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1.
J Gastrointestin Liver Dis ; 29(3): 473-475, 2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-761169
2.
Medicine (Baltimore) ; 99(35): e21810, 2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740205

ABSTRACT

RATIONALE: The clinical manifestations of the SARS-CoV-2 infection are mainly respiratory but the virus can cause a variety of symptoms. Dermatological findings are less well-characterized. Data is scarce on their timing, type and correlation with the immune response. PATIENT CONCERNS: We present the case of SARS-CoV-2 infection in a previously healthy woman who presented with respiratory symptoms and developed anosmia, diarrhea, and an erythematous maculo-papular rash on day 15 from symptom onset. DIAGNOSIS: The nasopharyngeal swab tested by real time PCR for COVID-19 was positive. We interpreted this as a viral exanthema likely caused by an immune response to SARS-CoV-2 nucleotides. INTERVENTIONS: She was treated with Hydroxychloroquine, Azithromycin and Lopinavir/Ritonavir, and the rash with topical corticosteroids. OUTCOMES: All symptoms resolved except for anosmia which persisted for 6 weeks. At the 4- and 6-weeks follow-up the IgG titers for SARS-CoV-2 were high. LESSONS: We must consider that SARS-CoV-2 has a multi-organ tropism. In our case, the SARS-CoV-2 infection had lung, nasopharyngeal, neurological, digestive, and skin manifestations. Identifying the different manifestations is useful for understanding the extent of SARS-CoV-2 infection. We not only present a rare manifestation but also suggest that cutaneous manifestations may correlate with immunity.


Subject(s)
Azithromycin/administration & dosage , Betacoronavirus , Coronavirus Infections , Exanthema , Glucocorticoids/administration & dosage , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pandemics , Pneumonia, Viral , Ritonavir/administration & dosage , Administration, Topical , Adult , Antiviral Agents/administration & dosage , Betacoronavirus/immunology , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Drug Combinations , Exanthema/diagnosis , Exanthema/drug therapy , Exanthema/etiology , Exanthema/immunology , Female , Humans , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Symptom Assessment/methods , Treatment Outcome
3.
Am J Gastroenterol ; 115(10): 1716-1718, 2020 10.
Article in English | MEDLINE | ID: covidwho-732652

ABSTRACT

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.


Subject(s)
Antiviral Agents/adverse effects , Coronavirus Infections/drug therapy , Jaundice/chemically induced , Lopinavir/adverse effects , Pneumonia, Viral/drug therapy , Ritonavir/adverse effects , Aged , Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Combinations , Female , Humans , Intensive Care Units/statistics & numerical data , Jaundice/diagnosis , Jaundice/epidemiology , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prospective Studies , Retrospective Studies , Ritonavir/administration & dosage , Severity of Illness Index , Standard of Care/statistics & numerical data
4.
Int J Antimicrob Agents ; 56(4): 106142, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-726536

ABSTRACT

This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57-79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3-5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08-117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03-1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36-12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.


Subject(s)
Anti-Infective Agents/administration & dosage , Azithromycin/administration & dosage , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Ritonavir/administration & dosage , Aged , Anti-Infective Agents/adverse effects , Azithromycin/adverse effects , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Biomarkers/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Coronavirus Infections/virology , Disease Progression , Drug Combinations , Female , Humans , Hydroxychloroquine/adverse effects , Intensive Care Units , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/physiopathology , Lopinavir/adverse effects , Lymphocytes/pathology , Lymphocytes/virology , Male , Middle Aged , Neutrophils/pathology , Neutrophils/virology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Prognosis , Proportional Hazards Models , Retrospective Studies , Ritonavir/adverse effects , Treatment Outcome , Troponin I/blood
6.
J Antimicrob Chemother ; 75(9): 2657-2660, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-705983

ABSTRACT

BACKGROUND: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir. OBJECTIVES: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir. PATIENTS AND METHODS: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored. RESULTS: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735). CONCLUSIONS: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Intensive Care Units/trends , Lopinavir/blood , Pneumonia, Viral/blood , Respiration, Artificial/trends , Ritonavir/blood , Administration, Oral , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/blood , Drug Therapy, Combination , Female , Humans , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/pharmacokinetics , Pneumonia, Viral/drug therapy , Prospective Studies , Ritonavir/administration & dosage
7.
Medwave ; 20(6): e7967, 2020 Jul 15.
Article in English | MEDLINE | ID: covidwho-680506

