ABSTRACT
Severe acute respiratory syndrome, caused by SARS-CoV-2 disease (COVID-19), was first reported in China, and has laid the entire globe at a standstill, with an uncertain future, and a possible economic disaster. The World Health Organization (WHO), on March 11th 2020, avowed COVID-19 a pandemic considering its global pervasiveness. The multi-dimensional challenges include the combat with present available treatment options while simultaneously hastening scientific research for the development of definitive therapeutics and vaccine for this pandemic. The research advancement related to earlier epidemics of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) by the same coronavirus family provides the understanding of basic and clinical virology, pathogenesis and therapeutics of SARS-CoV-2. The dearth of definitive therapeutics and vaccine ren-ders COVID-19 pandemic a public health challenge globally. This comprehensive review of virology, pathogenesis, and management will abet quarters of public health authorities and medical fraternity to better understand COVID-19.Copyright © 2020 Bentham Science Publishers.
ABSTRACT
COVID-19 is a respiratory infection caused by a newer strain of coronavirus known as SARS-CoV-2. The major problem of COVID-19 infections is the ARDS, followed by respiratory failure, organ failure, and even death with multiple organ dysfunction, including cardiovascular collapse. Moreover, it affects the old age population with co-morbid conditions. The deficiency of diet, micronutrients, and vitamins also plays a key role in diminishing the immune power, and increases the rate of viral infectivity. The possible reasons and management methods are discussed in this review. The management methods enhance the host immune system via multi-functional and multi-targeted actions. The global rate of COVID-19 outbreak necessitates the need to develop newer medicines. The drug discovery process is based on the exposure of viral proteins, genome sequence, replication mechanisms, pathophysiological mechanisms, and host cell components (as a target) reactions. This article highlights the overview of coronavirus components, the replications process, and possible targets for the management of coronavirus infections. It may lead to the rapid development of newer medicines for the treatment of coronavirus in-fections.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Background: Coronavirus disease 2019 (COVID-19) was originated first in Wuhan, Chi-na, in December 2019, and it is known to be caused by severe acute respiratory syndrome coron-avirus-2 (SARS CoV-2). The management of COVID-19 could be achieved by means of the usage of the repurposed drugs, inhibiting the viral entry and/or viral fusion such as umifenovir, Barici-tinib, Camostat mesylate, Nafamostat mesylate, and the drugs blocking the viral replication, which include favipiravir, remdesivir, Lopinavir/ritonavir, Ribavirin, Sofosbuvir, chloroquine and Hydrox-ychloroquine. Objective(s): Along with the drugs that target the SARS-CoV-2 virus, adjunctive therapies are also employed. This review focuses on the adjuvant therapies employed to manage the COVID-19-asso-ciated complications, such as cytokine storm, acute respiratory distress syndrome (ARDS), respiratory failure, cardiac injury, coagulopathy, and multi-organ failure. Method(s): The literature was searched in databases such as Medline/PubMed Central/PubMed, Goo-gle Scholar, Science Direct, EBSCO, Scopus, EMBASE, Directory of open access journals (DOA-J), and reference lists to identify relevant articles. Result(s): Various studies have been identified for the use of corticosteroids, interferons, monoclon-al antibodies, etoposide, ruxolitinib, anticoagulants, convalescent plasma, immunoglobulins, mes-enchymal stem cells, natural killer (NK) cells, and inhaled nitric oxide (NO) as adjuvant therapy to manage the patients with COVID-19 along with the repurposed drugs targeting SARS-CoV-2. Conclusion(s): The safety and efficacy of adjuvant therapy are needed to be confirmed by various ongoing randomized controlled clinical trials.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
The COVID-19 pandemic reached five waves in three years, with over 6.5 million deaths across the globe. Knowing the differential susceptibility to the novel betacoronavirus has allowed us to better understand the pathophysiology and inflammatory complications and dissect the response against the virus. As in other viral infections, CD8+ T lymphocytes and NK cells stand out as key players, together with viral sensors, type 1 interferons, an exaggerated inflammatory response by NLRP3, and a storm that includes cytokines IL-6 and IL-8. Whole-exome sequencing has identified several genes with pathogenic germline variants in patients with severe COVID-19;said genes would account for around 5% of all severe cases. In addition, up to 20% of hospitalized adults harbor autoantibodies against type-I and III interferons. These findings translate into novel genetic etiologies, whereas autoantibodies explain the worse prognosis of the elderly, linked to the inflammaging phenomenon. In general, patients with known primary immune deficiencies who acquired COVID-19 fared well, with global survival rates over 80% and a predominance of mild courses. The exceptions were patients with severe-combined immune deficiency, and with the autoimmune polyglandular syndrome 1, the latter because they develop autoantibodies against interferon. Neither have there been reports of greater severity in patients with autoimmune or autoinflammatory disorders. However, those receiving immunosuppressant treatments usually have a more protracted course. Patients with NLRP3 or STAT1 gain of function might be especially susceptible to systemic inflammatory complications. In this review, we summarize the global experience in the caretaking of patients with immune alterations who were infected by SARS-CoV-2. © 2022 Instituto Nacional de Pediatria. All rights reserved.
