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1.
Acta Trop ; 214: 105778, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1064688

ABSTRACT

We are living through an unprecedented crisis with the rapid spread of the new coronavirus disease (COVID-19) worldwide within a short time. The timely availability of thousands of SARS-CoV-2 genomes has enabled the scientific community to study the origin, structures, and pathogenesis of the virus. The pandemic has spurred research publication and resulted in an unprecedented number of therapeutic proposals. Because the development of new drugs is time consuming, several strategies, including drug repurposing and repositioning, are being tested to treat patients with COVID-19. Researchers have developed several potential vaccine candidates that have shown promise in phase II and III trials. As of 12 November 2020, 164 candidate vaccines are in preclinical evaluation, and 48 vaccines are in clinical evaluation, of which four have cleared phase III trials (Pfizer/BioNTech's BNT162b2, Moderna's mRNA-1273, University of Oxford & AstraZeneca's AZD1222, and Gamaleya's Sputnik V vaccine). Despite the acquisition of a vast body of scientific information, treatment depends only on the clinical management of the disease through supportive care. At the pandemic's 1-year mark, we summarize current information on SARS-CoV-2 origin and biology, and advances in the development of therapeutics. The updated information presented here provides a comprehensive report on the scientific progress made in the past year in understanding of SARS-CoV-2 biology and therapeutics.


Subject(s)
COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Animals , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/transmission , COVID-19 Vaccines , Chloroquine/therapeutic use , Clinical Trials as Topic , Coronavirus/genetics , Coronavirus Infections/transmission , Drug Combinations , Drug Repositioning , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Indoles/therapeutic use , Ivermectin/therapeutic use , Lopinavir/therapeutic use , Mutation , Pandemics , Phytotherapy , Plant Extracts/therapeutic use , Pyrazines/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus , Tinospora , Viral Zoonoses
2.
Medicine (Baltimore) ; 100(4): e24475, 2021 Jan 29.
Article in English | MEDLINE | ID: covidwho-1061053

ABSTRACT

ABSTRACT: To evaluate the antiviral effect and safety of arbidol and Lianhuaqingwen Capsule (LH) in treating patients with Coronavirus disease 2019 (COVID-19).108 patients with COVID-19 were divided into 2 groups, including 40 patients in the arbidol group and 68 patients in the arbidol + LH group. Patients in the arbidol + LH group received 200 mg of arbidol and 1400 mg of LH per 8 hour, and the arbidol group was given 200 mg arbidol per 8 hour. Blood routine examination, blood biochemistry detection, SARS-CoV-2 nucleic acid detection, and chest CT scans were performed to evaluate the clinical effects between the 2 groups.No statistically significant differences were observed between the 2 groups in terms of preoperative characteristics including the baseline characteristics, laboratory indicators, and chest CT. On day 7 after admission, patients in the arbidol + LH group showed a higher level of Lymphocytes count, and a lower level of serum amyloid A and C-reactive protein levels (P < .05). Moreover, the median time from admission to the first negative result of the SARS-CoV-2 nucleic acid detection was shorter in the arbidol + LH group (P < .05). Analysis based on CT scan results showed a better extinction of lung inflammation in the arbidol + LH group. No apparent side effects were found in both groups. No patients were transferred to the intensive care unit (ICU) treatment.Arbidol combined with LH treatment may be more effective in improving the prognosis and accelerating the SARS-CoV-2 clearance in patients with COVID-19.


Subject(s)
COVID-19 Drug Treatment , Drugs, Chinese Herbal/therapeutic use , Indoles/therapeutic use , Pneumonia, Viral/drug therapy , Capsules , Drug Therapy, Combination , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2
3.
Medicine (Baltimore) ; 100(2): e23923, 2021 Jan 15.
Article in English | MEDLINE | ID: covidwho-1039765

ABSTRACT

ABSTRACT: Coronavirus disease 2019 (COVID-19) is an emerging disease caused by severe acute respiratory syndrome coronavirus 2; no specific effective medication to treat the disease has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19.This single-center, retrospective, observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Data on demographics, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and 8 patients with mild and severe symptoms, respectively.All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all 8 severe-group patients (median treatment: 17.5 days; 4 received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all 8 in the severe group (median treatment: 9 days; 2 received linezolid). Moreover, 7 patients (12.72%) were treated with glucocorticoids and 9 (16.36%) with immunomodulators.Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary. Randomized, double-blind, and controlled trials remain necessary for more accurate conclusions.


