Highlights
- •Prolonged symptoms after COVID-19, also known as the post-COVID-19 condition, is a chronic, multisystemic disease causing various symptoms.
- •After adjusting for potential comorbidities and confounders, certain prolonged symptoms, including headache, chest discomfort, dysgeusia, and dysosmia, were found to be independently associated with a history of COVID-19, which was diagnosed two or more months previously.
- •Patients with a previous history of COVID-19 had significantly lower EQ-5D-5L and higher SSS-8 scores, indicating that prolonged symptoms after contracting COVID-19 might have impacted their quality of life and overall somatic symptom burden.
- •Respondents who received the COVID-19 booster vaccine were associated with higher EQ-5D-5L and lower SSS-8 scores, suggesting the COVID-19 booster vaccination may mitigate some of the symptoms suggestive of post-COVID condition.
Abstract
Background
Methods
Results
Conclusion
Keywords
Introduction
World Health Organization. Post COVID-19 condition (Long COVID). https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition Last accessed 02052023
- Perlis RH
- Santillana M
- Ognyanova K
- et al.
Methods
Study participants
JACSIS study. JACSIS study. https://jacsis-study.jp/about/Last accessed 02052023
Rakuten Insight. Rakuten Insight internet search https://insight.rakuten.co.jp/en/aboutus.html. Last accessed 02052023
Data collection
- Lubetkin EI
- Long D
- Haagsma JA
- Janssen MF
- Bonsel GJ.
Statistical analysis
- Perlis RH
- Santillana M
- Ognyanova K
- et al.
Results

Total (n = 19,784) | Respondents with COVID-19 (n = 2,397) | Respondents without COVID-19 (n = 17,387) | P-value | |
---|---|---|---|---|
Age, median (IQR) years | 49 (34-67) | 35 (27-44) | 51 (36-68) | < 0.001 |
Male gender | 9,585 (48.5) | 1,274 (53.2) | 8,311 (47.8) | < 0.001 |
Education | < 0.001 | |||
High school or lower | 7,994 (40.4) | 833 (34.8) | 7,161 (41.2) | |
College or higher | 11,790 (59.6) | 1,564 (65.3) | 10,226 (58.8) | |
Income [Japanese yen] | < 0.001 | |||
< 4 million | 6,154 (31.11) | 553 (23.1) | 5,601 (32.2) | |
≧ 4 million | 9,374 (47.4) | 1,485 (62.0) | 7,889 (45.4) | |
N/A | 4,256 (21.5) | 359 (15.0) | 3,897 (22.4) | |
Partner | 12,182 (61.6) | 1,479 (61.7) | 10,703 (61.6) | 0.89 |
Employment status | < 0.001 | |||
Executive, employer, or self-employed | 2,127 (10.8) | 293 (12.2) | 1,834 (10.6) | |
Employee | 9,057 (45.8) | 1,582 (66.0) | 7,475 (43.0) | |
Homewife or house-husband | 4,033 (20.4) | 246 (10.3) | 3,787 (21.8) | |
