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Publication
Journal: Iranian Journal of Pharmaceutical Research
February/22/2022
Abstract
This was a randomized, double-blind clinical trial to compare the efficacy and safety of Atazanavir/Ritonavir (ATZ/RTV) with Lopinavir/Ritonavir (LPV/RTV) in moderate Coronavirus disease 2019 (COVID-19). Participants were randomly assigned to receive a single dose of hydroxychloroquine (HCQ) plus ATZ/RTV or LPV/RTV for a minimum of 5 to a maximum of 10 days. The primary outcomes were the reduced length of hospital stay and clinical recovery within 10 days from starting the intervention. The rate of intensive care unit (ICU) admission, intubation, and mortality, the lengths of ICU stay and being intubated, recovery within 14 days, and the frequency of adverse reactions were considered as secondary outcomes. Among 132 enrolled patients, 62 cases in each arm were analyzed at the end of the intervention. Fifty-one (82.3%) cases in the ATZ/RTV arm versus 41 (66.1%) in the LPV/RTV arm were discharged within 10 days (P = 0.06). The median number of the intervention days was 6 (IQR: 5-8) in ATZ/RTV arm versus 7 (IQR: 6-9) in LPV/RTV arm (P = 0.01). The rate and length of ICU admission and intubation (P ≥ 0.99), rate of mortality (P = 0.49), and recovery within 14 days (P = 0.09) were not statistically different between groups. The most reported adverse reactions were nausea and vomiting that all cases were in the LPV/RTV arm (P = 0.006). ATZ/RTV is better tolerated in comparison with LPV/RTV; however, it did not show more efficacy than LPV/RTV in clinical outcomes of COVID-19 in this study.
Keywords: Atazanavir; COVID-19; Hospital stay; Lopinavir; Mortality; Safety.
Publication
Journal: An Pediatr (Engl Ed)
February/22/2022
Abstract
Introduction: Many antiviral agents, such as hydroxychloroquine, have been used to treat COVID-19, without being broadly accepted. QTc prolongation is a worrisome adverse effect, scarcely studied in pediatrics.
Patients and methods: Paediatric patients affected from COVID-19 who received antivirals were matched (1:2) with controls not infected nor exposed. Electrocardiograms were prospectively analyzed at baseline, during the first 72 h of treatment and after 72 h.
Results: Eleven (22.9%) out of 48 patients admitted due to COVID-19 (March-July 2020) received antiviral therapy. All had underlying diseases: congenital heart disease (4/11; 36.4%) and immunosuppression (3/11; 27.3%) stand out. 5/11 (45.5%) received treatment at baseline with a potential effect on QTc. There where no differences observed in the baseline QTc between cases and controls: 414.8 ms (49.2) vs 416.5 ms (29.4), (P = .716). Baseline long QT was observed in 2/11 cases and 2/22. Among cases, 10/11 (90.9%) received hydroxychloroquine, mainly associated with azithromycin (8/11; 72.7%), 3 received lopinavir/ritonavir and one remdesivir. The median increase in QTc after 72 h under treatment was 28.9 ms [IQR 48.7] (P = .062). 4/11 (36.4%) patients had a long QTc at 72 h, resulting in 3 patients ≥500 ms; treatment was stopped in one (QTc 510 ms) but ventricular arrhythmias were not documented.
Conclusions: The use of antivirals caused an increase on the QTc interval after 72 h of treatment, being the QTc long in 36.3% of the patients, although no arrhythmic events were observed. The use of hydroxychloroquine and antivirals requires active QTc monitoring and it is recommended to discontinue treatment if QTc > 500 ms.
Keywords: Azitromicin; Azitromicina; COVID-19; Child; Electrocardiograma; Electrocardiography; Hidroxicloroquina; Hydroxychloroquine; Long QT syndrome; Lopinavir; Pediatría; QT largo; Remdesivir; Ritonavir; SARS-CoV-2; Sars-CoV-2.
Publication
Journal: Iranian Journal of Pharmaceutical Research
February/22/2022
Abstract
Coronavirus disease -19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials.
Keywords: Antiviral; COVID-19; Favipiravir; Lopinavir-ritonavir; SARS-CoV-2.
