COVID-19 - Coronavirus
SYNOPSIS
Students at North American universities risk disenrollment due to third-dose COVID-19 vaccine mandates. We present a risk-benefit assessment of boosters in this age group and provide five ethical arguments against mandates.
TITLE
COVID-19 Vaccine Boosters for Young Adults: A Risk-Benefit Assessment and Five Ethical Arguments Against Mandates at Universities
K. Bardosh, A. Krug, E. Jamrozik, T. Lemmens, S. Keshavjee, V. Prasad, M.A. Makary, S. Baral, H. Stefan, B. Tracy, “COVID-19 Vaccine Boosters for Young Adults: A Risk-Benefit Assessment and Five Ethical Arguments against Mandates at Universities” (August 31, 2022). Available at SSRN: https://ssrn.com/abstract=4206070 or http://dx.doi.org/10.2139/ssrn.4206070
Students at North American universities risk disenrollment due to third-dose COVID-19 vaccine mandates. We present a risk-benefit assessment of boosters in this age group and provide five ethical arguments against mandates. We estimate that 22,000 – 30,000 previously uninfected adults aged 18-29 must be boosted with an mRNA vaccine to prevent one COVID-19 hospitalization. Using CDC and sponsor-reported adverse event data, we find that booster mandates may cause a net expected harm: per COVID-19 hospitalization prevented in previously uninfected young adults, we anticipate 18 to 98 serious adverse events, including 1.7 to 3.0 booster-associated myocarditis cases in males, and 1,373 to 3,234 cases of grade ≥3 reactogenicity which interferes with daily activities. Given the high prevalence of post-infection immunity, this risk-benefit profile is even less favorable. University booster mandates are unethical because: 1) no formal risk-benefit assessment exists for this age group; 2) vaccine mandates may result in a net expected harm to individual young people; 3) mandates are not proportionate: expected harms are not outweighed by public health benefits given the modest and transient effectiveness of vaccines against transmission; 4) US mandates violate the reciprocity principle because rare serious vaccine-related harms will not be reliably compensated due to gaps in current vaccine injury schemes; and 5) mandates create wider social harms. We consider counter-arguments such as a desire for socialization and safety and show that such arguments lack scientific and/or ethical support. Finally, we discuss the relevance of our analysis for current 2-dose Covid-19 vaccine mandates in North America.
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SYNOPSIS
As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection.
TITLE
Conformational Flexibility in Neutralization of SARS-CoV-2 by Naturally Elicited Anti-SARS-CoV-2 Antibodies
Li, R., Mor, M., Ma, B. et al. Conformational flexibility in neutralization of SARS-CoV-2 by naturally elicited anti-SARS-CoV-2 antibodies. Commun Biol 5, 789 (2022). https://doi.org/10.1038/s42003-022-03739-5
As new variants of SARS-CoV-2 continue to emerge, it is important to assess the cross-neutralizing capabilities of antibodies naturally elicited during wild type SARS-CoV-2 infection. In the present study, we evaluate the activity of nine anti-SARS-CoV-2 monoclonal antibodies (mAbs), previously isolated from convalescent donors infected with the Wuhan-Hu-1 strain, against the SARS-CoV-2 variants of concern (VOC) Alpha, Beta, Gamma, Delta and Omicron. By testing an array of mutated spike receptor binding domain (RBD) proteins, cell-expressed spike proteins from VOCs, and neutralization of SARS-CoV-2 VOCs as pseudoviruses, or as the authentic viruses in culture, we show that mAbs directed against the ACE2 binding site (ACE2bs) are more sensitive to viral evolution compared to anti-RBD non-ACE2bs mAbs, two of which retain their potency against all VOCs tested. At the second part of our study, we reveal the neutralization mechanisms at high molecular resolution of two anti-SARS-CoV-2 neutralizing mAbs by structural characterization. We solve the structures of the Delta-neutralizing ACE2bs mAb TAU-2303 with the SARS-CoV-2 spike trimer and RBD at 4.5 Å and 2.42 Å resolutions, respectively, revealing a similar mode of binding to that between the RBD and ACE2. Furthermore, we provide five additional structures (at resolutions of 4.7 Å, 7.3 Å, 6.4 Å, 3.3 Å, and 6.1 Å) of a second antibody, TAU-2212, complexed with the SARS-CoV-2 spike trimer. TAU-2212 binds an exclusively quaternary epitope, and exhibits a unique, flexible mode of neutralization that involves transitioning between five different conformations, with both arms of the antibody recruited for cross linking intra- and inter-spike RBD subunits. Our study provides additional mechanistic understanding about how antibodies neutralize SARS-CoV-2 and its emerging variants and provides insights on the likelihood of reinfections.
