reported a high
incidence of long COVID (30.2% [18.5–41.8%] within the past 1–6 months)15. However, further long-term
follow-up studies are necessary to establish a treatment plan for long COVID.
Although some studies have reported that long COVID persists for 24 months after COVID-1914,16, there
is still a limited number of long-term follow-up studies. Moreover, it has been reported that vaccination before
or after COVID-1913–15 reduces the risk of developing long COVID17. However, to the best of our knowledge,
no study has analyzed long-term COVID-19 including the presence or absence of reinfection and the history
of vaccination after COVID-19 to date. Therefore, this study aimed to comprehensively assess the longitudinal
Division of Infectious Diseases, Department of Internal Medicine, School of Medicine, Kyungpook National University
Hospital, Kyungpook National University, 130, Dongdeok‑ro, Jung‑gu, Daegu 41944, Republic of Korea. *email:
[email protected]
Scientific Reports | (2023) 13:11207 | https://doi.org/10.1038/s41598-023-36995-4 1
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progression of health outcomes in COVID-19 survivors who did not experience reinfection up to 24 months
after acute infection and evaluate the impact of long COVID on the daily lives of such patients.
Methods
Study design and population. In this study, three prospective online surveys were conducted with
patients diagnosed with COVID-19 (age 16–70 years) from February 13 to March 13, 2020 in Daegu using the
clinical data provided by the Daegu Infectious Diseases Control and Prevention. These patients were diagnosed
via real-time reverse transcription polymerase chain reaction using nasopharyngeal swabs or other upper res-
piratory tract samples.
The online survey was conducted at Kyungpook National University Hospital, Daegu. The first survey was
conducted at 5–6 months after the onset of COVID-19 symptoms or COVID-19 diagnosis between September
8 and September 10, 2020. The second survey was conducted at 11–12 months after COVID-19 symptom onset
or diagnosis between May 26 and June 1, 2021. The third survey was conducted 24 months after COVID-19
symptom onset or diagnosis between May 26 and June 2, 2022. Sex, birth year and date, and the last four digits
of cellular phone numbers were used to distinguish and match the responders of the first and second online
surveys with those of the third survey.
Long COVID was defined as the presence of at least one sequelae symptom based on the case definition of
long COVID2, confirmed intermittently or continuously. Participants were considered in the no symptom group
if they no longer experienced symptoms at the time of completion of the survey. Responders who were found to
be reinfected based on the documented data were excluded.
The individualized questionnaire list included questions related to sex, birth year and date, residential address,
COVID-19 diagnosis date, symptoms categorized according to the 45 symptom classification during or after
acute COVID-19, oxygen treatment history, admission place during acute COVID-19, vaccination history after
COVID-19, newly diagnosed diseases after COVID-19, and outpatient treatment history for COVID-19-related
persistent symptoms or signs. Clinical data were obtained from the Daegu Center for Infectious Diseases Control
and Prevention registry for COVID-19 diagnosis date, first symptom onset date, disease severity, and reinfec-
tion history.
The EuroQol-5 dimension (EQ5D) index was used to assess the quality of life associated with long COVID.
The EQ5D score was classified into five categories: mobility, self-care, usual activities (e.g., work, study, house-
work, family, or leisure activities), pain/discomfort, and anxiety/depression. Further, each category had five levels
indicating the severity of problems (no, slight, moderate, severe, and extreme problems). Respondents indicated
their health status by selecting the most appropriate statement for each category. The scores for five categories
were then combined to form a five-digit number representing the respondent’s health status18.
The severity scores during acute COVID-19 were classified as follows: (1) asymptomatic, no symptoms or
discomfort throughout the disease period, with a body temperature of < 37.5 °C; (2) mild, presence of symptoms
with or without fever (≥ 37.5 °C) but no manifestation or identification of pneumonia; (3) moderate, pneumonia
diagnosed by a clinician but not requiring oxygenation therapy other than room air; (4) severe, pneumonia
diagnosed by a clinician and requiring oxygenation therapy (nasal prong, facial mask, or high-flow oxygen
therapy); and (5) critical, pneumonia diagnosed by a clinician and requiring mechanical ventilation therapy or
extracorporeal membrane oxygenation t herapy8.
Statistical analysis. We conducted a descriptive analysis. Continuous variables were presented as median
(interquartile range [IQR]) values, whereas categorical variables were presented as numbers (percentages). Cat-
egorical variables were analyzed using Fisher’s exact or chi-square test, whereas noncategorical variables were
analyzed using Student’s t or Mann–Whitney U test. Notably, these tests were used to determine the differ-
ences in the clinical characteristics and lifestyle changes of the responders with and without long COVID after
24 months of acute COVID-19 and to identify the differences in the prevalence of long COVID over time (from
6 to 24 months) after acute COVID-19. Multivariate logistic regression analysis was performed to determine the
potential factors associated with major long COVID symptoms 24 months after the infection. Further, adjusted
odds ratios (ORs) with 95% confidence intervals were calculated. A P-value of < 0.05 was considered statisti-
cally significant. Statistical analyses were performed using R statistics version 4.0.2 (The R Foundation; https://
www.r-project.org).
Ethics approval statement. This study was reviewed and approved by the Institutional Review Board of
Kyungpook National University Hospital (approval no.: 2021-02-003). All methods were performed in accord-
ance with the relevant guidelines and regulations by including a statement in the methods section. All respond-
ents provided digital informed consents before the questionnaire was administered.
Results
Demographics and characteristics of long COVID for 24 months. Among the 5,252 individuals,
900 responded to the first online survey, and 241 responded to the second online survey. Overall, 150 respond-
ents completed all three surveys, resulting in a total response rate was 62.2% (150 out of 241 respondents).