ABSTRACT

Objective: Provide a timely, rigorous, and continuously updated summary of the evidence on the role of lopinavir/ritonavir in the treatment of patients with COVID-19. Methods: We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in PubMed, Embase, CENTRAL, and other 33 sources. We searched for randomized trials and non-randomized studies evaluating the effect of lopinavir/ritonavir versus placebo or no treatment in patients with COVID-19. Two reviewers independently evaluated potentially eligible studies, according to predefined selection criteria, and extracted data using a predesigned standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. Results: Our search strategy yielded 862 references. Finally, we identified 12 studies, including two randomized trials, evaluating lopinavir/ritonavir, in addition to standard care versus standard care alone in 250 adult inpatients with COVID-19. The evidence from randomized trials shows lopinavir/ritonavir may reduce mortality (relative risk: 0.77; 95% confidence interval: 0.45 to 1.3; low certainty evidence), but the anticipated magnitude of the absolute reduction in mortality, varies across different risk groups. Lopinavir/ritonavir also had a slight reduction in the risk of requiring invasive mechanical ventilation, developing respiratory failure, or acute respiratory distress syndrome. However, it did not lead to any difference in the duration of hospitalization and may lead to an increase in the number of total adverse effects. The overall certainty of the evidence was low or very low. Conclusions: For severe and critical patients with COVID-19, lopinavir/ritonavir might play a role in improving outcomes, but the available evidence is still limited. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon.


Subject(s)
Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Ritonavir/administration & dosage , Adult , Antiviral Agents/adverse effects , Drug Combinations , Humans , Lopinavir/adverse effects , Pandemics , Randomized Controlled Trials as Topic , Ritonavir/adverse effects , Treatment Outcome
8.
Trials ; 21(1): 646, 2020 Jul 14.
Article in English | MEDLINE | ID: covidwho-670196

ABSTRACT

OBJECTIVES: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. TRIAL DESIGN: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. PARTICIPANTS: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently. INTERVENTION AND COMPARATOR: Participants will be randomised 1:1:1:1 to: Group 1: standard of care; Group 2: lopinavir (400mg) / ritonavir (100mg) twice daily for 10 days in tablet form; Group 3: hydroxychloroquine (800mg) 4x200mg administered 12 hours apart on Day 1, followed by 400mg twice a day for 6 days; Group 4: lopinavir /ritonavir plus hydroxychloroquine. MAIN OUTCOMES: Proportion of participants alive and not having required intensive respiratory support (invasive or non-invasive ventilation) at 15 days after enrolment. A range of clinical and virological secondary outcomes will also be evaluated. RANDOMISATION: The randomisation schedule will be generated by an independent statistician. Randomisation will be stratified by site and will be in permuted blocks of variable block size. The randomised sequence allocation will only be accessible to the data management group, and site investigators will have individual participant allocation provided through a web-based trial enrolment platform. BLINDING (MASKING): This is an open-label study, with researchers assessing the laboratory outcomes blinded to treatment allocation. No unblinding procedures relating to potential adverse effects are therefore required. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We assumed that 5% of participants receiving standard of care would meet the primary outcome, aimed to evaluate whether interventions could lead to a relative risk of 0.5, assuming no interaction between intervention arms. This corresponds to a required sample size of 610 per arm, with a 5% two-sided significance level (alpha) and 80% power. The total sample size therefore is planned to be 2440. TRIAL STATUS: ASCOT protocol version 3, May 5, 2020. Recruitment opened April 4, 2020 and is ongoing, with planned completion of enrolment July 31, 2021. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12620000445976 ). Prospectively registered April 6, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Hydroxychloroquine/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Randomized Controlled Trials as Topic , Ritonavir/administration & dosage , Standard of Care , Drug Therapy, Combination , Hospitalization , Humans , Pandemics
9.
J Antimicrob Chemother ; 75(9): 2657-2660, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-657048

ABSTRACT

BACKGROUND: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir. OBJECTIVES: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir. PATIENTS AND METHODS: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored. RESULTS: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735). CONCLUSIONS: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.


