Higher Survival Rate Associated with Thymosin Alpha 1 use in Critical COVID-19: A Retrospective Multicenter Cohort Study

doi:10.21203/rs.3.rs-123265/v1

Download PDF

Research Article

Higher Survival Rate Associated with Thymosin Alpha 1 use in Critical COVID-19: A Retrospective Multicenter Cohort Study

https://doi.org/10.21203/rs.3.rs-123265/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background

Currently no satisfactory pharmaceutical intervention is available for COVID-19. This retrospective study aimed to determine the therapeutic effect of thymosin alpha1 in critical COVID-19.

Results

We enrolled 109 critically ill severe acute respiratory syndrome-related coronavirus-2 RNA positive patients from 15 hospitals. The mortality rate in critical patients treated with thymosin alpha1 was 11%, compared to 56% in critical patients not treated with thymosin alpha1. With confounding factors adjusted in multivariate logistic regression, thymosin alpha1 treatment was identified as a protective factor for critical COVID-19.

Conclusion

Our observation advocates the treatment of critical COVID-19 with thymosin alpha1.

Critical Care & Emergency Medicine

pharmaceutical intervention

COVID-19

therapeutic effect

coronavirus-2

The clinical presentations of the Coronavirus Disease 2019 (COVID-19) have two conflicting sides. On one side, the excessive response of the immune system, represented by high levels of proinflammatory cytokines and chemokines, is considered the major mechanism for critical illness and mortality of COVID-19[1, 2]. For this reason, suppression of patients’ immune system with glucocorticoid has been common in the management of COVID-19[3–5]. On the other side, severe lymphocytopenia was frequently observed in COVID-19, especially in aged and severe cases[1, 6]. Recently, Liu et al. reported that thymosin alpha 1 (Ta1) may benefit COVID-19 patients by restoring their immune capacity[7]. However, this study did not address the potential influences of the confounding factors.

To determine the therapeutic effect of Ta1 in critical COVID-19, we conducted a retrospective cohort study and found that use of Ta1 caused beneficial outcomes including a much lower mortality rate.

We reviewed the medical records of 410 suspected COVID-19 patients. Excluding 56 records for negative RNA test, 24 for duplicated records, 219 for non-critical condition, and 2 for the lack of relevant data, we enrolled 109 critically ill[8] severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) RNA positive patients hospitalized at 15 hospitals in Jingzhou and Dongguan, China, from January 16 to March 30, 2020 (Fig. 1).

Treatment of COVID-19 followed the Diagnosis and Treatment Guideline for COVID-19, National Health Commission of the People’s Republic of China. Most patients were treated with oxygen supplementation, respiratory support, antibiotics, usually Moxifloxacin, and antivirus drugs, usually Lopinavir and Ritonavir. Mechanical ventilation was conducted when indicated by exacerbating or persistent hypoxemia and dyspnea after non-invasive oxygen supplementation. Based on physician’s preference, 18 of the critical patients exhibiting persistent positive results for SARS-CoV-2 RNA or lymphocyte count < 1.5 × 10⁹/L were treated with Ta1 (Ta1 group) at a dosage of 1.6 mg per 12 or 24hr subcutaneously for the length of critical illness. The other 91 critical patients were not treated with Ta1 (non-Ta1 group).

Multivariate logistic regressions were performed to identify clinical features and treatments associated with Ta1 treatment and mortality, respectively, and were adjusted with potential confounders identified from univariate regressions.

Eighteen of the 109 critically ill COVID-19 patients (17%) were treated with Ta1. Compared to the 91 critical patients not treated with Ta1, the Ta 1 treated patients were more often from Dongguan People’s Hospital (Guangdong Province) (Table 1), exhibited a lower serum procalcitonin level on admission (Table 2), and more often treated with immunoglobulin and albumin (Table 1).

