Table 1.
Retrospective studies that analyzed thyroid function in COVID-19 patients during admission.
| Author | Number of patients | Comorbidity | Severity | Thyroid function markers | Hyperthyroidism (%) | Main statistical findings | Thyroid function and clinical outcomes |
|---|---|---|---|---|---|---|---|
| Local Month/year | Men’s n (%) – Age | Length of stay | Mortality | Inflammatory markers | NTIS (%) | Limitations | |
| Wang et al | 84 | Not mentioned | Moderate 25% Critical 75% |
TSH, TT3, TT4 | Overt thyrotoxicosis 4% Subclinical thyrotoxicosis 4% |
TT3 and TSH levels were significantly lower in COVID-19 patients (p < 0.001). Thyroid dysfunction was more commonly found in critical than in mild/moderate cases (74.6 vs 23.8%, p < 0.001). The group with thyroid dysfunction also had an increased level of leukocytes (p < 0.001), neutrophils (p < 0.001), CRP (p = 0.002), and PCT (p = 0.054); and a decreased level of lymphocytes (p < 0.001). |
Thyroid dysfunction tended to be associated with longer viral nucleic acid cleaning time (14.13 ± 9.39 vs. 10.56 ± 8.29 days, p = 0.088). |
| China Feb/2021 (102) |
53 (63.1%) 57.3 ± 14.5 |
Not mentioned | 0% | Procalcitonin, PCR, IL-6, IL-10, TNF-α, interferon-γ | Not mentioned | Small sample size. Free T3, free T4, and reverse T3 were not measured. | |
| Gao et al | 100 | Not mentioned | Moderate 34% Critical 66% |
TSH, FT4, FT3 | Overt thyrotoxicosis 17% | FT3 levels are lower in severe ill patients (4.40 ± 0.88 vs 3.41 ± 0.90, p < 0.001). TSH levels are lower in severe ill patients (2.03 (1.24, 3.31) vs 1.20 (0.45, 2.05), p = 0.002). |
The lower (versus upper) two-thirds of FT3 were associated with all-cause mortality HR (95% CI) of 9.23 (2.01, 42.28). |
| China Nov/2020 (97) |
52 (52%) 66.1 ± 16 |
14 days ± 6 | 22% | PCR, D-dimer, IL-6, TNF-alfa, NT-proBNP | 28% | Small sample size. Sample composed mainly of patients with severe COVID-19. | |
| Sun et al | 336 | Hypertension 35.3% Diabetes 15.3% CVD 9.3% |
Mild/Moderate 92.3% Critical 7.7% |
FT3, FT4, TT3, TT4 | Not mentioned | TT3, FT3, TT4 and FT4 were significantly lower in moderate/critical patients; TT3 AUROC 0.96. | Thirty-six of the clinical and laboratory features analyzed were found to be statistically associated with severe/critical symptoms of COVID-19. |
| China Jul/2020 (103) |
117 (34.8%) 50 |
Not mentioned | 0% | CD3, CD4, CD19, CRP | Not mentioned | TSH and reverse T3 were not measured. | |
| Lania et al | 287 | Hypertension 49.5% Diabetes 24.4% CVD 14.3% COPD 12.2% |
Critical (100% ICU) | TSH, FT3, FT4 | Overt thyrotoxicosis 10.8% Subclinical thyrotoxicosis 19.9% |
In the multivariate analysis, thyrotoxicosis was associated with higher IL-6 levels (odds ratio: 3.25, 95% CI: 1.97-5.36; P < 0.001). 16% of patients with overt thyrotoxicosis developed thromboembolic events. |
The in-hospital mortality rate was higher in patients with either thyrotoxicosis or hypothyroidism. In discharged patients, the duration of hospitalization resulted to be significantly longer in cases with thyrotoxicosis as compared to those with either normal TSH or hypothyroidism. |
| Italy Oct/2020 (104) |
