Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

Probiotics and COVID-19: is there any link?

Understanding mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for prevention and/or treatment. This could be achieved via the inhibition of viral entry and/or replication, or by suppression of the immunologic response that is provoked by the infection (known as the cytokine storm). Probiotics are defined as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. There is scarcity of evidence about the relationship between COVID-19 and gut microbiota. So, whether or not these supplements can prevent or ameliorate COVID-19-associated symptoms is not fully understood. The aim of this study is to provide an indirect evidence about the utility of probiotics in combating COVID-19 or its associated symptoms, through the review of its antiviral and anti-inflammatory properties in vitro, animal models and human trials. SIGNIFICANCE AND IMPACT OF THE STUDY: The role of probiotics in alleviation of the novel COVID-19 has not been established. This review provides an insight about the anti-inflammatory, antiviral effects of probiotics in vitro, animal models and human. The latter can provide an indirect evidence and/or hypothesis-driven approach to investigate the use of probiotics as adjunctive therapy in the prophylaxis and/or alleviation of COVID-19 symptoms.

A Review of Stellate Ganglion Block as an Adjunctive Treatment Modality.

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state is created by increased levels of nerve growth factor (NGF), which causes a cascade of sympathetic sprouting resulting in increased norepinephrine (NE) systemically. Reversal of this cascade by local anesthetic injection into the stellate ganglion thereby reduces NGF and sympathetic sprouting subsequently lowering overall norepinephrine levels. This is the unifying theory by which SGB is able to provide resolution for the varied clinical conditions described in this article.  This review article discusses the physiology of several conditions where stellate ganglion blocks are being investigated as an adjunct treatment modality, including anosmia, PTSD, long-COVID, chronic fatigue syndrome, menopausal hot flashes, and ventricular tachyarrhythmias. Overall, the current literature supporting the use of stellate ganglion blocks for several esoteric conditions is limited; however, case reports to date have shown promising evidence-based results supporting their use as an adjunctive treatment among patients with refractory symptoms to existing treatment algorithms. In conclusion, SGB should be considered among patients with refractory symptoms for medical management in the conditions discussed in this article. Further research is needed to delineate which patients will benefit from the use of SGB, the use of subsequent blocks and timelines in between injections, and unilateral versus bilateral blockade.

Are herbal-peptides effective as adjunctive therapy in Coronavirus disease COVID-19?

BACKGROUND: Plant antiviral peptides [AVP] are macromolecules that can inhibit the pathogenesis of viruses by affecting their pathogenic mechanism, but most of these peptides can bind to cell membranes, inhibit viral receptors, and prevent viruses. Recently, due to the coronavirus pandemic, the availability of appropriate drugs with low side effects is needed. In this article, the importance of plant peptides in viral inhibition, especially viral inhibition of the coronavirus family, will be discussed. METHODS: By searching the databases of PubMed, Scopus, Web of Science, the latest articles on plant peptides effective on the COVID-19 virus were collected and reviewed. RESULTS: Some proteins can act against the COVID-19 virus by blocking sensitive receptors in COVID-19, such as angiotensin-converting enzyme 2 [ACE2]. The 23bp sequence of the ACE2 alpha receptor chain can be considered as a target for therapeutic peptides. Protease and RNAP inhibitors and other important receptors that are active against COVID-19 should also be considered. CONCLUSION: Herbal medicines with AVP, especially those with a long history of antiviral effects, might be a good choice in complement therapy against the COVID-19 virus.

Exploring the Potential of Metal Nanoparticles as a Possible Therapeutic Adjunct for Covid-19 Infection.

The WHO has declared the Covid-19 outbreak as a global health emergency with a mortality rate of approximately 3%, across 200 countries. There has been a considerable risk involved with drug repurposing in Covid-19 treatment, particularly in patients with underlying chronic disorders. Intervention of appropriate adjunct to primary drug therapy at subclinical or clinical doses may help to reduce unintended consequences involved in Covid-19 therapy. Metal nanoparticles due to their intrinsic structural and functional properties, not only contribute to anti-viral properties but also help to reduce the risk for associated complications. Although, silver nanoparticles hold great promise as an effective biocidal agent, while other metal nanoparticles also fueled interest against virus infection. The present review discusses the important properties of selected metal nanoparticles, their antiviral principle with possible toxic consequences, provides invaluable information for scientists and clinicians about an appropriate metal nanoparticle as an adjunct for Covid-19 treatment.

Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial.