Table 1

, Demographics and clinical characteristics of COVID-19 patients on admission
	Critically ill (n = 109)		p value
	Thymosin treatment (n = 18)	No thymosin treatment (n = 91)
Age, years
≥ 60	11 (61%)	62 (68%)	0.563
Sex
Female	6 (33%)	38 (42%)	0.506
Male	12 (67%)	53 (58%)	0.506
Location
Dongguan, Guangdong	9 (50%)	4 (4%)	< 0.001
Jingzhou, Hubei	9 (50%)	87 (96%)	< 0.001
Signs and symptoms
Fever (≥ 37.3℃)	15 (83%)	72 (79%)	0.932
Cough	12 (67%)	67 (74%)	0.546
Dyspnea	10 (56%)	43 (47%)	0.520
Sputum	7 (39%)	26 (29%)	0.384
Myalgia	3 (17%)	19 (21%)	0.932
Diarrhoea	2 (11%)	13 (14%)	1.000
Cephalalgia	1 (6%)	12 (13%)	0.607
Hemoptysis	0	2 (2%)	1.000
Comorbidities
Hypertension	9 (50%)	40 (44%)	0.638
Diabetes	3 (17%)	16 (18%)	1.000
Digestive tract disease	2 (11%)	8 (9%)	1.000
Cardiovascular disease	0	10 (11%)	0.209
Cerebrovascular disease	1 (6%)	4 (4%)	1.000
Malignancy	1 (6%)	4 (4%)	1.000
Liver disease	1 (6%)	5 (5%)	1.000
Chronic lung disease	1 (6%)	6 (7%)	1.000
Treatments
Antiviral treatment	15 (83%)	84 (92%)	0.448
Interferon	1 (6%)	16 (18%)	0.353
Antibiotics	15 (83%)	83 (91%)	0.558
Corticosteroids	11 (61%)	61 (67%)	0.628
Immunoglobulin	8 (44%)	18 (20%)	0.025
Albumin	8 (44%)	3 (3%)	< 0.001
Supplemental oxygen	18 (100%)	89 (98%)	1.000
Outcomes
ARDS	9 (50%)	54 (59%)	0.463
Mechanical ventilation	3 (17%)	43 (47%)	0.032
ECMO	1 (6%)	3 (3%)	1.000
ICU admission	18 (100%)	61 (67%)	0.003
Mortality	2 (11%)	51 (56%)	0.001
Length of hospital stay (survival),days	27.5 (17.3–31.5)	19.0 (15.0–25.0)	0.309
Data are median (IQR) or n (%). p values comparing thymosin treatment and non-thymosin treatment are from Mann-Whitney U test, Chi-Square test, or Fisher’s exact test, as appropriate. COVID-19 = Coronavirus Disease 2019. ECMO = extracorporeal membrane oxygenation. ARDS = acute respiratory distress syndrome. ICU = intensive care unit.

Table 2

, Laboratory findings of critical COVID-19 patients on admission
	Reference values	Critically ill (n = 109)		p value
		Thymosin treatment (n = 18)	No thymosin treatment (n = 91)
White blood cell count (X10⁹/L)	4.00–10.00	6.60 (4.41–8.75)	7.73 (5.12–11.11)	0.121
Lymphocyte count (X10⁹/L)	1.50-4.00	0.76 (0.42–1.09)	0.85 (0.65–1.20)	0.119
Neutrophil count (X10⁹/L)	2.00–7.00	5.45 (2.57–7.17)	5.74 (3.55–8.80)	0.215
NLR	0.78–3.53	8.14 (2.02–16.76)	5.44 (3.27–10.56)	0.862
Monocyte count (X10⁹/L)	0.12-1.00	0.34 (0.22–0.46)	0.37 (0.23–0.58)	0.118
Platelet count (X10⁹/L)	99.00-303.00	187.00 (161.75–218.50)	190.00 (154.00-273.00)	0.317
APTT(s)	21.00–37.00	34.20 (31.98–38.53)	31.40 (24.59–36.43)	0.198
fibrinogen (g/L)	2.00–4.00	3.70 (3.22–5.19)	3.48 (2.65–4.66)	0.137
D-dimer (µg/mL)	0.00-0.55	1.15 (0.35–1.71)	0.57 (0.37–1.11)	0.592
Procalcitonin (ng/mL)	0.00-0.50	0.11 (0.10–0.28)	0.29 (0.15–0.44)	< 0.001
CRP(mg/L)	0.00–10.00	34.86 (6.01–103.90)	24.28 (7.68–76.69)	0.979
ESR (mm/1 h)	0.00–30.00	28.00 (19.00–66.00)	34.00 (26.00-64.20)	0.469
Creatine kinase (U/L)	25.00-200.00	68.60 (39.95-132.05)	147.35 (66.50-179.75)	0.768
Lactate dehydrogenase (U/L)	91.00-230.00	223.00 (192.15–311.70)	226.00 (167.00-331.00)	0.975
Creatinine (µmol/L)	44.00-112.00	67.40 (50.48–75.20)	83.00 (65.70-110.40)	0.107
BUN (mmol/L)	2.50–7.10	5.41 (4.70–9.35)	6.36 (4.77–9.56)	0.616
AST (U/L)	0.00–40.00	28.10 (20.63-38.00)	38.00 (28.40–57.00)	0.282
ALT (U/L)	0.00–50.00	23.00 (18.60-50.03)	41.80 (28.00–61.00)	0.230
Total bilirubin (µmol/L)	3.00–21.00	18.10 (8.73–20.95)	19.70 (13.90–28.50)	0.053
Data are median (IQR). p values comparing thymosin treatment and non-thymosin treatment are from Mann-Whitney U test or Student's t test, as appropriate. NLR = neutrophil-to-lymphocyte ratio. APTT = activated partial thromboplastin time. ESR = Erythrocyte sedimentation rate. CRP = C-reactive protein. BUN = blood urea nitrogen. AST = aspartate transaminase. ALT = alanine aminotransferase.

