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Cardiac findings in a phase II double-blind randomized placebo-controlled trial of combination therapy (HAZDPac) to treat COVID-19 patients.
Hazan, S, Vidal, AC, Hulscher, N, Goudzwaard, A, McCullough, PA, Steinberg, AA
BMC cardiovascular disorders. 2024;(1):710
Abstract
OBJECTIVE Hydroxychloroquine paired with Azithromycin, Vitamin C, Vitamin D, and Zinc (HAZDPac), was used as a multidrug therapy method to treat COVID-19 illness and superimposed secondary bacterial pneumonia. Concerns have been raised though about such combinations regarding cardiac QTc interval prolongation and risks of arrhythmias, which we set out to address in this study. DESIGN We evaluated cardiac safety in a Phase II Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy to Treat COVID-19 Infections study, conducted by ProgenaBiome. Acutely ill patients with COVID-19 had QTc intervals recorded in an outpatient setting utilizing a continuously worn EKG monitor for the duration of the 10 days treatment. QTc intervals were normally distributed. Two-sample t-tests were used to measure any significant differences in QTc intervals between treatment and placebo groups. RESULTS Between March 2020 and June 2021, 118 COVID-19 patients were recruited and signed informed consent, of which 83 were enrolled for a Double-Blind Randomized Placebo-Controlled Trial. Of the 83, 52 patients were randomly assigned to receive HAZDPac treatment, and 31 patients to receive placebo. Overall, and in stratified analysis by gender, maximum QTc values of patients in the treatment arm were normal and no differences were observed when compared to maximum QTc values from patients in the placebo arm (p ≥ 0.15). There were no adverse events related to HAZDPac treatment. CONCLUSION We found that the outpatient treatment of COVID-19 patients with HAZDPac which includes Hydroxychloroquine and Azithromycin, was not associated with prolongation of QTc compared to placebo and QTc remained within normal range. CLINICAL TRIAL Clinical Trial NCT04482686, clinicaltrials.gov, date of registration 07/21/2020.
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COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign.
Mead, MN, Seneff, S, Wolfinger, R, Rose, J, Denhaerynck, K, Kirsch, S, McCullough, PA
Cureus. 2024;(1):e52876
Abstract
Our understanding of COVID-19 vaccinations and their impact on health and mortality has evolved substantially since the first vaccine rollouts. Published reports from the original randomized phase 3 trials concluded that the COVID-19 mRNA vaccines could greatly reduce COVID-19 symptoms. In the interim, problems with the methods, execution, and reporting of these pivotal trials have emerged. Re-analysis of the Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) in the vaccine group. Numerous SAEs were identified following the Emergency Use Authorization (EUA), including death, cancer, cardiac events, and various autoimmune, hematological, reproductive, and neurological disorders. Furthermore, these products never underwent adequate safety and toxicological testing in accordance with previously established scientific standards. Among the other major topics addressed in this narrative review are the published analyses of serious harms to humans, quality control issues and process-related impurities, mechanisms underlying adverse events (AEs), the immunologic basis for vaccine inefficacy, and concerning mortality trends based on the registrational trial data. The risk-benefit imbalance substantiated by the evidence to date contraindicates further booster injections and suggests that, at a minimum, the mRNA injections should be removed from the childhood immunization program until proper safety and toxicological studies are conducted. Federal agency approval of the COVID-19 mRNA vaccines on a blanket-coverage population-wide basis had no support from an honest assessment of all relevant registrational data and commensurate consideration of risks versus benefits. Given the extensive, well-documented SAEs and unacceptably high harm-to-reward ratio, we urge governments to endorse a global moratorium on the modified mRNA products until all relevant questions pertaining to causality, residual DNA, and aberrant protein production are answered.
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Barbaloin: an amazing chemical from the 'wonder plant' with multidimensional pharmacological attributes.