Of these 150 respondents, 18 were excluded due to reinfection. Finally, 132 respondents were included in the
analysis. The median number of days from diagnosis to the date of survey was 819 (IQR 816–823). Among the
respondents, 90 (68.2%) were females, representing the majority.
The median age of participants at COVID-19 diagnosis was 38 (IQR 24.0–50.5) years, and the age range of
17–29 years was the most common (38.6%). Overall, 26.5% respondents were aged > 50 years. No significant
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differences were found in sex and age distribution between the groups with and without 24-month long COVID
symptoms (P > 0.05) (Supplementary Table 1).
Overall, 77.3% of respondents belonged to the mild COVID-19 group, while 15.9% had moderate or severe
COVID-19.
Sixteen respondents (12.1%) were diagnosed with new conditions after acute COVID-19, and eight respond-
ents (6.1%) sought outpatient treatment for long COVID symptoms. Notably, all respondents were vaccinated
after acute COVID-19. Among the 132 respondents, 127 (96.2%) were vaccinated, and there were no differences
in the number of vaccinations between the two groups (Table 1).
The prevalence of long COVID after 24 months of acute COVID‑19. Out of the 132 respondents,
79 (59.8%) reported experiencing one or more long COVID symptoms at 6 months after acute COVID-19, and
the most common symptoms were cognitive dysfunction (26.5%), amnesia (25.8%), depression (25.0%), anxiety
(24.2%), and concentration difficulties (23.5%).
At 12 months after acute COVID-19, 70 (53.0%) respondents reported experiencing one or more long COVID
symptoms, and the most common symptoms at this time point were cognitive dysfunction (23.5%), concentra-
tion difficulties (22.0%), amnesia (21.2%), fatigue (17.4%), and anxiety (15.9%).
At 24 months after acute COVID-19, 94 (71.2%) respondents reported experiencing one or more long COVID
symptoms. Fatigue (34.8%) was the most frequent symptom, followed by amnesia (30.3%), concentration dif-
ficulties (24.2%), insomnia (20.5%), and depression (19.7%) (Fig. 1).
Three (2.3%) respondents exhibited long COVID at 24 months after COVID-19, which was not identified at
12 months after COVID-19. Follow-up examinations at 6, 12, and 24 months from the date of COVID-19 diag-
nosis or symptom onset showed a high incidence of symptoms at 6 and 12 months after COVID-19, whereas the
symptoms remained at the same level even after 24 months. After 6 months, there was no incidence of seizures;
however, the incidence of symptoms related to amnesia increased to 30.3%, which was higher than the rates
reported at each previous time point. Amnesia, concentration difficulties, alopecia, dizziness, and paresthesia
were identified in 15–30% of respondents even 24 months after acute COVID-19 (Fig. 1, Supplementary Figs. 1,
2). In particular, changes in concentration difficulties and amnesia from 1 to 24 months after the date of diag-
nosis or symptom onset remained at a similar level (25–30%) until 24 months after acute COVID-19 (Fig. 2).
Statistical analysis revealed that the prevalence of fatigue increased over time as cognitive impairment
improved (P = 0.007). However, no significant changes were found in the other seven symptoms. Moreover,
no statistically significant difference was confirmed in the increase or decrease in the prevalence of the other
symptoms over time (P > 0.05; Supplementary Fig. 3).
Sankey flow diagram analysis was used to assess the frequency of changes in the nine main symptoms from
their initial stages over time. The results revealed that these neuropsychiatric symptoms continued to be associ-
ated with each other over time at 6, 12, and 24 months (Supplementary Fig. 4).
The impact of long COVID on quality of life and lifestyle changes. The distribution of EQ5D-5L
average scores at 12 and 24 months after COVID-19, measured using five EQ5D categories, revealed that the
distribution at 12 months after COVID-19 was similar to that at 24 months after the infection (Supplementary
Fig. 5).
Specific answers showed similar distributions in each of the five categories for 12 and 24 months. Thus, it was
confirmed that COVID-19 may continue to affect the quality of life of individuals even 24 months after acute
infection (Fig. 3).
To determine the effects of long COVID on lifestyle, we compared the lifestyle changes of the participants in
the 24-month long COVID symptom presence and absence groups. The results indicated that the long COVID
symptom presence group (52.1%) had a higher tendency to consume healthy foods than the absence group
(21.1%) (P = 0.003). Moreover, the long COVID symptom presence group (36.2%) had a higher tendency to
engage in physical activity than the absence group (18.4%); however, no statistical difference was observed
between the two groups (P = 0.075). Furthermore, no statistical differences were identified between the two
groups in terms of smoking or alcohol intake (P ≥ 0.05) (Supplementary Table 2).
Assessing risk factors for long COVID 24 months after acute COVID‑19. Risk factor analysis
revealed that moderate or severe disease activity during acute COVID-19 is a statistically significant risk factor
for long-term symptoms of fatigue (odds ratio, 3.02 [1.17–8.05]; P = 0.023). Other symptoms, including anxiety,
depression, insomnia, concentration difficulty, and cognitive dysfunction, were not associated with moderate
or severe disease activity, age of ≥ 50 years, and sex at the time of acute COVID-19 (P > 0.05). The risk of occur-
rence of amnesia tended to increase by 2.31 times in people aged > 50 years; however, this was not statistically
significant (P = 0.059) (Table 2).
Discussion
To the best of our knowledge, this is the first study to assess the long-term impact of COVID-19 at 24 months
after acute COVID-19 in patients with documented COVID-19 vaccination and without history of reinfection.
Based on the findings of this study, long COVID symptoms improved over time and neuropsychiatric symptoms
tended to persist longer than other symptoms up to 24 months after COVID-19.
The clinical spectrum of long COVID comprises a wide range of symptoms. A previous systematic review
reported that common symptoms of long COVID include fatigue, dyspnea, concentration impairment, anxiety,
sleep disorder, memory impairment, and cognitive i mpairment4. According to the United Kingdom (UK) Office
for National Statistics survey, fatigue continued to be the most commonly reported symptom among individuals
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Characteristics No symptom (N = 38) Symptom (N = 94) Total (N = 132) P-value

