Chemoprophylaxis against COVID-19 among health-care workers using Ivermectin in low- and middle-income countries: A systematic review and meta-analysis.

Coronavirus disease-2019 (COVID-19) is a novel viral infectious disease that the World Health Organization (WHO) has announced to be a pandemic. This meta-analysis was aimed at providing evidence for the use of ivermectin to prevent COVID-19 among hospital workers in low-resource countries. Medical databases including African Journals online, Google Scholar, PubMed, Cochrane library, EMBASE, COVID-19 research database (WHO), Clinicaltrials.gov, and SCOPUS were searched for studies on Ivermectin as a chemoprophylactic drug against COVID-19 among hospital personnel in settings with limited resources. Preprint servers such as bioRxiv and medRxiv as well as the gray literature were also searched. Studies adjudged to be eligible were identified using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses algorithm. Statistical analyses were done using Stata version 14.3. Seven studies were selected for the meta-analysis. The total sample size was 2652. There were two randomized controlled trials and five nonrandomized studies. Some studies dosed Ivermectin daily while some dosed it weekly. However, one of the studies dosed it monthly. The studies reported variable clinical benefits. I2 statistic was 92%, and random effect model was used. The pooled odd ratio was 0.11 (95% confidence interval 0.09-0.13). This implies that 89% of the participants benefited from taking Ivermectin as a form of preexposure chemoprophylaxis. Ivermectin has a significant clinical benefit as a preventive drug against COVID-19 for hospital personnel in settings with limited resources.

Towards Goals to Refine Prophylactic and Therapeutic Strategies Against COVID-19 Linked to Aging and Metabolic Syndrome.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gave rise to the coronavirus disease 2019 (COVID-19) pandemic. A strong correlation has been demonstrated between worse COVID-19 outcomes, aging, and metabolic syndrome (MetS), which is primarily derived from obesity-induced systemic chronic low-grade inflammation with numerous complications, including type 2 diabetes mellitus (T2DM). The majority of COVID-19 deaths occurs in people over the age of 65. Individuals with MetS are inclined to manifest adverse disease consequences and mortality from COVID-19. In this review, we examine the prevalence and molecular mechanisms underlying enhanced risk of COVID-19 in elderly people and individuals with MetS. Subsequently, we discuss current progresses in treating COVID-19, including the development of new COVID-19 vaccines and antivirals, towards goals to elaborate prophylactic and therapeutic treatment options in this vulnerable population.

Prophylaxis against covid-19: living systematic review and network meta-analysis.

OBJECTIVE: To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. STUDY SELECTION: Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. CONCLUSIONS: Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Deep vein thrombosis in noncritically ill patients with coronavirus disease 2019 pneumonia: deep vein thrombosis in nonintensive care unit patients.

BACKGROUND: Venous thromboembolic events have been one of the main causes of mortality among hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia. The aim of our study was to describe the prevalence of deep vein thrombosis (DVT) in noncritically ill patients with COVID-19 pneumonia and correlate such observations with the thromboprophylaxis received. METHODS: We performed a prospective cohort study of 67 patients admitted to the hospital for COVID-19 pneumonia. The diagnosis was confirmed using polymerase chain reaction testing of nasopharyngeal specimens. The deep veins were examined using compression duplex ultrasonography with the transducer on B-mode. The patients were separated into two groups for statistical analysis: those receiving low-molecular-weight heparin prophylaxis and those receiving intermediate or complete anticoagulation treatment. Risk analysis and logistic regression were performed. RESULTS: Of the 67 patients, 57 were included in the present study after applying the inclusion and exclusion criteria; 49.1% were women, and the patient mean age was 71.3 years. All 57 patients had undergone compression duplex ultrasonography. Of these 57 patients, 6 were diagnosed with DVT, for an in-hospital rate of DVT in patients with COVID-19 pneumonia of 10.5%. All the patients who had presented with DVT had been receiving low-molecular-weight heparin prophylaxis. The patients receiving prophylactic anticoagulation treatment had a greater risk of DVT (16.21%; 95% confidence interval, 0.04-0.28; P = .056) compared with those receiving intermediate or complete anticoagulation treatment. We also found a protective factor for DVT in the intermediate or complete anticoagulation treatment group (odds ratio, 0.19; 95% confidence interval, 0.08-0.46; P < .05). CONCLUSIONS: Noncritically ill, hospitalized patients with COVID-19 pneumonia have a high risk of DVT despite receipt of correct, standard thromboprophylaxis.

