Herbal Immunomodulators and COVID-19

Novel Coronavirus (COVID-19) globally affects the people's health and social life, and it became a challenging task for pharma and research communities. Several medical research or scientific institutions are trying to develop potent antiviral vaccine/drugs against the coronavirus. There are urgent needs to explore all the possibilities against the pandemic disease, and, among that, it is well cited in many literature that Ayurveda has an important role since ancient time against many viral diseases. The Ayurvedic medicinal system is mainly based on herbal formulations, which boost the immune system or work synergistically to protect our body against invading harmfull micro-organisms. The herbal medicinal system has identified several herbs used in various home remedies. It is thought to effectively fight corona and improve health immunity;the current chapter describes the therapeutics of plants Phyllanthus emblica, Azadirachta indica, and Swertia chirata in the current scenario against COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Antiviral Chemotherapy and Immunomodulatory Drugs

• Most antiviral drugs available for treatment of feline and canine viral infections are nucleoside analogues with greatest activity against retroviruses, herpesviruses and coronaviruses. • Antiviral drugs also affect the function of host cell machinery;therefore, they have considerable potential for toxicity. • Antiviral drugs are widely used in human medicine for treatment of HIV infection, herpesvirus infection, and other viral. Much less is known about these medications in cats and dogs, and there are only few diseases of cats and dogs for which efficacy has been demonstrated. • There are important differences between human and animal virus infections;therefore, it should not be assumed that the use of an antiviral agent in humans can be translated to a use in animals unless there is evidence of safety and efficacy. • The most common indication for antiviral drugs in animals is treatment of FHV-1 infections with famciclovir and cidofovir. Zidovudine, an antiretroviral drug, has been used to treat FIV and FeLV infections. In addition, new antiviral drugs are now used to treat FIP. • Antiviral drugs can act synergistically with immunomodulatory agents. • Immunomodulators include microbial products, plant-derived immunomodulators, naturally occurring mammalian proteins, and synthetic drugs. The effect of many of these drugs on outcome in cats and dogs with infectious diseases has not been fully evaluated with well-designed studies. • The parenteral use of natural or recombinant human cytokines in cats and dogs can produce neutralizing antibodies after 1 to 2 weeks of treatment, which can cross-react with endogenous proteins. • Antiviral treatments are intended to suppress viral entry, multiplication, or transmission. Some of these antiviral agents can produce a remission or assist the patient's immune system to limit the course of the viral disease. © 2021 Elsevier Inc. All rights reserved.

Pharmacological Properties and Safe Use of 12 Medicinal Plant Species and Their Bioactive Compounds Affecting the Immune System

This paper presents raw plant materials and their characteristic compounds which may affect the immune system. Plant-derived agents in specific doses affect the body's non-specific, antigen-independent defense system. They have immunostimulatory effects on the entire immune regulatory system. They can enhance the immune response through various factors such as macrophages, leukocytes, and granulocytes, as well as through mediators released by the cellular immune system. This paper was inspired by the threats caused by the COVID-19 pandemic. The proper functioning of the immune system is important in limiting the effects of viral infection and restoring the normal functioning of the body. This paper also emphasizes the importance of the skillful use of plant immunostimulants by potential patients, but also by those who prescribe drugs. It is important not only to choose the right plant drug but above all to choose the correct dose and duration of treatment.

Covid-19: New Use of Therapeutics

Severe acute respiratory syndrome novel virus (SARS-CoV-2), after its origin from probably bats in Wuhan, China, has spread all over the world within around 2–3 months of origin, called as Covid-19 pandemic. The virus has infected nearly 10 million people globally with over 500, 000 deaths. Industry and academia globally are involved in developing repurposed drugs and vaccines as also developing new drugs, monoclonal antibodies and vaccines. Over 1200 molecules (including monoclonal antibodies and stem cells) and 180 plus vaccines are in clinical trials or under development. Hydroxychloroquine, remdesivir, favipiravir and a number of antivirals are in clinical use to save lives. Dexamethasone, a life-saving drug, has also been used in critical patients on support system. A monoclonal antibody and about five vaccines have reached Phase II–III clinical trials;one vaccine in India has entered Phase I clinical trial. BCG, mycobacterium W and polio vaccine are also under trial to treat Covid-19. © The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.

