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1.
International Journal of Current Pharmaceutical Research ; 14(2):11-14, 2022.
Article in English | EMBASE | ID: covidwho-1822679

ABSTRACT

Covid 19, the disease first identified in the Chine city of Wuhan in December 2019 had been declared as a pandemic by WHO. This pandemic caused by Sars Cov 2 has resulted in 165.5 million infections and 3.5 million deaths globally, as of now. Till now no drug isavailable to fight against this deadly disease. The strategy adopted by drug discovery groups is drug repurposing which has not met much success with chloroquine as well as remdesivir. A relatively new candidate in the fray is favipravir which was originally developed by Toyama chemical company against influenza strains. Few synthetic routes are developed for this compound and the safety concerns are relatively few. If favourable results from the ongoing clinicaltrials arise, that may provide the therapeutic community a lethalweapon against the virus.

2.
Biomedical and Pharmacology Journal ; 15(1):543-552, 2022.
Article in English | EMBASE | ID: covidwho-1822622

ABSTRACT

The primary motive of this study was to examine advantages of allometry scaling strategies for correct prediction of pharmacokinetics of Baricitinib in human from preclinical species. Baricitinib is basically Janus kinase (JAK) inhibitor used for the treatment of rheumatoid arthritis. Currently approved by FDA in combination with remdesivir for treatment of COVID-19 hospitalized patient. The literature published pharmacokinetic parameters (Cl and Vd) of preclinical species (Rat, Dog and monkey) were utilized for the allometry scaling of Baricitinib. The connection among the primary pharmacokinetic parameters [Volume of distribution (Vd) and clearance (Cl)] and body weight (BW) were studied across three preclinical species, we used the double logarithmic plots for prediction of the human pharmacokinetic parameters i.e. Cl and Vd with use of simple allometry and with additional correction factors for better prediction. The dose extrapolation of baricitinib was carried out by FDA guidelines. By application of the allometric scaling methods and principles correlation was found to be satisfactory for the prediction of intravenous human Cl and Vd for baricitinib. The volume of distribution (Vd) predicted by simple allometry (65.3 L) was found to be in agreement with the reported value (75.5 L);clearance (Cl) prediction by simple allometry was found to be at least 1.06 -closer to the reported value (245 mL/min);CF were used to predict the clearance. Both brain weight (B.W) and maximum life span potential (MLP) predicted the Cl with 0.52- and 0.61 -fold difference. The application of monkey liver blood flow predicted Cl with 0.81 fold which was also in close agreement with reported value. The Cl prediction was also extrapolated using LBF (Liver blood flow) method and observed that the higher species (Dog and Monkey) have predicted Cl with better accuracy than rat. Overall, the simple allometry (SA), monkey liver blood flow (MLBF) and application of liver blood flow (LBF) methods showed excellent correlation with human. The time vs. plasma concentration simulated graph also showed the similar closeness with human profile. The inclusion of plasma protein binding factor didn't improve the prediction accuracy. The FIH dose extrapolation were showed that PK guided approach and exponent for BSA based approach was found closer to actual human dose of 4.0 mg/Kg. Oriental Scientific Publishing Company

3.
Chinese Medicine (United Kingdom) ; 17(1), 2022.
Article in English | EMBASE | ID: covidwho-1822198

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. Purpose: In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS’s clinical efficacy and safety in COVID-19. Methods: The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. Results: The results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α). Conclusion: LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.

4.
International Journal of Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-1821282

ABSTRACT

Objectives The effectiveness of 3-days course remdesivir to prevent severe disease in COVID-19 solid organ transplant (SOT) recipients is unknown. We wanted to study the efficacy of this therapeutic option in COVID-19 SOT recipients in preventing both hospitalisations, if outpatients, and clinical worsening due to COVID-19, if already hospitalised for other reasons. Methods This is a single-centre, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted all the data of COVID-19 SOT recipients who received and did not receive pre-emptive remdesivir between 23 December 2021 and 26 February 2022. We used a Cox proportional hazard model to assess whether receiving pre-emptive remdesivir was associated with lower rates of hospitalisation. Results Twenty-four SOT patients were identified. Among these, seven patients (29,1%) received pre-emptive remdesivir, whereas 17 (70,9%) patients did not. Receiving remdesivir significantly reduced the hospitalisation rate in SOT outpatients and the clinical worsening of already hospitalised SOT patients (HR 0.05;CI [0.00–0.65] p = 0.01). Conclusion In our cohort of SARS-CoV-2 infected SOT recipients, pre-emptive remdesivir was effective in reducing the hospitalisation rate due to COVID-19 and in preventing the clinical worsening of the SOT patients hospitalized for reasons other than COVID-19.