Two patients (11%) in the Ta1 died compared to 51 patients (56%) in the non-Ta1 group. Similarly, 3 patients (17%) in the Ta1 group required mechanical ventilation, compared to 43 patients (47%) in the non-Ta1 group (Table 1). After adjusting for potential confounding factors including age, gender, location of the hospitals, comorbidities, treatment with immunoglobulin and albumin, Ta1 treatment was identified as a protective factor for mortality, with an adjusted odds ratio of 0.02 (95%CI: 0.00-0.35) (Table 3). However, no correlation was observed between Ta1 treatment and the requirement for mechanical ventilation after adjustment for confounding factors (Table 4).

Table 3

, Logistic univariate and multivariate regression analyses on the association between the mortality rate and the clinical features
	Univariable OR (95%CI)	p value	Multivariable OR (95%CI)	p value	Adjust factors
Age ≥ 60 years	1.28 (0.81–2.03)	0.293
Sex	0.86 (0.53–1.40)	0.536
Comorbidities
Hypertension	1.45 (0.82–2.56)	0.201
Diabetes	1.11 (0.45–2.73)	0.819
Treatments
Thymosin α1	0.13 (0.03–0.54)	0.006	0.02 (0.00-0.35)	0.009	age, sex, hypertension, diabetes, antiviral treatment, interferon, antibiotics, corticosteroids, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Antiviral treatment	0.94 (0.64–1.40)	0.763	0.70 (0.12–4.21)	0.696	age, sex, hypertension, diabetes, thymosin α1, interferon, antibiotics, corticosteroids, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Interferon	7.50 (1.72–32.80)	0.007	1.31 (0.17-10.00)	0.792	age, sex, hypertension, diabetes, thymosin α1, antiviral treatment, antibiotics, corticosteroids, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Antibiotics	0.92 (0.62–1.37)	0.686	0.67 (0.11–4.10)	0.667	age, sex, hypertension, diabetes, thymosin α1, antiviral treatment, interferon, corticosteroids, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Corticosteroids	1.88 (1.16–3.05)	0.011	8.61 (2.27–32.61)	0.002	age, sex, hypertension, diabetes, thymosin α1, antiviral treatment, interferon, antibiotics, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Intravenous immunoglobin	2.25 (0.98–5.18)	0.056	2.97 (0.29–30.27)	0.359	age, sex, hypertension, diabetes, thymosin α1, antiviral treatment, interferon, antibiotics, corticosteroids, albumin, region, procalcitonin (on admission)
Albumin	0.57 (0.17–1.95)	0.372	2.99 (0.16–56.31)	0.465	age, sex, hypertension, diabetes, thymosin α1, antiviral treatment, interferon, antibiotics, corticosteroids, intravenous immunoglobin, region, procalcitonin (on admission)
ARDS	2.00 (1.19–3.38)	0.009	4.08 (1.76–9.48)	0.001	age, sex, comorbidities
Location (Dongguan)	0.07 (0.01–0.56)	0.012	0.05 (0.00-0.53)	0.014	age, sex, comorbidities
Procalcitonin (on admission)	1.44 (0.84–2.46)	0.186
OR = odds ratio. CI = confidence interval. ARDS = acute respiratory distress syndrome.