Hemofiltration as an alternative for IL-6 inhibitors in COVID-19 cytokines storm associated with underlaying bacterial infections: A review Article.

SARS-CoV-2 causes mostly mild cases. However, a considerable number of patients develop fatal acute respiratory distress syndrome due to the cytokine storm and imbalanced immune response. Several therapies depending on immunomodulation have been used, including glucocorticoids and IL-6 blockers. However, their efficacy is not perfect with all patients and patients with concomitant bacterial infections and sepsis. Accordingly, studies on different immunomodulators, including extracorporeal techniques, are crucial to save this category of patients. In this review, we overviewed the different immunomodulation techniques shortly, with a brief review of extracorporeal methods.

SARS-CoV-2 Pandemic-Therapeutics in Warp Speed.

Ever since the coronavirus disease 2019 (COVID-19) pandemic struck, the challenges posed to the scientific community by its causative agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been countless, and still continue to emerge. Even though a host of repurposed and new therapeutic agents as well as vaccines have been, and are being assessed at a breakneck speed, this contagion continues to create havoc, returning back in waves, with appearance of newer viral variants which are associated with numerous challenges, which include greater transmissibility, increased virulence, immune escape, etc. In this study, we discuss the current status of various therapeutic agents which are being used, or in the various stages of preclinical/clinical trials for managing COVID-19.

Anakinra as a potential treatment for COVID-19.

On November 8, 2022, the United States Food and Drug Administration (FDA) issued an emergency use authorization for the interleukin-1 (IL-1) inhibitor anakinra for the treatment of patients with COVID-19 pneumonia. The authorization was specifically intended for patients requiring supplemental oxygen who are at risk of progression to respiratory failure and are likely to have an elevated plasma soluble urokinase plasminogen activator receptor. Anakinra is a modified, recombinant human IL-1 receptor antagonist used to treat rheumatoid arthritis, neonatal-onset multisystem inflammatory disease and other inflammatory diseases. This manuscript examines what is known about the role of IL-1 receptor antagonism in the treatment of patients with COVID-19 and examines how anakinra may be used in the future to address the SARS-CoV-2 infection pandemic.

Mortality analysis of COVID-19 cases during the second wave and its comparison with the first wave: A hospital-based study.

Objectives: This study was undertaken to determine the characteristics of COVID-19 deaths during the second wave and to compare these characteristics with the mortality during the first wave in a dedicated COVID hospital (DCH). Study Design: It was a hospital record-based descriptive study. Methodology: The study was conducted in a tertiary care COVID hospital, using a standard death audit proforma. The data were analyzed to know various demographic characteristics and factors related to mortality during the second wave from March to June 2021. The findings were compared with the mortality data during the first wave from April to July 2020 at the same hospital. Results: A total of 264 deaths occurred at the center during the study period with a mortality rate of 22.8%. Male cases were more in number, the age group was 21-70 years, the highest number of mortality was seen in the mid of the study period, duration of stay was five days on average and common causes of death were pneumonia alone or with acute respiratory distress syndrome with sepsis. In comparison to the first wave, the mortality rate was four times higher, the age group was younger and opportunistic infections viz. mucormycosis and aspergillosis were present during the second wave. Conclusion: The mortality rate was significantly higher and the younger age groups were involved during the second wave, with opportunistic fungal infections due to the use of immunomodulators.

Fourteen immunomodulatory alkaloids and two prenylated phenylpropanoids with dual therapeutic approach for COVID-19: molecular docking and dynamics studies.