5.
Antiviral Research ; : 105329, 2022.
Article in English | ScienceDirect | ID: covidwho-1819427

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, has infected over 260 million people over the past 2 years. Remdesivir (RDV, VEKLURY®) is currently the only antiviral therapy fully approved by the FDA for the treatment of COVID-19. The parent nucleoside of RDV, GS-441524, exhibits antiviral activity against numerous respiratory viruses including SARS-CoV-2, although at reduced in vitro potency compared to RDV in most assays. Here we find in both human alveolar and bronchial primary cells, GS-441524 is metabolized to the pharmacologically active GS-441524 triphosphate (TP) less efficiently than RDV, which correlates with a lower in vitro SARS-CoV-2 antiviral activity. In vivo, African green monkeys (AGM) orally dosed with GS-441524 yielded low plasma levels due to limited oral bioavailability of <10%. When GS-441524 was delivered via intravenous (IV) administration, although plasma concentrations of GS-441524 were significantly higher, lung TP levels were lower than observed from IV RDV. To determine the required systemic exposure of GS-441524 associated with in vivo antiviral efficacy, SARS-CoV-2 infected AGMs were treated with a once-daily IV dose of either 7.5 or 20 mg/kg GS-441524 or IV RDV for 5 days and compared to vehicle control. Despite the reduced lung TP formation compared to IV dosing of RDV, daily treatment with IV GS-441524 resulted in dose-dependent efficacy, with the 20 mg/kg GS-441524 treatment resulting in significant reductions of SARS-CoV-2 replication in the lower respiratory tract of infected animals. These findings demonstrate the in vivo SARS-CoV-2 antiviral efficacy of GS-441524 and support evaluation of its orally bioavailable prodrugs as potential therapies for COVID-19.

6.
Journal of Medical Virology ; n/a(n/a), 2022.
Article in English | Wiley | ID: covidwho-1819371

ABSTRACT

We aimed to assess longitudinal changes in clinical indexes of Covid-19 patients with mild pulmonary infection during 5 days of remdesivir therapy, and determine the effect of age and gender on remdesivir adverse effects (AE). Patients' clinical data including inflammatory markers, liver and renal function tests, and heart rate (HR) were extracted from medical records. Linear mixed model (LMM) was used to analyze longitudinal changes in patients' clinical indexes. Gender and age were inserted in LMM as covariates to find their correlation with AE and clinical indexes. Of 84 patients, 35 patients met our criteria for the study. There were significant increases in mean levels of white blood cell (WBC) (p=0.005), alanine aminotransferase (ALT) (p=0.001), aspartate aminotransferase (AST) (p=0.001), blood urea nitrogen (BUN) (p=0.001), and creatinine (p=0.006) while mean levels of erythrocyte sedimentation rate (ESR) (p=0.005), C-reactive protein (CRP) (p=0.001), alkaline phosphatase (ALP) (p=0.001), and potassium (p=0.003) decreased, significantly. Estimated glomerular filtration rate (eGFR) (p=0.001) and HR (p=0.001) showed a notable decline over the course of treatment. LMM analysis showed that mean changes in WBC (?=0.94, p=0.029), creatinine (?=0.12, p=0.020), and HR (?=6.47, p=0.008) were greater in males than females. Also, age of patients had a significant effect on the mean changes of WBC (?= -0.02, p=0.023), sodium (?= -0.06, p=0.010), BUN (?=0.23, p=0.001), and HR (?= -0.29, p=0.001). Despite no renal and liver dysfunction, Covid-19 patients with mild pulmonary infection may develop some remdesivir AE, and attributed side effects might be affected by gender and age of patients.This article is protected by copyright. All rights reserved.

