β-Thalassemia Heterozygotes: Comparison
Please note this is a comparison between Version 2 by Camila Xu and Version 3 by Camila Xu.

β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority.

  • β-thalassemia
  • risk
  • coronavirus

1. Introduction

Identifying medical conditions with a high or potentially deadly impact on the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a critical initial step towards containment of associated morbidity and mortality risks. Given that viral stress from SARS-CoV-2 elicits anabolic responses supported by increasing blood pressure to meet enhanced oxygen needs of vital organs and organ systems, hypoxemia is rendered a high-risk medical condition [1][2]. As the most common blood disorder affecting approximately one third of the global population, anemia presents a low tolerance to hypoxemia and may have either acquired polysystemic or inherited poly- or monogenic background [3]. Monogenic anemia—which is caused by abnormal hemoglobin—is a rather prevalent medical disorder with 270 million carriers worldwide [4][5][6]. β-Thalassemia is the most common inherited single gene disorder in the world. Approximately one-third of all hemoglobinopathies and/or nearly 1.5% of the global population carry the β-thalassemia trait [7]. In this context, β-thalassemia heterozygosity is a strong candidate condition for assessing an individual’s susceptibility to COVID-19.

2. Associations

Association of β-thalassemia heterozygosity with severe and critical COVID-19 symptoms. Considering the clinical spectrum of COVID-19 as a primary outcome, patients were categorized into three groups (asymptomatic and mild/ moderate/ severe and critical). No difference in chest X ray or CT scan was observed among study participants. In univariate analysis, sex (p = 0.047), age (p < 0.001), atrial fibrillation (p = 0.022), coronary disease (p = 0.041), hyperlipidemia (p = 0.014), hypertension (p < 0.001), and being heterozygous for thalassemia (p = 0.004) were associated with severe COVID-19 symptoms (Table 1). In multivariate analysis, male sex (p = 0.023), increased age (p < 0.001), and being heterozygous for thalassemia (p = 0.002) were identified as independent risk factors for severe and critical clinical COVID-19 symptoms. Specifically, males had a 1.81 times (95% CI, 1.09 to 3.01) increased possibility for severe or critical clinical symptoms; increased age was associated with increased odds of severe and clinical symptoms with OR = 1.06 (95% CI, 1.04 to 1.08). A finding of great interest is that patients who were heterozygous for thalassemia were 2.89 times (95% CI, 1.49 to 5.62) more likely to have severe and critical clinical symptoms of COVID-19 (Figure 1).
Table 1. Characteristics and COVID-19 clinical spectrum.
Severity Univariate Multivariate Ordinal Logistic Regression (Severe and Critical vs. Others)
Mild (%) Moderate (%) No (%)Severe and Critical (%) p-Value
p = 0.505).
Table 3. Characteristics and ICU admission due to COVID-19.
ICU Univariate MultivariateBinary Logistic Regression
p-Value p-Value aOR with 95% CI
OR with 95% CI RR with 95% CI p-Value aOR with 95% CI
Yes (%) No (%) p-Value OR with 95% CI RR with 95% CI p-Value aOR with 95% CI
Sex (M/F) 34/34 67/46 52/22 0.047 * 0.023 1.81 (1.09–3.01)
Sex (M/F) 50/20 103/82 0.022 * 1.99 (1.10–3.61) 1.67 (1.06–2.64) 0.036 2.09 (1.05–4.18)
Sex (M/F) 36/17 117/85 0.186 * 1.54 (0.81–2.92) 1.41 (0.84–2.37) 0.305 1.45 (0.72–2.93)
Age (median, IQR) 51.5 (34) 64.0 (17) 70.5 (15) <0.001 ± <0.001 1.06 (1.04–1.08)
Age (median, IQR) 72.5 (15) 61.0 (24) <0.001 ±
Age (median, IQR) 66.2 (17) 60.4 (24) 0.030- ± -- -<0.001 1.06 (1.03–1.09)
0.649 1.01 (0.98–1.04) Atrial Fibrillation 17 (25.0) 32 (28.3) 33 (44.6) 0.022 * 0.787 0.92 (0.49–1.71)
Atrial Fibrillation 33 (47.1) 49 (26.5) 0.002 * 2.48 (1.40–4.39) 1.88 (1.28–2.78) 0.201 1.64 (0.77–3.48) 0.191* Respiratory Disease 5 (7.4) 13 (11.5)
Atrial Fibrillation 21 (36.9) 61 (30.2) 1.52 (0.81–2.84) 1.39 (0.85–2.25) 0.966 0.98 (0.43–2.23) Respiratory Disease14 (18.9) 0.104 * 0.325 1.47 (0.68–3.15)
14 (20.0) 18 (9.7) 0.027 * 2.32 (1.08–4.97) 1.74 (1.11–2.74) 0.297 1.61 (0.66–3.95)
Respiratory Disease 11 (20.8) 21 (10.4) 0.043 * 2.26 (1.01–5.04) 1.83 (1.05–3.17) 0.205 1.80 (0.73–4.46) Coronary Disease 7 (10.3) 23 (20.4) 20 (27.0) 0.041 * 0.955 1.02 (0.50–2.09)
Coronary Disease 20 (28.6) 30 (16.2) 0.027 * 2.07 (1.08–3.96)
Coronary Disease 16 (30.2) 34 (16.8)1.64 (1.08–2.49) 0.808 0.90 (0.39–2.09) 0.029 * 2.14 (1.07–4.27) 1.77 (1.08–2.92) 0.393 1.48 (0.61–3.59) Diabetes 10 (14.7) 25 (22.1) 18 (24.3) 0.331 * 0.619 0.85 (0.45–1.60)
Diabetes 18 (25.7) 35 (18.9) 0.233 * 1.48 (0.77–2.84) 1.32 (0.85-2.05) 0.758 0.87 (0.41–1.91)
Diabetes 10 (18.9) 43 (21.3) 0.699 * 0.86 (0.40–1.85) 0.87 (0.48–1.64)Neoplasia 7 (10.3) 11 (9.7) 11 (14.9) 0.529 * 0.209 0.61 (0.28–1.32)
Neoplasia 10 (14.3) 19 (10.3) 0.367 * 1.46 (0.64-3.31) 1.30 (0.75–2.24) 0.395 0.67 (0.26–1.70) Hyperlipidemia 21(30.9) 60 (53.1) 32 (43.2) 0.014 * 0.138 0.65 (0.37–1.15)
0.098 0.49 (0.21–1.14)
Neoplasia 4 (7.5) 25 (12.4) 0.466 0.58 (0.19–1.74) 0.64 (0.25–1.63) 0.102 0.37 (0.11–1.22) Hyperlipidemia 30 (42.9) 83 (44.9) 0.773 * 0.92 (0.53–1.61) 0.94 (0.63–1.41) 0.008 0.38 (0.19–0.78)
Hyperlipidemia 22 (41.5) 91 (45.0) 0.644 * 0.87 (0.47–1.60) 0.89 (0.55–1.45) Hypertension
0.033 0.44 (0.21–0.94) Hypertension24 (35.3) 62 (54.9) 56 (75.7)
Hypertension 42 (79.2) 100 (49.5)<0.001 * <0.104 0.0011.67 (0.90–3.08)
* 3.90 (1.90–7.99) 3.04 (1.64–5.63) 0.001 5.12 (2.04–12.87) β-Thalassemia Heterozygotes 5 (7.4) 19 (16.8) 21 (28.4) 0.004 * 0.002 2.89 (1.49–5.62)
* Chi-square test, ± Mann–Whitney test; Bold is for the statistically significant results (p-value < 0.05).
Figure 1. Proportion of β-thalassemia heterozygotes relative to non-carriers regarding clinical symptoms to COVID-19.