Unemployed, retired, or student | 4,567 (23.1) | 276 (11.5) | 4,291 (24.7) | |
Smoking | 7,126 (36.0) | 1,040 (43.4) | 6,086 (35.0) | < 0.001 |
Alcohol | 11,275 (57.0) | 1,525 (63.6) | 9,750 (56.1) | < 0.001 |
Comorbidities | ||||
Hypertension | 5,681 (28.7) | 704 (29.4) | 4,977 (28.6) | 0.45 |
Diabetes mellitus | 1,947 (9.8) | 462 (19.3) | 1,485 (8.5) | < 0.001 |
Dyslipidemia | 3,996 (20.2) | 567 (23.7) | 3,429 (19.7) | < 0.001 |
Asthma | 2,625 (13.3) | 608 (25.4) | 2,017 (11.6) | < 0.001 |
Cardiovascular disease | 1,061 (5.4) | 341 (14.2) | 720 (4.1) | < 0.001 |
Cerebral vascular disease | 837 (4.2) | 334 (13.9) | 503 (2.9) | < 0.001 |
COPD | 590 (3.0) | 320 (13.4) | 270 (1.6) | < 0.001 |
CKD | 845 (4.3) | 328 (13.7) | 517 (3.0) | < 0.001 |
Chronic liver disease | 753 (3.8) | 328 (13.7) | 425 (2.4) | < 0.001 |
Immunocompromised status | 951 (4.8) | 346 (14.4) | 605 (3.5) | < 0.001 |
Malignancy | 1,726 (8.7) | 353 (14.7) | 1,373 (7.9) | < 0.001 |
Number of COVID-19 vaccines | < 0.001 | |||
0 | 2,562 (13.0) | 399 (16.7) | 2,163 (12.4) | |
1 | 120 (0.6) | 52 (2.2) | 68 (0.4) | |
2 | 2,507 (12.7) | 554 (23.1) | 1,953 (11.2) | |
3 or 4 | 14,595 (73.8) | 1,392 (58.1) | 13,203 (75.9) |
Sample, n | Prevalence, n (%) | Adjusted rate, % (95% CI) | Absolute difference of adjusted prevalence (%) | Adjusted OR (95% CI) | |
---|---|---|---|---|---|
GI upset | |||||
Respondents with COVID-19 | 2,397 | 331 (13.8) | 13.3 (11.8-14.7) | +1.0 | 1.10 (0.96-1.25) |
Respondents without COVID-19 | 17,387 | 2,121 (12.2) | 12.3 (11.8-12.8) | Reference | |
Back pain | |||||
Respondents with COVID-19 | 2,397 | 536 (22.4) | 24.4 (22.6-26.3) | +2.0 | 1.13 (1.01-1.26) |
Respondents without COVID-19 | 17,387 | 3,936 (22.6) | 22.4 (21.8-23.0) | Reference | |
Arm/Leg/Joint pain | |||||
Respondents with COVID-19 | 2,397 | 312 (13.0) | 17.7 (15.9-19.5) | -0.1 | 0.99 (0.86-1.14) |
Respondents without COVID-19 | 17,387 | 3,199 (18.4) | 17.8 (17.2-18.3) | Reference | |
Headache | |||||
Respondents with COVID-19 | 2,397 | 369 (15.4) | 12.1 (10.9-13.3) | +1.9 | 1.22 (1.07-1.39) |
Respondents without COVID-19 | 17,387 | 1,712 (9.8) | 10.2 (9.8-10.7) | Reference | |
Chest discomfort | |||||
Respondents with COVID-19 | 2,397 | 96 (4.0) | 2.5 (1.9-3.1) | +0.6 | 1.34 (1.01-1.77) |
Respondents without COVID-19 | 17,387 | 305 (1.8) | 1.9 (1.7-2.1) | Reference | |
Dyspnea | |||||
Respondents with COVID-19 | 2,397 | 171 (7.1) | 5.7 (4.7-6.6) | +0.9 | 1.20 (0.97-1.48) |
Respondents without COVID-19 | 17,387 | 807 (4.6) | 4.8 (4.5-5.1) | Reference | |
Dizziness | |||||