7.
Revue Medicale Suisse ; 17(756):1850-1854, 2021.
Article in French | EMBASE | ID: covidwho-1819193

ABSTRACT

Between mid-October 2020 and mid-January 2021, during the second wave of COVID-19 pandemia, 125 patients have been admitted in the intensive care units of Neuchâtel network hospitals. To manage this flow, the bed capacity of intensive care unit increased by 240%. Each patient received corticosteroids, an increased prophylactic anticoagulation and an antibiotic. Similarly to the first wave, 51% patients received mechanical ventilation, 55% of which in prone position. Concerning the drug treatments, 16 patients were treated with tocilizumab and 4 with remdesivir. Despite an unprecedented rise in the number of ventilated beds, 15 patients were transferred out of the region of Neuchâtel in order to prevent a saturation point of the system. The mortality rate in the intensive care unit reached 16% of the admitted and non-transported patients.

8.
Journal of Nephropathology ; 11(2):1-8, 2022.
Article in English | Academic Search Complete | ID: covidwho-1819109

ABSTRACT

Introduction: Kidney transplant recipients appear to be at high risk for severe COVID-19 illness due to chronic immunosuppression and coexisting conditions. Objectives: We aimed to study the clinical characteristics, laboratory and radiological results, treatment aspects and clinical outcomes of kidney transplant patients with COVID-19. Patient and Methods: Twenty consecutive kidney transplant patients with COVID-19 pneumonia from two tertiary care centers from India were retrospectively studied from July 1 to Oct 31, 2020. Results: Of 20 patients, 18 required admission;mean age was 42.8±9.39 years and 18 out of 20 (90%) were male. Symptom onset to testing time was a mean of 3.05±1.47 days. All patients were on triple immunosuppression. The median time since transplantation to COVID-19 was 3.75 years (IQR 2.37-5.41). Fever, cough and breathlessness were the most common presenting symptoms. Nine out of twenty (45%) had severe COVID-19 while six out of 20 (30%) required intensive care. Twelve (60%) patients had lymphopenia. Additionally mycophenolate was withheld in seventeen out of twenty (85 %) and enoxaparin and intravenous methylprednisolone were administered in all hospitalized patients while remdesivir was prescribed in 16 out of 20 (80%). Moreover, acute kidney injury (AKI) was seen in five out of 20 (25%) since one of died (5%). After a median hospital stay of 8.5 days (IQR 6.75-15.5), seventeen patients were discharged from the hospital. Conclusion: COVID-19 infection in kidney transplant recipients is usually a moderate-severe form. COVID-19 should be a differential diagnosis for fever in this high-risk population however lymphopenia may not be seen in all. Antimetabolite withdrawal, intravenous steroid, anticoagulation and early remdesivir were all found to be safe and effective strategies for improving outcomes. Early diagnosis and timely treatment may decrease mortality in this high-risk population. [ FROM AUTHOR] Copyright of Journal of Nephropathology is the property of Isfahan University of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

9.
Chinese Pharmacological Bulletin ; 37(8):1037-1041, 2021.
Article in Chinese | EMBASE | ID: covidwho-1818309

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. The life cycle of SARS-CoV-2 is not clear, which is one of the reasons that only Remdesivir has been approved by FDA for treating COVID-19. Although some new vaccines have been a- vailable, the quick mutations of SARS-CoV-2 affect the effectiveness of vaccines, calling for further assessment of the persistence and safety of vaccines. Therefore, drug treatment and prevention are still effective ways to deal with the epidemic of SARS-CoV-2. The article briefly summarizes the molecular mechanism of SARS-CoV-2 entry based on the existing literature. This virus enters the cell through two main ways, that is, spike protein mediating membrane fusion with plasma membrane or endosome membrane. According to the targets, the article summarizes the reported inhibitors of SARS-CoV-2 entry into cells, aiming to provide a reference for following research and clinical application of anti-SARS-CoV-2 drugs.