BACKGROUND: Melatonin has been known as an anti-inflammatory agent and immune modulator that may address progressive pathophysiology of coronavirus disease 2019 (COVID-19). AIM OF THE STUDY: To evaluate the clinical efficacy of adjuvant, use of melatonin in patients with COVID-19. METHODS: This single-center, double-blind, randomized clinical trial included 74 hospitalized patients with confirmed mild to moderate COVID-19 at Baqiyatallah Hospital in Tehran, Iran, from April 25, 2020-June 5, 2020. Patients were randomly assigned in a 1:1 ratio to receive standard of care and standard of care plus melatonin at a dose of 3 mg three times daily for 14 d. Clinical characteristics, laboratory, and radiological findings were assessed and compared between two study groups at baseline and post-intervention. Safety and clinical outcomes were followed up for four weeks. RESULTS: A total of 24 patients in the intervention group and 20 patients in the control group completed the treatment. Compared with the control group, the clinical symptoms such as cough, dyspnea, and fatigue, as well as the level of CRP and the pulmonary involvement in the intervention group had significantly improved (p <0.05). The mean time of hospital discharge of patients and return to baseline health was significantly shorter in the intervention group compared to the control group (p <0.05). No deaths and adverse events were observed in both groups. CONCLUSIONS: Adjuvant use of melatonin has a potential to improve clinical symptoms of COVID-19 patients and contribute to a faster return of patients to baseline health.

Convalescent plasma as a treatment modality for Coronavirus Disease 2019 in Indonesia: A case reports.

INTRODUCTION AND IMPORTANCE: Coronavirus Disease 2019 (COVID-19) has become a pandemic since the beginning of 2020. COVID-19 is also spreading very rapidly in Indonesia and so far, no definitive therapy has been found. CASE PRESENTATION: We report two cases of confirmed COVID-19 with moderate pneumonia, who received 400 ml of convalescent plasma and showed improvements in clinical, laboratory and radiological examinations. CLINICAL DISCUSSION: Passive immunotherapy is generally more effective when given early. Plasma transfusion is more beneficial when given before clinical conditions become severe. Some studies have shown that therapy with convalescent plasma can contribute to a longer survival and a lower length of stay. CONCLUSION: Convalescent plasma can be used as an adjunctive therapy option for patients with moderate COVID-19.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Targeting host cell proteases as a potential treatment strategy to limit the spread of SARS-CoV-2 in the respiratory tract.

As the death toll of Coronavirus disease 19 (COVID-19) continues to rise worldwide, it is imperative to explore novel molecular mechanisms for targeting SARS-CoV-2. Rather than looking for drugs that directly interact with key viral proteins inhibiting its replication, an alternative and possibly add-on approach is to dismantle the host cell machinery that enables the virus to infect the host cell and spread from one cell to another. Excellent examples of such machinery are host cell proteases whose role in viral pathogenesis has been demonstrated in numerous coronaviruses. In this review, we propose two therapeutic modalities to tackle SARS-CoV-2 infections; the first is to transcriptionally modulate the expression of cellular proteases and their endogenous inhibitors and the second is to directly inhibit their enzymatic activity. We present a nonexhaustive collection of clinically investigated drugs that act by one of these mechanisms and thus represent promising candidates for preclinical in vitro testing and hopefully clinical testing in COVID-19 patients.

COVID-19 Therapeutic Options Under Investigation.

Since its emergence in China in December 2019, COVID-19 has quickly spread around the globe causing a pandemic. Vaccination or the development of herd immunity seems the only way to slow down the spread of the virus; however, both are not achievable in the near future. Therefore, effective treatments to mitigate the burden of this pandemic and reduce mortality rates are urgently needed. Preclinical and clinical studies of potential antiviral and immunomodulatory compounds and molecules to identify safe and efficacious therapeutics for COVID-19 are ongoing. Two compounds, remdesivir, and dexamethasone have been so far shown to reduce COVID-19-associated death. Here, we provide a review of the potential therapeutic agents being considered for the treatment and management of COVID-19 patients.

COVID-19: The Immune Responses and Clinical Therapy Candidates.

The pandemic of coronavirus disease 2019 (COVID-19), with rising numbers of patients worldwide, presents an urgent need for effective treatments. To date, there are no therapies or vaccines that are proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several potential candidates or repurposed drugs are under investigation, including drugs that inhibit SARS-CoV-2 replication and block infection. The most promising therapy to date is remdesivir, which is US Food and Drug Administration (FDA) approved for emergency use in adults and children hospitalized with severe suspected or laboratory-confirmed COVID-19. Herein we summarize the general features of SARS-CoV-2's molecular and immune pathogenesis and discuss available pharmacological strategies, based on our present understanding of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) infections. Finally, we outline clinical trials currently in progress to investigate the efficacy of potential therapies for COVID-19.

Potential pharmacological agents for COVID-19.

A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.

Narratives between science and politics in chloroquine activism

The current sanitary and pandemic crisis generated a set of global tensions, schemes and conflicts in different scientific, politic-party and economic spaces. The drugs hydroxychloroquine and chloroquine gained fame and expectations. What until then served only to treat malaria, now had a "cure possibility" for Covid-19. In this article we sought to understand the debate between science and politics that was generated through a research with chloroquine (Chlorocovid-19) and developed in Manaus, Amazonas. Through an ethnography woven with documents such as videos, notes, letters and messages broadcast on social media, we described and analyzed: (a) what we call chloroquine activity in Manaus and its offensive;(b) the consequent academic reaction to the attacks. Both poles-pro and contra-made efforts in the construction of a truth, in which science and politics cross-link. © 2020.