Publication
Journal: Journal of Molecular Liquids
February/22/2022
Abstract
The widespread outbreak of the novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the main health challenge worldwide. This pandemic has attracted the attention of the research communities in various fields, prompting efforts to discover rapid drug molecules for the treatment of the life-threatening COVID-19 disease. This study is aimed at investigating 4H-chromen-4-one scaffold-containing flavonoids that combat the SARS-CoV-2 virus using computational and in vitro approaches. Virtual screening studies of the molecule's library for 4H-chromen-4-one scaffold were performed with the recently reported coronavirus main protease (Mpro, also called 3CLpro) because it plays an essential role in the maturation and processing of the viral polyprotein. Based on the virtual screening, the top hit molecules such as isoginkgetin and afzelin molecules were selected for further estimating in vitro antiviral efficacies against SARS-CoV-2 in Vero cells. Additionally, these molecules were also docked with RNA-dependent RNA Polymerase (RdRp) to reveal the ligands-protein molecular interaction. In the in vitro study, isoginkgetin showed remarkable inhibition potency against the SARS-CoV-2 virus, with an IC50 value of 22.81 μM, compared to remdesivir, chloroquine, and lopinavir with IC50 values of 7.18, 11.63, and 11.49 μM, respectively. Furthermore, the complex stability of isoginkgetin with an active binding pocket of the SARS-CoV-2 Mpro and RdRp supports its inhibitory potency against the SARS-CoV-2. Thus, isoginkgetin is a potent leading drug candidate and needs to be used in in vivo trials for the treatment of SARS-CoV-2 infected patients.
Keywords: Computational virtual screening; In vitro assay; Isoginkgetin; SARS-CoV-2 Mpro and RdRp; SARS-CoV-2, H-chromen-4-one.
Publication
Journal: Science of the Total Environment
February/18/2022
Abstract
In coronavirus disease 2019 (COVID-19), among many protocols, lopinavir and ritonavir in individual or combined forms with other drugs have been used, causing an increase in the concentration of antiviral drugs in the wastewater and hospital effluents. In conventional wastewater treatment plants, the removal efficiency of various antiviral drugs is estimated to be low (<20%). The high values of predicted no-effect concentration (PNEC) for lopinavir and ritonavir (in ng∙L-1) reveal their high chronic toxicity to aquatic organisms. This indicates that lopinavir and ritonavir are current priority antiviral drugs that need to be thoroughly monitored and effectively removed from any water and wastewater samples. In this study, we attempt to explore the impacts of two photo-induced processes (photolysis and photocatalysis) on the toxicity of treated water and wastewater samples containing lopinavir and ritonavir to zebrafish (Danio rerio) and marine bacteria (Allivibrio fischeri). The obtained results reveal that traces of lopinavir in water under photo-induced processes may cause severe problems for Danio rerio, including pericardial edema and shortening of the tail, affecting its behavior, and for Allivibrio fischeri as a result of the oxygen-depleted environment, inflammation, and oxidative stress. Hence, lopinavir must be removed from water and wastewater before being in contact with light. In contrast, the photo-induced processes of ritonavir-containing water and wastewater reduce the toxicity significantly. This shows that even if the physicochemical parameters of water and wastewater are within the standard requirements/limits, the presence of traces of antiviral drugs and their intermediates can affect the survival and behavior of Danio rerio and Allivibrio fischeri. Therefore, the photo-induced processes and additional treatment of water and wastewater containing ritonavir can minimize its toxic effect.
Keywords: Antiviral drugs; Ecotoxicity; Lopinavir; Photocatalysis; Photolysis; Ritonavir.
Publication
Journal: Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine
February/16/2022
Abstract
Importance: Coronavirus 2019 pandemic (COVID 19) is caused by the Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) virus. The pandemic is affecting the livelihood of millions of people all over the world. At the time of preparing this report, the pandemic has affected 1 827 284 patients, with 113 031 deaths in 185 countries as per Johns Hopkins University. With no proven treatment for the disease, prevention of the disease in the community and healthcare setting is need of the hour.
Objective: To perform a comprehensive literature search for preventive measures and experimental treatment options. In this review, we have focused our discussion on the risk of disease transmission, supportive treatment, and possible treatment options based on available evidence.
Evidence review: We performed a literature search on google scholar, PubMed, and society guidelines for literature related to COVID 19 and previous coronavirus pandemics. We included data review articles, observational studies, and controlled trials to synthesize the treatment options for COVID 19.
Findings: In this article, we have extensively reviewed and discussed recommendations from various world organizations for the public and healthcare workers. We have also discussed currently available experimental treatments since there is no proven treatment for COVID 19. The best method of dealing with the current outbreak is to reduce the community spread and thus "flatten the curve." Although Hydroxychloroquine, Remdesivir, Lopinavir/Ritonavir, and Azithromycin have been tried, passive immunity through convalescent serum and vaccine is still at an experimental stage. Patients with severe COVID 19 infections could be considered for this experimental treatment through various national randomized control trials, which may eventually lead to an evidence-based treatment strategy.