Subject(s)
COVID-19 Drug Treatment , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , China , Female , Glucocorticoids/therapeutic use , Humans , Immunologic Factors/therapeutic use , Indoles/therapeutic use , Linezolid/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Moxifloxacin/therapeutic use , Retrospective Studies , Ritonavir/therapeutic use
4.
Ann Palliat Med ; 10(1): 707-720, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1030457

ABSTRACT

The whole world is battling through coronavirus disease 2019 (COVID-19) which is a fatal pandemic. In the early 2020, the World Health Organization (WHO) declared it as a global health emergency without definitive treatments and preventive approaches. In the absence of definitive therapeutic agents, this thorough review summarizes and outlines the potency and safety of all molecules and therapeutics which may have potential antiviral effects. A number of molecules and therapeutics licensed or being tested for some other conditions were found effective in different in vitro studies as well as in many small sample-sized clinical trials and independent case studies. However, in those clinical trials, there were some limitations which need to be overcome to find the most promising antiviral against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In conclusion, many of above-mentioned antivirals seems to have some therapeutic effects but none of them have been shown to have a strong evidence for their proper recommendation and approval in the treatment of COVID-19. Constantly evolving new evidences, exclusive adult data, language barrier, and type of study (observational, retrospective, small-sized clinical trials, or independent case series) resulted to the several limitations of this review. The need for multicentered, large sample-sized, randomized, placebo-controlled trials on COVID-19 patients to reach a proper conclusion on the most promising antiviral agent is warranted.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Amides/pharmacology , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Azetidines/pharmacology , Azetidines/therapeutic use , Chloroquine/pharmacology , Chloroquine/therapeutic use , Drug Combinations , Humans , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Immunization, Passive , Indoles/pharmacology , Indoles/therapeutic use , Interferons/pharmacology , Interferons/therapeutic use , Ivermectin/pharmacology , Ivermectin/therapeutic use , Lopinavir/pharmacology , Lopinavir/therapeutic use , Nitro Compounds , Oseltamivir/pharmacology , Oseltamivir/therapeutic use , Purines/pharmacology , Purines/therapeutic use , Pyrazines/pharmacology , Pyrazines/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Ribavirin/pharmacology , Ribavirin/therapeutic use , Ritonavir/pharmacology , Ritonavir/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Thiazoles/pharmacology , Thiazoles/therapeutic use , COVID-19 Serotherapy
5.
Ann Palliat Med ; 10(3): 2429-2438, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1029919

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the causative agent of coronavirus disease 2019 (COVID-19). Lung lesions are considered to be the main damage caused by SARSCoV-2 infection. In addition, liver injury has also been reported to occur during the course of the disease in severe cases. However, the effect of antiviral treatment on liver injury in critically ill patients is not yet clear. METHODS: We retrospectively evaluated the effect of antiviral treatment and antiviral drug arbidol on liver injury in COVID-19 critically ill patients. Baseline characteristics were collected from patients who were admitted to intensive care units of Tongji Hospital in Wuhan, China, and confounders were balanced by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. RESULTS: Both the PSM (OR=2.77; 95% CI: 1.03, 7.48; P=0.045) and the IPTW-adjusted (OR=2.33; 95% CI: 1.02, 5.34; P=0.047) results showed that COVID-19 critically ill patients receiving antiviral treatment had a significantly higher risk of liver injury. However, arbidol treatment did not have a significant effect on liver injury (IPTW: OR=2.11; 95% CI: 0.79, 5.67; P=0.14). CONCLUSIONS: Our results show that although arbidol treatment does not seem to be significantly associated with liver injury complications, the overall use of antiviral drugs increases the risk of liver injury for critically ill patients with COVID-19. Antiviral drugs are widely used to treat COVID-19, but we recommend that for critically ill patients, antiviral treatment should be used with caution considering both effectiveness and potential adverse effects.


