Incidence and clinical characteristics changes of Long COVID in patients with hypothyroidism

doi:10.3969/j.issn.1674-8115.2026.10.006

Abstract

Abstract:

Objective ·To retrospectively observe the clinical characteristics of long coronavirus disease (Long COVID) in patients with hypothyroidism, as well as changes in thyroid function, levothyroxine sodium dose, and physical activity levels. Methods ·A retrospective analysis of the occurrence of Long COVID and clinical characteristics in 116 patients with hypothyroidism was conducted, and the patients were divided into 4 subgroups according to the etiology and the presence or absence of Long COVID, including HL group (Hashimoto thyroiditis with Long COVID), HNL group (Hashimoto thyroiditis without Long COVID), NHL group (non‑Hashimoto hypothyroidism with Long COVID), and NNL group (non‑Hashimoto hypothyroidism without Long COVID). Clinical data were collected via electronic medical records and follow‑up questionnaires, encompassing general patient information, information related to SARS-CoV-2 infection and Long COVID, levothyroxine sodium doses and antibody levels at baseline and 1, 3, 6, 12, and 24 months after SARS-CoV-2 infection. Physical activity levels were assessed using the International Physical Activity Questionnaire. Results ·A total of 113 patients had a history of SARS-CoV-2 infection, of whom 77 (68.14%) had Long COVID. The proportion of patients with a history of hyperlipidemia was significantly higher in the Long COVID group than in the group without Long COVID (P=0.008). Among patients with Long COVID, 90.9% had their levothyroxine sodium dose adjusted within two years after infection, showing a dynamic pattern of an initial increase followed by a decrease. Patients in the HL group were more likely to experience headaches, dizziness, and brain fog than those in the NHL group. More than two years after SARS-CoV-2 infection, physical activity levels in patients with Long COVID were significantly lower than both their pre-infection levels and those of patients without Long COVID (both P<0.05). Conclusion ·Patients with hypothyroidism exhibit a high incidence of Long COVID, which significantly impacts their physical activity levels and thyroid hormone homeostasis, accompanied by a staged increase in levothyroxine dose requirements.

Key words: hypothyroidism, Long COVID, thyroid function, levothyroxine sodium

CLC Number:

R581.2

Gong Yuwei, Zhang Yihan, Li Bingxin, Feng Xiaoyun, Xu Huanbai, Liu Fang, Wang Yufan, Peng Yongde, Chen Ruihua. Incidence and clinical characteristics changes of Long COVID in patients with hypothyroidism[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(10): 1366-1374.