Conclusions and relevance: Awareness of currently available experimental treatment among healthcare providers and exploration of possible treatment options through evidence is need of the hour. We have discussed the most recently available literature and evidence behind experimental treatment in this article.
Keywords: COVID-19; RT-PCR; Remdesivir; Wuhan; coronavirus; pandemic.
Publication
Journal: Future Virology
February/10/2022
Abstract
Aim: To evaluate the efficacy and safety of lopinavir-ritonavir (LPV/r) therapy in treating hospitalized COVID-19 patients. Materials & methods: Data from randomized and observational studies were included in meta-analyses. Primary outcomes were length of stay, time for SARS-CoV-2 test conversion, mortality, incidence of mechanical ventilation, time to body temperature normalization and incidence of adverse events. Results: Twenty-four studies (n = 10,718) were included. LPV/r demonstrated no significant benefit over the control groups in all efficacy outcomes. The use of LPV/r was associated with a significant increase in the odds of adverse events. Conclusion: Given the lack of efficacy and increased incidence of adverse events, the clinical use of LPV/r in hospitalized COVID-19 patients is not recommended.
Keywords: SARS-CoV-2; adverse events; antiviral; covid-19; lopinavir; mortality; ritonavir.
Publication
Journal: Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive
February/10/2022
Abstract
Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has exploded and led to a global crisis. Currently, the global case numbers topped 200 million, and toll of dead exceeded 4 million around the world. The pathogenesis of coronavirus disease 2019 (COVID-19) is driven by two processes. During the first stage of the infection that lasts around 5-7 days, replication of SARS-CoV-2 occurs. In the second stage, the disease may progress due to an exaggerated inflammatory response leading to tissue damage. Therefore, it is anticipated that antiviral agents would be effective during the early phase of the disease, while immunomodulator agents are likely to be more beneficial in the second stage of COVID-19. This basic concept of disease development led to explore several antiviral and immunomodulator agents for the treatment of COVID-19. Currently, remdesivir is the only available Food and Drug Administration-approved antiviral agent for the treatment of COVID-19. However, some other agents have been approved by various mechanisms, including Emergency Use Authorizations, Emergency Investigational New Drug applications, compassionate use or expanded access programs. In addition, a variety of repurposed agents that were approved for other indications are being investigated for the treatment of COVID19 in clinical trials. A myriad of publications including randomized controlled trials (RCTs) are emerging continuously and are accessible as peer-reviewed, pre-print and press release formats. Considering the critical importance of RCTs in generating evidence and providing further guidance on COVID-19 treatment, we herein reviewed only RCTs and meta-analyses. The discussion includes antiviral agents (hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir and ivermectin) and, various immunomodulatory drugs (corticosteroids, tocilizumab, baricitinib, and IL-1 inhibitors). Other investigational therapies including darunavir/cobicistat, umifenovir, sofosbuvir/daclatasvir, sofobuvir/ledipasvir, ribavirin, nitazoxanide and interferon-based regimens were not evaluated due to insufficient data on the efficacy and safety of these agents.
Keywords: COVID-19; SARS-CoV-2; baricitinib; dexamethasone; remdesivir.
Publication
Journal: Frontiers in Public Health
February/6/2022
Abstract
Background: COVID-19 is causing a grave global health and economic crisis and the fight against the pandemic has led to unprecedented scientific activity. Bibliometrics could be a useful tool for guiding future researches lines and promoting international collaboration for an effective treatment. For this purpose, we have conducted a bibliometric analysis of scientific publications on drugs and therapies used to treat COVID-19 during 2020.
Methods: Data source: Web of Science. We gathered data on scientific production relating to drugs used to treat COVID-19. We calculated impact factors and analyzed production by institution, country, and journal, visualizing our results in bibliometric networks.
Results: In 1 year, production relating to COVID-19 exceeded 100 000 publications, with over 6,500 on Drugs and COVID-19. Research into hydroxychloroquine and chloroquine, remdesivir, lopinavir and ritonavir, tocilizumab and convalescent plasma is particularly noteworthy. Mean citations/study range from 11.9 to 15.4. Producer institutions fall into three groups: one in the US and centered on Harvard Medical School; another in Europe led by INSERS; and another in China led by Huazhong University of Science and Technology. Production by journal is widespread but the Journal of Medical Virology, International Journal of Antimicrobial Agents, and American Journal of Transplantation are noteworthy.