ABSTRACT
Severity of a new coronavirus infection (COVID-19) caused by the SARS-COV-2 virus is largely due to abnormal immune condi-tion in these patients. Lymphopenia is observed in 85% of patients with severe COVID-19 that may be associated with enhanced apoptosis of lymphocytes. Objective. To analyze apoptotic death of lymphocytes and changes in proteins regulating apoptosis in patients with severe COVID-19. Material and methods. We analyzed 93 ICU patients. All patients were divided into three groups depending on severity and outcomes of disease: group 1 consisted of 53 patients with favorable course and outcomes of disease, group 2 included 26 patients with unfavorable course and favorable outcomes of disease, group 3 included 14 patients with unfavorable course and outcomes of disease. Blood sampling for analysis of apoptosis markers was carried out in 5-12 and 14-18 days after clinical manifestation of disease. Quantitative parameters of lymphocyte apoptosis were evaluated using flow cytometry. Regulatory proteins of apop-tosis (phosphorylated AKT, JNK, BAD, BCL-2, p-53, active caspase 8 and 9) were determined on the Luminex platform. We also assessed concentration of leukocytes, relative and absolute lymphocyte count, concentration of C-reactive protein (CRP), procal-citonin and lactate dehydrogenase. Results. Study groups significantly differed in NEWS score (p=0.001), SOFA score (p=0.001), CRP level (p=0.001), severity of lymph-openia (p=0.001) and level of CD14+HLA-DR+ monocytes (p=0.001). Quantitative parameters of lymphocyte apoptosis did not cor-relate with lymphopenia. The highest rates of lymphocyte apoptosis were observed in patients with favorable course and outcomes of disease. There was no correlation between concentration of lymphocytes in venous blood and level of proteins regulating apoptosis. Conclusion. Patients with severe COVID-19 are characterized by abnormal induction of lymphocyte apoptosis through external and internal activation pathways in response to viral aggression. In deceased patients, pro-apoptotic factors prevailed while activity of anti-apoptotic factors was decreased. © 2023, Media Sphera Publishing Group. All rights reserved.