10.
Journal of Pharmacopuncture ; 24(4):165-172, 2021.
Article in English | EMBASE | ID: covidwho-1818249

ABSTRACT

The COVID-19, the most infectious pandemic disease arising due to SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused huge issues globally. In this review, we discuss the impact of COVID-19 on the immune system of the human body and the protective mechanisms of the host immune system opposing viral infections. Here, we summarize the effect of the pandemic of the novel coronavirus disease on the immune system such as sleep and Behavioral Immune System (BIS) together with consideration of researcher’s observation points of view. We draw particular attention to recent up-to-date reports concerning COVID-19 drugs as well as information about the landscape document for COVID-19 vaccines released by WHO (World Health Organization), and some adverse events of COVID-19 vaccination. Additionally, can take part in the preventive appraise in opposition within this pandemic severe COVID-19 infections disease may affect some outcome in physical exercise, physical movement, healthy diets, and good nutrition are significant for supporting the immune systems and summarize AYUSH (Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy) Indian medicinal systems guidelines for immunity boosting procedures during COVID-19 pandemic.

11.
Ren Replace Ther ; 7(1): 59, 2021.
Article in English | MEDLINE | ID: covidwho-1817287

ABSTRACT

BACKGROUND: The Japanese Association of Dialysis Physicians, the Japanese Society for Dialysis Therapy, and the Japanese Society of Nephrology jointly established COVID-19 Task Force Committee and began surveying the number of newly infected patients. METHODS: This registry of the COVID-19 Task Force Committee was used to collect data of dialysis patients; a total of 1010 dialysis patients with COVID-19 were included in the analysis. Overall survival of patients was investigated with stratification by age group, complication status, and treatment. In addition, predictive factors for mortality were also investigated. The overall survival was estimated by Kaplan-Meier methods and compared by using log-rank test. Multivariate analysis was performed to identify the risk factor of mortality. For all statistical analyses, p < 0.05 was considered to be statistically significant. RESULTS: The mortality risk was increased with age (p < 0.001). The mortality risk was significantly higher in patients with peripheral arterial disease (HR: 1.49, 95% CI 1.05-2.10) and significantly lower in patients who were treated with remdesivir (HR: 0.60, 95% CI 0.37-0.98). Multivariate analysis showed increased risk of mortality with increment in BMI, and increment in CRP, and decreased risk with increment in albumin. CONCLUSION: Dialysis patients have a high severity of illness and a high risk of mortality in cases of COVID-19. Treatment with remdesivir might be effective in shortening the duration of hospitalization and reducing the risk of mortality.

12.
Clinical and Translational Science ; 15(4):813-815, 2022.
Article in English | EMBASE | ID: covidwho-1816543
13.
International Journal of Pharmacy Practice ; 30(SUPPL 1):i5, 2022.
Article in English | EMBASE | ID: covidwho-1816109

ABSTRACT

Introduction: Despite COVID-19 being a viral illness, antibiotic use has been more prevalent. In addition, co-infection (3.5%) and secondary infection (14.3%) were relatively low in hospitalised patients with COVID-19. A major concern is the increased risk of antimicrobial resistance (AMR) due to inappropriate antibiotic consumption (1). Aim: This review aims to evaluate antimicrobial consumption (excluding repurposed drugs such as remdesivir) in hospitals and determine the prevalence of COVID-19 patients who received antibiotic therapy using meta-analysis. Methods: The review was conducted according to PRISMA guidelines (2). The two investigators independently developed and applied eligibility criteria to examine original articles. Studies were eligible for inclusion if they met the following criteria: (i) original research studies with a minimum sample of 50 patients;(ii) focussed on antibiotic consumption (AMC);(iii) patients with COVID-19 or consumption amid COVID-19 pandemic;(iv) any age group or gender;and (v) reported in the English language. The included articles were retrieved from MEDLINE, CINAHL, WHO COVID-19 databases, including studies published in EMBASE, Scopus, WHO-COVID, and LILACS between December 2019 to July 2021. The modified version of Newcastle-Ottawa Scale (NOS) was used to measure biases in included studies after the consensus by both authors. The random-effects model was used to estimate the pooled prevalence or proportion of AMC among hospitalized COVID-19 patients. Results: A total of 34 studies conducted among hospitalised COVID-19 patients were included. The extracted studies presented AMC in defined daily doses (DDD) or frequency and percentages. Azithromycin was the most frequently prescribed antibiotic in almost all studies. The meta-analysis that examined overall AMC using data from 25 studies (17 studies from high income countries and eight from low-middle income countires) revealed 69% (95% CI:63%-74%) of hospitalized COVID-19 received at least one course of antibiotics. The sub-group analysis of studies from high income countries (HICs) revealed 59% (95% CI: 51%-66%) consumed antibiotics compared with 89% (95% CI: 82% to 94%) among hospitalised COVID-19 patients in low-middle income countries (LMICs). Conclusion: This review highlights the trend of antibiotic consumption in hospitalised COVID-19 patients. A significant rise in antibiotic consumption was observed in LMICs and increased antibiotic consumption in the first few months of the COVID-19 pandemic in HIC. The review outcomes emphasised the importance of rational and judicious use of antimicrobial therapy as well as to strenghting the antimicrobial stewardship policies and activities, particularly during a global pandemic. The limitation of the review undertaken was not identified incidence of co-infection and don't include studies on reported AMC in immunocompromised patients.