Conclusions: The volume of research that is currently under way is comparable to the magnitude of the pandemic itself. Such a high volume of studies is infrequent and the impact they have achieved has no known precedent. The producing countries are those with highest incidence of the pandemic and greatest scientific potential; moreover, inter-agency and international collaboration has reached extraordinarily high levels.
Keywords: COVID-19; SARS-CoV-2; bibliometric analysis; bibliometric network; pharmacologic treatments; scientific production; visualization.
Publication
Journal: Journal of Pediatric Gastroenterology and Nutrition
February/6/2022
Abstract
Abstract: Histamine is a biogenic amine distributed extensively in the human cells. Histamine is linked with different inflammatory and allergic disorders through promoting of chemoatractant activity and endothelial changes. Antihistamine drugs are effective in the treatment and prevention of infection of influenza H7N9 through inhibition of viral entry to the host cells. A multiplicity of search strategies including experimental, preclinical and clinical studies were taken on and assumed to review the potential role of H1, H2 or their combination in the management of Coronavirus disease 2019 (Covid-19). Histamine release is associated with early and late pathology of Covid-19 and clinical presentation. Despite the potential effect of famotidine in attenuating the pathogenesis of Covid-19, famotidine has no direct effect on the replication of SARS-CoV-2. However, azelastine (H1receptor blocker) used for allergic rhinitis as nasal spray has potential anti-SARS-CoV-2 activity comparable to that of remdesivir, lopinavir and chloroquine. Azelastine is more effective than other agents that are used in the management of Covid-19 due to significant inhibition of endosomal acidification at respiratory epithelial cells. However, famotidine and cetirizine combination improve clinical outcome and reduce intubation and duration of hospitalization in Covid-19 patients. Taken together, hospitalised Covid-19 patients treated with famotidine only showed more complications as compared with those treated with combination of famotidine and cetirizine.
Conclusions: Both H1 and H2 blockade are effective in the management of Covid-19 patients through antiviral and anti-inflammatory properties, which together reduce the risk of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).
Keywords: Coronavirus disease 2019, Acute lung injury (ALI), Acute respiratory distress syndrome (ARDS)..
Publication
Journal: Saudi Pharmaceutical Journal
February/6/2022
Abstract
Background: Since the World Health Organization declared coronavirus disease (COVID-19) as a pandemic, most countries started treating their patients with various therapies. However, the data regarding their safety and effectiveness is still lacking.
Objectives: We aimed to evaluate the adverse drug reactions (ADRs) incidence and their predisposing factors among COVID-19 patients.
Methods: A retrospective observational study that was conducted at a tertiary academic hospital from March - June 2020. Patients were included if they were ≥ 18 years old, inpatient, had a reverse transcriptase-polymerase chain reaction (PCR) positive for COVID-19, and were treated with; (lopinavir-ritonavir, hydroxychloroquine, chloroquine, favipiravir, ribavirin, or interferon-ß) either as monotherapy or combination therapy for three days or longer. The data of eligible patients were retrieved from the electronic medical records. A standardized data collection form was designed to collect patient demographics, COVID-19 severity based on the Saudi Ministry of Health management protocols, antiviral therapies, duration of therapy, and length of stay (LOS). The ADRs were identified via conducting a comprehensive review using predefined triggers and were evaluated using Naranjo Score.
<strong class="sub-title"> Results: </strong> A total of 155 patients were included of which 123 (79.4%) were males. In our sample, the incidence proportion of ADRs per patient was 72.3%. A total of 287 ADRs were identified most of them were hepatic (n = <b>101</b>, 35.2%), gastrointestinal (n = <b>59</b>, 20.6%), hematological (n = <b>47</b>, 16%), and endocrine (n = <b>45</b>, 15%). Hydroxychloroquine was the most common drug associated with ADRs (n = <b>155</b>). The length of stay (10 - 20 days) was the only statistically significant with the ADR incidence (p-value = 0.008; 95 %CI 1.216:3.568).
Conclusions: The ADRs are prevalent among COVID-19 patients, which assure the importance of implementing active hospital-based pharmacovigilance systems.
Keywords: Adverse drug events; Adverse drug reactions; Coronavirus disease 2019; Infectious diseases; Pharmacoepidemiology; Pharmacovigilance.