ABSTRACT
The pandemic outbreak of coronavirus disease (COVID-19) has emerged as the most threat-ening public health challenge. The clinical presentation ranges from asymptomatic and mild clinical symptoms to acute respiratory-distress syndrome (ARDS) and death. Apart from the respiratory system, other organ systems like cardiovascular, renal, and gastrointestinal systems are also involved. Cytokine storm is a condition of systemic inflammatory cytokine rampage through the bloodstream leading to life-threatening complications. There is an urgent need for the prevention of infection and effective man-agement. Yoga is a profound science with both immunity-boosting and immune-modulating capacity. We propose that yoga-based intervention may aid in improving health with its immunity-boosting potential and preventing the exuberant inflammatory cytokine storm, thus reducing the severity of the disease. It can also reduce stress, anxiety, and co-morbid depression by promoting neuroplasticity and prevents persistent activation of the hypothalamus pituitary adrenal axis and thus may reduce disease severity. It may also enhance the immunity of caretakers and make them more emotionally resilient. Thus, yoga can be useful for enhancing immunity, stress reduction and may prevent the exaggerated immune response to the cytokine storm.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
INTRODUCTION: One of the promising treatments for COVID-19 aimed at correcting the immune response and re-ducing the level of pro-inflammatory cytokines is the use of mesenchymal stem cells (MSCs). There is evidence that MSCs, due to various mechanisms, are able to suppress the cytokine storm in patients with COVID-19. Thus, the use of MSCs can contribute to the suppression of inflammation and the regulation of immune homeostasis in patients with severe COVID-19. OBJECTIVE: Evaluation of the ef-fect of mesenchymal stem cell (MSC) therapy on the course of severe forms of novel coronavirus infection, accompanied by "cytokine storm”. MATERIALS AND METHODS: A prospective single-center study included 39 patients treated for coronavirus infection on the basis of the intensive care unit and, after randomization, randomly divided into control (n = 16) and study groups (n = 23). An assessment of clinical, laboratory parameters in both groups and a cytokine profile in the study group was carried out. Outcomes were compared, the incidence of complications and clinical and laboratory parameters in both groups, and the cytokine profile in the study group. RESULTS: The use of MSCs in patients with severe forms of COVID-19 affected the outcomes of the disease, the duration of stay on mechanical ventilation, the course of acute respiratory distress syndrome (ARDS) (an increase in the oxygenation index in patients of the study group by 5, 7 days from administration in comparison with the control group). CONCLUSIONS: In patients treated with MSCs, there was a significant decrease in a number of pro-inflam-matory cytokines. © 2023, Practical Medicine Publishing House LLC. All rights reserved.
ABSTRACT
INTRODUCTION: One of the promising treatments for COVID-19 aimed at correcting the immune response and re-ducing the level of pro-inflammatory cytokines is the use of mesenchymal stem cells (MSCs). There is evidence that MSCs, due to various mechanisms, are able to suppress the cytokine storm in patients with COVID-19. Thus, the use of MSCs can contribute to the suppression of inflammation and the regulation of immune homeostasis in patients with severe COVID-19. OBJECTIVE: Evaluation of the ef-fect of mesenchymal stem cell (MSC) therapy on the course of severe forms of novel coronavirus infection, accompanied by "cytokine storm”. MATERIALS AND METHODS: A prospective single-center study included 39 patients treated for coronavirus infection on the basis of the intensive care unit and, after randomization, randomly divided into control (n = 16) and study groups (n = 23). An assessment of clinical, laboratory parameters in both groups and a cytokine profile in the study group was carried out. Outcomes were compared, the incidence of complications and clinical and laboratory parameters in both groups, and the cytokine profile in the study group. RESULTS: The use of MSCs in patients with severe forms of COVID-19 affected the outcomes of the disease, the duration of stay on mechanical ventilation, the course of acute respiratory distress syndrome (ARDS) (an increase in the oxygenation index in patients of the study group by 5, 7 days from administration in comparison with the control group). CONCLUSIONS: In patients treated with MSCs, there was a significant decrease in a number of pro-inflam-matory cytokines. © 2023, Practical Medicine Publishing House LLC. All rights reserved.