Respondents with COVID-19 | 2,397 | 191 (8.0) | 5.9 (5.0-6.8) | -0.4 | 0.93 (0.77-1.11) |
Respondents without COVID-19 | 17,387 | 1,040 (6.0) | 6.3 (5.9-6.7) | Reference | |
Sleep disturbance | |||||
Respondents with COVID-19 | 2,397 | 418 (17.4) | 17.5 (15.9-19.1) | -1.0 | 0.93 (0.83-1.06) |
Respondents without COVID-19 | 17,387 | 3,215 (18.5) | 18.5 (17.9-19.1) | Reference | |
Hearing loss | |||||
Respondents with COVID-19 | 2,397 | 158 (6.6) | 8.8 (7.4-10.2) | +1.2 | 1.18 (0.96-1.44) |
Respondents without COVID-19 | 17,387 | 1,373 (7.9) | 7.6 (7.2-8.0) | Reference | |
Dysgeusia | |||||
Respondents with COVID-19 | 2,397 | 70 (2.9) | 1.7 (1.2-2.3) | +0.8 | 2.05 (1.39-3.04) |
Respondents without COVID-19 | 17,387 | 136 (0.8) | 0.9 (0.7-1.0) | Reference | |
Dysosmia | |||||
Respondents with COVID-19 | 2,397 | 64 (2.7) | 2.3 (1.6-3.0) | +1.3 | 1.96 (1.35-2.84) |
Respondents without COVID-19 | 17,387 | 200 (1.2) | 1.2 (1.0-1.3) | Reference | |
Memory impairment | |||||
Respondents with COVID-19 | 2,397 | 134 (5.6) | 5.9 (4.9-7.1) | +0.5 | 1.11 (0.90-1.37) |
Respondents without COVID-19 | 17,387 | 947 (5.4) | 5.4 (5.1-5.7) | Reference | |
Poor concentration | |||||
Respondents with COVID-19 | 2,397 | 248 (10.3) | 9.6 (8.4-10.8) | -0.6 | 0.94 (0.80-1.09) |
Respondents without COVID-19 | 17,387 | 1,752 (10.1) | 10.2 (9.7-10.6) | Reference | |
Hair loss | |||||
Respondents with COVID-19 | 2,397 | 202 (8.4) | 8.5 (7.3-9.7) | +1.7 | 1.29 (1.09-1.53) |
Respondents without COVID-19 | 17,387 | 1,176 (6.8) | 6.8 (6.4-7.1) | Reference | |
Decreased libido | |||||
Respondents with COVID-19 | 2,397 | 164 (6.8) | 6.8 (5.7-7.8) | +1.0 | 1.18 (0.97-1.43) |
Respondents without COVID-19 | 17,387 | 1,014 (5.8) | 5.8 (5.5-6.2) | Reference | |
Erectile dysfunction | |||||
Respondents with COVID-19 | 1,274 | 110 (8.6) | 12.1 (9.9-14.4) | +2.0 | 1.25 (0.98-1.59) |
Respondents without COVID-19 | 8,311 | 877 (10.6) | 10.1 (9.5-10.7) | Reference | |
Fatigue | |||||
Respondents with COVID-19 | 2,397 | 564 (23.5) | 12.1 (9.9-14.4) | +2.0 | 1.25 (0.98-1.59) |
Respondents without COVID-19 | 17,387 | 3,507 (20.2) | 10.1 (9.5-10.7) | Reference | |
Cough | |||||
Respondents with COVID-19 | 2,397 | 83 (3.5) | 4.0 (3.1-4.9) | +0.6 | 1.21 (0.93-1.59) |
Respondents without COVID-19 | 17,387 | 595 (3.4) | 3.4 (3.1-3.6) | Reference | |
Fever | |||||
Respondents with COVID-19 | 2,397 | 18 (0.8) | 0.4 (0.2-0.7) | -0.2 | 0.70 (0.39-1.25) |
Respondents without COVID-19 | 17,387 | 101 (0.6) | 0.6 (0.5-0.8) | Reference |
Total (n = 19,784) | COVID-19 infection | Number of COVID-19 vaccines | |||||