Publication
Journal: European Journal of Clinical Pharmacology
January/27/2022
Abstract
Purpose: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has affected millions all over the world and has been declared pandemic, as of 11 March 2020. In addition to the ongoing research and development of vaccines, there is still a dire need for safe and effective drugs for the control and treatment against the SARS-CoV-2 virus infection. Numerous repurposed drugs are under clinical investigations whose reported adverse events can raise worries about their safety. The aim of this review is to illuminate the associated adverse events related to the drugs used in a real COVID-19 setting along with their relevant mechanism(s).
Method: Through a literature search conducted on PubMed and Google Scholar database, various adverse events suspected to be induced by eight drugs, including dexamethasone, hydroxychloroquine, chloroquine, remdesivir, favipiravir, lopinavir/ritonavir, ivermectin, and tocilizumab, administered in COVID-19 patients in clinical practice and studies were identified in 30 case reports, 3 case series, and 10 randomized clinical trials.
Results: Mild, moderate, or severe adverse events of numerous repurposed and investigational drugs caused by various factors and mechanisms were observed. Gastrointestinal side effects such as nausea, abdominal cramps, diarrhea, and vomiting were the most frequently followed by cardiovascular, cutaneous, and hepatic adverse events. Few other rare adverse drug reactions were also observed.
Conclusion: In light of their ineffectiveness against COVID-19 as evident in large clinical studies, drugs including hydroxychloroquine, lopinavir/ritonavir, and ivermectin should neither be used routinely nor in clinical studies. While lack of sufficient data, it creates doubt regarding the reliability of chloroquine and favipiravir use in COVID-19 patients. Hence, these two drugs can only be used in clinical studies. In contrast, ample well-conducted studies have approved the use of remdesivir, tocilizumab, and dexamethasone under certain conditions in COVID-19 patients. Consequently, it is significant to establish a strong surveillance system in order to monitor the proper safety and toxicity profile of the potential anti-COVID-19 drugs with good clinical outcomes.
Keywords: Adverse drug reactions; Adverse events; COVID-19; Pharmacovigilance.
Publication
Journal: Journal of Hazardous Materials
January/24/2022
Abstract
The use of antiviral drugs has surged as a result of the COVID-19 pandemic, resulting in higher concentrations of these pharmaceuticals in wastewater. The degradation efficiency of antiviral drugs in wastewater treatment plants has been reported to be too low due to their hydrophilic nature, and an additional procedure is usually necessary to degrade them completely. Photocatalysis is regarded as one of the most effective processes to degrade antiviral drugs. The present study aims at synthesizing multiphase photocatalysts by a simple calcination of industrial waste from ammonium molybdate production (WU photocatalysts) and its combination with WO3 (WW photocatalysts). The X-ray diffraction (XRD) results confirm that the presence of multiple crystalline phases in the synthesized photocatalysts. UV-Vis diffuse reflectance spectra reveal that the synthesized multiphase photocatalysts absorb visible light up to 620 nm. Effects of calcination temperature of industrial waste (550-950 °C) and WO3 content (0-100%) on photocatalytic activity of multiphase photocatalysts (WU and WW) for efficient removal of SARS-CoV-2 antiviral drugs (lopinavir and ritonavir) in model and real wastewaters are studied. The highest k1 value is observed for the photocatalytic removal of ritonavir from model wastewater using WW4 (35.64 ×10-2 min-1). The multiphase photocatalysts exhibit 95% efficiency in the photocatalytic removal of ritonavir within 15 of visible light irradiation. In contrast, 60 min of visible light irradiation is necessary to achieve 95% efficiency in the photocatalytic removal of lopinavir. The ecotoxicity test using zebrafish (Danio rerio) embryos shows no toxicity for photocatalytically treated ritonavir-containing wastewater, and the contrary trend is observed for photocatalytically treated lopinavir-containing wastewater. The synthesized multiphase photocatalysts can be tested and applied for efficient degradation of other SARS-CoV-2 antiviral drugs in wastewater in the future.
Keywords: Antiviral drugs; Industrial waste; Multiphase photocatalyst; SARS-CoV-2; Water pollution; Water purification.