Venous thromboembolism among patients hospitalized with COVID-19 at Veterans Health Administration Hospitals.

Patients with coronavirus disease 2019 (COVID-19) are at heightened risk of venous thromboembolic events (VTE), though there is no data examining when these events occur following a COVID-19 diagnosis. We therefore sought to characterize the incidence, timecourse of events, and outcomes of VTE during the COVID-19 pandemic in a national healthcare system using data from Veterans Affairs Administration.

Prophylaxis and treatment of COVID-19 related venous thromboembolism.

COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients.

Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study.

BACKGROUND: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers. METHODS: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection. RESULTS: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection. CONCLUSION: Two-dose ivermectin prophylaxis at a dose of 300 µg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic.

A living WHO guideline on drugs to prevent covid-19.

CLINICAL QUESTION: What is the role of drugs in preventing covid-19? WHY DOES THIS MATTER?: There is widespread interest in whether drug interventions can be used for the prevention of covid-19, but there is uncertainty about which drugs, if any, are effective. The first version of this living guideline focuses on the evidence for hydroxychloroquine. Subsequent updates will cover other drugs being investigated for their role in the prevention of covid-19. RECOMMENDATION: The guideline development panel made a strong recommendation against the use of hydroxychloroquine for individuals who do not have covid-19 (high certainty). HOW THIS GUIDELINE WAS CREATED: This living guideline is from the World Health Organization (WHO) and provides up to date covid-19 guidance to inform policy and practice worldwide. Magic Evidence Ecosystem Foundation (MAGIC) provided methodological support. A living systematic review with network analysis informed the recommendations. An international guideline development panel of content experts, clinicians, patients, an ethicist and methodologists produced recommendations following standards for trustworthy guideline development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. UNDERSTANDING THE NEW RECOMMENDATION: The linked systematic review and network meta-analysis (6 trials and 6059 participants) found that hydroxychloroquine had a small or no effect on mortality and admission to hospital (high certainty evidence). There was a small or no effect on laboratory confirmed SARS-CoV-2 infection (moderate certainty evidence) but probably increased adverse events leading to discontinuation (moderate certainty evidence). The panel judged that almost all people would not consider this drug worthwhile. In addition, the panel decided that contextual factors such as resources, feasibility, acceptability, and equity for countries and healthcare systems were unlikely to alter the recommendation. The panel considers that this drug is no longer a research priority and that resources should rather be oriented to evaluate other more promising drugs to prevent covid-19. UPDATES: This is a living guideline. New recommendations will be published in this article and signposted by update notices to this guideline. READERS NOTE: This is the first version of the living guideline for drugs to prevent covid-19. It complements the WHO living guideline on drugs to treat covid-19. When citing this article, please consider adding the update number and date of access for clarity.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

Glycyrrhizin: An old weapon against a novel coronavirus.

Currently, over 100 countries are fighting against a common enemy, the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes COVID-19. This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario. Glycyrrhizin (GZ) is a promising agent against SARS-CoV-2 as its antiviral activity against SARS-CoV has already been confirmed. It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS-CoV and SARS-CoV-2. There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid-bilayer membrane, and binding to the ACE2 receptor. In this review, we discuss the possible use of GZ in the COVID-19 setting, where topical administration appears to be promising, with the nasal and oral cavity notably being the potent location in terms of viral load. The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2.

Post-hospital discharge venous thromboembolism prophylaxis in medically ill patients.

There is a widely expressed concern about an unmet need for post hospitalization venous thromboembolism (VTE) prophylaxis in medically ill patients, however, physicians and hospitals have been slow to implement this measure. Recommendations against extended VTE prophylaxis in medical patients from the American Society of Hematology (ASH) in 2018 and the withholding of approval of betrixiban by the European Medicines Agency also in 2018 may have been influential in this regard. Furthermore, rivaroxaban the other drug approved for this indication in the U.S has not yet been approved in Europe. In addition, hospital administrators, those monitoring expenses in the U.S, have been reluctant to support a treatment which will mostly involve outpatients. Internal medicine physicians, hospitalists and nursing home physicians have not shared the fervor for post hospital VTE prophylaxis, whether with anticoagulants or aspirin, that their orthopedic surgery colleagues have, particularly in hip and knee arthroplasty. This is despite an increased risk of post hospital discharge thrombosis in both groups of patients. Enter hospitalized patients with COVID-19, a potentially severe medical illness with high hospitalization related thrombosis risk, and questions arise as to whether these medical patients, who are clearly more hypercoagulable during hospitalization than those in previous studies, should warrant post hospital discharge prophylaxis.