193 (67.2%) 66 (27-92) |
Not mentioned | 21.4% | IL-6 | Not mentioned | In several patients, thyroid function was assessed in the course of treatment with low-molecular-weight heparin. | |
| Sen et al | 60 | Not mentioned | Mild 43.3% Moderate 26.7% Critical 30% |
TSH, FT3, FT4, TT3, TT4, TPOAb | Not mentioned | 35% of the patients showed one or more abnormality in thyroid function. The commonest abnormality was low TSH, found in 11 patients (18.33%). |
FT4 is associated with the severity of the disease (P = 0.009). |
| India Jan/2021 (105) |
Not mentioned | Not mentioned | 0% | Ferritin, D-dimer | Not mentioned | Small sample size. | |
| Chen et al | 50 | Not mentioned | Mild 30% Moderate 46% Critical 24% |
TSH, FT3, FT4 | 56% | 64% of the patients had abnormal thyroid function parameters. |
The more severe the COVID-19, the lower the levels of TSH and TT3 (p <0.001). |
| China Jan/2021 (106) |
33 (66%) 48,4 ± 13,7 |
Not mentioned | 0% | Albumin | Not mentioned | Small sample size. | |
| Guo et al | 121 | Not mentioned | Critical 100% | FT4, FT3 | Not mentioned | In the ROC curve, the FT3 variable was the best laboratory variable in predicting hospital mortality (AUC 0.863), 3.25 pmol/L cut-off. | Not mentioned. |
| China Jan/2021 (95) |
57.0% 66 (56–72) |
Not mentioned | 28.9% | IL-2R, IL-6, IL-8, IL-10, TNF-α, NT-proBNP, troponin, and hs-CRP | Not mentioned | Small sample size. TSH and reverse T3 were not measured. | |
| Schwarz et al | 54 | Hypertension 38.8% Diabetes 33.3% CVD 29.6% |
Moderated 68.5% Critical 31.4% |
TSH, FT4, FT3 | Not mentioned | Patients in the lowest FT3 tertile had significantly lower mean room air oxygen saturation on presentation (81%, 92.7%, and 93.7%, respectively; p = 0.006). | Patients in the lowest FT3 tertile had a significantly higher mortality rate (40%, 5.9%, and 5.9% in the first, second, and third tertiles, respectively; P = 0.008), more mechanical ventilation (45%, 29.4%, and 0.0%, respectively; P = 0.007), and ICU hospitalization (55%, 29.4%, and 5.9%, respectively; P = 0.006). |
| Israel Feb/2021 (96) |
37 (68.5%) 58.7 ± 17.5 |
Not mentioned | 10% | CRP, D-dimer, ferritin, troponin, LDH | Not mentioned | Small sample size. Reverse T3 was not dosed. | |
| Vassiliadi et al. | 87 | Not mentioned | Moderate 47.1% Critical 52.9% |
TSH, FT4, TT3, TG | Overt thyrotoxicosis 6.9% Subclinical thyrotoxicosis 6.8% |
T3 and TSH levels were lower in the ICU patients (70.5 ± 31.9 vs 89.7 ± 42.0, P = 0.001 and 0.95 ± 0.93 vs 1.66 ± 1.46, P ≤ 0.001, respectively). | The prevalence of thyroid hormone abnormalities increased with increasing disease severity. |
| Greece Jun/2021 (107) |
69 (66.3%) 59.3 ± 18.3 |
Not mentioned | 14.9% | IL-6 | 47.1% | Small sample size. Free T3 and reverse T3 were not measured. | |
| Yazan et al | 205 | Hypertension 42.6% Diabetes 26.3% CVD 15.2% COPD 12.3% Neoplasia 5.8% |
Moderate 85% Critical 15% |
TSH, FT3, FT4, TGAb, TPOAb | Overt thyrotoxicosis 3.9% Subclinical thyrotoxicosis 4.3% |
Thyroid dysfunction rate was 65.8% in this study. FT3 (rho = -0.34, p < 0.001), and TSH (rho = -0.21, p = 0.002) had weak negative correlations with WHO illness severity scores. |