Publication
Journal: World Journal of Hepatology
January/23/2022
Abstract
Coronavirus disease 2019 has a wide range of clinical spectrum from asymptomatic infection to severe infection resulting in death within a short time. Currently, it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only cause a respiratory tract infection but a more complicated disease that can lead to multiple system involvement including the liver. Herein, we evaluate the epidemiology, the impact of liver injury/ dysfunction on disease prognosis, the pathophysiological mechanisms and management of liver injury. More than one-fourth of the patients have abnormal liver function tests, mostly a mild-to-moderate liver dysfunction. Liver injury is significantly associated with a poor clinical outcome. Direct cytotoxic effect of SARS-CoV-2, the immune response ("cytokine storm"), the complications related to the disease, and drugs used in the treatments are the pathophysiological mechanisms responsible for liver injury. However, the exact mechanism is not yet clearly explained. The binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 receptors and entering the hepatocyte and cholangiocytes can cause cytotoxic effects on the liver. Excessive immune response has an important role in disease progression and causes acute respiratory distress syndrome and multi-organ failures accompanied by liver injury. Treatment drugs, particularly lopinavir/ritonavir, remdesivir and antibiotics are a frequent reason for liver injury. The possible reasons should be meticulously investigated and resolved.
Keywords: COVID-19; Chronic liver disease; Liver dysfunction; Liver injury; Pathophysiology; SARS-CoV-2.
Publication
Journal: World Journal of Hepatology
January/23/2022
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.
Keywords: COVID-19 treatment; COVID-19 vaccine; Chronic liver disease; Gastrointestinal side effects; Hepatic side effects; Liver transplantation.
Publication
Journal: Ginekologia Polska
January/23/2022
Abstract
Objectives: The current study aimed to describe the incidence of abnormal liver function tests (LFTs) in pregnant COVID-19 patients, explore the association between LFTs with current medication, and provide a reference for medical therapy of pregnant patients with COVID-19.
Material and methods: This retrospective single tertiary center cohort study included 122 pregnant patients with confirmed COVID-19 admitted and treated from April 1, 2020, to May 31, 2020. We defined abnormal LFTs as the elevation of the following liver enzymes in serum per our hospital's laboratory reference range standards: AST > 35 U/L, ALT > 35 U/L, and TBIL > 1.2 mg/dL. We evaluated patients for demographic and clinical features, laboratory parameters, medications, and hospital length of stay (LOS).
Results: Patients in this cohort had clinical presentations of fever (84.4%), dry cough (78.6%), and shortness of breathing (6.5%). In total, 17 (13.9%) patients had abnormal LFTs during hospitalization. Critically ill patients were three-fold higher in the abnormal LFTs group (11.8%) than in the normal LFTs group (3.8%, p = 0.16). The proportion of patients who used hydroxychloroquine and lopinavir/ritonavir were significantly higher in patients with abnormal LFTs (88.2% and 35.3%, respectively) than those with normal LFTs (62.9% and 15.2%, p = 0.04 and p = 0.04, respectively). The hospital length of stay (LOS) was significantly longer in the abnormal LFTs group (8.2 ± 5.8 days) than in the normal LFT group (6.0 ± 2.8 days, p = 0.02).
Conclusions: SARS-CoV-2 may induce liver injury and the LFT abnormality was generally mild in pregnant patients with COVID-19. Abnormal LFTs are associated with prolonged hospital LOS. Drug use was the most crucial risk factor for liver injury during hospitalization. The use of lopinavir/ritonavir and hydroxychloroquine were significantly higher, and the course of treatment of these drugs was significantly longer in pregnant women with abnormal LFTs than the patients with normal LFTs. Therefore, pregnant women with COVID-19 who received antiviral treatment should be closely monitored for evaluating LFTs.
Keywords: COVID-19; SARS-CoV-2; liver function test; pregnancy.
Publication
Journal: Biology
January/20/2022
Abstract
(1) Background: The antiviral treatment for COVID-19 disease started to be largely used in 2020 and has been found to be efficient, although it is not specific for SARS-CoV-2 virus. There were some concerns that it may produce liver damage or other side effects. (2) Methods: The aim of this study was to observe if antiviral therapy is affecting liver parameters or producing other side-effects in patients hospitalized for COVID-19 disease. The study included a group of patients hospitalized in the internal medicine department of Oradea Municipal Clinical Hospital, Romania, between August 2020-June 2021, diagnosed with SARS-CoV-2 viral infection by RT-PCR method or rapid antigen test. During hospitalization, patients were treated with a Lopinavir/Ritonavir (Kaletra) combination, or with Favipiravir or Remdesivir. In addition to monitoring the evolution of the disease (clinical and biochemical), also hepatic parameters were analyzed at admission, during hospitalization, and at discharge. (3) Results: In the group of studied patients, the mean value of aspartat aminotrensferase did not increase above normal at discharge, alanin aminotransferase increased, but below twice the normal values, and cholestasis registered a statistically insignificant slight increase. (4) Conclusions: In our study, we found that all three antivirals were generally well tolerated and their use did not alter liver function in a significant manner.