14.
Journal of Aerosol Medicine and Pulmonary Drug Delivery ; 35(2):A2, 2022.
Article in English | EMBASE | ID: covidwho-1815946

ABSTRACT

SARS-CoV-2 is a coronavirus that infects epithelial cells in the naso- and oropharynx before infecting epithelial cells of the lower airways and alveoli and in severe COVID-19 spreading systemically and inducing a systemic inflammatory response. SARS-CoV-2 is spread mainly by virus particles in droplets and aerosols. This suggests that inhaled therapies may be useful in the treatment of early COVID-19 disease before severe respiratory systemic features develop and potentially in reducing transmission of the virus in the community. To be effective any inhaled therapy must be rapidly acting to prevent viral replication in respiratory epithelial cells to prevent the disease spreading down the respiratory tract and into the systemic circulation. It also needs to be safe and available for early prescription in order to prevent severe disease and hospitalisation. The development of inhaled therapies for COVID-19 may involved repurposing of existing inhaled therapies or developing inhaled formulations of new drugs with antiviral effects. Patients with asthma and COPD were reported to be less likely to be hospitalised with SARS-CoV-2 infection despite the concern that this coronavirus would have severe consequences for these patients as coronaviruses are known to trigger severe exacerbations. One possibility was that this may be due to the widespread treatment with inhaled corticosteroids (ICS), which are known to suppress ACE2 and TMPRSS2 on epithelial cells that are key entry receptors for the virus and also reduce virus replication in vitro. A community based open label parallel group phase 2 study of the ICS budesonide (800 lg bid until recovery) in people with early symptoms (within 7 days of onset) of COVID-19 and confirmed by PCR testing (STOIC) showed that only 1/69 people in the ICS group developed severe disease compared with 10/70 in the usual care group.1 Clinical recovery was also shorter in the ICS group. This finding was confirmed in an open label study of inhaled budesonide in individuals over the age of 65 years at risk from severe COVID-19 (PRINCIPLE), which showed a reduction in time to recovery and a trend towards reduced hospitalisation and death.2 Several other trials, including double-blind studies, of ICS in early COVID-19 are currently underway with different corticosteroids, including ciclesonide, which appears to be the most effective against SARS-CoV-2 in vitro.3 However, a recent double-blind study of nasal and inhaled ciclesonide failed to show any benefit in early COVID-19, although the population was mainly young adults who have a low risk of disease progression.4 The mechanism of action of ICS in COVID- 19 has not yet been established, but may involve reduced viral entry due to suppression of ACE2 and TMPRSS2 in airway epithelial cells, reduced viral proliferation or reduced inflammatory mediators secreted by airway epithelial cells that may promote viral spreading. Interferon b1 is currently approve for treating multiple sclerosis. Nebulised IFN-b1a (SNG001) gave a greater degree of clinical improvement in hospitalised COVID-19 patients and a reduction on symptoms (mainly dyspnoea) compared to with placebo and was well tolerated.5 However, studies in early disease are underway but have not yet been reported, although there are logistical problems in the need for a nebuliser to deliver the drug. Inhaled PUL-42 is a combination of a TLR2/6 and a TLR9 inhibitors which is effective in a single inhaled dose against SARS-CoV and MERS-CoV infection in mice and reduces the lung viral load.6 This drug is now in clinical trials for COVID-19. Other inhaled drugs, including antivirals such as remdesivir and niclosamide, are also in development.