Subject(s)
Antiviral Agents/adverse effects , COVID-19 Drug Treatment , Indoles/adverse effects , Liver/drug effects , Antiviral Agents/therapeutic use , Chemical and Drug Induced Liver Injury , China , Critical Illness , Humans , Indoles/therapeutic use , Liver/pathology , Retrospective Studies
6.
Medicine (Baltimore) ; 99(51): e23547, 2020 Dec 18.
Article in English | MEDLINE | ID: covidwho-1010676

ABSTRACT

ABSTRACT: This study aims to investigate the clinical characteristics and viral shedding kinetics of asymptomatic patients with coronavirus disease 2019 (COVID-19).The data of 38 asymptomatic patients positive for SARS-CoV-2 nucleic acid were collected from February to March 2020 in Tuanfeng County, Huanggang, Hubei, China. The epidemiology, laboratory examination, chest imaging, viral nucleic acid test results, clinical characteristics, and viral shedding time were summarized in this retrospective study.The study included 20 family members of patients with COVID-19, 10 medical personnel participating in COVID-19 treatment or working in a fever clinic, 6 personnel from quarantine places, 1 individual with a close contact history with confirmed patients, and 1 local epidemic prevention personnel. All were positive for SARS-CoV-2 nucleic acid. The white blood cell (WBC) count, the absolute value of lymphocytes, C-reactive protein (CRP), and D-dimer were normal. Pneumonia manifestations were not found in the chest computed tomography (CT) scan of 36 patients; the remaining 2 cases included a 1-year-old child and a pregnant woman, and they did not undergo chest CT. The viral shedding time was 6 days.All asymptomatic patients with COVID-19 had a history of close contact or exposure. Laboratory tests were normal. Chest imaging did not show any pneumonia manifestation. The viral shedding time was <10 days, which is shorter than that of patients with COVID-19. A timely discovery of such asymptomatic infections is crucial for blocking the spread of the virus and strengthening the prevention and control measures.


Subject(s)
Asymptomatic Infections/epidemiology , COVID-19/virology , SARS-CoV-2 , Virus Shedding , Adolescent , Adult , Asymptomatic Infections/therapy , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/epidemiology , Child , China/epidemiology , Female , Humans , Indoles/therapeutic use , Infant , Male , Medicine, Chinese Traditional , Middle Aged , Radiography, Thoracic , Retrospective Studies , Young Adult
7.
Int J Mol Sci ; 22(1)2020 Dec 30.
Article in English | MEDLINE | ID: covidwho-1006950

ABSTRACT

Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.


Subject(s)
Anticoagulants/pharmacology , Hemorrhage/etiology , Indoles/pharmacology , Protein Kinase Inhibitors/pharmacology , Anticoagulants/therapeutic use , Antidotes/pharmacology , Antineoplastic Agents/pharmacology , Blood Coagulation Disorders/complications , Blood Coagulation Disorders/drug therapy , COVID-19/complications , COVID-19/metabolism , Drug Interactions , Hemorrhage/epidemiology , Humans , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/adverse effects , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Risk Factors , COVID-19 Drug Treatment
8.
Medicine (Baltimore) ; 99(30): e21402, 2020 Jul 24.
Article in English | MEDLINE | ID: covidwho-982089

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is highly contagious, and the epidemic has spread to hundreds of countries around the world, and seriously threatens the life safety of people around the world. Arbidol is an antiviral drug with high potential against COVID-19, but evidence of effectiveness and safety is lacking. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of arbidol for COVID-19. METHODS: The retrieval time will be from the database establishment to June 2020. The retrieval database will include the Cochrane Library, PubMed, Embase, OVID, CNKI, Wanfang, VIP, CBM, etc. The primary outcome will be clinical efficacy, and the secondary results will be accompanying symptoms, time for the temperature to return to normal, time of novel coronavirus nucleic acid turning negative, blood sample test, Computed Tomography examination, length of hospitalization, adverse reactions, and adverse events. RevManV.5.3 software will be used for meta-analysis, and fixed effects model, random-effects model, subgroup analysis, and descriptive analysis will be adopted according to the heterogeneity of the research results. RESULTS: To provide the latest evidence of clinical efficacy and safety of arbidol in the treatment of COVID-19. CONCLUSION: Our study will provide the latest evidence analysis of the efficacy and safety of arbidol for COVID-19, to provide evidence-based medicine for the prevention and control of this epidemic. REGISTRATION DETAILS: PROSPERO CRD42020189203.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Indoles/therapeutic use , Pneumonia, Viral/drug therapy , COVID-19 , Coronavirus Infections/virology , Drug Therapy, Combination , Humans , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , COVID-19 Drug Treatment
10.
J Med Virol ; 93(3): 1378-1386, 2021 03.
Article in English | MEDLINE | ID: covidwho-891893

ABSTRACT

Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.