ABSTRACT
The new COVID-19 presents some comorbidities, such as obesity, Alzheimer's, and coronary risk, among others. We argue that the current understanding of some of these clinical conditions may illuminate the design of future COVID-19 studies to account for a bias that may be the cause of the para-doxical associations between COVID-19 mortality and cytokine storm. Given that we know some of the genetic mechanisms behind these diseases, it is possible to circumscribe these studies to some key genes that help us understand why some patients experience a cytokine storm and what the treatment strategies might be. In this paper, we discuss the role of A2M and APOE genes. A2M encodes a multifaceted protein which is highly expressed in the liver and released to the bloodstream associated with the apolipopro-tein E. This association depends on the APOE genotype. A2M has protease-clearing activity binding of a broad range of proteases, such as thrombin and Factor Xa. It also presents the ability to bind to proin-flammatory ligands, like cytokines. Further, A2M acts as chaperone of misfolded substrates, like beta-amyloid peptide. The last two molecular functions grant it a key role in regulating both inflammatory processes, as well as extracellular protein homeostasis. For these reasons, we conclude that A2M-APOE association will have prophylactic, therapeutic, and prognostic implications;and the proper understanding of the physiological role of APOE and A2M in controlling inflammatory processes can shed further light on the putative treatment of COVID-19-derived cytokine storm.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
Introduction: Interleukin-18 is produced in the early stages of viral infections and is crucial for host defense. Interferon Gamma Induced Protein 10kDa is a molecule associated with thrombosis in many studies. In this study, we aimed to investigate the levels of these two molecules, which are thought to be biomarkers in the evaluation of the severity of COVID-19 disease, in clinically different patient groups and to see their relationship with other inflammatory markers. Material(s) and Method(s): This study was conducted at Ondokuz Mayis University Faculty of Medicine Hospital between 01.04.2021 and 01.09.2021 with 60 patients with positive Severe Acute Respiratory Syndrome Coronavirus 2 polymerase chain reaction test and 30 healthy volunteers. Patients were divided into groups according to the definitions in the "Coronavirus disease 2019 diagnosis and treatment guideline" according to their clinical appearance. Interleukin-18 and Interferon Gamma Induced Protein 10kDa levels in blood samples taken from patients were studied by Enzyme-Linked ImmunoSorbent Assay method. Result(s): Interleukin-18 and Interferon Gamma Induced Protein 10kDa levels were found to be significantly higher in patients with mild to moderate pneumonia than in patients with severe pneumonia. The Interferon Gamma Induced Protein 10kDa level did not differ significantly between the mild-moderate patient group and the control group. No correlation was found between Interleukin-18 and Interferon Gamma Induced Protein 10kDa levels and C-reactive protein, D-dimer, ferritin, procalcitonin, neutrophil/lymphocyte levels. Interleukin-18 and Interferon Gamma Induced Protein 10kDa levels were not found to be associated with mortality. Conclusion(s): Interleukin-18 and Interferon Gamma Induced Protein 10kDa levels are not of vital importance in demonstrating disease severity alone. Serial measurements at specific times may better clarify its role in disease outcome. Larger studies are needed to confirm these findings.Copyright © 2023 by the authors.
ABSTRACT
An emergent coronavirus, now named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic on the 22nd March 2020. It has since caused unprece-dented pressures on the healthcare systems worldwide, leading to over five million cases and over three hundred thousand deaths. This has resulted in a global struggle to fight this disease, without any known cure or any definite treatment and with no vaccine. This challenge is exemplified by many with COVID-19 (Coronavirus Disease 2019) rapidly deteriorating to critical illness, developing respiratory failure, multi-organ dysfunction or failure, and septic shock. This rapid deteriora-tion is thought to be due to the activation of the cytokine storm. The cytokine storm is characterised by mass cytokine and chemokine release, leading to wide-spread multi-organ damage. One of these such cytokines that plays a role in the cytokine storm is Interleukin (IL-) 6. Raised levels of IL-6 in many diseases have been observed to both correlate with disease severity and predict poor outcomes. Early studies began to show high levels of IL-6 in those with severe and critical COVID-19, and there is ongoing research into immune modulators to block IL-6, in the hope of halting disease progression and improving the chance of recovery. This article will explore the role that IL-6 plays in COVID-19 and whether an IL-6 blockade can prevent poor outcomes and reduce mortality.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has taken over the world, and more than 38 lakh deaths had been reported till now due to this infectious disease. It has been declared a global pandemic by the world health organization. SARS-CoV-2 causes coronavirus disease of 2019 (COVID-19), and the major problem called "Cytokine storm" is reported, which may lead to death among the COVID-19 patients. This study aimed to review the Cytokine storm and its mechanism along with few immunomodulatory therapies for SARSCoV-2 infection suppression effectively. Method(s): The recently published works of literature were selected and reviewed based on the subject of this study. The databases, including Pubmed, ScienceDirect, Scopus, and Google Scholar, were searched extensively. Result(s): The review of the literature showed that an uncontrolled immune response causes excess inflammation. Evidence from recent trials has demonstrated that cytokine storms can be an important factor in the COVID-19 severity, leading to multiple organ failure and death. Conclusion(s): This study reviewed immunomodulatory therapies and strategies for SARS-CoV-2 infected patients to suppress the immune response. Ultimately, the cytokine storm can prove to be a boon and reduce the significant death tolls to SARS-CoV-2 infection.Copyright © 2022 Bentham Science Publishers.