Subject(s)
Betacoronavirus , Coronavirus Infections/blood , Intensive Care Units/trends , Lopinavir/blood , Pneumonia, Viral/blood , Respiration, Artificial/trends , Ritonavir/blood , Administration, Oral , Coronavirus Infections/drug therapy , Cytochrome P-450 CYP3A Inhibitors/administration & dosage , Cytochrome P-450 CYP3A Inhibitors/blood , Drug Therapy, Combination , Female , Humans , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pharmaceutical Solutions/administration & dosage , Pharmaceutical Solutions/pharmacokinetics , Pneumonia, Viral/drug therapy , Prospective Studies , Ritonavir/administration & dosage
10.
Medwave ; 20(6): e7967, 2020 Jul 15.
Article in English | MEDLINE | ID: covidwho-652986

ABSTRACT

Objective: Provide a timely, rigorous, and continuously updated summary of the evidence on the role of lopinavir/ritonavir in the treatment of patients with COVID-19. Methods: We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in PubMed, Embase, CENTRAL, and other 33 sources. We searched for randomized trials and non-randomized studies evaluating the effect of lopinavir/ritonavir versus placebo or no treatment in patients with COVID-19. Two reviewers independently evaluated potentially eligible studies, according to predefined selection criteria, and extracted data using a predesigned standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. Results: Our search strategy yielded 862 references. Finally, we identified 12 studies, including two randomized trials, evaluating lopinavir/ritonavir, in addition to standard care versus standard care alone in 250 adult inpatients with COVID-19. The evidence from randomized trials shows lopinavir/ritonavir may reduce mortality (relative risk: 0.77; 95% confidence interval: 0.45 to 1.3; low certainty evidence), but the anticipated magnitude of the absolute reduction in mortality, varies across different risk groups. Lopinavir/ritonavir also had a slight reduction in the risk of requiring invasive mechanical ventilation, developing respiratory failure, or acute respiratory distress syndrome. However, it did not lead to any difference in the duration of hospitalization and may lead to an increase in the number of total adverse effects. The overall certainty of the evidence was low or very low. Conclusions: For severe and critical patients with COVID-19, lopinavir/ritonavir might play a role in improving outcomes, but the available evidence is still limited. A substantial number of ongoing studies should provide valuable evidence to inform researchers and decision-makers soon.


Subject(s)
Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Ritonavir/administration & dosage , Adult , Antiviral Agents/adverse effects , Drug Combinations , Humans , Lopinavir/adverse effects , Pandemics , Randomized Controlled Trials as Topic , Ritonavir/adverse effects , Treatment Outcome
12.
Article in English | MEDLINE | ID: covidwho-654072

ABSTRACT

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.


Subject(s)
Antiviral Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/drug therapy , Interferon-alpha/therapeutic use , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Child , China/epidemiology , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Drug Therapy, Combination , Female , Hospital Mortality , Host Microbial Interactions/drug effects , Humans , Indoles/administration & dosage , Interferon-alpha/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Retrospective Studies , Ritonavir/administration & dosage , Treatment Outcome , Young Adult
13.
Chin J Integr Med ; 26(9): 648-655, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-648556

ABSTRACT

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Interferon-alpha/administration & dosage , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Severe Acute Respiratory Syndrome/drug therapy , Administration, Inhalation , Adult , China , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Integrative Medicine , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Risk Assessment , Severe Acute Respiratory Syndrome/diagnosis , Severe Acute Respiratory Syndrome/mortality , Severity of Illness Index , Survival Rate
17.
Trials ; 21(1): 622, 2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-635315