Figures/Tables 6

TrendMD

References 28

[1]	Du Z W, Wang Y C, Bai Y, et al. Estimate of COVID-19 deaths, China, December 2022-February 2023[J]. Emerg Infect Dis, 2023, 29(10): 2121-2124.
[2]	Bai Y, Peng Z H, Wei F Y, et al. Study on the COVID-19 epidemic in mainland China between November 2022 and January 2023, with prediction of its tendency[J]. J Biosaf Biosecur, 2023, 5(1): 39-44.
[3]	Soriano J B, Murthy S, Marshall J C, et al. A clinical case definition of post-COVID-19 condition by a Delphi consensus[J]. Lancet Infect Dis, 2022, 22(4): e102-e7.
[4]	Crook H, Raza S, Nowell J, et al. Long covid: mechanisms, risk factors, and management[J]. BMJ, 2021: n1648.
[5]	Gupta G, Buonsenso D, Wood J, et al. Mechanistic insights into long COVID: viral persistence, immune dysregulation, and multi-organ dysfunction[J]. Compr Physiol, 2025, 15(3): e70019.
[6]	Taylor P N, Medici M M, Hubalewska-Dydejczyk A, et al. Hypothyroidism[J]. Lancet, 2024, 404(10460): 1347-1364.
[7]	Nham E, Song E Y, Hyun H, et al. Concurrent subacute thyroiditis and Graves' disease after COVID-19: a case report[J]. J Korean Med Sci, 2023, 38(18): e134.
[8]	Sebők S, Gyires K. Long COVID and possible preventive options[J]. Inflammopharmacology, 2023, 31(6): 2807-2817.
[9]	Jostel A, Ryder W D, Shalet S M. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index[J]. Clin Endocrinol, 2009, 71(4): 529-534.
[10]	Yagi H, Pohlenz J, Hayashi Y, et al. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3, 5, 3'-triiodothyroinine binding affinity[J]. J Clin Endocrinol Metab, 1997, 82(5): 1608-1614.
[11]	Chen X X, Zhou Y L, Zhou M X, et al. Diagnostic values of free triiodothyronine and free thyroxine and the ratio of free triiodothyronine to free thyroxine in thyrotoxicosis[J]. Int J Endocrinol, 2018, 2018: 4836736.
[12]	Qin S J, Zhang Y N, Li Y H, et al. Long COVID facts and findings: a large-scale online survey in 74, 075 Chinese participants[J]. Lancet Reg Health West Pac, 2024, 52: 101218.
[13]	Nabavi N. Long covid: how to define it and how to manage it[J]. BMJ, 2020: m3489.
[14]	Asadi-Pooya A A, Akbari A, Emami A, et al. Risk factors associated with Long COVID syndrome: a retrospective study [J]. Iran J Med Sci, 2021, 46(6): 428-436.
[15]	Astin R, Banerjee A, Baker M R, et al. Long COVID: mechanisms, risk factors and recovery[J]. Exp Physiol, 2023, 108(1): 12-27.
[16]	Bae G, Yang Z Q, Bucci D, et al. Longitudinal lipoprotein and inflammatory mediators analysis uncover persisting inflammation and hyperlipidemia following SARS-CoV-2 infection in long COVID-19[J]. Metabolomics, 2025, 21(3): 65.
[17]	Huang L A, Lo S C, Yang Y S, et al. Association of COVID-19 infection with subsequent thyroid dysfunction: an international population-based propensity score matched analysis[J]. Thyroid, 2024, 34(4): 442-449.
[18]	Lania A, Sandri M T, Cellini M, et al. Thyrotoxicosis in patients with COVID-19: the THYRCOV study[J]. Eur J Endocrinol, 2020, 183(4): 381-387.
[19]	Khoo B, Tan T, Clarke S A, et al. Thyroid function before, during, and after COVID-19[J]. J Clin Endocrinol Metab, 2021, 106(2): e803-e811.
[20]	Jung Y H, Ha E H, Park J, et al. Neurological and psychiatric manifestations of post-COVID-19 conditions[J]. J Korean Med Sci, 2023, 38(11): e83.
[21]	Song W J, Hui C K M, Hull J H, et al. Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses[J]. Lancet Respir Med, 2021, 9(5): 533-544.
[22]	Soh H S, Cho B. Long COVID-19 and health-related quality of life of mild cases in Korea: 3-months follow-up of a single community treatment center[J]. J Korean Med Sci, 2022, 37(46): e326.
[23]	Woodruff M C, Ramonell R P, Nguyen D C, et al. Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19[J]. Nat Immunol, 2020, 21(12): 1506-1516.
[24]	Najjar S, Pahlajani S, de Sanctis V, et al. Neurovascular unit dysfunction and blood-brain barrier hyperpermeability contribute to schizophrenia neurobiology: a theoretical integration of clinical and experimental evidence[J]. Front Psychiatry, 2017, 8: 83.
[25]	Hoogland I C, Houbolt C, van Westerloo D J, et al. Systemic inflammation and microglial activation: systematic review of animal experiments[J]. J Neuroinflammation, 2015, 12: 114.
[26]	Feter N, Caputo E L, Delpino F M, et al. Physical activity and long COVID: findings from the Prospective Study About Mental and Physical Health in Adults cohort[J]. Public Health, 2023, 220: 148-154.
[27]	Palau P, Calvo B, Sastre C, et al. Unraveling the mechanisms behind exercise intolerance and recovery in long COVID[J]. Am J Med, 2025, 138(2): 362-367.
[28]	Aschman T, Wyler E, Baum O, et al. Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles[J]. Acta Neuropathol Commun, 2023, 11(1): 193.