Nonadministration of pharmacologic venous thromboembolism prophylaxis is less common in hospitalized patients with COVID-19.

INTRODUCTION: The incidence of venous thromboembolism (VTE) in patients hospitalized with COVID-19 is higher than most other hospitalized patients. Nonadministration of pharmacologic VTE prophylaxis is common and is associated with VTE events. Our objective was to determine whether nonadministration of pharmacologic VTE prophylaxis is more common in patients with COVID-19 versus other hospitalized patients. MATERIALS AND METHODS: In this retrospective cohort analysis of all adult patients discharged from the Johns hopkins hospital between Mar 1 and May 12, 2020, we compared demographic, clinical characteristics, VTE outcomes, prescription and administration of VTE prophylaxis between COVID-19 positive, negative, and not tested groups. RESULTS: Patients tested positive for COVID-19 were significantly older, and more likely to be Hispanic, have a higher median body mass index, have longer hospital length of stay, require mechanical ventilation, develop pulmonary embolism and die (all p < 0.001). COVID-19 patients were more likely to be prescribed (aOR 1.51, 95% CI 1.38-1.66) and receive all doses of prescribed pharmacologic VTE prophylaxis (aOR 1.48, 95% CI 1.36-1.62). The number of patients who missed at least one dose of VTE prophylaxis and developed VTE was similar between the three groups (p = 0.31). CONCLUSIONS: It is unlikely that high rates of VTE in COVID-19 are due to nonadministration of doses of pharmacologic prophylaxis. Hence, we should prioritize research into alternative approaches to optimizing VTE prevention in patients with COVID-19.

Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection.

BACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose. OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020. MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily). SAMPLE SIZE: 154 cases. RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died (P=.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4-17.6, P<.001). CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study. CONFLICT OF INTEREST: None.

Questions and Answers on Practical Thrombotic Issues in SARS-CoV-2 Infection: A Guidance Document from the Italian Working Group on Atherosclerosis, Thrombosis and Vascular Biology.

In patients with coronavirus disease 2019 (COVID-19), the prevalence of pre-existing cardiovascular diseases is elevated. Moreover, various features, also including pro-thrombotic status, further predispose these patients to increased risk of ischemic cardiovascular events. Thus, the identification of optimal antithrombotic strategies in terms of the risk-benefit ratio and outcome improvement in this setting is crucial. However, debated issues on antithrombotic therapies in patients with COVID-19 are multiple and relevant. In this article, we provide ten questions and answers on risk stratification and antiplatelet/anticoagulant treatments in patients at risk of/with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on the scientific evidence gathered during the pandemic.

Deep vein thrombosis in hospitalized patients with coronavirus disease 2019.