Subject(s)
COVID-19/complications , Indoles/therapeutic use , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/metabolism , COVID-19/pathology , Humans , Lung/pathology , Patient Discharge , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Severity of Illness Index , Signal Transduction
11.
Immunol Lett ; 217: 25-30, 2020 01.
Article in English | MEDLINE | ID: covidwho-888577

ABSTRACT

In a previous work we demonstrated that inhibition of mouse indoleamine 2,3-dioxygenase (IDO) by methyltryptophan (MT) exacerbated the pathological actions of mouse hepatitis virus (MHV-A59) infection, suggesting that tryptophan (TRP) catabolism was involved in viral effects. Since there is a second enzyme that dioxygenates TRP, tryptophan-2, 3-dioxygenase (TDO), which is mainly located in liver, we decided to study its role in our model of MHV-infection. Results showed that in vivo TDO inhibition by LM10, a derivative of 3-(2-(pyridyl) ethenyl) indole, resulted in a decrease of anti- MHV Ab titers induced by the virus infection. Besides, a reduction of some alarmin release, i.e, uric acid and high-mobility group box1 protein (HMGB1), was observed. Accordingly, since alarmin liberation was related to the expression of autoantibodies (autoAb) to fumarylacetoacetate hydrolase (FAH), these autoAb also diminished. Moreover, PCR results indicated that TDO inhibition did not abolish viral replication. Furthermore, histological liver examination did not reveal strong pathologies, whereas mouse survival was hundred percent in control as well as in MHV-infected mice treated with LM10. Data presented in this work indicate that in spite of the various TDO actions already described, specific TDO blockage could also restrain some MHV actions, mainly suppressing autoimmune reactions. Such results should prompt further experiments with various viruses to confirm the possible use of a TDO inhibitor such as LM-10 to treat either viral infections or even autoimmune diseases triggered by a viral infection.


Subject(s)
Autoimmune Diseases/enzymology , Autoimmunity/drug effects , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Liver/enzymology , Murine hepatitis virus/immunology , Tryptophan Oxygenase/antagonists & inhibitors , Tryptophan Oxygenase/metabolism , Alarmins/metabolism , Animals , Autoantibodies/drug effects , Autoantibodies/immunology , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Autoimmune Diseases/virology , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , HMGB1 Protein/blood , HMGB1 Protein/metabolism , Hydrolases/immunology , Indoles/therapeutic use , Liver/drug effects , Liver/immunology , Liver/pathology , Mice , Mice, Inbred BALB C , Murine hepatitis virus/drug effects , Murine hepatitis virus/growth & development , Tryptophan/metabolism , Tryptophan Oxygenase/genetics , Uric Acid/blood , Uric Acid/metabolism , Virus Replication/drug effects , Virus Replication/immunology
12.
Virol J ; 17(1): 162, 2020 10 23.
Article in English | MEDLINE | ID: covidwho-887489

ABSTRACT

OBJECTIVE: We aimed to describe the features of 220 nonemergency (mild or common type) COVID-19 patients from a shelter hospital, as well as evaluate the efficiency of antiviral drug, Arbidol in their disease progressions. METHODS: Basic clinical characteristics were described and the efficacy of Arbidol was evaluated based on gender, age, maximum body temperature of the patients. RESULTS: Basically, males had a higher risk of fever and more onset symptoms than females. Arbidol could accelerate fever recovery and viral clearance in respiratory specimens, particularly in males. Arbidol also contributed to shorter hospital stay without obvious adverse reactions. CONCLUSIONS: In the retrospective COVID-19 cohort, gender was one of the important factors affecting patient's conditions. Arbidol showed several beneficial effects in these patients, especially in males. This study brought more researches enlightenment in understanding the emerging infectious disease.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Indoles/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2 , COVID-19 Drug Treatment
13.
BMJ Support Palliat Care ; 11(1): 45-52, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-788171