2.1. Association of β-Thalassemia Heterozygotes with Mortality Due to COVID-19

Regarding mortality associated with COVID-19 infection, in univariate analysis sex (p = 0.022), age (p < 0.001), atrial fibrillation (p = 0.002), respiratory disease (p = 0.027), coronary disease (p = 0.027), hypertension (p < 0.001), and being heterozygous for thalassemia (p = 0.005) were associated with mortality (Table 2). In logistic regression analysis, male patients had a 2.09 times (95% CI, 1.05 to 4.18) greater possibility of dying and patients with increased age were 1.06 times (95% CI, 1.03 to 1.09) more likely to die. It is worth noting that hyperlipidemia plays a beneficial role in COVID-19 mortality, as the odds ratio of mortality in patients with hyperlipidemia is 0.65 (95% CI 0.37–1.15). It should be highlighted that patient who are heterozygous for thalassemia have a 2.79 times (95% CI, 1.28 to 6.09) greater possibility of dying than other patients (Figure 2).
Table 2. Characteristics and mortality due to COVID-19.
Mortality Univariate MultivariateBinary Logistic Regression
Yes (%)
52 (74.3)
90 (48.6)
<
0.001
*
3.05 (1.66–6.60) 2.30 (1.43–3.70) 0.198 1.67 (0.77–3.62)
β-Thalassemia Heterozygotes 20 (28.6) 25 (13.5) 0.005 * 2.56 (1.31–4.99) 1.87 (1.24–2.80) 0.010 2.79 (1.28–6.09)
* Chi-square test, ± Mann–Whitney test; Bold is for the statistically significant results (p-value < 0.05).
Figure 2. Proportion of β-thalassemia heterozygotes relative to non-carriers regarding mortality due to COVID-19.

2.2. Admission of COVID-19 Infected β-Thalassemia Heterozygotes to the ICU

Regarding the requirement for ICU care, it was found through univariate analysis that age (p = 0.03), respiratory disease (p = 0.043), coronary disease (p = 0.029) and hypertension (p < 0.001) were associated with ICU admission (Table 3). Through logistic regression analysis, patients with hypertension had 5.12 times (95% CI, 2.04 to 12.87) greater risk of requiring ICU care than patients without hypertension. On the contrary, hyperlipidemia was identified as a protective factor against ICU admission, with OR = 0.44 (95% CI, 0.21 to 0.94). Furthermore, in relation to the requirement for ICU care, being heterozygous for thalassemia had no effect on the possibility of admission to the ICU (
β-Thalassemia Heterozygotes
11 (20.8)
34 (16.8)
0.505 *
1.29 (0.61–2.77) 1.22 (0.68–2.18) 0.508 1.33 (0.57–3.06)
* Chi-square test, ± Mann–Whitney test, † Fisher’s exact test; Bold is for the statistically significant results (p-value < 0.05).

2.3. Length of Hospitalization until Death

When comparing the median length of hospitalization (days) between patients being heterozygous for thalassemia and non-carriers, a statistically significant difference was observed (p = 0.046) (Figure 3). More specifically, the median duration of hospitalization among carriers and non-carriers was 12 and 17.5 days, respectively.
Figure 3.
Days of hospitalization until death between carries and non-carriers.

2.4. Length of Hospitalization among Patients Who Survived

Regarding days of hospitalization among patients that survived COVID-19, the median duration was eight days for patients that were heterozygous for thalassemia and six days for non-carriers (p = 0.014) (Figure 4).
Figure 4. Days of hospitalization between carries and non-carriers that survived.

References

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