Days from COVID-19 diagnosis to survey 820.0 [816.0;821.0] 819.0 [816.0;823.0] 819.0 [816.0;823.0] 0.493
Sex 0.159
Male 16 (42.1%) 26 (27.7%) 42 (31.8%)
Female 22 (57.9%) 68 (72.3%) 90 (68.2%)
Age, median (IQR; years) 29.5 [23.0;47.0] 40.0 [25.0;52.0] 38.0 [24.0;50.5] 0.097
Age distribution (years) 0.295
18–29 19(50.0%) 32(34.0%) 51 (38.6%)
30–39 4 (10.5%) 15 (16.0%) 19 (14.4%)
40–49 9 (23.7%) 18 (19.1%) 27 (20.5%)
50–59 4 (10.5%) 19 (20.2%) 23 (17.4%)
60–70 2 (5.3%) 10 (10.6%) 12 (9.1%)
Age (years) 0.119
< 50 32 (84.2%) 65 (69.1%) 97 (73.5%)
≥ 50 6 (15.8%) 29 (30.9%) 35 (26.5%)
Disease severity 0.002
Asymptomatic 7 (18.4%) 2 (2.1%) 9 (6.8%)
Mid 29 (76.3%) 73 (77.7%) 102 (77.3%)
Moderate 2 (5.3%) 17 (18.1%) 19 (14.4%)
Severe 0 (0.0%) 2 (2.1%) 2 (1.5%)
Critical 0 (0.0%) 0 (0.0%) 0 (0.0%)
Disease severity 0.062
< Moderate 36 (94.7%) 75 (79.8%) 111 (84.1%)
≥ Moderate 2 (5.3%) 19 (20.2%) 21 (15.9%)
Isolation placea 0.046
Secondary or tertiary hospital 14 (36.8%) 57 (60.6%) 71 (53.8%)
Therapeutic living center 22 (57.9%) 34 (36.2%) 56 (42.4%)
Self-home isolation 2 (5.3%) 3 (3.2%) 5 (3.8%)
Oxygen treatment 0.626
Yes 0 (0.0%) 2 (2.1%) 2 (1.5%)
No 38 (100.0%) 92 (97.9%) 130 (98.5%)
Newly diagnosed diseases following acute COVID-19 0.016
Yes 0 (0.0%) 16 (17.0%) 16 (12.1%)
No 38 (100.0%) 78 (83.0%) 116 (87.9%)
Outpatient clinic visits due to long COVID 0.146
Yes 0 (0.0%) 8 (8.5%) 8 (6.1%)
No 38 (100.0%) 86 (91.5%) 124 (93.9%)
COVID-19 vaccination historyb 1.000
Yes 37 (97.4%) 90 (95.7%) 127 (96.2%)
No 1 (2.6%) 4 (4.3%) 5 (3.8%)
Number of COVID-19 vaccination 1.000
<2 2 (5.3%) 5 (5.3%) 7 (5.3%)
≥2 36 (94.7%) 89 (94.7%) 125 (94.7%)
Number of COVID-19 vaccination 0.454
0 1 (2.6%) 4 (4.3%) 5 (3.8%)
1 1 (2.6%) 1 (1.1%) 2 (1.5%)
2 10 (26.3%) 26 (27.7%) 36 (27.3%)
3 18 (47.4%) 31 (33.0%) 49 (37.1%)
4 8 (21.1%) 32 (34.0%) 40 (30.3%)
Table 1. Clinical characteristics of 132 respondents according to the presence of persistent symptoms or
signs identified 24 months after the diagnosis or symptom onset of acute COVID-19. COVID-19 coronavirus
disease 2019, IQR interquartile range. a Isolation place: the place where patients were quarantined after being
diagnosed with COVID-19 for the first time. b All respondents had received COVID-19 vaccination following
acute COVID-19.
Vol:.(1234567890)
6 months 12 months 24 months