Length of hospitalization, rate of oxygen demand, ICU admission and mortality were lower in euthyroid patients. FT3 and TSH levels were significantly lower in patients admitted to ICU (p < 0.001 and p = 0.005, respectively). |
| Turkey Aug/2021 (108) |
113 (55.1%) | Not mentioned | 4.3% | CRP, D-dimer, ferritin, DHL | 52.6% | Absence of a control group. | |
| Ahn J et al. | 119 | Hypertension 52.1% Diabetes 30.3% CVD 18.4% COPD 5.9% |
Moderate 26.9% Critical 73.1% |
TSH, FT3, FT4 | Overt thyrotoxicosis 0% Subclinical thyrotoxicosis 14.3% |
Patients with severe to critical COVID-19 disease had lower TSH (median: 0.90 mIU/L vs 1.67 mIU/L, p = 0.006) and T3 (median: 0.82 ng/mL vs 1.11 ng/mL, p < 0.001) levels compared with those with non-severe disease. T3 was negatively correlated with hs-CRP (r=−0.373, p < 0.001) and WBC count (r=−0.463, p < 0.001). |
COVID-19 patients in the lower third of T3 levels (compare to middle and upper third of T3 levels) had poor outcomes: ICU admission (61.5% vs 32.5% vs. 30%, p = 0.005), mechanical ventilation (46.2% vs 27.5% vs 12.5%, p = 0.001), and death (48.7% vs 32.5% vs 5%, p < 0.001). The Kaplan-Meier curves for survival showed increased mortality of the lowest third T3 (log-rank P=0.014). |
| Korea Aug/2021 (109) |
62 (52.1) 64.3 ± 16.8 |
Not mentioned | 28.6% | CRP | 18.5% | Sample composed mainly of patients with severe COVID-19. Reverse T3 was not measured. | |
| Clausen et al. | 116 | Hypertension 46% Diabetes 33% Asthma 10% COPD 8% |
Moderate 83% Critical 17% |
TSH, FT4 | Overt thyrotoxicosis 1.7% Subclinical thyrotoxicosis 9.5% |
18.1% patients had biochemically thyroid dysfunction. IL-8 (r = –0.248, P = 0.008), IL-10 (r = –0.253, P = 0.007), IL-15 (r = –0.213, P =0.02), IP-10 (r = –0.334, P = 0.0003) and GM-CSF (r =–0.254, P =0.007) were inversely correlated with TSH. IL-8 levels, IP-10, and GM-CSF were higher in patients with serum TSH < 0.4 mIU/L. |
Neither TSH in the whole cohort nor in the group with TSH levels <0.4 mIU/L was associated with 30- and 90-day mortality in crude and adjusted logistic regression models (adjusted for age, sex, and IL-6). |
| Denmark Set/2021 (110) |
44 (38%) | Not mentioned | 24% | 35 cytokines | 1.7% | Small sample size. Free T3 and reverse T3 were not measured. | |
| Okwor et al | 90 (45 control) |
Not mentioned | Not mentioned | TSH, FT3, FT4 | Overt thyrotoxicosis 2.2% | Plasma levels of FT3 (4.19 ± 1.32 vs 2.42 ± 0.83) and TSH (2.60 ± 1.04 vs 1.68 ± 0.67) were significantly higher in COVID-19 patients compared to healthy controls (p< 0.001). | Amongst COVID-19 patients 7 (15.6%) presented euthyroid sick syndrome whereas no cases were found in the control group. |
| Nigeria Set/2021 (111) |
34 (75.6%) 35.3 ± 12.4 |
Not mentioned | 0% | CPR | 15.6% | Small sample size. Young population and mostly men. Severity criteria were not used. |
|
| Dutta et al | 236 | Hypertension 43.2% Diabetes 50.4% Hypothyroidism 18% CVD 8% |
Moderate 94.1% Critical 5.9% |
TSH, FT3, FT4 | Subclinical thyrotoxicosis 3,8% |