---|---|---|---|---|---|---|---|
Respondents with COVID-19 (n = 2,397) | Respondents without COVID-19 (n = 17,387) | 0 (n = 2,562) | 1 (n = 120) | 2 (n = 2,507) | 3 or 4 (n = 14,595) | ||
SSS-8 [IQR] | 5 (2-10) | 8 (3-14) | 5 (2-9) | 6 (1-12) | 10 (4.5-15.5) | 6 (2-11) | 5 (2-9) |
Stomach or bowel problem | 9,119 (46.1) | 1,411 (58.9) | 7,708 (44.3) | 1,207 (47.1) | 85 (70.8) | 1,170 (46.7) | 6,657 (45.6) |
Back pain | 11,448 (57.9) | 1,589 (66.3) | 9,859 (56.7) | 1,410 (55.0) | 84 (70.0) | 1,450 (57.8) | 8,504 (58.3) |
Pain in arms, legs or joints | 9,853 (49.8) | 1,320 (55.1) | 8,533 (49.1) | 1,198 (46.8) | 75 (62.5) | 1,117 (44.6) | 7,463 (51.1) |
Headache | 8,242 (41.7) | 1,436 (59.9) | 6,806 (39.1) | 1,171 (45.7) | 79 (65.8) | 1,268 (50.6) | 5,724 (39.2) |
Chest pain or shortness of breath | 6,167 (31.2) | 1,063 (44.4) | 5,104 (29.4) | 914 (35.7) | 67 (55.8) | 822 (32.8) | 4,364 (29.9) |
Dizziness | 5,674 (28.7) | 1,002 (41.8) | 4,672 (26.9) | 863 (33.7) | 69 (57.5) | 848 (33.8) | 3,894 (26.7) |
Feeling tired or having low energy | 11,918 (60.2) | 1,703 (71.1) | 10,215 (58.8) | 1,519 (59.3) | 78 (65.0) | 1,611 (64.3) | 8,710 (59.7) |
Trouble sleeping | 10,104 (51.1) | 1,424 (59.4) | 8,680 (49.9) | 1,350 (52.7) | 80 (66.7) | 1,299 (51.8) | 7,375 (50.5) |
EQ-5D-5L [IQR] | 1.0 (0.8-1.0) | 0.9 (0.8-1.0) | 1.0 (0.8-1.0) | 1.0 (0.8-1.0) | 0.9 (0.5-1.0) | 1.0 (0.8-1.0) | 1.0 (0.8-1.0) |
Mobility | 2,427 (12.3) | 549 (22.9) | 1,878 (10.8) | 442 (17.3) | 48 (40.0) | 278 (11.1) | 1,659 (11.4) |
Self-care | 1,327 (6.7) | 469 (19.6) | 858 (4.9) | 320 (12.5) | 45 (37.5) | 203 (8.1) | 759 (5.2) |
Usual activity | 2,035 (10.3) | 529 (22.1) | 1,506 (8.7) | 410 (16.0) | 46 (38.3) | 288 (11.5) | 1,291 (8.9) |
Pain/Discomfort | 7,281 (36.8) | 928 (38.7) | 6,353 (36.5) | 973 (38.0) | 61 (50.8) | 818 (32.6) | 5,429 (37.2) |
Anxiety/Depression | 5,408 (27.3) | 890 (37.1) | 4,518 (26.0) | 871 (34.0) | 58 (48.3) | 812 (32.4) | 3,667 (25.1) |
Variables | EQ-5D-5L | SSS-8 | ||||||
---|---|---|---|---|---|---|---|---|
β | P-value | 95% | CI | β | P-value | 95% | CI | |
Age | 0.0010 | < 0.001 | 0.0008 | 0.0011 | -0.07 | < 0.001 | -0.07 | -0.06 |
Sex | ||||||||
Female sex (ref) | ||||||||
Male sex | 0.0157 | < 0.001 | 0.0109 | 0.0205 | -1.64 | < 0.001 | -1.82 | -1.45 |
Education | ||||||||
High school or lower (ref) | ||||||||
College or higher | 0.0070 | 0.001 | 0.0028 | 0.0111 | -0.25 | 0.002 | -0.41 | -0.09 |
Income | ||||||||
< 4 million (ref) | ||||||||
≧ 4 million | 0.0218 | < 0.001 | 0.0168 | 0.0268 | -0.70 | < 0.001 | -0.89 | -0.50 |