The pandemic outbreak of COVID-19 caused by the new severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a global health burden. To date, there is no highly effective antiviral therapy to eradicate the virus; as a result, researchers are racing to introduce new potential therapeutic agents. Alternatively, traditional immunity boosters and symptomatic treatment based on natural bioactive compounds are also an option. The 3-chymotrypsin-like protease (3CLpro) crystal structure, the main proteolytic enzyme of SARS-CoV-2, has been unraveled, allowing the development of effective protease inhibitors via in silico and biological studies. In COVID-19 infected patients, the loss of lung function, and mortality are reported to be linked to several inflammatory mediators and cytokines. In this context, the approach of introducing immunomodulatory agents may be considered a dual lifesaving strategy in combination with antiviral drugs. This study aims to provide immunomodulatory natural products exhibiting potential protease inhibitory activities. Selected groups of alkaloids of different classes and two prenylated phenylpropanoids from the Brazilian green propolis were in silico screened for their ability to inhibit COVID-19 3CLpro protease. Results showed that compounds exhibited binding energy scores with values ranging from -6.96 to -3.70 compared to the reference synthetic protease inhibitor O6K with a binding energy score of -7.57. O6K binding energy was found comparable with lead phytochemicals in our study, while their toxicity and drug-likeness criteria are better than that of O6K. The activities of these molecules are mainly ascribed to their ability to form hydrogen bonding with 3CLpro crucial amino acid residues of the catalytic site. In addition, the molecular dynamics simulations further showed that some of these compounds formed stable complexes as evidenced by the occupancy fraction measurements. The study suggested that the major immunomodulators 3ß, 20α-diacetamido-5α-pregnane, (20S)-(benzamido)-3ß-(N,N-dimethyamino)-pregnane, and baccharin are 3CLpro inhibitors. Biological screenings of these phytochemicals will be valuable to experimentally validate and consolidate the results of this study before a rigid conclusion is reached, which may pave the way for the development of efficient modulatory bioactive compounds with dual bioactions in COVID-19 intervention.Communicated by Ramaswamy H. Sarma.

Procalcitonin Values Fail to Track the Presence of Secondary Bacterial Infections in COVID-19 ICU Patients.

The development of secondary bacterial infections in COVID-19 patients has been associated with increased mortality and worse clinical outcomes. Consequently, many patients have received empirical antibiotic therapies with the potential to further exacerbate an ongoing antimicrobial resistance crisis. The pandemic has seen a rise in the use of procalcitonin testing to guide antimicrobial prescribing, although its value remains elusive. This single-centre retrospective study sought to analyse the efficacy of procalcitonin in identifying secondary infections in COVID-19 patients and evaluate the proportion of patients prescribed antibiotics to those with confirmed secondary infection. Inclusion criteria comprised patients admitted to the Grange University Hospital intensive care unit with SARS-CoV-2 infection throughout the second and third waves of the pandemic. Data collected included daily inflammatory biomarkers, antimicrobial prescriptions, and microbiologically proven secondary infections. There was no statistically significant difference between PCT, WBC, or CRP values in those with an infection versus those without. A total of 57.02% of patients had a confirmed secondary infection, with 80.2% prescribed antibiotics in Wave 2, compared to 44.07% with confirmed infection and 52.1% prescribed antibiotics in Wave 3. In conclusion, procalcitonin values failed to indicate the emergence of critical care-acquired infection in COVID-19 patients.

Case report: High-risk acute promyelocytic leukemia and COVID-19-related myocarditis one patient, two cytokine storms.