Table 4

, Logistic univariate and multivariate regression analyses on the association between the mechanical ventilation and the clinical features
	Univariable OR (95%CI)	p value	Multivariable OR (95%CI)	p value	Adjust factors
Age ≥ 60 years	0.87 (0.55–1.38)	0.559
Sex	0.81 (0.49–1.31)	0.386
Comorbidities
Hypertension	0.82 (0.46–1.43)	0.476
Diabetes	0.90 (0.37–2.22)	0.819
Treatments
Thymosin α1	0.20 (0.06–0.69)	0.011	0.23 (0.03–1.87)	0.168	age, sex, hypertension, diabetes, antiviral treatment, interferon, antibiotics, corticosteroids, intravenous immunoglobin, albumin, region, procalcitonin (on admission)
Antiviral treatment	0.68 (0.45–1.01)	0.058
Interferon	1.43 (0.54–3.75)	0.469
Antibiotics	0.75 (0.50–1.12)	0.159
Corticosteroids	1.00 (0.63–1.59)	1.000
Intravenous immunoglobin	1.00 (0.46–2.16)	1.000
Albumin	0.38 (0.10–1.41)	0.147
ARDS	1.63 (0.98–2.70)	0.061
OR = odds ratio. CI = confidence interval. ARDS = acute respiratory distress syndrome.

Most of the critical patient in both study groups exhibited similarly severe lymphocytopenia on admission. Before discharge, the lymphocyte counts of many patients treated with Ta1 were restored to the normal range, and were significantly higher than those in the non-Ta1 group (Table 2, 5).

Table 5

, Laboratory findings of critical COVID-19 patients before discharge
	Reference values	Critically ill (n = 109)		p value
		Thymosin treatment (n = 18)	No thymosin treatment (n = 91)
White blood cell count (X10⁹/L)	4.00–10.00	5.50 (3.77–9.56)	7.90 (5.87–11.64)	0.125
Lymphocyte count (X10⁹/L)	1.50-4.00	1.14 (0.97–1.84)	0.73 (0.53–1.11)	0.026
Neutrophil count (X10⁹/L)	2.00–7.00	3.01 (1.51–6.23)	5.92 (3.85–8.58)	0.044
NLR	0.78–3.53	2.59 (1.47–4.32)	8.30 (4.38–13.53)	< 0.001
Monocyte count (X10⁹/L)	0.12-1.00	0.34 (0.19–0.65)	0.48 (0.29–0.65)	0.191
Platelet count (X10⁹/L)	99.00-303.00	209.50 (155.00-285.25)	196.00 (128.00-275.00)	0.737
APTT(s)	21.00–37.00	34.00 (31.80-36.08)	35.20 (27.15–42.55)	0.453
fibrinogen (g/L)	2.00–4.00	3.71 (2.76–4.69)	3.27 (2.05–4.33)	0.164
D-dimer (µg/mL)	0.00-0.55	0.95 (0.40–2.43)	0.87 (0.38–5.50)	0.795
Procalcitonin (ng/mL)	0.00-0.50	0.10 (0.10–0.30)	0.32 (0.21–0.48)	0.351
CRP(mg/L)	0.00–10.00	22.33 (5.00-74.18)	49.45 (16.91-135.83)	0.004
ESR (mm/1 h)	0.00–30.00	40.50 (12.00–59.00)	46.00 (32.00–83.00)	0.231
Creatine kinase (U/L)	25.00-200.00	32.00 (23.60–60.00)	180.00 (54.15–365.50)	0.514
Lactate dehydrogenase (U/L)	91.00-230.00	241.30 (175.93–312.00)	313.00 (203.75–541.50)	0.335
Creatinine (µmol/L)	44.00-112.00	60.65 (41.00-78.98)	83.00 (65.95-142.45)	0.063
BUN (mmol/L)	2.50–7.10	5.90 (4.08–7.86)	7.63 (5.39–17.93)	0.203
AST (U/L)	0.00–40.00	36.20 (26.23–68.75)	64.00 (43.25–109.00)	0.266
ALT (U/L)	0.00–50.00	36.75 (23.13–98.75)	65.50 (43.55-136.65)	0.121
Total bilirubin (µmol/L)	3.00–21.00	15.30 (9.78–21.28)	27.00 (19.40-33.88)	0.628
SOFA		4.00 (3.00-6.25)	9.00 (4.00–13.00)	< 0.001
Data are median (IQR). p values comparing thymosin treatment and non-thymosin treatment are from Mann-Whitney U test or Student's t test, as appropriate. NLR = neutrophil-to-lymphocyte ratio. APTT = activated partial thromboplastin time. ESR = Erythrocyte sedimentation rate. CRP = C-reactive protein. BUN = blood urea nitrogen. AST = aspartate transaminase. ALT = alanine aminotransferase. SOFA = Sequential Organ Failure Assessment.