Low FT3, high TSH and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. | Cox regression analysis showed that low FT3 was associated with severe COVID-19 (P =0.032, HR 0.302; CI 0.101–0.904). The duration of hospital stay correlated negatively with both FT3 and TSH. |
| India Nov/2021 (112) |
159 (6%) 54 (15-91) |
Eight days (1-44) | 4.7% | CPR, D-dimer, IL-6, ferritin, DHL. | 23,7% | Most patients with moderate disease. | |
| Lang et al | 127 | Hypertension 41.7% Diabetes 21,3% CVD 10.2% COPD 10.2% |
Mild 44.1% Moderate 42.5% Critical 13.4% |
TSH, FT4, FT3 | Not mentioned | The serum levels of TSH [0.8 (0.5–1.7) vs. 1.9 (1.0–3.1) μIU/mL, P = .031] and FT3 [2.9 (2.8–3.1) vs. 4.2 (3.5–4.7) pmol/L, P <.001] were lower in non-survivors than in survivors. | Patients with low FT3 (<3.1 pmol) had a higher risk of death (adjusted OR 13.2, 95% CI 3.87–55, p < 0.001). |
| China Nov/2021 (113) |
62 (48.8%) 66 (53-71) |
Not mentioned | 8.6% | CRP, D-dimer, IL-6. | 16,5% | Small sample size. Corticosteroids in the treatment of COVID-19. | |
| Zheng et al. | 235 | Hypertension 35.3% Diabetes 15.3% DCV 9.3% COPD 5.9% |
Moderate 20.8% Critical 79.2% |
TSH, FT3, FT4 | Not mentioned | The proportion of subclinical hypothyroidism was 7.23% in COVID-19 patients. Patients with NTIS had higher CRP (17.6 (2.6) vs 67.4 (7.4), p<0.001), WBC count (6.26 (0.2) vs 7.59 (0.6), p=0.001) and ESR (43.9 (2.7) vs 81.5 (8.5), p<0.001). |
Patients with NTIS had higher incidences of COVID-related complications, including ARDS (9.1–13.0% vs 0.0–1.1%), acute cardiac injury (54.5–70.0% vs 15.3–23.5%), acute kidney injury (21.7–27.3% vs 0.0–2.7%), shock (36.4 47.8% vs 0.0–1.6%), hypoalbuminemia (45.5–52.2% vs 18.6– 23.5%), and coagulopathy (27.3–30.0% vs 0.0–10.9%), as well as higher severe types of COVID-19 (100% vs 75.5–76.5%) compared to patients with normal thyroid function. . |
| China Nov/2021 (114) |
112 (47.6%) 61 (51-69) |
Not mentioned | 6.8% | PCR, D-dimer, IL-6, BNP | 14.47% | Most critically ill patients. Reverse T3 was not measured. | |
| Sethi et al | 57 | Not mentioned | Mild 33.3% Moderate 33.3% Critical 33.3% |
TSH, FT3, FT4 | Overt thyrotoxicosis 28% Subclinical thyrotoxicosis 9% |
28% of the patients had raised T4 and around 9% had decreased TSH. A negative correlation was found between TSH and CRP (r=-0.541). |
T3 (H = 11.98, p =0.02) and T4 (H = 6.71, p = 0.035) were lower in higher disease severity (p <0.05). |
| India May/2022 (115) |
39/57 (68%) 47.1 |
Not mentioned | Not mentioned | CPR | Not mentioned | Small sample size. | |
| Okoye et al | 95 | Not mentioned | Mild 55.4% Moderate 19.3% Critical 25.3% |
TSH, FT3, FT4 | Not mentioned | There is no difference in the incidence of NTIS between patients with COVID-19 (66.3%) and patients with non-COVID-19 pneumonia (67,9%) (p = 0.82). | Among COVID-19 patients, a slightly lower mortality of NTIS patients was observed (23.8% vs 31.2% respectively, p=0.43), while non-COVID-19 patients with NTIS showed a three times higher mortality than non-NTIS (14.5% vs 3.8% respectively, p=0.09). |
| Italy May/2022 (116) |
52.6% 81.9 ± 7.8 |
Not mentioned | 26.3% | CPR | 66.3% | Small sample size. Only hospitalized elderly. |