Mitra, SS, Ghorai, M, Nandy, S, Mukherjee, N, Kumar, M, Radha, , Ghosh, A, Jha, NK, Proćków, J, Dey, A
Naunyn-Schmiedeberg's archives of pharmacology. 2022;(12):1525-1536
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Abstract
Aloe vera (L.) Burm.f. is nicknamed the 'Miracle plant' or sometimes as the 'Wonder plant'. It is a plant that has been used since ancient times for the innumerable health benefits associated with it. It is one of the important plants that has its use in conventional medicinal treatments. It is a perennial succulent, drought-tolerant member of the family Asphodelaceae. There are scores of properties associated with the plant that help in curing various forms of human ailments. Extracts and gels obtained from plants have been shown to be wonderful healers of different conditions, mainly various skin problems. Also, this plant is popular in the cosmetics industry. The underlying properties of the plant are now mainly associated with the natural phytochemicals present in the plant. Diverse groups of phytoingredients are found in the plant, including various phenolics, amino acids, sugars, vitamins, and different other organic compounds, too. One of the primary ingredients found in the plant is the aloin molecule. It is an anthraquinone derivative and exists as an isomer of Aloin A and Aloin B. Barbaloin belonging to the first group is a glucoside of the aloe-emodin anthrone molecule. Various types of pharmacological properties exhibited by the plant can be attributed to this chemical. Few significant ones are antioxidant, anti-inflammatory, anti-diabetic, anti-cancer, anti-microbial, and anti-viral, along with their different immunity-boosting actions. Recently, molecular coupling studies have also found the role of these molecules as a potential cure against the ongoing COVID-19 disease. This study comprehensively focuses on the numerous pharmacological actions of the primary compound barbaloin obtained from the Aloe vera plant along with the mechanism of action and the potent application of these natural molecules under various conditions.
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Multifaceted role of natural sources for COVID-19 pandemic as marine drugs.
Rahman, MM, Islam, MR, Shohag, S, Hossain, ME, Shah, M, Shuvo, SK, Khan, H, Chowdhury, MAR, Bulbul, IJ, Hossain, MS, et al
Environmental science and pollution research international. 2022;(31):46527-46550
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COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.
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COVID-19 mortality and its predictors in the elderly: A systematic review.
Dadras, O, SeyedAlinaghi, S, Karimi, A, Shamsabadi, A, Qaderi, K, Ramezani, M, Mirghaderi, SP, Mahdiabadi, S, Vahedi, F, Saeidi, S, et al
Health science reports. 2022;(3):e657
Abstract
BACKGROUND AND AIMS Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to systematically review the mortality in coronavirus disease 2019 (COVID-19) patients and its predictors in this age group. METHODS We searched PubMed, Web of Science, and Science Direct using relevant keywords. Retrieved records underwent a two-step screening process consisting of title/abstract and full-text screenings to identify the eligible studies. RESULTS Summarizing findings of 35 studies demonstrated that older patients have higher mortality rates compared to the younger population. A review of articles revealed that increasing age, body mass index, a male gender, dementia, impairment or dependency in daily activities, presence of consolidations on chest X-ray, hypoxemic respiratory failure, and lower oxygen saturation at admission were risk factors for death. High d-dimer levels, 25-hydroxy vitamin D serum deficiencies, high C-reactive protein (≥5 mg/L) levels plus any other abnormalities of lymphocyte, higher blood urea nitrogen or lactate dehydrogenase, and higher platelet count were predictors of poor prognosis and mortality in the elderly. Studies have also shown that previous treatment with renin-angiotensin-aldosterone system inhibitors, pharmacological treatments of respiratory disorders, antibiotics, corticosteroids, vitamin K antagonist, antihistamines, azithromycin, Itolizumab (an anti-CD6 monoclonal antibody) in combination with other antivirals reduces COVID-19 worsening and mortality. Vaccination against seasonal influenza might also reduce COVID-19 mortality. CONCLUSION Overall, a critical consideration is necessary for the care and management of COVID-19 in the aged population considering the drastic contrasts in manifestation and prognosis compared to other age groups. Mortality from COVID-19 is independently associated with the patient's age. Elderly patients with COVID-19 are more vulnerable to poor outcomes. Thus, strict preventive measures, timely diagnosis, and aggressive therapeutic/nontherapeutic care are of great importance to reduce acute respiratory distress syndrome and severe complications in older people.
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Clinical and Scientific Rationale for the "MATH+" Hospital Treatment Protocol for COVID-19.