Cognitive dysfunction 26.5% Cognitive dysfunction 23.5% Fatigue 34.8%
Amnesia 25.8% Concentration difficulties 22.0% Amnesia 30.3%
Depression 25.0% Amnesia 21.2% Concentration difficulties 24.2%
Anxiety 24.2% Fatigue 17.4% Insomnia 20.5%
Concentration difficulties 23.5% Anxiety 15.9% Depression 19.7%
Fatigue 22.7% Insomnia 15.2% Anxiety 18.2%
Insomnia 20.5% Depression 14.4% Itchy skin 17.4%
Social phobia 20.5% Alopecia 14.4% Globus pharyngeus 16.7%
Alopecia 15.9% Social phobia 12.1% Arthralgia 15.9%
Itchy skin 15.2% Itchy skin 12.1% Alopecia 14.4%
Dizziness 14.4% Dizziness 12.1% Dizziness 12.9%
Paresthesia 12.1% Paresthesia 11.4% Sputum 11.4%
Long COVID symptoms (%)
Arthralgia 11.4% Sore throat 9.8% Paresthesia 11.4%

Headache 10.6% Arthralgia 9.1% Cognitive dysfunction 11.4%
Gastrointestinal discomfort 10.6% Obsessive thinking 9.1% Tinnitus 10.6%
Anosmia 9.8% Sputum 7.6% Sore throat 10.6%
Sore throat 9.1% Headache 6.8% Decreased visual acuity 9.8%
Chest discomfort 9.1% Rhinorrhea 6.8% Myalgia 9.8%
Rhinorrhea 9.1% Gastrointestinal discomfort 6.1% Palpitation 9.8%
Skin rashes 9.1% Chest discomfort 6.1% Chest discomfort 9.8%
Sputum 8.3% Skin rashes 6.1% Headache 9.8%
Obsessive thinking 8.3% Tinnitus 6.1% Obsessive thinking 9.8%
Tinnitus 6.8% Abnormal directional sensibility 6.1% Fever 7.6%
Ageusia 6.8% Chilly sense 6.1% Cough 7.6%
Abnormal directional… 6.8% Anosmia 4.5% Anosmia 7.6%
Swollen fingers 6.8% Swollen fingers 3.8% Ageusia 6.8%
Myalgia 6.1% Conjunctivitis 3.8% Skin rashes 6.8%
Chilly sense 6.1% Cough 3.8% Rhinorrhea 6.8%
Nausea & Vomiting 6.1% Palpitation 3.8% Conjunctivitis 6.1%
Fever 5.3% Myalgia 3.0% Gastrointestinal discomfort 6.1%
Conjunctivitis 5.3% Fever 3.0% Chilly sense 6.1%
Anorexia 5.3% Anorexia 3.0% Social phobia 6.1%
Cough 4.5% Dyspnea 2.3% Diarrhea 5.3%
Diarrhea 4.5% Covid toes 2.3% Arrhythmia 5.3%
Dyspnea 3.8% Arrhythmia 2.3% Abnormal directional sensibility 5.3%
Palpitation 3.0% Hypoacusis 2.3% Dyspnea 3.8%
Covid toes 3.0% Ageusia 1.5% Anorexia 3.0%
Arrhythmia 1.5% Hallucination 1.5% Hallucination 2.3%
Hallucination 1.5% Nausea & Vomiting 0.8% Swollen fingers 2.3%
Hypoacusis 1.5% Diarrhea 0.0% Covid toes 0.8%
Seizure 0.8% Seizure 0.0% Hypoacusis 0.8%
Globus pharyngeus 0.0% Globus pharyngeus 0.0% Seizure 0.0%
Decreased visual acuity 0.0% Decreased visual acuity 0.0% Nausea & Vomiting 0.0%
0% 10% 20% 30% 40% 50% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0%
Percent of patients (%) Percent of patients (%) Percent of patients (%)
Figure 1. Distribution of 45 persistent symptoms or signs at 6, 12, and 24 months after acute COVID-19.
≥ 1 months ≥ 3 months ≥ 6 months ≥ 12 months ≥ 24 months