Acute promyelocytic leukemia (APL) is a unique, highly curable subtype of acute myeloid leukemia, owing to the therapeutic advances of the last decades which led to high complete remission rates and excellent long-term survival. Nevertheless, it remains associated with high early mortality rates. Early death is the major cause of treatment failure in APL and is mainly attributed to coagulopathy, differentiation syndrome, and less commonly, infectious events. Timely recognition of each complication plays a crucial role in the management of patients diagnosed with APL. Coronavirus Infectious Disease 2019 (COVID-19) has shown great heterogeneity in patient presentation. Clinical manifestations range from asymptomatic disease to severe forms, mainly characterized by a hyperinflammatory syndrome leading to acute respiratory distress and multiorgan failure. Patients with acute leukemia and concomitant COVID-19-related hyperinflammatory syndrome have particularly poor outcomes. We hereby report the case of a 28-year-old male patient who was diagnosed with high-risk APL, with severe associated coagulopathy at presentation. He was treated with chemotherapy according to the AIDA regimen. The first week of induction therapy was complicated by a differentiation syndrome manifesting as fever not attributable to infection and respiratory distress with pulmonary infiltrates, resolved after ATRA discontinuation and corticotherapy. On the fourth week of treatment, he tested positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with minor pulmonary involvement. Clinical manifestations over the following days included tachycardia and hypotension, associated with elevated inflammatory markers and cardiac biomarkers (troponin I x58 upper NV). Cardiovascular magnetic resonance imaging was consistent with myocarditis. COVID-19-associated myocarditis was successfully treated with methylprednisolone, intravenous immunoglobulins and Anakinra. Differentiation syndrome and COVID-19-associated myocarditis are two life-threatening complications that adversely impact survival. However, early recognition and prompt treatment initiation can improve clinical outcomes, as was the case of our patient.

Natural Ingredients to Improve Immunity.

The immune system protects the body from infectious agents such as bacteria, viruses, or fungi. Once encountered with pathogens or antigens, the innate and adaptive arms of the immune system trigger a strong immune response to eliminate them from the system and protect the body. Thus, well-balanced immunity is pivotal for maintaining human health, as an insufficient level of immune defense leads to infections and tumors. In contrast, the excessive functioning of the immune system causes the development of autoimmune diseases and allergies. Strong immunity requires adequate nutrition, dietary interventions, and sufficient intake of certain vitamins (vitamin C, vitamin D, and folic acid) and minerals (magnesium, zinc, and selenium). Therefore, nutritional and micronutrient deficiencies lead to compromised immunity. Several natural ingredients have shown potent immunomodulatory properties. The immune-enhancing properties of many plants and fungi are due to containing bioactive phytoconstituents such as polyphenols, terpenoids, ß-glucans, vitamins, etc. Probiotics and prebiotics can be used as innovative tools to reduce intestinal inflammation and downregulate hypersensitivity reactions. Plant sources of melatonin, a multifunctional molecule with proven anti-inflammatory and immunomodulatory properties, have been discovered relatively recently. The bioactive compounds augment the immune response by directly increasing the cytotoxic activity of natural killer cells, macrophages, and neutrophils. Many phytoconstituents prevent cell damage due to their powerful antimicrobial, antioxidant, and anti-inflammatory properties. The present review attempts to understand the molecular mechanisms underlying the immune-enhancing properties of some bioactive compounds from plants, fungi, animals, microorganisms, and other natural sources.

Clinical Features and Management of COVID-19

Much has been learnt about severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) since the beginning of theCoronavirus disease 2019 (COVID-19) pandemic, including its clinical manifestations, diagnosis, and management. Unlike its zoonotic predecessor SARS-CoV which was largely a symptomatic disease where fever was a hallmark, a significant proportion of SARS-CoV-2 infections can be asymptomatic (40%), while severe disease (requiring oxygen supplementation or ventilatory support) occurs in approximately 20%, and mortality in about 2% of infected patients. Extra-pulmonary COVID-19 manifestations are also more protean, compared to SARS. Supportive care is the mainstay of treatment for most patients, but for those who progress to severe COVID-19, antivirals such as remdesivir and immunomodulatory treatment (such as corticosteroids or theJAK-inhibitor, baricitinib) may improve outcomes. While further advances in the management of COVID-19 are anticipated (including novel therapies), prevention of infection through public health measures (including vaccination), will remain as vital facets in confronting this pandemic. © 2023 by World Scientific Publishing Co. Pte. Ltd.