ABSTRACT
The hyperferritinemic syndromes include macrophage activation syndrome, adult onset Still's disease, catastrophic antiphospholipid syndrome, and septic shock. The syndrome is characterized by life-threatening disease due to the development of a cytokine storm, multiorgan damage, elevated ferritin levels, and the response to similar therapies. In the third phase of SARS-COV2 infection, the hyperinflammatory phase, elevated ferritin levels and the development of a cytokine storm are present. A new entity, multisystem inflammatory syndrome, described predominantly in pediatric patients, mimics MAS, yet develops without a previous symptomatic disease. In these patients, hyperferritinemia is prominent. Elevated ferritin levels in COVID-19 intensive care unit patients predict mortality. Ferritin levels in nonsurvivors are much higher than those who survive. Consecutive measurements of a rising ferritin level may predict the need for assisted ventilation. Treatments such as corticosteroids, biologics, and IVIG may also be beneficial for COVID-19 as they are for the other hyperferritinemic syndromes. In this review, we present proof of concept for COVID-19 to be included with the other entities in the hyperferritinemic syndrome. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
In COVID-19, pneumonia develops simultaneously with cytokine storm syndrome (CSS). A number of cytokines and inflammation parameters were measured in 226 patients with COVID-19 pneumonia (median lung involvement of 60%) and 36 COVID-19 related deaths, during first wave of epidemic. The comparison group consisted of 49 MAS and 52 SS fatal cases, collected, retrospectively. Profile of cytokines and laboratory biomarkers in lethal COVID-19 cases resembled both pathologies, but in COVID-19 it was distinguished by high NLR/IL-6 and low IFN-γ/TNF-α. The new CSS score integrated serum levels of IL-6, IL-10, IL-18, and PCT, giving a range of 0-4 points for each biomarker, and sum from 0 to 12 points. Over five points indicated higher risk of unfavorable outcome. CSS score was validated on separate cohort of 121 patients. Surprisingly CSS parameters were higher in patients of risk groups (older and comorbid). Integrated CSS score can predict severe cases of COVID-19 disease. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
The replication cycle of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) shares many features with other human Coronaviruses such as SARS-CoV and Middle East respiratory syndrome Coronavirus (MERS-CoV). Recent studies have elucidated the viral strategies of antagonizing the host immune response, including a multitude of mechanisms by which SARS-CoV-2 can dampen the interferon-mediated innate immunity. Furthermore, an imbalance and delay in interferon production, and exaggerated secretion of pro-inflammatory cytokines contribute to the severe immunopathology of Coronavirus disease 2019 (COVID-19). This chapter summarizes our current understanding of the intimate relationship between SARS-CoV-2 and the host innate and adaptive immune responses. The strategies that the virus utilizes to exploit cellular resources and to evade the innate immune system are described. The chapter provides a detailed discussion of interferonmediated innate immunity, interferon evasion and antagonism by SARSCoV- 2 and human Coronaviruses. © 2023 by World Scientific Publishing Co. Pte. Ltd.
ABSTRACT
The 2019 novel coronavirus disease (COVID-19) is a newly defined infectious and highly contagious acute disease caused by the severe acute respiratory syndrome coronavirus 2 ( (SARS-CoV-2). COVID-19 is mainly characterized by an acute respiratory disease however it can also affect multiple other organ systems such as the kidney, gastrointestinal tract, heart, vascular system, and the central nervous system. Kidney involvement is frequent in patients with COVID-19 and this review aims to explore the available data on kidney and COVID-19. In conclusion, COVID-19 infection can affect renal function and may cause acute kidney injury (AKI), due to several mechanisms that need to be fully elucidated. As only supportive management strategies are available for treating AKI in COVID-19, it is necessary to identify and preserve renal function during SARS-CoV-2 infection.Copyright © 2021 The Author(s).