50%
45%
40%
Percentage of the responders
35%
30%
25%
20%
15%
10%
5%
0%
Fatigue Anxiety Depression Insomnia Concentration Cognitive Amnesia Anosmia Ageusia
difficulties dysfunction
Long COVID symptoms
Figure 2. Duration of key long COVID symptoms according to the symptom persistent period at 1, 3, 6, 12,
and 24 months after acute COVID-19.
with long COVID (70% of patients with self-reported long COVID), followed by difficulty concentrating (48%)19.
Furthermore, in China, a follow-up study on long COVID in 4% of all patients admitted to the intensive care unit
confirmed that fatigue was the most common s ymptom14. Additionally, a previous study suggested that postviral
somatic and mental symptoms had neuroimmune and neuro-oxidative o rigins20. In the present study, fatigue and
mental symptoms accounted for the majority of long COVID symptoms at 24 months after acute COVID-19.
According to a previous study, the risk of mood and anxiety disorders subsides 1–2 months after infection,
whereas the risk of psychotic disorders, cognitive deficits, and dementia may remain high even 2 years after
COVID-1921. In the present study, compared with the other symptoms, the incidence of concentration difficulties
and amnesia remained high even after 24 months of infection, similar to the incidence after the occurrence of
initial symptoms. However, compared with 1 month after COVID-19, the symptoms of depression and anxiety
improved by > 50% at 24 months after COVID-19. Moreover, significant improvement was noted in cognitive
dysfunction at 24 months after COVID-19. Thus, it is difficult to exclude the possibility of the effects of mood
disorders on cognitive dysfunction due to the tendency of these cognitive dysfunctions to decrease with the
improvement in mood disorder. Major depression has commonly been associated with cognitive p roblems22.
Moreover, it has been reported that depressive psychopathology most commonly affects cognitive performance
Vol.:(0123456789)
No 91.7 98.5 82.6 75.8 59.1