Evaluation of Inosine-Acedoben-Dimepranol as an immunomodulator in broiler chicks vaccinated with Infectious bronchitis virus vaccine

Protecting livestock against diseases by enhancing its immunity is essential and required in poultry industry. Therefore, the aim of the present study was to evaluate the possible immunoenhancing effects of Inosine-Acedoben-Dimepranol (IAD) in broiler chicks. A total of 150 chicks were used in the present study, divided into 6 groups (25 for each) and subjected to different treatments. It has been found that IAD significantly (P 0.05) increased total leukocytic count, with increased granulocyte (neutrophils, eosinophils, basophils), lymphocyte and monocyte counts compared to control chicks. IAD significantly (P 0.05) increased total protein as a result of increased globulins in plasma when compared with those of control. IAD has been found to significantly (P 0.05) increase immune response of IB vaccine in IAD + IB vaccine-treated groups compared to control measured by ELISA. IAD exhibited antiviral effect indicated by increased survival percent of chicks challenged with virulent IB virus with survival 100% in the groups received IAD large dose plus vaccine. Data of the present study may indicate that supplying chicks with IAD in drinking water is a good recommendation in poultry industry based on its immune enhancing properties.

Cytokine Storm and Immunomodulation in COVID-19: A Review

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.

Medicinal Plants in Peru as a Source of Immunomodulatory Drugs Potentially Useful Against COVID-19.

The current COVID-19 pandemic, characterized by a highly contagious severe acute respiratory syndrome, led us to look for medicinal plants as an alternative to obtain new drugs, especially those with immunomodulatory abilities, capable of acting against the pulmonary infection caused by coronavirus 2 (SARS-CoV-2). Despite medical advances with COVID-19 drugs and vaccines, plant-based compounds could provide an array of suitable candidates to test against this virus, or at the very least, to alleviate some symptoms. Therefore, this review explores some plants widely used in Peru that show immunomodulatory properties or, even more, contain phytoconstituents potentially useful to prevent or alleviate the COVID-19 infection. More interestingly, the present review highlights relevant information from those plants to support the development of new drugs to boost the immune system. We used three criteria to choose nine vegetal species, and a descriptive search was then conducted from 1978 to 2021 on different databases, using keywords focused on the immune system that included information such as pharmacological properties, phytochemical, botanical, ethnobotanical uses, and some clinical trials. From these literature data, our results displayed considerable immunomodulation activity along with anti-inflammatory, antiviral, antioxidant, and antitumoral activities. Noticeably, these pharmacological activities are related with a wide variety of bioactive phytoconstituents (mixtures or isolated compounds) which may be beneficial in modulating the overt inflammatory response in severe COVID-19. Further scientific research on the pharmacological activities and clinical utilization of these potential plants are warranted. Supplementary Information: The online version contains supplementary material available at 10.1007/s43450-023-00367-w.

Preventative and therapeutic potential of animal milk components against COVID-19: A comprehensive review.

The global pandemic of COVID-19 is considered one of the most catastrophic events on earth. During the pandemic, food ingredients may play crucial roles in preventing infectious diseases and sustaining people's general health and well-being. Animal milk acts as a super food since it has the capacity to minimize the occurrence of viral infections due to inherent antiviral properties of its ingredients. SARS-CoV-2 virus infection can be prevented by immune-enhancing and antiviral properties of caseins, α-lactalbumin, ß-lactoglobulin, mucin, lactoferrin, lysozyme, lactoperoxidase, oligosaccharides, glycosaminoglycans, and glycerol monolaurate. Some of the milk proteins (i.e., lactoferrin) may work synergistically with antiviral medications (e.g., remdesivir), and enhance the effectiveness of treatment in this disease. Cytokine storm during COVID-19 can be managed by casein hydrolyzates, lactoferrin, lysozyme, and lactoperoxidase. Thrombus formation can be prevented by casoplatelins as these can inhibit human platelet aggregation. Milk vitamins (i.e., A, D, E, and B complexes) and minerals (i.e., Ca, P, Mg, Zn, and Se) can have significantly positive effects on boosting the immunity and health status of individuals. In addition, certain vitamins and minerals can also act as antioxidants, anti-inflammatory, and antivirals. Thus, the overall effect of milk might be a result of synergistic antiviral effects and host immunomodulator activities from multiple components. Due to multiple overlapping functions of milk ingredients, they can play vital and synergistic roles in prevention as well as supportive agents during principle therapy of COVID-19.