ABSTRACT

BACKGROUND: The outbreak of COVID-19 (caused by SARS-Cov-2) is very serious, and no effective antiviral treatment has yet been confirmed. The adage "old drug, new trick" in this context may suggest the important therapeutic potential of existing drugs. We found that the lopinavir/ritonavir treatment recommended in the fifth edition of the Treatment Plan of China can only help to improve a minority of throat-swab nucleic-acid results (3/15) in hospitals. Our previous use of chloroquine to treat patients with COVID-19 infection showed an improvement in more throat-swab nucleic-acid results (5/10) than the use of lopinavir/ritonavir. METHODS/DESIGN: This is a prospective, open-label, randomized controlled, multicenter clinical study. The study consists of three phases: a screening period, a treatment period of no more than 10 days, and a follow-up period for each participant. Participants with COVID-19 infection who are eligible for selection for the study will be randomly allocated to the trial group or the control group. The control group will be given lopinavir/ritonavir treatment for no more than 10 days. The trial group will be given chloroquine phosphate treatment for no more than 10 days. The primary outcome is the clinical recovery time at no more than 28 days after the completion of therapy and follow-up. The secondary outcomes include the rate of treatment success after the completion of therapy and follow-up, the time of treatment success after no more than 28 days, the rate of serious adverse events during the completion of therapy and follow-up, and the time to return to normal temperature (calculated from the onset of illness) during the completion of therapy and follow-up. Comparisons will be performed using two-sided tests with a statistical significance level of 5%. DISCUSSION: This experiment should reveal the efficacy and safety of using chloroquine versus lopinavir/ritonavir for patients with mild/general COVID-19 infection. If the new treatment including chloroquine shows a higher rate of throat-swab SARS-CoV-2 real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) negativity and is safe, it could be tested as a future COVID-19 treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR2000029741 . Registered on 11 February 2020.


Subject(s)
Betacoronavirus , Chloroquine/therapeutic use , Coronavirus Infections/drug therapy , Lopinavir/administration & dosage , Pneumonia, Viral/drug therapy , Ritonavir/administration & dosage , Chloroquine/adverse effects , Drug Therapy, Combination , Humans , Lopinavir/adverse effects , Pandemics , Prospective Studies , Ritonavir/adverse effects
19.
Biomed Pharmacother ; 129: 110500, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-622561

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19)2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD)3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19. METHODS: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment. RESULTS: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P <  0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P <  0.05), and C-reactive protein and creatine kinase were the most pronounced (P <  0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P >  0.05). CONCLUSION: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here.


Subject(s)
Antiviral Agents/administration & dosage , Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/administration & dosage , Pneumonia, Viral/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Coronavirus Infections/mortality , Coronavirus Infections/virology , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Indoles/administration & dosage , Interferons/administration & dosage , Length of Stay , Lopinavir/administration & dosage , Male , Middle Aged , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
20.
Farm Hosp ; 44(7): 49-52, 2020 06 12.
Article in English | MEDLINE | ID: covidwho-603418

ABSTRACT

As in other areas of the health system, COVID-19 has had a dramatic impact on  hospital compounding. This area has faced numerous challenges, including the  shortage of frequent-use products (hydroalcoholic solutions, lopinavir/ritonavir  suspension), the use of new preparations for SARS-CoV-2 (tocilizumab,  remdesivir), or requests from overwhelmed wards unable to assume the safe  preparation of a high volume of medications (intravenous solutions). The  demand for all types of preparations (topic and oral medications, intravenous  solutions) has increased dramatically. This increase has highlighted the shortage of resources allocated to this area, which has made it difficult to meet the high  demand for preparations. In addition, the pandemic has revealed the scarcity of  research on such basic aspects as agent stability and drug compatibility. One of  the most relevant conclusions drawn from the COVID-19 pandemic is that the  basic areas of hospital pharmacy, along with other, must be maintained and  reinforced, as these are the areas that make us essential.


Subject(s)
Betacoronavirus , Coronavirus Infections/drug therapy , Drug Compounding , Pandemics , Pharmacy Service, Hospital/organization & administration , Pneumonia, Viral/drug therapy , Administration, Oral , Antiviral Agents/supply & distribution , Antiviral Agents/therapeutic use , Blood Component Transfusion , Disinfection , Drug Administration Routes , Drug Interactions , Drug Stability , Equipment Contamination/prevention & control , Excipients , Forecasting , Home Care Services , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/chemistry , Infusions, Intravenous , Lopinavir/administration & dosage , Personal Protective Equipment/supply & distribution , Platelet-Rich Plasma , Ritonavir/administration & dosage , Solutions
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