Keywords: COVID-19; antivirals; coronavirus; hepatic parameters.
Publication
Journal: World Journal of Gastroenterology
January/19/2022
Abstract
Background: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity.
Aim: To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes.
Methods: We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes.
Results: The prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028).
Conclusion: Patients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.
Keywords: COVID-19; Disease severity; Gastrointestinal manifestations; Intensive care unit admission; Mechanical ventilation; Mortality.
Publication
Journal: Archiv der Pharmazie
January/17/2022
Abstract
The outbreak of the coronavirus pandemic COVID-19 created by its severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) variant, known for producing a very severe acute respiratory syndrome, has created an unprecedented situation by its continual assault around the world. The crisis caused by the SARS-CoV-2 variant has been a global challenge, calling to mitigate this unprecedented pandemic that has engulfed the whole world. Since the outbreak and spread of COVID-19, many researchers globally have been grappling to find new clinically trialed active drugs with anti-COVID-19 activity, from antimalarial drugs to JAK inhibitors, antiviral drugs, immune suppressants, and so forth. This article presents a brief discussion on the activity and synthesis of some active molecules such as favipiravir, hydroxychloroquine, pirfenidone, remdesivir, lopinavir, camostat, chloroquine, baricitinib, molnupiravir, and so forth, which are under trial.
Keywords: COVID-19 pandemic; Delta+ variant; SARS-CoV-2 variant; lopinavir; remdesivir.
Publication
Journal: Molecular Diversity
January/9/2022
Abstract
Coronavirus disease 2019 (COVID-19) is caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2). Its main protease, 3C-like protease (3CLpro), is an attractive target for drug design, due to its importance in virus replication. The analysis of the radial distribution function of 159 3CLpro structures reveals a high similarity index. A study of the catalytic pocket of 3CLpro with bound inhibitors reveals that the influence of the inhibitors is local, perturbing dominantly only residues in the active pocket. A machine learning based model with high predictive ability against SARS-CoV-2 3CLpro is designed and validated. The model is used to perform a drug-repurposing study, with the main aim to identify existing drugs with the highest 3CLpro inhibition power. Among antiviral agents, lopinavir, idoxuridine, paritaprevir, and favipiravir showed the highest inhibition potential. Enzyme - ligand interactions as a key ingredient for successful drug design.
Keywords: 3CLpro; COVID-19; Drug repurposing; Paritaprevir; QSAR; Radial distribution function.
Publication
Journal: Journal of Cardiovascular Pharmacology and Therapeutics
January/9/2022
Abstract
Background: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population.
Methods: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms).
Results: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation (P = .004 for the likelihood-ratio test).
Conclusion: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.
Keywords: COVID-19; QTc; SARS-CoV-2; critically ill; prolongation.
Publication
Journal: Drug Resistance Updates
January/6/2022
Abstract
The COVID-19 pandemic is one of the greatest threats to human health in the 21st century with more than 257 million cases and over 5.17 million deaths reported worldwide (as of November 23, 2021. Various agents were initially proclaimed to be effective against SARS-CoV-2, the etiological agent of COVID-19. Hydroxychloroquine, lopinavir/ritonavir, and ribavirin are all examples of therapeutic agents, whose efficacy against COVID-19 was later disproved. Meanwhile, concentrated efforts of researchers and clinicians worldwide have led to the identification of novel therapeutic options to control the disease including PAXLOVID™ (PF-07321332). Although COVID-19 cases are currently treated using a comprehensive approach of anticoagulants, oxygen, and antibiotics, the novel Pfizer agent PAXLOVID™ (PF-07321332), an investigational COVID-19 oral antiviral candidate, significantly reduced hospitalization time and death rates, based on an interim analysis of the phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomized, double-blind study of non-hospitalized adult patients with COVID-19, who are at high risk of progressing to severe illness. The scheduled interim analysis demonstrated an 89 % reduction in risk of COVID-19-related hospitalization or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint). However, there still exists a great need for the development of additional treatments, as the recommended therapeutic options are insufficient in many cases. Thus far, mRNA and vector vaccines appear to be the most effective modalities to control the pandemic. In the current review, we provide an update on the progress that has been made since April 2020 in clinical trials concerning the effectiveness of therapies available to combat COVID-19. We focus on currently recommended therapeutic agents, including steroids, various monoclonal antibodies, remdesivir, baricitinib, anticoagulants and PAXLOVID™ summarizing the latest original studies and meta-analyses. Moreover, we aim to discuss other currently and previously studied agents targeting COVID-19 that either show no or only limited therapeutic activity. The results of recent studies report that hydroxychloroquine and convalescent plasma demonstrate no efficacy against SARS-CoV-2 infection. Lastly, we summarize the studies on various drugs with incoherent or insufficient data concerning their effectiveness, such as amantadine, ivermectin, or niclosamide.