ABSTRACT

BACKGROUND: Because of the lack of vaccination, it is urgent to find effective antiviral agents for COVID-19 treatment. METHOD: Online databases were searched for articles published before or on 22 June 2020. Studies reporting the effectiveness and safety of antiviral agents for COVID-19 were analysed. RESULTS: A total of 42 studies were included in this analysis. Hydroxychloroquine (HCQ) was not associated with the incidence of death (risk ratio (RR)=1.08; 95% CI 0.81 to 1.44) and severe cases (RR=1.05; 95% CI 0.61 to 1.81). Patients treated with HCQ obtained few benefits with respect to the clearance of viral RNA and were more likely to have adverse reactions. HCQ treatment could shorten the body temperature recovery time (weighted mean difference = -1.04; 95% CI -1.64 to -0.45). Lopinavir/ritonavir (LPV/r) (RR=0.90; 95% CI 0.76 to 1.07) and Arbidol (RR=1.09; 95% CI 0.92 to 1.29) were not associated with the negative conversion rate. Integrative Chinese-Western medicine alleviated clinical symptoms and decreased the incidence of severe cases (RR=0.38; 95% CI 0.25 to 0.59). Remdesivir treatment reduced the 14-day mortality rate of patients with severe COVID-19 (RR=0.64; 95% CI 0.44 to 0.94). Convalescent plasma (CP) tended to increase the negative conversion rate (RR=2.47; 95% CI 1.70 to 3.57). CONCLUSION: HCQ, LPV/r and Arbidol bring little benefit in COVID-19 treatment. Integrative Chinese-Western medicine improved the clinical symptoms of patients with COVID-19. Remdesivir and CP might be the potential treatments for patients with severe COVID-19. However, large-scale clinical randomised trials are needed to validate our conclusions.


Subject(s)
Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Immunologic Factors/therapeutic use , Medicine, Chinese Traditional , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Indoles/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , COVID-19 Drug Treatment , COVID-19 Serotherapy
14.
Expert Rev Respir Med ; 15(2): 257-265, 2021 02.
Article in English | MEDLINE | ID: covidwho-780247

ABSTRACT

OBJECTIVE: To understand the clinical effectiveness and safety of Shufeng Jiedu Capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19. METHODS: A retrospective cohort study was used to analyze the case data of 200 inpatients diagnosed with common-type COVID-19 at Wuhan Hospital. Participants were divided into a control group and an experimental group. The control group was treated with Arbidol hydrochloride capsules while the experimental group was treated with combination Arbidol hydrochloride capsules and Shufeng Jiedu Capsules (SFJDC) for 14 days. RESULTS: Defervescence was achieved more rapidly in the experimental group (P < 0.05). The white blood cell count and the lymphocyte percentage in the experimental group were higher than that of the control group (P < 0.05). CRP and IL-6 levels in the experimental group were significantly lower than those in the control group (P < 0.05). The proportion of chest CT studies showing resolution of pneumonia in the experimental group was significantly higher than that in the control group (P < 0.05). CONCLUSIONS: A treatment regimen of Shufeng Jiedu Capsules combined with Arbidol to treat common-type COVID-19, combining traditional Chinese and western allopathic medicine, improves time to recovery, has better clinical effectiveness, and is safe.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Drugs, Chinese Herbal/therapeutic use , Indoles/therapeutic use , Aged , C-Reactive Protein/analysis , Case-Control Studies , China , Cohort Studies , Drug Therapy, Combination , Female , Humans , Interleukin-6/blood , Leukocyte Count , Lung/diagnostic imaging , Lymphocyte Count , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
15.
Virus Res ; 286: 198057, 2020 09.
Article in English | MEDLINE | ID: covidwho-773200

ABSTRACT

The fight against the novel coronavirus pneumonia (namely COVID-19) that seriously harms human health is a common task for all mankind. Currently, development of drugs against the novel coronavirus (namely SARS-CoV-2) is quite urgent. Chinese medical workers and scientific researchers have found some drugs to play potential therapeutic effects on COVID-19 at the cellular level or in preliminary clinical trials. However, more fundamental studies and large sample clinical trials need to be done to ensure the efficacy and safety of these drugs. The adoption of these drugs without further testing must be careful. The relevant articles, news, and government reports published on the official and Preprint websites, PubMed and China National Knowledge Infrastructure (CNKI) databases from December 2019 to April 2020 were searched and manually filtered. The general pharmacological characteristics, indications, adverse reactions, general usage, and especially current status of the treatment of COVID-19 of those potentially effective drugs, including chemical drugs, traditional Chinese medicines (TCMs), and biological products in China were summarized in this review to guide reasonable medication and the development of specific drugs for the treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drugs, Chinese Herbal/therapeutic use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Betacoronavirus/immunology , COVID-19 , China/epidemiology , Chloroquine/therapeutic use , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Combinations , Humans , Indoles/therapeutic use , Interferons/therapeutic use , Lopinavir/therapeutic use , Lung/drug effects , Lung/pathology , Lung/virology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Pyrazines/therapeutic use , Ribavirin/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Survival Analysis
16.
J Med Virol ; 93(2): 794-802, 2021 02.
Article in English | MEDLINE | ID: covidwho-649243