ABSTRACT
The term "cytokine storm” was first proposed in 1993 by Ferrara et al. In 1991, Chatenaud described a systemic clinical picture called "Cytokine Release Syndrome” very similar to "Cytokine Storm Syndrome” so these terms can be used synonymously. During the COVID-19 pandemic, high-risk individuals (>65 years, with comorbidities) may develop cytokine storms as a consequence of multiorgan involvement seen during the acute and post-COVID-19 phases. On the other hand, the term immune neuroendocrine system was first proposed by Besedovsky H et al. Evidences obtained during COVID-19 infection demonstrated that SARS-CoV-2 infections can affect the immune neuroendocrine system, both in its invasion stage of different organs and tissues and in the recovery stage. This damage is caused by viral infection and/or cytokine storm. This chapter analyzes the devastating effect of SARS-CoV-2 infection and the cytokine storm on the immune neuroendocrine system. These evidences may lead to new therapeutic proposals. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
Novel coronavirus (nCoV-19) infection has been declared a pandemic by WHO. More than 223 countries are under the attack of this emergency situation. Primarily, pneumocytes encountered by the nCoV-19 via ACE-2 receptor cause pulmonary edema, damage to alveolar cells, production of inflammatory cells, and hypoxia. It has been found that patients with co-existing cardiovascular diseases are more prone to the infection, and severe cardiovascular dysfunction was further observed when infected with nCoV-19. There is no substantial mechanism available for the pathogenesis of this cardiovascular dysfunction;therefore, we herein present a possible mechanistic approach of cardiotoxicity by nCov-19 infection. The hypothesis of this study is based on immunopathology of nCoV-19 in pneumocytes, presence of ACE-2 on cardiomyocytes membrane, cytokine storm, genomic analysis of virus in cardiac tissue, and several reports published on the cardiovascular complications in nCoV-19 across the globe. We have also analyzed the cardiotoxic profile of recently used repurposed and investigational drugs and highlighted their possible cardiotoxic consequences and drug interactions with cardiovascular medicines, such as statins and anti-coagulants.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
Treatment of COVID-19 can be categorized into prophylactic treatment, early-stage treatment, and late-stage treatment. Prophylactic treatment, as either pre or postexposure passive immunization with monoclonal antibodies, is currently limited to high-risk groups, with preexisting risk factors for severe disease and death in case of contracting COVID-19. Additional prophylactic treatment for hospitalized patients includes anticoagulation. In early treatment, when the infectious state is dominant, antiviral agents are used as well as passive immunization with monoclonal antibodies. Late-stage treatment in progressive and-inflammatory disease characterized by a cytokine storm and lung involvement in most severe/critical patients, includes corticosteroids, interluekin-6 inhibitors, and JAK inhibitors. Oxygen support is mandatory in severe patients and in patients with moderate to severe adult respiratory distress syndrome and refractory hypoxemia. Rescue procedures include protonation, alveolar recruitment maneuvers, neuromuscular blockade, pulmonary vasodilators, and extracorporeal membrane oxygenation. Additional potential treatments that have not been yet authorized are beyond the scope of this discussion. © 2023 Elsevier Inc. All rights reserved.
ABSTRACT
Forests contain nearly all of the natural resources required by humans. Apart from food, the community makes use of forest products for medicinal purposes. Betel (Piper betle L.) is one of the numerous forest plants that thrive in the forests of North Sulawesi. The leaves and fruits are used by indigenous people as anti-inflammatory medications, deodorizing body odors, and for maintaining health. Natural medicine has recently been included in clinical trials as immunomodulators in COVID-19 patients. This study aimed to identify novel immunomodulatory compounds derived from betel leaf for the treatment of COVID-19 symptoms, particularly proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and nuclear factor kappa B). These cytokines are critical in modulating immune responses. Bioactive compounds from betel leaves were extracted and identified using gas chromatography-mass spectrometry. These compounds were used as ligands for PyRx-based molecular docking. The admetSAR and SwissADME were used to predict ADMET (absorption, distribution, metabolism, excretion, and toxicity) and Lipinski’s rule of five parameters of the studied compounds. This study discovered that 17 compounds exhibited higher binding energy than the control immunomodulatory agents (β-glucan and thiopurine). Only one of the compounds violated Lipinski’s rule of five. ADMET predictions indicated that the compounds possess favorable and safe pharmacokinetic properties, making them suitable for development as drug candidates. The research findings suggest that bioactive compounds derived from betel leaf may prove beneficial in the treatment of COVID-19, particularly in the context of cytokine storms. © 2022. Fatimawali et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).