15.
Naunyn-Schmiedeberg's Archives of Pharmacology ; 395(SUPPL 1):S21-S22, 2022.
Article in English | EMBASE | ID: covidwho-1813652

ABSTRACT

Question: Prominent opinions, media coverage and guidelines may have an impact on drug usage and subsequent harmful adverse events (AE). The impact of the public attention to drugs by media coverage has been estimated for both prescriptions and purchases. Consequences on drug therapy safety are largely unknown. Methods: We analysed U.S. American pharmacovigilance data using OpenVigil 2 to identify drugs used against coronavirus infections (coded as preferred terms of the Standardized MedDRA Query 'COVID-19 (SMQ)') and their other indications and depicted them weekly aggregated. EMA and FDA approvals and withdrawals, news headlines concerning these drugs and the publication date of scientific papers were annotated in order to explain the temporal change of spontaneous reporting. Results: AE were most commonly reported for the drugs (in descending order): hydroxychloroquine (n=1873, 15.7%), remdesivir (14.2%), bamlanivimab (9.2%), azithromycin (8.2%), tocilizumab (6.2%), ritonavir/lopinavir (4.8%), dexamethasone (4%). Recently emerging trending drugs like ivermectin are yet a minority (0.38%). For all off-label cases, the reported adverse events were mostly not a consequence of the disease but the inappropriate or excess use of the drug. The extracted reports showed, that not only approvals/withdrawals, on- and off-label recommendations, clinical guidelines based on expert opinions and scientific articles, but also prominent lay opinions and rumors in social networks contribute to drug usage and thus subsequent adverse events. E.g., for hydroxychloroquine, the coverage of a prominent opinion in lay media and a subsequent scientific article nine weeks later had the strongest impact on its off-label use against coronavirus infections (fig. 1). Commonly reported adverse events, ranked by their proportional reporting ratio (PRR) were: cardiac arrhythmias like prolonged QT time 27.6 and ventricular extrasystoles 5.8, type IV allergies like eosinophilia 23.2, AGEP 18.4 or DRESS 25.9, electrolyte disturbances like hypernatraemia 20.3. The mortality for the event prolonged QT time associated with hydroxychloroquine was 20.5% when used against COVID-19, as compared to only 11.1% for all other indications (Odds ratio 2.1, p<0.01). Conclusion: Media coverage has an influence on drug usage and subsequent adverse events. A high mortality suggests a patient relevant impact. Lay opinions and social media may account for a loss of drug therapy safety.

17.
Acta Medica Mediterranea ; 38(2):1051-1059, 2022.
Article in English | EMBASE | ID: covidwho-1798621

ABSTRACT

Background/Aim: There is no proven specific or effective treatment for COVID-19 infection;therefore, many drugs are used empirically to establish control of the infection. Viral infection creates an immunologic environment and facilitate drug sensitization. With the advent of new vaccines, the future holds promise for optimism in establishing control of the pandemic. However, even vaccines are not devoid of side effects. In part II of these review series, we aimed to review the published data on mucocutaneous reactions induced by medications used for COVID-19 infection and vaccines used for COVID-19 prophylaxis. Materials and methods: Literature search was performed in the databases PubMed, Scopus, and Web of Science for the relevant studies, starting from the beginning of COVID-19 pandemic until October 2021. Research on animals, studies utilizing in vitro techniques and publications irrelevant to the study’s framework were excluded. Results: The mucocutaneous side effects liable to medications (antimalarials, azithromycin, lopinavir/ritonavir, remdesivir, ribavirin/interferon, oseltamivir/favipiravir, darunavir, imatinib, tocilizumab, anakinra baricitinib, and other Janus kinase inhibitors, immunoglobulin therapy, colchicine, anti-TNF-α biologics, low molecular weight heparins, camostat mesylate) and vaccines used for COVID-19 infection are reviewed herein. Conclusion: There is a great amount of accumulated data regarding the mucocutaneous side effects of drugs and vaccines used for COVID-19 infection. In the pandemic era, it is a major goal to diagnose drug or vaccine-related mucocutaneous eruptions and distinguish them from pathognomonic, specific, or SARS-CoV-2 virus-related cutaneous eruptions. Timely diagnosis of a mucocutaneous drug/ vaccine reaction will allow for identification of the culprit and appropriate management and protect the patient from forthcoming severe drug/ vaccine reactions. Therefore, it is essential for physicians to update their knowledge regularly on mucocutaneous side effects of COVID-19 therapeutics and vaccines.