Group	Age/year	Male/n(%)	Alcohol/n(%)	Smoking/n(%)	BMI/(kg·m^-2)	Hyperlipidemia/n(%)	Obesity/n(%)
L (n=77)	48.49±14.14	17 (22.1)	20 (26.0)	24 (31.2)	23.85±3.22	26 (33.8)	9 (11.7)
NL (n=36)	46.83±16.35	11 (30.6)	5 (13. 9)	9 (25.0)	23.12±3.14	3 (8.3)	3 (8.3)
χ² /t value	-0.553	0.946	2.079	0.452	-1.125	7.038	0.045
P value	0.581	0.331	0.149	0.502	0.263	0.008	0.832
HL (n=33)	48.45±13.39	7 (21.2)	6 (18.2)	7 (21.2)	24.46±3.44	9 (27.3)	6 (18.2)
NHL (n=44)	48.52±14.83	10 (22.7)	14 (31.8)	17 (38.6)	23.39±3.00	17 (38.6)	3 (6.8)
HNL (n=20)	45.7±16.95	7 (35.0)	3 (15.0)	4 (20.0)	22.57±3.02	1 (5.0)	1 (5.0)
NNL (n=16)	48.25±15.99	4 (25.0)	2 (12.5)	5 (31.3)	23.82±3.25	2 (12.5)	2 (12.5)
χ² /F value	0.186	1.446	3.638	3.765	1.613	9.918	3.118
P value	0.906	0.725	0.300	0.290	0.190	0.017	0.385

Group	Age/year	Male/n(%)	Alcohol/n(%)	Smoking/n(%)	BMI/(kg·m^-2)	Hyperlipidemia/n(%)	Obesity/n(%)
L (n=77)	48.49±14.14	17 (22.1)	20 (26.0)	24 (31.2)	23.85±3.22	26 (33.8)	9 (11.7)
NL (n=36)	46.83±16.35	11 (30.6)	5 (13. 9)	9 (25.0)	23.12±3.14	3 (8.3)	3 (8.3)
χ² /t value	-0.553	0.946	2.079	0.452	-1.125	7.038	0.045
P value	0.581	0.331	0.149	0.502	0.263	0.008	0.832
HL (n=33)	48.45±13.39	7 (21.2)	6 (18.2)	7 (21.2)	24.46±3.44	9 (27.3)	6 (18.2)
NHL (n=44)	48.52±14.83	10 (22.7)	14 (31.8)	17 (38.6)	23.39±3.00	17 (38.6)	3 (6.8)
HNL (n=20)	45.7±16.95	7 (35.0)	3 (15.0)	4 (20.0)	22.57±3.02	1 (5.0)	1 (5.0)
NNL (n=16)	48.25±15.99	4 (25.0)	2 (12.5)	5 (31.3)	23.82±3.25	2 (12.5)	2 (12.5)
χ² /F value	0.186	1.446	3.638	3.765	1.613	9.918	3.118
P value	0.906	0.725	0.300	0.290	0.190	0.017	0.385

Group	T>38 ℃/n(%)	Loss or reduction of smell and taste /n(%)	Myalgia/n(%)	Chest tightness/n(%)	Nausea/n(%)	Vomiting/n(%)
L (n=77)	58 (75.3)	32 (41.6)	44 (57.1)	39 (50.6)	34 (44.2)	27 (35.1)
NL (n=36)	21 (58.3)	5 (13.9)	10 (27.8)	11 (30.6)	7 (19.4)	6 (16.7)
χ² value	3.367	8.528	8.478	4.015	6.480	4.016
P value	0.067	0.003	0.004	0.045	0.011	0.045
HL (n=33)	21 (63.6 )	19 (57.6)^②	17 (51.5)	16 (48.5)	17 (51.5)	12 (36.4)
NHL (n=44)	37 (84.1 )^①	13 (29.5)	27 (61.4)	23 (52.3)^①	17 (38.6)^①	15 (34.1)^①
HNL (n=20)	13 (65.0 )	4 (20.0)	4 (20.0)	9 (45.0)	7 (35.0)	6 (30.0 )
NNL (n=16)	8 (50.0 )	1 (6.3)	6 (37.5)	2 (12.5)	0 (0)	0 (0)
χ² value	8.068	15.648	10.302	7.931	14.709	9.568
P value	0.044	0.001	0.016	0.049	0.002	0.021