OBJECTIVE: The pandemic of coronavirus disease 2019 (COVID-19) has caused devastating morbidity and mortality worldwide. In particular, thromboembolic complications have emerged as a key threat for patients with COVID-19. We assessed our experience with deep vein thrombosis (DVT) in patients with COVID-19. METHODS: We performed a retrospective analysis of all patients with COVID-19 who had undergone upper or lower extremity venous duplex ultrasonography at an academic health system in New York City from March 3, 2020 to April 12, 2020 with follow-up through May 12, 2020. A cohort of hospitalized patients without COVID-19 (non-COVID-19) who had undergone venous duplex ultrasonography from December 1, 2019 to December 31, 2019 was used for comparison. The primary outcome was DVT. The secondary outcomes included pulmonary embolism, in-hospital mortality, admission to the intensive care unit, and antithrombotic therapy. Multivariable logistic regression was performed to identify the risk factors for DVT and mortality. RESULTS: Of 443 patients (COVID-19, n = 188; and non-COVID-19, n = 255) who had undergone venous duplex ultrasonography, the COVID-19 cohort had had a greater incidence of DVT (31% vs 19%; P = .005) than had the non-COVID-19 cohort. The incidence of pulmonary embolism was not significantly different statistically between the COVID-19 and non-COVID-19 cohorts (8% vs 4%; P = .105). The DVT location in the COVID-19 group was more often distal (63% vs 29%; P < .001) and bilateral (15% vs 4%; P < .001). The duplex ultrasound findings had a significant impact on the antithrombotic plan; 42 patients (72%) with COVID-19 in the DVT group had their therapy escalated and 49 (38%) and 3 (2%) had their therapy escalated and deescalated in the non-DVT group, respectively (P < .001). Within the COVID-19 cohort, the D-dimer level was significantly greater in the DVT group at admission (2746 ng/mL vs 1481 ng/mL; P = .004) and at the duplex examination (6068 ng/mL vs 3049 ng/mL; P < .01). On multivariable analysis, male sex (odds ratio [OR], 2.27; 95% confidence interval [CI], 1.06-4.87; P = .035), intensive care unit admission (OR, 3.42; 95% CI, 1.02-11.44; P = .046), and extracorporeal membrane oxygenation (OR, 5.5; 95% CI, 1.01-30.13; P = .049) were independently associated with DVT. CONCLUSIONS: Given the high incidence of venous thromboembolic events in this population, we support the decision to empirically initiate therapeutic anticoagulation for patients with a low bleeding risk and severe COVID-19 infection. Duplex ultrasonography should be reserved for patients with a high clinical suspicion of venous thromboembolism for whom anticoagulation therapy could result in life-threatening consequences. Further study of patients with COVID-19 is warranted to elucidate the etiology of vascular thromboembolic events and guide the prophylactic and therapeutic interventions for these patients.

Thromboelastography findings in critically ill COVID-19 patients.

The rate of venous and arterial thrombotic events among patients infected with severe acute respiratory syndrome coronavirus-2 (SAR-CoV-2) is high. This may be due to a hypercoagulable state induced by the severe inflammation that results from the SAR-CoV-2 infection. We aimed to determine hypercoagulable states' incidence based on thromboelastography study and its association with thrombotic events in critically ill patients with coronavirus disease 2019 (COVID-19). Fifty-two COVID-19 patients who had thromboelastography study were retrospectively included. All patients received pharmacologic thromboprophylaxis. The hypercoagulable state was observed in 16 patients (30.8%). Among them, maximum amplitude and a-angle were elevated in 75% and 25%, respectively. Reaction time and K were low in only 12.5% for both of them. Inflammatory and coagulation markers, as well as thromboprophylaxis regimens, were not associated with a hypercoagulable state. Fourteen patients (27%) experienced a total of 16 thrombotic events, including 8 (57%) deep venous thrombosis, 6 (43%) pulmonary embolism, and 2 (14.3%) arterial thrombosis. The hypercoagulable state was not significantly associated with thrombotic events. In summary, we observed a lower rate of hypercoagulable state on thromboelastography study in critically ill COVID-19 patients. Also, the hypercoagulable state was not associated with the occurrence of thrombotic events.

Natural products for COVID-19 prevention and treatment regarding to previous coronavirus infections and novel studies.

Recently, the novel life-threatening coronavirus infection (COVID-19) was reported at the end of 2019 in Wuhan, China, and spread throughout the world in little time. The effective antiviral activities of natural products have been proved in different studies. In this review, regarding the effective herbal treatments on other coronavirus infections, promising natural products for COVID-19 treatment are suggested. An extensive search in Google Scholar, Science Direct, PubMed, ISI, and Scopus was done with search words include coronavirus, COVID-19, SARS, MERS, natural product, herb, plant, and extract. The consumption of herbal medicine such as Allium sativum, Camellia sinensis, Zingiber officinale, Nigella sativa, Echinacea spp. Hypericum perforatum, and Glycyrrhiza glabra, Scutellaria baicalensis can improve the immune response. It seems that different types of terpenoids have promising effects in viral replication inhibition and could be introduced for future studies. Additionally, some alkaloid structures such as homoharringtonine, lycorine, and emetine have strong anti-coronavirus effects. Natural products can inhibit different coronavirus targets such as S protein (emodin, baicalin) and viral enzymes replication such as 3CLpro (Iguesterin), PLpro (Cryptotanshinone), helicase (Silvestrol), and RdRp (Sotetsuflavone). Based on previous studies, natural products can be introduced as preventive and therapeutic agents in the fight against coronavirus.