SJIF Impact Factor: 5.464 WORLD JOURNAL OF ADVANCE ISSN: 2457-0400 Chavan et al. PageVolume: 1 of 251 4. HEALTHCARE RESEARCH Issue: 4. Page N. 247-251 Year: 2020 Review Article www.wjahr.com THYMULIN – A HOPE OUT OF THE BOX IN COVID-19 DISASTER Dr. Chavan Vishal, MD1*, Kasumbiwal Ajay MD2 and Kasumbiwal Ripal M.Tech3 1Assistant Professor, Department of Pediatrics, S.V.N. Government Medical College, Yavatmal, Maharashtra, India. 445001. 2Associate Professor, Department of Pediatrics, S.V.N. Government Medical College, Yavatmal, Maharashtra, India. 445001. 3Bioinformatics Research Associate, Corteva Agriscience, Atria Block, Plot no. 17, Madhapur, Hyderabad, India. 500081. Received date: 21 June 2020 Revised date: 11 July 2020 Accepted date: 01 August 2020 *Corresponding author: Dr. Chavan Vishal, MD Assistant Professor, Department of Pediatrics, S.V.N. Government Medical College, Yavatmal, Maharashtra, India. 445001. ABSTRACT The COVID-19 pandemic is a challenge to medical science. Till date we do not have any definitive treatment for it nor do we have vaccines available against SARS-CoV-2. Cytokine storm syndrome, through immune dis-regulation is the most important mechanism in the death of serious patients of COVID-19. Regulating the immune system may reduce mortality in COVID-19 cases. In this review, we see Thymulin, a thymic peptide as a modality for treatment of serious COVID-19 cases through control of cytokine storm. KEYWORDS: Thymulin, COVID-19, cytokine storm. INTRODUCTION articles using term Thymulin, Thymulin functions, Thymulin as immunomodulator, COVID-19 and The COVID-19 pandemic is challenging to medical cytokine storm. Only online available English literature science and to humanity as well. The world is still trying included in the review. to understand COVID-19 disease and SARS-CoV-2 virus. Both disease and virus are regularly surprising us Thymus and Thymulin with different pathogenesis, pathophysiology and Thymus is considered a lymphoid organ with internal immunogenicity in hosts of different age groups and milieu consisting of thymocytes, thymic epithelial cells gender. As of today we do not have any definitive and thymic stromal cells. Many hormones like ACTH, treatment for the COVID-19, nor do we have any kind of TSH, Prolactin and LH exert their regulatory influence preventive vaccines against SARS-CoV-2 virus. on thymic functions.[1–3] Thymulin also called as Cytokine storm syndrome, through immune dis- Nonathymulin, Serum thymic factor.[4] It is a zinc regulation is the most important mechanism in the death dependent nonapeptide, one of the hormones produced of serious patients of COVID-19. Regulating the immune by thymus involved in intrathymic and extrathymic T system may reduce mortality in COVID-19 cases. cell differentiation.[5,6] It has a tridimensional role as an interface in neuro-immuno-endocrine messaging.[7] In research literature, Thymulin peptide has been Thymulin also plays a hypophysiotropic role through researched and studied as an immuno-modulator, during feedback loop on neuroendocrine targets postnataly and the last 3-4 decades with no definitive medical as an important physiological mediator for recommendations and use in humans till date. Here we neuroendocrine maturation during perinatal period.[2] W. are trying to open a window of hope in severe cases of Savino, in his review discussed thymus physiology and COVID-19 through reviewing Thymulin peptide its bidirectional interaction with neuroendocrine molecule to protect against severe cytokine storm of the structures, confirming importance of thymulin as disease. immunomodulator in the system of internal homeostasis.[3] Thymulin seems to be in role of natural Search strategy remedy for body. Production of thymulin has been Data articles for this review were searched online observed in extrathymic cells on exposure to oxidative through Google scholar, Pubmed, references of relevant [8] stress, apoptosis and necrosis. So it will be interesting World Journal of Advance Healthcare Research Volume 4, Issue 4. 2020 Chavan et al. Page 248 of 251 to evaluate the effect of Thymulin on stress induced by activity of FIX, FXI and FXII in intrinsic coagulation cytokine storm in COVID-19 cases. pathway and imposes a distinct tendency of hypo- coagulability.[17] In this manner, Thymulin may play a Pathogenesis And Pathophysiology Of Covid-19 crucial role in prevention of complications and Disease decreasing mortality in COVID-19 patients. The treatment guidelines of COVID-19 are frequently changing because of the new insights on pathogenesis Thymulin levels are low in immunodeficiency and and pathophysiology of disease and the causative virus. autoimmune diseases. It plays important role in the Whole world is evaluating both and finding definitive interaction between the immune system and the neuro- solution. Qin et. al. evaluated 452 adult cases of COVID- endocrine system.