Kory, P, Meduri, GU, Iglesias, J, Varon, J, Marik, PE
Journal of intensive care medicine. 2021;(2):135-156
Abstract
In December 2019, COVID-19, a severe respiratory illness caused by the new coronavirus SARS-CoV-2 (COVID-19) emerged in Wuhan, China. The greatest impact that COVID-19 had was on intensive care units (ICUs), given that approximately 20% of hospitalized cases developed acute respiratory failure (ARF) requiring ICU admission. Based on the assumption that COVID-19 represented a viral pneumonia and no anti-coronaviral therapy existed, nearly all national and international health care societies' recommended "supportive care only" avoiding other therapies outside of randomized controlled trials, with a specific prohibition against the use of corticosteroids in treatment. However, early studies of COVID-19-associated ARF reported inexplicably high mortality rates, with frequent prolonged durations of mechanical ventilation (MV), even from centers expert in such supportive care strategies. These reports led the authors to form a clinical expert panel called the Front-Line COVID-19 Critical Care Alliance (www.flccc.net). The panel collaboratively reviewed the emerging clinical, radiographic, and pathological reports of COVID-19 while initiating multiple discussions among a wide clinical network of front-line clinical ICU experts from initial outbreak areas in China, Italy, and New York. Based on the shared early impressions of "what was working and what wasn't working," the increasing medical journal publications and the rapidly accumulating personal clinical experiences with COVID-19 patients, a treatment protocol was created for the hospitalized patients based on the core therapies of methylprednisolone, ascorbic acid, thiamine, heparin and co-interventions (MATH+). This manuscript reviews the scientific and clinical rationale behind MATH+ based on published in-vitro, pre-clinical, and clinical data in support of each medicine, with a special emphasis of studies supporting their use in the treatment of patients with viral syndromes and COVID-19 specifically. The review concludes with a comparison of published multi-national mortality data with MATH+ center outcomes.
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Impact of the third wave of the COVID-19 pandemic and interventions to contain the virus on society and patients with kidney disease in Cambodia.
Nov, T, Hyodo, T, Kitajima, Y, Kokubo, K, Naganuma, T, Wakai, H, Yamashita, A, Phon, E, Kawanishi, H
Renal replacement therapy. 2021;(1):53
Abstract
Cambodia detected its first case of COVID-19 just 3 days before WHO declared that the outbreak constituted as PHEIC. As of February 15, 2021, and after two major outbreaks, only 479 cases had been reported, 396 (83%) of which were imported. This small number of cases was largely thanks to stringent measures and policies put in place by the government to curb the spread. Despite these efforts, a third cluster outbreak was declared on February 20, 2021. It has disrupted all aspects of life in Cambodia. As in many other countries affected by the virus, economic hardship, lockdowns in cities, and food insecurity ensued. Against the backdrop of this widespread impact on the citizens of Cambodia, we conducted this review article to better understand the situation of healthcare workers in nephrology and dialysis patients and the challenge they face in providing and receiving essential medical care. Healthcare providers have continued working to serve their patients despite facing a high risk of catching SARS-CoV-2 and other challenges including difficulties in traveling to work, increased physical and mental burden, and higher stress due to measures taken to minimize the risk of transmission during patients' care. Some healthcare workers have been discriminated against by neighbors. The most difficult mission is when having to deal with families whose loved one is denied access to a hemodialysis session due to suspected COVID-19 while waiting for PCR test results. Hemodialysis patients reported facing economic hardship and increasingly difficult circumstances. When access to food is limited, patients have eaten canned or dried salted food rather than an appropriate hemodialysis diet. Because hemodialysis centers are concentrated in a few cities, access has become even harder during the travel ban. In-center hemodialysis rules are stricter and does not allow family members or escorts to enter the unit. Only a few hemodialysis patients have been vaccinated. Before COVID-19, hemodialysis patients already faced major burdens. The pandemic appears to be decreasing their quality of life and survival even further. Through this study, we have revealed current hardships and the need to improve the situations for both healthcare workers in nephrology and hemodialysis patients in Cambodia.
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Extracorporeal membrane oxygenation support for SARS-CoV-2: a multi-centered, prospective, observational study in critically ill 92 patients in Saudi Arabia.
Alhumaid, S, Al Mutair, A, Alghazal, HA, Alhaddad, AJ, Al-Helal, H, Al Salman, SA, Alali, J, Almahmoud, S, Alhejy, ZM, Albagshi, AA, et al
European journal of medical research. 2021;(1):141
Abstract
BACKGROUND Extracorporeal membrane oxygenation (ECMO) has been used as a rescue strategy in patients with severe with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection, but there has been little evidence of its efficacy. OBJECTIVES To describe the effect of ECMO rescue therapy on patient-important outcomes in patients with severe SARS-CoV-2. METHODS A case series study was conducted for the laboratory-confirmed SARS-CoV-2 patients who were admitted to the ICUs of 22 Saudi hospitals, between March 1, 2020, and October 30, 2020, by reviewing patient's medical records prospectively. RESULTS ECMO use was associated with higher in-hospital mortality (40.2% vs. 48.9%; p = 0.000); lower COVID-19 virological cure (41.3% vs 14.1%, p = 0.000); and longer hospitalization (20.2 days vs 29.1 days; p = 0.000), ICU stay (12.6 vs 26 days; p = 0.000) and mechanical ventilation use (14.2 days vs 22.4 days; p = 0.000) compared to non-ECMO group. Also, there was a high number of patients with septic shock (19.6%) and multiple organ failure (10.9%); and more complications occurred at any time during hospitalization [pneumothorax (5% vs 29.3%, p = 0.000), bleeding requiring blood transfusion (7.1% vs 38%, p = 0.000), pulmonary embolism (6.4% vs 15.2%, p = 0.016), and gastrointestinal bleeding (3.3% vs 8.7%, p = 0.017)] in the ECMO group. However, PaO2 was significantly higher in the 72-h post-ECMO initiation group and PCO2 was significantly lower in the 72-h post-ECMO start group than those in the 12-h pre-ECMO group (62.9 vs. 70 mmHg, p = 0.002 and 61.8 vs. 51 mmHg, p = 0.042, respectively). CONCLUSION Following the use of ECMO, the mortality rate of patients and length of ICU and hospital stay were not improved. However, these findings need to be carefully interpreted, as most of our cohort patients were relatively old and had multiple severe comorbidities. Future randomized trials, although challenging to conduct, are highly needed to confirm or dispute reported observations.