No 83.3 97.7 81.1 66.7 67.4
Slight 5.3 0.8 15.2 18.2 34.1

Slight 15.2 2.3 18.9 31.1 27.3
Degree of problems
Rates
Degree of problems
Rates
75
75
Moderate 3 0 1.5 4.5 0
50 Moderate 0.8 0 0 1.5 3.8
50
25
25
0
0
Severe 0 0.8 0.8 1.5 0
Severe 0.8 0 0 0.8 0.8
Extreme 0 0 0 0 0
Extreme 0 0 0 0 0.8
MOBILITY SELF-CARE USUAL ACTIVITIES PAIN / ANXIETY /

DISCOMFORT DEPRESSION MOBILITY SELF-CARE USUAL ACTIVITIES PAIN / ANXIETY /
DISCOMFORT DEPRESSION
EQ5D ECVGIQT[ EQ5D ECVGIQT[
PRQWKV PRQWKV
Figure 3. Assessment of quality of life (EQ5D) 12 and 24 months after acute COVID-19 according to the data
collected from an online survey involving 132 responders.
Univariate OR Multivariate OR
Persistent symptoms or signs Factors 95% CI P-value 95% CI P-value
≥ Moderate severity 3.02 (1.17–8.05) 0.023 3.02 (1.17–8.05) 0.023
Fatigue ≥ 50 years old 1.35 (0.60–3.00) 0.456 – –
Female 0.95 (0.44–2.06) 0.887 – –
Anxiety ≥ 50 years old 1.18 (0.42–3.04) 0.745 – –
Female 0.92 (0.37–2.46) 0.86 – –
Depression ≥ 50 years old 1.30 (0.49–3.26) 0.587 1.30 (0.49–3.26) 0.885
Female 1.34 (0.53–3.70) 0.551 1.34 (0.53–3.70) 0.478
≥ Moderate severity 1.71 (0.56–4.79) 0.319 – –
Insomnia ≥ 50 years old 2.32 (0.94–5.65) 0.065 2.32 (0.94–5.65) 0.065
Female 1.14 (0.46–2.99) 0.784 – –
Concentration difficulty ≥ 50 years old 2.01 (0.84–4.70) 0.109 1.69 (0.66–4.19) 0.264
Female 1.26 (0.54–3.15) 0.607 – –
Cognitive dysfunction ≥ 50 years old 2.02 (0.63–6.11) 0.216 1.71 (0.48–5.63) 0.382
Female 0.93 (0.31–3.14) 0.874 0.98 (0.32–3.40) 0.969
Amnesia ≥ 50 years old 2.56 (1.14–5.79) 0.023 2.31 (0.96–5.55) 0.059
Female 1.93 (0.84–4.74) 0.133 2.07 (0.88–5.28) 0.109
Anosmia ≥ 50 years old 4.81 (1.29–19.94) 0.021 3.61 (0.85–16.23) 0.080
Female 1.95 (0.46–13.33) 0.411 – –
Ageusia ≥ 50 years old 6.48 (1.61–32.26) 0.011 4.70 (1.02–25.25) 0.051
Female 1.69 (0.39–11.67) 0.526 – –
Table 2. Univariate and multivariate logistic regression analyses for the factors associated with long COVID
24 months following COVID-19. CI confidence interval, COVID-19 coronavirus disease 2019, OR odds ratio.
as it interacts with cognitive functions in determining the quality of life23. Additionally, Sankey flow diagrams
showed correlations among neuropsychological symptoms.
In a previous study, 1 year after acute COVID-19, long COVID developed more frequently in patients with
moderate or higher illness severity than in asymptomatic p atients24. A prospective observational study of post-
COVID-19 chronic fatigue syndrome reported that it was associated with symptom s everity25. Previous studies
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involving 24 month-follow-ups of patients with COVID-19 have suggested that patients with severe disease
activity are 1.45 and 1.54 times more likely to develop fatigue or muscle weakness and anxiety or depressive
symptoms, respectively14. Moreover, moderate or higher disease severity during acute COVID-19 was identified
as a risk factor, with an odds ratio of 3.02 for long-term fatigue symptoms 24 months after acute COVID-19.
However, in our study, anxiety or depressive symptoms were not associated with disease activity 24 months after
acute COVID-19.
Notably, individuals with long COVID symptoms for 2 years exhibited poor health-related quality of life
(HRQoL), high mental health abnormality, and increased healthcare use after discharge compared to those
without long COVID symptoms. Moreover, previous studies reported that the quality of life may worsen during
follow-up for COVID-1926, and compared to participants without COVID-19, COVID-19 survivors continued
to exhibit higher symptom prevalence with more pain or discomfort and anxiety or depressive symptoms 2 years
after the infection. However, their HRQoL continued to improve for nearly all domains, particularly for anxiety
or depression, with the proportion of participants reporting anxiety or depressive symptoms decreasing signifi-
cantly from 23 at 6 months to 12% at 2 years after COVID-1914. In the present study, compared with the ability
to perform usual activities and pain/discomfort of the patients at 12 months after COVID-19, those at 24 months
after the infection improved. However, the number of people with reduced quality of life because of anxiety