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in the intestines and feces, but its clinical significance is not completely clear. We aim to characterize the longitudinal test results of SARS-CoV-2 RNA in anal swabs and to explore the association with disease severity. METHODS: We included laboratory-confirmed coronavirus disease 2019 (COVID-19) patients, who were hospitalized in Guangzhou Eighth People's Hospital and excluded those who had not received anal swabs for SARS-COV-2 RNA testing. Epidemiological, clinical, and laboratory data were obtained. Throat swabs and anal swabs were collected periodically for SARS-COV-2 RNA detection. RESULTS: Two hundred and seventeen eligible patients (median aged 50 years, 50.2% were females) were analyzed. 21.2% (46/217) of the patients were detected with SARS-CoV-2 RNA in anal swabs. The duration of viral RNA was longer, but the viral load was lower in anal swabs than throat swabs in the early stage of the disease. During a median follow-up of 20 days, 30 (13.8%) patients were admitted to the intensive care unit (ICU) for high-flow nasal cannula or higher-level oxygen support measures to correct hypoxemia. Detectable viral RNA in anal swabs (adjusted hazard ratio [aHR], 2.50; 95% confidence interval [CI], 1.20-5.24), increased C-reactive protein (aHR, 3.14; 95% CI, 1.35-7.32) and lymphocytopenia (aHR, 3.12; 95% CI, 1.46-6.67) were independently associated with ICU admission. The cumulative incidence of ICU admission was higher among patients with detectable viral RNA in anal swabs (26.3% vs 10.7%, P = .006). CONCLUSION: Detectable SARS-CoV-2 RNA in the digestive tract was a potential warning indicator of severe disease.


Subject(s)
Anal Canal/virology , COVID-19/diagnosis , Lymphopenia/diagnosis , RNA, Viral/genetics , SARS-CoV-2/genetics , Adult , Antiviral Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , COVID-19 Testing , Chloroquine/therapeutic use , Female , Hospitalization/statistics & numerical data , Humans , Indoles/therapeutic use , Intensive Care Units/statistics & numerical data , Lymphopenia/pathology , Lymphopenia/therapy , Lymphopenia/virology , Male , Middle Aged , Oseltamivir/therapeutic use , Pharynx/virology , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Viral Load/drug effects
17.
Am J Chin Med ; 48(6): 1263-1277, 2020.
Article in English | MEDLINE | ID: covidwho-751463

ABSTRACT

In December 2019, a novel coronavirus SARS-CoV-2, causing the disease COVID-19, spread from Wuhan throughout China and has infected people over 200 countries. Thus far, more than 3,400,000 cases and 240,000 deaths have occurred worldwide, and the coronavirus pandemic continues to grip the globe. While numbers of cases in China have been steadying, the number of infections outside China is increasing at a worrying pace. We face an urgent need to control the spread of the COVID-19 epidemic, which is currently expanding to a global pandemic. Efforts have focused on testing antiviral drugs and vaccines, but there is currently no treatment specifically approved. Traditional Chinese medicine (TCM) is grounded in empirical observations and the Chinese people use TCM to overcome these sorts of plagues many times in thousands of years of history. Currently, the Chinese National Health Commission recommended a TCM prescription of Qing-Fei-Pai-Du-Tang (QFPDT) in the latest version of the "Diagnosis and Treatment guidelines of COVID-19" which has been reported to provide reliable effects for COVID-19. While doubts about TCM still exist today, this review paper will describe the rationalities that QFPDT is likely to bring a safe and effective treatment of COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus , COVID-19 , Chloroquine/therapeutic use , Coronavirus Infections/immunology , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/immunology , Drug Combinations , Humans , Indoles/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Lopinavir/therapeutic use , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral/immunology , Ritonavir/therapeutic use , SARS-CoV-2 , COVID-19 Drug Treatment
18.
mBio ; 11(4)2020 08 20.
Article in English | MEDLINE | ID: covidwho-724620