The laboratory results before discharge were similar to those on admission in that both study groups exhibited elevated inflammatory markers such as C-reactive protein (CRP) and Erythrocyte sedimentation rate (Table 2, 5). Importantly, the CRP level was significantly lower in the Ta1 group compared to the non-Ta1 group before discharge. Similarly, other inflammatory markers such as the neutrophil count and the neutrophil-to-lymphocyte ratio fell into the normal range in all patients treated with Ta1 (Table 5). Before discharge, markers of tissue damage for liver, kidney, and muscle in the Ta1 group exhibited a trend of decreased level compared to the non-Ta1 group, in line with the lower Sequential Organ Failure Assessment (SOFA) score in Ta1 group (Table 5).

With our patients, Ta1 is the best pharmaceutical intervention for critical COVID-19 achieving a much reduced mortality rate (11%), compared to the mortality rate in the non-Ta1 group (56%). Our data also indicated that the reduced mortality rate by Ta1 is linked with the increased counts of lymphocytes and the prevention of infections and injuries of multiple organs. Therefore, Ta1 may have protected the patients by boosting the antiviral capacity of the immune system.

Our observations are in concert with a recent report that Ta1 increased lymphocyte counts and thymus output, and reversed T cell exhaustion in severe COVID-19[7]. Similar outcomes were observed with influenza virus infected mice. When treated with Ta1, these mice exhibited increased NK-cell activity, CD4 and CD8 cell counts and activity in the lung, reduced viral titers and increased survival[9]. Besides viral infection, Ta1 has been successful in the treatment of severe sepsis, a condition known for high mortality rate. Patients with severe sepsis often present multi-organ failure in septic shock characterized by over-stimulation of the immune system in response to infection, and are commonly treated with immune suppressive drugs such as glucocorticoids. Counter-intuitively, several studies have demonstrated benefits of Ta1 in the treatment of severe sepsis, including higher survival rates[10].

The timing of the Ta1 treatment may be critical, because evidence has been presented for over-active immune system in causing the critical illness and mortality in COVID-19[1, 2]. Our patients received Ta1 at times when severe symptoms presented with persistent viral infection or lymphocytopenia, likely in a status of immune exhaustion. Monitoring serum cytokine levels may provide additional help in making the decision on whether to use and when to use Ta1.

The therapeutic mechanism of Ta1 remains largely unknown. Through up-regulation of TLR2 and TLR9 expression, the pleiotropic effects of Ta1 include not only enhanced functions of NK cells, CD4 + and CD8 + T cells[9, 11], but also FoxP3 + Treg cells that promotes immune tolerance[12–14]. Before further evidence from mechanistic study is available, we cannot rule out the possibility that the benefits of Ta1 in critical COVID-19 was mediated by the Ta1 stimulation of the proliferation of FoxP3 + Treg cells, which consequently led to a more balanced immune activity.

Our study has several limitations. Firstly, this is a retrospective study based on chart review, wherein the validity of the diagnosis and the evaluation factors might have led to information bias. Secondly, COVID-19 is a sudden epidemic, the supply of medical resources might affect the treatment which may led to selection bias. Thirdly, there was a relatively small sample size in Ta1 group. Thus, further research is necessary to evaluate the external validation and applicability with a larger sample size.

COVID-19, Coronavirus Disease 2019;

CRP, C-reactive protein;

SARS-CoV-2, severe acute respiratory syndrome-related coronavirus-2;

SOFA, Sequential Organ Failure Assessment;

Ta1, Thymosin alpha 1.

Ethics approval, guidelines and consent to participate

This study was approved by the Institutional Review Boards of Sun Yat-sen University and the participating hospitals. The study was performed in accordance with the ethical standards of the Declaration of Helsinki (1964) and its subsequent amendments. Informed consent was waived by the Clinical Research Ethics Committee of The Sixth Affiliated Hospital of Sun Yat-sen University since this study was a retrospective chart review and did not involve any patient tissue or interview.

Consent for publication

Not applicable.