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Impact of daily high dose oral vitamin D therapy on the inflammatory markers in patients with COVID 19 disease.
Lakkireddy, M, Gadiga, SG, Malathi, RD, Karra, ML, Raju, ISSVPM, Ragini, , Chinapaka, S, Baba, KSSS, Kandakatla, M
Scientific reports. 2021;(1):10641
Abstract
COVID 19 is known to cause immune dysregulation and vitamin D is a known immunomodulator. This study aims to objectively investigate the impact of Pulse D therapy in reducing the inflammatory markers of COVID-19. Consented COVID-19 patients with hypovitaminosis D were evaluated for inflammatory markers (N/L ratio, CRP, LDH, IL6, Ferritin) along with vitamin D on 0th day and 9th/11th day as per their respective BMI category. Subjects were randomised into VD and NVD groups. VD group received Pulse D therapy (targeted daily supplementation of 60,000 IUs of vitamin D for 8 or 10 days depending upon their BMI) in addition to the standard treatment. NVD group received standard treatment alone. Differences in the variables between the two groups were analysed for statistical significance. Eighty seven out of one hundred and thirty subjects have completed the study (VD:44, NVD:43). Vitamin D level has increased from 16 ± 6 ng/ml to 89 ± 32 ng/ml after Pulse D therapy in VD group and highly significant (p < 0.01) reduction of all the measured inflammatory markers was noted. Reduction of markers in NVD group was insignificant (p > 0.05). The difference in the reduction of markers between the groups (NVD vs VD) was highly significant (p < 0.01). Therapeutic improvement in vitamin D to 80-100 ng/ml has significantly reduced the inflammatory markers associated with COVID-19 without any side effects. Hence, adjunctive Pulse D therapy can be added safely to the existing treatment protocols of COVID-19 for improved outcomes.
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Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial.
Abd-Elsalam, S, Soliman, S, Esmail, ES, Khalaf, M, Mostafa, EF, Medhat, MA, Ahmed, OA, El Ghafar, MSA, Alboraie, M, Hassany, SM
Biological trace element research. 2021;(10):3642-3646
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No specific treatment for COVID-19 infection is available up till now, and there is a great urge for effective treatment to reduce morbidity and mortality during this pandemic. We aimed to evaluate the effect of combining chloroquine/hydroxychloroquine (CQ/HCQ) and zinc in the treatment of COVID-19 patients. This was a randomized clinical trial conducted at three major University hospitals in Egypt. One hundred ninety-one patients with a confirmed diagnosis of COVID-19 infection were randomized into two groups: group I (96) patients received both HCQ and zinc, and group II (95) received HCQ only. The primary endpoints were the recovery within 28 days, the need for mechanical ventilation, and death. The two groups were matched for age and gender. They had no significant difference regarding any of the baseline laboratory parameters or clinical severity grading. Clinical recovery after 28 days was achieved by 79.2% in the zinc group and 77.9% in zinc-free treatment group, without any significant difference (p = 0.969). The need for mechanical ventilation and the overall mortality rates did not show any significant difference between the 2 groups either (p = 0.537 and 0.986, respectively). The age of the patient and the need for mechanical ventilation were the only risk factors associated with the patients' mortality by the univariate regression analysis (p = 0.001 and < 0.001, respectively). Zinc supplements did not enhance the clinical efficacy of HCQ. More randomized studies are needed to evaluate the value of adding zinc to other therapies for COVID 19. ClinicalTrials.gov Identifier: NCT04447534.