ABSTRACT

We assessed various newly generated compounds that target the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and various previously known compounds reportedly active against SARS-CoV-2, employing RNA quantitative PCR (RNA-qPCR), cytopathicity assays, and immunocytochemistry. Here, we show that two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, exerted potent activity against SARS-CoV-2 in cell-based assays performed using VeroE6 cells and TMPRSS2-overexpressing VeroE6 cells. While GRL-0820 and the nucleotide analog remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred. No significant anti-SARS-CoV-2 activity was found for several compounds reportedly active against SARS-CoV-2 such as lopinavir, nelfinavir, nitazoxanide, favipiravir, and hydroxychroloquine. In contrast, GRL-0920 exerted potent activity against SARS-CoV-2 (50% effective concentration [EC50] = 2.8 µM) and dramatically reduced the infectivity, replication, and cytopathic effect of SARS-CoV-2 without significant toxicity as examined with immunocytochemistry. Structural modeling shows that indole and chloropyridinyl of the derivatives interact with two catalytic dyad residues of Mpro, Cys145 and His41, resulting in covalent bonding, which was verified using high-performance liquid chromatography-mass spectrometry (HPLC/MS), suggesting that the indole moiety is critical for the anti-SARS-CoV-2 activity of the derivatives. GRL-0920 might serve as a potential therapeutic for coronavirus disease 2019 (COVID-19) and might be optimized to generate more-potent anti-SARS-CoV-2 compounds.IMPORTANCE Targeting the main protease (Mpro) of SARS-CoV-2, we identified two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, active against SARS-CoV-2, employing RNA-qPCR and immunocytochemistry and show that the two compounds exerted potent activity against SARS-CoV-2. While GRL-0820 and remdesivir blocked SARS-CoV-2 infection, viral breakthrough occurred as examined with immunocytochemistry. In contrast, GRL-0920 completely blocked the infectivity and cytopathic effect of SARS-CoV-2 without significant toxicity. Structural modeling showed that indole and chloropyridinyl of the derivatives interacted with two catalytic dyad residues of Mpro, Cys145 and His41, resulting in covalent bonding, which was verified using HPLC/MS. The present data should shed light on the development of therapeutics for COVID-19, and optimization of GRL-0920 based on the present data is essential to develop more-potent anti-SARS-CoV-2 compounds for treating COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Indoles/pharmacology , Pneumonia, Viral/drug therapy , Amino Acid Sequence , Animals , Betacoronavirus/enzymology , COVID-19 , Chlorocebus aethiops , Chloroquine/pharmacology , Coronavirus 3C Proteases , Coronavirus Infections/virology , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/genetics , Cysteine Endopeptidases/metabolism , Indoles/chemistry , Indoles/therapeutic use , Models, Molecular , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Vero Cells , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism
19.
J Affect Disord ; 277: 337-340, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-722855

ABSTRACT

BACKGROUND: In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms. CASE REPORT: Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS). LIMITATION: This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool. CONCLUSION: This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.


Subject(s)
Bipolar Disorder/etiology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Antibodies, Viral/cerebrospinal fluid , Antipsychotic Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , Bipolar Disorder/cerebrospinal fluid , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Brain/diagnostic imaging , COVID-19 , COVID-19 Testing , Chest Pain , China , Clinical Laboratory Techniques , Cobicistat/therapeutic use , Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Darunavir/therapeutic use , Dyspnea , Fever , Glucocorticoids/therapeutic use , Humans , Indoles/therapeutic use , Magnetic Resonance Imaging , Male , Methylprednisolone/therapeutic use , Middle Aged , Moxifloxacin/therapeutic use , Olanzapine/therapeutic use , Pandemics , Pharyngitis , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2
20.
Arch Virol ; 165(11): 2419-2438, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-709996

ABSTRACT

Coronavirus disease 2019, also known as COVID-19, is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2. The infection has now catapulted into a full-blown pandemic across the world, which has affected more than 2 million people and has led to approximately 150,000 fatalities all over the world (WHO). In this review, we elaborate all currently available data that shed light on possible methods for treatment of COVID-19, such as antiviral drugs, corticosteroids, convalescent plasma, and potentially effective vaccines. Additionally, ongoing and discontinued clinical trials that have been carried out for validating probable treatments for COVID-19 are discussed. The review also elaborates the prospective approach and the possible advantages of using convalescent plasma and stem cells for the improvement of clinical symptoms and meeting the demand for an instantaneous cure.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/prevention & control , Immunologic Factors/therapeutic use , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/pathology , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Coronavirus Infections/virology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive/methods , Indoles/therapeutic use , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pyrazines/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Viral Vaccines/administration & dosage , COVID-19 Serotherapy
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