N/A | 0.0108 | < 0.001 | 0.0052 | 0.0164 | -0.53 | < 0.001 | -0.75 | -0.31 |
Partner | 0.0177 | < 0.001 | 0.0129 | 0.0224 | -0.03 | 0.783 | -0.21 | 0.16 |
Employment | ||||||||
Executive, employer, or self-employed (ref) | ||||||||
Employee | 0.0144 | < 0.001 | 0.0076 | 0.0213 | -0.06 | 0.676 | -0.32 | 0.21 |
Homewife or house-husband | -0.0028 | 0.508 | -0.0113 | 0.0056 | -0.53 | 0.002 | -0.85 | -0.20 |
Unemployed, retired, or student | -0.0086 | 0.025 | -0.0161 | -0.0011 | -0.77 | < 0.001 | -1.06 | -0.48 |
Smoking | -0.0279 | < 0.001 | -0.0325 | -0.0232 | 1.00 | < 0.001 | 0.82 | 1.18 |
Alcohol | 0.0075 | < 0.001 | 0.0033 | 0.0117 | -0.11 | 0.179 | -0.27 | 0.05 |
Comorbidities | ||||||||
Hypertension | -0.0231 | < 0.001 | -0.0283 | -0.0179 | 1.38 | < 0.001 | 1.18 | 1.58 |
Diabetes mellitus | -0.0237 | < 0.001 | -0.0313 | -0.0160 | 0.62 | < 0.001 | 0.32 | 0.91 |
Dyslipidemia | -0.0215 | < 0.001 | -0.0270 | -0.160 | 1.21 | < 0.001 | 1.00 | 1.42 |
Asthma | -0.0320 | < 0.001 | -0.0381 | -0.0258 | 1.78 | < 0.001 | 1.54 | 2.02 |
Cardiovascular disease | -0.0340 | < 0.001 | -0.0446 | -0.0234 | 1.43 | < 0.001 | 1.02 | 1.84 |
Cerebral vascular disease | -0.0535 | < 0.001 | -0.0659 | -0.0411 | 0.07 | 0.777 | -0.41 | 0.55 |
COPD | -0.0264 | 0.001 | -0.0427 | -0.0101 | 0.62 | 0.054 | -0.01 | 1.25 |
CKD | -0.0398 | < 0.001 | -0.0522 | -0.0273 | 1.31 | < 0.001 | 0.83 | 1.79 |
Chronic liver disease | -0.0176 | 0.010 | -0.0310 | -0.0042 | 0.93 | < 0.001 | 0.41 | 1.45 |
Immunocompromised status | -0.0575 | < 0.001 | -0.0687 | -0.0462 | 2.05 | < 0.001 | 1.62 | 2.49 |
Malignancy | -0.0142 | < 0.001 | -0.0221 | -0.0064 | 0.34 | 0.029 | 0.03 | 0.64 |
Number of COVID-19 vaccines | ||||||||
0 (ref) | ||||||||
1 | -0.0208 | 0.120 | -0.0470 | 0.0054 | -0.60 | 0.251 | -1.61 | 0.42 |
2 | 0.0236 | < 0.001 | 0.0158 | 0.0315 | -0.20 | 0.196 | -0.51 | 0.10 |
3 or 4 | 0.0286 | < 0.001 | 0.0224 | 0.0347 | -0.25 | 0.038 | -0.49 | -0.01 |
Remote history of COVID-19 | -0.0230 | < 0.001 | -0.0295 | -0.0164 | 0.54 | < 0.001 | 0.28 | 0.79 |
Discussion
Prevention CfDCa. Post-COVID Conditions: Information for Healthcare Providers. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/post-covid-conditions.html Last accessed 02052023.
- Saunders C
- Sperling S
- Bendstrup E.
- Wong AW
- Shah AS
- Johnston JC
- Carlsten C
- Ryerson CJ.
- Mizrahi B
- Sudry T
- Flaks-Manov N
- et al.
Contributors
Data sharing statement
Ethics statement
Declaration of Competing Interests
Acknowledgements
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