[18] Thymulin has a protective role in 19 retrospectively, of which 286 were of severe lung diseases. It induces selective immunomodulatory infection. He found to have variable laboratory data effect by enhancing anti-inflammatory and inhibiting depending on severity. He documented lower levels of pro-inflammatory cytokines. It suppresses p38 both helper T cells and suppressor T cells along with (implicated in glucocorticoid-resistance) and inhibits NF- regulatory T cells in severe cases. Inflammatory markers κB activation, which has an important pathogenic role in and inflammatory cytokines were high in severe cases.[9] several lung diseases.[19] Effect of Thymulin 5CH, on Based on published data, D. Giannis, et al, quotes BCG induced granuloma in male adult Balb/c mice, coagulation disorder- prothombotic state and DIC in showed improvement in the granuloma inflammatory severe COVID-19 cases. Viral infections elicit systemic process and the infection remission, by modulating local inflammatory responses in severe illnesses, leading to and systemic phagocyte differentiation.[20] Thymulin as high level of D dimer and thrombocytopenia.[10] There is an anti-inflammatory medication, inhibits the endotoxin a diffuse alveolar damage, pulmonary edema, hyaline induced nuclear activation of NF-B and the transcription membrane formation and interstitial mononuclear factor required for the expression of proinflammatory infiltrate in severe cases causing death.[11] All these cytokines gene, in the hippocampus.[21] In mice with suggest high activity of inflammatory processes which is acute septic inflammation, Thymulin increases the anti- uncontrolled and unregulated. inflammatory activity of a specific inhibitor of the NF- κB signaling pathway, IκB kinase (IKK) inhibitor XII.[22] Cytokine Storm in Covid-19 Diseases In a study done on lipopolysaccharide treated mice, Cytokine storm syndrome, also called as cytokine release Thymulin suppressed the proinflammatory response, syndrome, is a state of severity with similar clinical reduced fever, apoptosis, increased splenic cell number, phenotype triggered by diverse conditions like and decreased cytokine production.[23,24] Thymic autoimmune diseases, malignancies and viral endocrine function (thymulin production) is the infections.[12] It is characterized by sever uncontrolled important part of chronobiological organization of inflammation, multi-organ failure, coagulation defect immune system.[25] Thus Thymulin is experimentally with high levels of inflammatory markers.[12] Ruan Q et proven to be effective in controlling the situation of al analyzed data of 150 patients of COVID-19, admitted uncontrolled, unsynchronized hyperactivity of in two hospitals from Wuhan. There were high levels of inflammatory mediators in cytokine storm and bring C reactive protein, mayoglobin, cardiac troponin and order to the system. interleukin 6, in death cases as compared to discharged cases, leading to conclusion that cytokine storm Thymulin and Covid-19 syndrome may contribute to mortality in COVID-19.[13] COVID-19 is showing gender and age bias in mortality. Chaolin Huang et al. found high level of prothrombin Deaths are more in males than women.[26] Female time and D dimer among ICU COVID-19 patients hormone, Prolactin can stimulate Thymulin synthesis and compared to that of non-ICU patients. He also secretion through Prolactin-Thymulin axis.[2] This may documented higher concentrations of GCSF, IP10, be the reason that plays protective role for women in MCP1, MIP1A, and TNFα in ICU COVID-19 patients, COVID-19 patients. Children are diagnosed of SARS- suggesting role of cytokine storm in disease severity.[14] COV-2 infection mostly by contact tracing. Majority of Another pre published data of 20662 COVID-19 patients younger age group are asymptomatic.[27–29] Immaturity of shows fibrinolytic hyperactivity with high level of C- immune system may be the one factor but higher titer of reactive protein, erythrocyte sedimentation rate, Thymulin and lower levels of thymulin inhibitory interleukin-6 and serum ferritin suggesting inflammatory molecule in younger children compared to adolescent storm.[15] This way cytokine storm syndrome plays age group may be the explanation.[30] crucial part in outcome of sever COVID-19 cases. Thymus peptide, Thymosin alpha 1 has been shown to Thymulin and Cytokine Storm reduce mortality in COVID-19 patients.[31] Compared All over the world, tiny diffuse blood clots were the one with untreated group, Tα1 treatment significantly of major unresolved puzzles, in mortality of COVID-19 reduces mortality of severe COVID-19 patients