Availability of data and materials

Data set is available on a reasonable requests from the corresponding author.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was partially supported by National Natural Science Foundation of China 81770571 (to LZ), 81774152 (to RZ), Guangdong Province “Pearl River Talent Plan” Innovation and Entrepreneurship Team Project 2019ZT08Y464 and the National Key Clinical Discipline of China.

Authors' contributions

LZ, GY, YZ and RZ conceived and designed this study. YL, SC, JK, JL, LS, RF, JG, YH and LZ collected data. YL, SC, JK, NJ and LZ prepared the first draft. All authors critically revised the manuscript and approved the final version.

Acknowledgements

We thank Prof. Yingfang Liu (Sun Yat-sen University School of Medicine) for critical review of the manuscript before submission.

Authors' information

The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China

Yichen Li, Jia Ke, Sijing Cheng, Lixin Zhu, Na Jiao, Yibo Huang & Yifeng Zou

The Third Clinical Medical College of Yangtze University, Jingzhou Hospital of Traditional Chinese Medicine, Jingzhou 434000, China

Jie Li & Guangjun Yan

Department of Intensive Care Medicine, Dongguan People’s Hospital, Southern Medical University, Dongguan 523059, China

Lihan Shen

School of Medicine, Sun Yat-sen University, Shenzhen 518107, China

Sijing Cheng & Rao Fu

The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China

Jieruo Gu

Putuo People's Hospital, Department of Bioinformatics, Tongji University, Shanghai 200092, China

Ruixin Zhu

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X et al: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395(10223):497-506.
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L et al: Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory medicine 2020, 8(4):420-422.
Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, Aaron JG, Claassen J, Rabbani LE, Hastie J et al: Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet 2020, 395(10239):1763-1770.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C et al: Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA internal medicine 2020.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X et al: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020, 395(10229):1054-1062.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y et al: Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. Jama 2020.
Liu Y, Pang Y, Hu Z, Wu M, Wang C, Feng Z, Mao C, Tan Y, Liu Y, Chen L et al: Thymosin alpha 1 (Talpha1) reduces the mortality of severe COVID-19 by restoration of lymphocytopenia and reversion of exhausted T cells. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020.
Fowler RA, Lapinsky SE, Hallett D, Detsky AS, Sibbald WJ, Slutsky AS, Stewart TE, Toronto SCCG: Critically ill patients with severe acute respiratory syndrome. Jama 2003, 290(3):367-373.
D'Agostini C, Palamara AT, Favalli C, Sivilia M, Febbraro G, Bue C, Garaci E: Efficacy of combination therapy with amantadine, thymosin alpha 1 and alpha/beta interferon in mice infected with influenza A virus. International journal of immunopharmacology 1996, 18(2):95-102.
King R, Tuthill C: Immune Modulation with Thymosin Alpha 1 Treatment. Vitamins and hormones 2016, 102:151-178.
Bozza S, Gaziano R, Bonifazi P, Zelante T, Pitzurra L, Montagnoli C, Moretti S, Castronari R, Sinibaldi P, Rasi G et al: Thymosin alpha1 activates the TLR9/MyD88/IRF7-dependent murine cytomegalovirus sensing for induction of anti-viral responses in vivo. International immunology 2007, 19(11):1261-1270.
Romani L, Bistoni F, Perruccio K, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Bistoni G, Rasi G, Velardi A et al: Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood 2006, 108(7):2265-2274.
Romani L, Bistoni F, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Zelante T, Moretti S, Rasi G, Garaci E et al: Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Annals of the New York Academy of Sciences 2007, 1112:326-338.
Romani L, Moretti S, Fallarino F, Bozza S, Ruggeri L, Casagrande A, Aversa F, Bistoni F, Velardi A, Garaci E: Jack of all trades: thymosin alpha1 and its pleiotropy. Annals of the New York Academy of Sciences 2012, 1269:1-6.

Download PDF

Version 1

posted

You are reading this latest preprint version

Higher Survival Rate Associated with Thymosin Alpha 1 use in Critical COVID-19: A Retrospective Multicenter Cohort Study

Status:

Version 1

Abstract

Figures

Introduction

Methods

Results

Discussion

Limitations

Abbreviations

Declarations

Ethics approval, guidelines and consent to participate

Consent for publication

Availability of data and materials

Competing interests

Funding

Authors' contributions

Acknowledgements

Authors' information

References

Status:

Version 1