Group	T>38 ℃/n(%)	Loss or reduction of smell and taste /n(%)	Myalgia/n(%)	Chest tightness/n(%)	Nausea/n(%)	Vomiting/n(%)
L (n=77)	58 (75.3)	32 (41.6)	44 (57.1)	39 (50.6)	34 (44.2)	27 (35.1)
NL (n=36)	21 (58.3)	5 (13.9)	10 (27.8)	11 (30.6)	7 (19.4)	6 (16.7)
χ² value	3.367	8.528	8.478	4.015	6.480	4.016
P value	0.067	0.003	0.004	0.045	0.011	0.045
HL (n=33)	21 (63.6 )	19 (57.6)^②	17 (51.5)	16 (48.5)	17 (51.5)	12 (36.4)
NHL (n=44)	37 (84.1 )^①	13 (29.5)	27 (61.4)	23 (52.3)^①	17 (38.6)^①	15 (34.1)^①
HNL (n=20)	13 (65.0 )	4 (20.0)	4 (20.0)	9 (45.0)	7 (35.0)	6 (30.0 )
NNL (n=16)	8 (50.0 )	1 (6.3)	6 (37.5)	2 (12.5)	0 (0)	0 (0)
χ² value	8.068	15.648	10.302	7.931	14.709	9.568
P value	0.044	0.001	0.016	0.049	0.002	0.021

Variables	HL group (n=33)	NHL group (n=44)	χ²/t value	P value
Fatigue/n(%)	22 (66.7)	29 (65.9)	0.005	0.945
Headache and dizziness/n(%)	23 (69.7)	15 (34.1)	9.564	0.002
Shortness of breath/n(%)	14 (42.4)	17 (38.6)	0.112	0.737
Memory decline/n(%)	18 (54.5)	27 (61.4)	0.361	0.548
Brain fog/n(%)	19 (57.6)	15 (34.1)	4.218	0.040
Motor function decline/n(%)	22 (66.7)	29 (65.9)	0.005	0.945
Palpitations/n(%)	19 (57.6)	22 (50.0)	0.435	0.510
Taste alteration/n(%)	6 (18.2)	12 (27.3)	0.87	0.351
Olfactory changes/n(%)	1 (3.0)	4 (9.1)	0.361	0.548
Chest pain/n(%)	12 (36.4)	10 (22.7)	1.718	0.190
Muscle or joint pain/n(%)	16 (48.5)	14 (31.8)	2.203	0.138
Sleep disturbance/n(%)	7 (21.2)	16 (36.4)	2.067	0.151
Depressive state/n(%)	4 (12.1)	12 (27.3)	1.790	0.181
Anxiety state /n(%)	9 (27.3)	9 (20.5)	0.489	0.484
Thirst/n(%)	15 (45.5)	20 (45.5)	0.000	>0.999
Vertigo/n(%)	17 (51.5)	16 (36.4)	1.768	0.184
Lymphadenopathy/n(%)	10 (30.3)	34 (22.7)	0.563	0.453
Chills/n(%)	18 (54.5)	16 (36.4)	2.528	0.112
Cough with sputum/n(%)	14 (42.4)	12 (27.3)	1.936	0.164
Sneezing/n(%)	12 (36.4)	14 (31.8)	0.174	0.676
Gastrointestinal discomfort/n(%)	15 (45.5)	15 (34.1)	1.024	0.312
Increased hair loss/n(%)	20 (60.6)	22 (50.0)	0.856	0.355
Number of symptoms	9.48±4.60	8.09±4.35	-1.359	0.178