18.
Pakistan Journal of Medical and Health Sciences ; 16(2):156-157, 2022.
Article in English | EMBASE | ID: covidwho-1798527

ABSTRACT

Aim: To examine the effect of remdesivir for treating non-hospitalized patients with COVID-19. Study design: Retrospective study Place and duration of study: Department of Medicine, Bolan Medical College, Quetta from 1st April 2021 to 30th September 2021. Methodology: One hundred patients were enrolled and divided into group A and group B within the age of 24-70 years. Group A was receiving remdesivir while group B is not receiving remdesivir. The clinical variables, BMI, comorbidities, duration of disease severity and viral load were determined. RT-PCR was conducted to determine viral load. Results: The mean age of study participants was 50±15 years with greater number of males. Diabetes was the major comorbidity. The time duration was decreased in group A upto 5 days and 8 days in group B. The viral load was decreased by mean value 6.32±1.76 to 6.2±1.78 in group B then group A respectively. Conclusion: Remdesivir is effective in COVID-19 treatment.

19.
Journal of Research in Medical and Dental Science ; 10(1):5, 2022.
Article in English | Web of Science | ID: covidwho-1798132

ABSTRACT

Background: COVID-19 is the ongoing pandemic that is adversely affecting millions of individuals all over the planet. Many changes have been done in course of treatment of COVID-19 to rectify the flaws. Mutations can pose serious threat and constant monitoring is needed. Summary: Mutations are the inevitable phenomenon shown by the virus. Novel coronavirus has reported several strains which has been originated from the original strain which was reported from the Chinese's province of Hubei. Mutations pose serious risks to the containment measures of the pandemic. Genome sequencing is used to identify the new strain of the virus. Treatments like HCQ, convalescent plasma therapy, Remdesivir etc. have become redundant and do more harm than good. Selective usage, if necessary, can be done to ensure less harms. Monoclonal antibody therapy is being said to be the next big thing in the treatment of COVID-19. Vaccination is currently the most useful tool available to mitigate the spread of the disease. Conclusion: More genome sequencing should be done to ensure the identification of each and every strain that is being roaming with humans all over the world. Even distribution of the vaccines can help to eliminate the virus from the human life and prevent further mutations.

20.
Infection ; 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1797459

ABSTRACT

PURPOSE: COVID-19 patients on anti-CD20 treatment can suffer a delayed viral clearance and worse clinical outcome. We aim to present our experience with remdesivir treatment in anti-CD20-treated patients with prolonged symptoms, a patient population for which no data from randomized controlled trials are available. METHODS: From the beginning of the pandemic until February 2021, we included all consecutive patients from our healthcare network on anti-CD20 treatment with prolonged COVID-19 symptoms, who received remdesivir. Patient informed consent was gathered and patients' charts were reviewed to collect baseline data, COVID-19 history including time of symptom onset, diagnosis, data on treatment and disease course. Patients or their next of kin were contacted in March 2022 to assess long-term outcomes. RESULTS: We included 11 patients, who received remdesivir at a median of 33 days after diagnosis. Eight patients showed clinical improvement along with reductions in viral loads, one patient with relapsing infection recovered after administration of convalescent plasma, and two patients died. No clinical relapses were reported (median follow-up 13 months), while follow-up PCRs were not performed. One patient died of underlying malignancy 8 months after recovery from COVID-19. CONCLUSIONS: We observed a benefit of antiviral therapy in a majority of COVID-19 patients on anti-CD20 treatment, without any clinical relapses in the 1-year follow-up. Although these data suggest that remdesivir might be a promising management option in patients with delayed viral clearance, the lack of a control group is an important limitation of the study design. TRIAL REGISTRATION: Ethikkommission Ostschweiz, Scheibenackerstrasse 4, CH-9000 St. Gallen approved this case series. Project-ID 2021-00349 EKOS 21/027.

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