Keywords: Baricitinib; COVID-19; Casirivimab; Dexamethasone; Imdevimab; Omicron; Paxlovid; Remdesivir; SARS-CoV-2; Sotrovimab; Tocilizumab.
Publication
Journal: Medical Journal of the Islamic Republic of Iran
December/26/2021
Abstract
Background: The COVID-19 infection is a novel virus without any specific targeted therapies; thus, focusing on primary epidemiologic concerns, preventive strategies, risk factors, exacerbation factors, and mortality-related factors are of great importance to better control this disorder. There are some controversies about the factors associated with COVID-19 in different theories, and addiction is no exception. Methods: We conducted a large cross-sectional study of 513 hospitalized Iranian patients with COVID-19 infection to evaluate the severity of disease courses in patients with or without history of opium addiction. We recorded these data retrospectively after patients' discharge from the hospital. For the quantitative data, we used independent-samples t and Mann-Whitney tests. The qualitative data were calculated using Fisher exact and chi-square tests in IBM SPSS Statistics Version 22. Also, p<0.05 was considered statistically significant. Results: There was no significant difference regarding mean days of hospitalization in opium positive and negative groups (7.95±8.39 vs 8.35±5.11, respectively) (p=0.771); however, the need for intensive care unit (ICU) admission was significantly higher in the opium positive group (36% vs 11%) (p=0.005). The mean days of ICU stay was significantly higher in the opium positive group (2.36±3.81 vs 0.86±2.90) (p=0.026). The percentage of febrile patients, anosmia/hyposmia, and dysgeusia at the initiation of hospitalization was significantly lower in the opium positive group (39% vs 66%; 8% vs 23%; 8% vs; 20%, respectively) (p=0.002, 0.018, and.031, respectively). In the laboratory tests, only the white blood cell (WBC) count and the segmented cells were higher in the opium positive group (10.1±6.60 vs 7.38±4.14 and 73±20.47 vs 56.5±32.60, respectively) (p=0.018 and.001, respectively) and lymphocytes were lower in the opium positive (15.60±8.25 vs18.70±10.12) (p=0.048). Opium addicts had a significantly lower rate of azithromycin and lopinavir/ritonavir prescription in their initiation therapy (19% vs 34%, and 47% vs 70%, respectively) (p=0.038 and 0.012, respectively). Conclusion: Opium addict patients with COVID infection may be more febrile and experience more disease-specific symptoms and more severe disease course. These patients may show more evidence of laboratory inflammation and probable superinfections, so may manage with more caution and somehow different therapeutic regimen.
Keywords: Addiction; COVID-19; Corona; Drug Abuse; Opium; Outcome; SARS-CoV-2; Severity; Substance.
Publication
Journal: Frontiers in Bioscience - Elite
December/22/2021
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a lethal virus that was detected back on 31st December 2019 in Wuhan, Hubei province in China, and since then this virus has been spreading across the globe causing a global outbreak and has left the world fighting against the virus. The disease caused by the SARS-CoV-2 was named COVID-19 and this was declared a pandemic disease by the World Health Organization on 11th March 2020. Several nations are trying to develop a vaccine that can save millions of lives. This review outlines the morphological features of the virus describing the outer and inner structures of the virus along with the entry mechanism of the virus into the host body and the infection process. Detailed reports of global outbreak along with preventive measures have also been included, with special emphasis on China, the United States of America, India, Italy, and South Korea. Broad-spectrum antiviral drugs being used at various health care centres around the world, namely Remdesivir, Camostat & Nafamostat, Famotidine, Chloroquine & Hydroxychloroquine, Lopinavir/ritonavir, Ivermectin, and Tocilizumab & Sarilumab have also been included. World Health Organization guidelines on preventive measures and use of soaps, alcohol-based hand-rubs and wearing face masks have also been described. The vaccines that are in one of the phases of human trials, namely Oxford University's vaccine, the United States-based Moderna's vaccine, India's Covaxin and the Russian vaccine, have also been incorporated in the review article.
Keywords: COVID-19; Global outbreak; Morphology; Oxford’s vaccine; Remdesivir; SARS-CoV-2.
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