and depressive symptoms did not significantly change (34.1% and 32.7% at 12 and 24 months after COVID-19,
respectively). In addition, 1.6% of the respondents who stated that they experienced severely reduced quality of
life because of anxiety and depressive symptoms were newly identified. Unlike a previous study with a median
participant age of 57 y ears14, our study included young people with a median age of 38 years, suggesting that the
younger age group is more affected by COVID-19 and long COVID symptoms than the older age group. This
finding is consistent with that of a previous study reporting that the risk of developing long COVID increases
with age27. Other factors affecting the decrease in HRQoL could be attributed to the emotional and social factors
related to the COVID-19 outbreak depending on the situation of each c ountry14. Additionally, social isolation
due to the long-lasting COVID-19 pandemic can be a major contributor to the depressive symptoms associated
with long COVID symptoms or poor quality of l ife28. According to a study on long COVID in patients discharged
from COVID-19-treatment specialized hospitals in Korea, the patients considered it challenging to return to
normal life owing to the presence of post-COVID-19 symptoms. In particular, returning to daily life was found
to be difficult for older people29. In the present study, 6.1% of respondents were receiving outpatient treatment
for long COVID, which consequently affected their daily quality of life. The present study included patients
exhibiting mild disease severity during acute illness. The findings revealed that long COVID could persist for a
long time in patients with COVID-19, suggesting that long COVID is a long-term social burden even in mildly
infected patients and can thus account for the majority of patients infected with COVID-19.
The findings of a UK-based survey suggest that post-infection vaccination reduces the symptomatic burden
of long COVID after the first dose, with sustained improvement after the second d ose17. Notably, patients with
long COVID and immune system dysregulation may benefit from a reset of autoimmune processes via vaccina-
tion (although whether this effect is long-lasting remains unestablished), and any residual viral reservoir may
also be destroyed due to the antibody response30.
In the present study, 96.2% of respondents were vaccinated after COVID-19. Furthermore, after 24 months,
71.2% of respondents reported > 1 suspected long COVID symptom. Amnesia was identified in 21.2% of respond-
ents at 12 months after COVID-19, and this rate increased to 30.3% at 24 months after the infection. Concentra-
tion difficulties were identified in 22.0% of the respondents at 12 months after COVID-19, and this rate increased
to 24.2% at 24 months after the infection. Notably, the decreased gray matter in the temporal lobe in patients
with COVID-19 highlighted the increased risk of later neurodegeneration and dementia due to viral invasion
of the central nervous system31. Moreover, previous studies have consistently reported an association between
COVID-19 and memory impairment32,33. As indicated by the results of the present study, the neuropsychological
effects of long COVID can significantly compromise the quality of life of adults exhibiting mild COVID-19. How-
ever, the impact of vaccination on people with long-term COVID symptoms remains controversial. Therefore,
well-designed research on the effects of COVID-19 vaccination on the improvement or persistence of long-term
COVID symptoms after acute COVID-19 and the long-term effects of COVID-19 vaccination is warranted.
This study has a few limitations. First, due to the long-term follow-up period of the study and nonhomo-
geneity of the patients, there may be limitations in interpreting whether persistent symptoms are related to
long COVID. Moreover, other factors such as sociocultural differences may have influenced the results of the
surveys. Therefore, further studies on different sociocultural backgrounds are needed to elucidate the effects of
long COVID. Second, because of the limitations of the online survey, no individualized tests of cognitive func-
tion could be performed for comparison. Thus, further studies using objective cognitive tests must be applied to