Preliminary In Vivo Evidence of Oral Selenium Supplementation as a Potentiating Agent on a Vector-Based COVID-19 Vaccine in BALB/c Mice.

Evidence of efficacy and toxicity of oral selenium supplementation in vaccine administration against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in mice models is scarce. In this study, 4 × 109 virus particles (40 µL) dose of Janssen COVID-19 intramuscular injection vaccine was supplemented with a commercial selenium supplement and sodium selenite orally in BALB/c mice (N = 18). Qualitative determination of anti-spike IgG antibody response using indirect Enzyme-Linked Immunosorbent Assay (ELISA) showed significant (p ≤ 0.001) increase in anti-spike IgG antibody response for mice groups immunized with vaccine and supplemented selenium. Furthermore, cytokine profiling using real-time quantitative polymerase chain reaction also showed an increase in IL-6 and IL-10 mRNA levels normalized using hypoxanthine phosphoribosyl transferase 1 (Hprt1) and glyceraldehyde 3-phosphate dehydrogenase (Gadph) housekeeping genes. There was no statistical significance (p < 0.465) among treated and untreated groups for alanine transaminase (ALT), aspartate transaminase (AST), urea, and creatinine parameters. The study presents preliminary findings and suggests that supplementing Janssen COVID-19 vaccines with selenium can generate more robust immune responses.

Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID-19 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS-CoV-2 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.

Isoprinosine along with Favipiravir or Oseltamivir in Patients with Moderate Covid-19 at RSD Dr. Soebandi Jember

Background: Isoprinosine is an immunomodulator that is now being used to treat Covid-19 patients. Objectives: To evaluate Isoprinosine with Favipiravir or Oseltamivir in moderate Covid-19. Methods: In a retrospective observational analysis, in-hospital moderate Covid-19 patients treated between June 2020 and June 2021 were included. Results: Inclusion criteria for 364 patients were met, with 135 receiving Favipiravir-Isoprinosine (Group 1) and 229 receiving Oseltamivir-Isoprinosine (Group 2). In group 1, the majority of patients (58.50%) were female (35.60%), had no comorbidities (71.60%), were discharged with a positive PCR (74.80%), did not require a breathing apparatus (99.26%), had leukocyte levels between 4,5-11,0 (82.22%), lymphocyte levels between 25-33 (34.07%), and were discharged with no ground-glass opacity (34.07%) (54.10%), LOS was 9-13 days (50.37%), while the mortality rate was 0.70%. In group 2, the majority of patients were male (54.10%), with the highest age range being 42-56 years (35.80%), without comorbidities (69.0%), discharged with a positive PCR (72.50 %), and without the need for a breathing apparatus (99.13%), with leukocyte levels ranging from 4.5 - 11.0 (81.22 %), with lymphocyte levels ranging from 25.0 - 33.0 (26.20 %), and were discharged with no ground-glass opacity (49.34 %), LOS was 9 - 13 days (34.06 %), and the mortality rate was 0.87%.Conclusion: In this trial, it was determined that combining isoprinosine with antivirals favipiravir or Oseltamivir could produce significant clinical improvement. [ FROM AUTHOR]