individuals, and differences should be substantiated by the literature. Third, it is difficult to state that the sample
was highly representative of any given population because, at the time of the survey, few respondents had severe
or critical disease activity during acute COVID-19, and older adults may have experienced difficulty participat-
ing in online surveys. Furthermore, individuals exhibiting long COVID symptoms may have participated more
actively in the survey, leading to a relatively high incidence of long COVID among respondents.
The strength of this study is that it revealed the long-term effects of COVID-19 in relatively young patients
with mild acute illness after excluding confounding factors and reinfection cases. Remarkably, long COVID
symptoms manifested in various forms up to 24 months after acute COVID-19 illness, even in patients who were
vaccinated after COVID-19. Furthermore, our results suggest that even 24 months after acute COVID-19, the
prevalence of long COVID symptoms and reduced quality of life in patients with COVID-19 is a concern that
represents a long-term social burden regardless of the severity of the disease.
Vol.:(0123456789)
Conclusions
Although long COVID usually improves over time, neuropsychiatric symptoms can persist for up to 24 months
after an acute infection and occur more frequently than other symptoms. Patients with mild COVID-19 disease,
who account for the majority of patients with COVID-19, may continue to have a poor quality of life. In addition,
the occurrence of long COVID does not appear to be significantly affected by COVID-19 vaccination or the
number of vaccinations received. Therefore, ongoing research on long COVID is needed to better understand
the potential long-term health consequences of COVID-19, including the persistence of symptoms, impact on
quality of life, and effectiveness of interventions such as vaccination.
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding
author upon reasonable request.
Received: 13 March 2023; Accepted: 14 June 2023
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Author contributions
Y.J.K. and S.W.K. designed and planned the study. Y.J.K. wrote the original manuscript draft and conducted
literature search. S.W.K. supervised the study including analysis, interpretation and writing of the manuscript.
Y.J.K., S.H.B., and H.H.C. performed the data collection and processing. Y.J.K. and S.W.K. conducted statistical
analysis. All authors read and critically revised the manuscript and agreed to the final version.
Funding
The present study was supported by the Research Program funded by the Korea Centers for Disease Control and
Prevention (Fund Code 2021-ER1901-00 and 2021-ER1901-01).
Competing interests
The authors declare no competing interests.
Additional information
Supplementary Information The online version contains supplementary material available at https://doi.org/
10.1038/s41598-023-36995-4.
Correspondence and requests for materials should be addressed to S.-W.K.
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© The Author(s) 2023, corrected publication 2023
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OPEN Long COVID prevalence and impact

Scientific Reports | (2023) 13:11207 | https://doi.org/10.1038/s41598-023-36995-4 1

Scientific Reports | (2023) 13:11207 | https://doi.org/10.1038/s41598-023-36995-4 2

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Characteristics No symptom (N = 38) Symptom (N = 94) Total (N = 132) P-value

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6 months 12 months 24 months

Arthralgia 11.4% Sore throat 9.8% Paresthesia 11.4%

Percent of patients (%) Percent of patients (%) Percent of patients (%)

≥ 1 months ≥ 3 months ≥ 6 months ≥ 12 months ≥ 24 months

Long COVID symptoms

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No 91.7 98.5 82.6 75.8 59.1

Slight 5.3 0.8 15.2 18.2 34.1

MOBILITY SELF-CARE USUAL ACTIVITIES PAIN / ANXIETY /

EQ5D ECVGIQT[ EQ5D ECVGIQT[

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Received: 13 March 2023; Accepted: 14 June 2023

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© The Author(s) 2023, corrected publication 2023

Scientific Reports | (2023) 13:11207 | https://doi.org/10.1038/s41598-023-36995-4 9

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