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SYNOPSIS
The burden of disease from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is large; however, suicide affects the population year after year.
TITLE
Comparison of Years of Life Lost to 1,565 Suicides Versus 10,650 Covid-19 Deaths in 2020 in Sweden: Four Times More Years of Life Lost Per Suicide Than Per COVID-19 Death
CITATION
R. Ljung, M. Grünewald, A. Sundström, L. Thunander Sundbom, & B. Zethelius (2022), “Comparison of Years of Life Lost to 1,565 Suicides Versus 10,650 Covid-19 Deaths in 2020 in Sweden: Four Times More Years of Life Lost Per Suicide Than Per COVID-19 Death,” Upsala Journal of Medical Sciences, 127(1), https://doi.org/10.48101/ujms.v127.8533.
SUMMARY
Years of life lost (YLL) to suicide affects Sweden year after year, foremost attributable to the younger age groups, whereas YLL to COVID-19 is foremost attributable to the elderly. On average, each suicide generates four times more YLL than a COVID-19 death. Enormous efforts and resources have been put on tackling the pandemic, and without these, the burden would probably have been much larger. However, from a public health perspective, it is important to not neglect other contributors to the total burden of disease where national efforts also may have an impact.
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At a time when people the world over are trying to understand how the COVID pandemic actually came about and questioning whether it may have been better handled by public health agencies, readers will become familiar with a side of Dr. Fauci that has thus far been kept out of the headlines.
TITLE
CHD Board Chair Robert F. Kennedy, Jr.’s latest book, “The Real Anthony Fauci: Bill Gates, Big Pharma, and the Global War on Democracy and Public Health,” hits bookstores November 16
Press Release
November 10, 2021
For immediate release
Washington, DC – On Tuesday, November 16, Children’s Health Defense’s board chair and lead counsel Robert F. Kennedy, Jr.’s long awaited book, The Real Anthony Fauci, will be available in bookstores throughout the U.S. and Canada. The New York Times bestselling author’s latest work promises to “alarm every American—Democrat or Republican—who cares about democracy, our Constitution, and the future of our children’s health.”
At a time when people the world over are trying to understand how the COVID pandemic actually came about and questioning whether it may have been better handled by public health agencies, readers will become familiar with a side of Dr. Fauci that has thus far been kept out of the headlines. The book not only covers the current health crisis but details Dr. Fauci’s long history at the National Institutes of Health (NIH) including his tenure at the National Institute of Allergies and Infectious Disease (NIAID) and his handling of the AIDS epidemic.
“Fauci created a template that he’s used over and over for the last 45 years, to develop toxic drug after toxic drug,” said Kennedy. “He eliminated early treatments, and suppressed any protocols that competed with his pharmaceutical enterprise. A lot of people have suffered or died as a result.”
Readers will be informed about:
- The most likely reasons the U.S. is at the top of worldwide COVID deaths
- How the COVID response was mishandled from the start
- How Big Pharma and our public health agencies have lied to the American people
- How, for over two decades, Bill Gates, Big Pharma and their cronies have been preparing for a bioterrorism epidemic through pandemic exercises, orchestrating over a dozen pandemic simulations that militarized and monetized a response that neglected public health
- The lack of transparent data and decisions not based on science coupled with the suppression of treatments and a “vaccine only” agenda that caused millions of Americans and people around the world to die needlessly
- How there is no scientific justification whatsoever for vaccinating healthy children, who are at very low risk of suffering any side effects from the COVID virus, with an experimental vaccine that lacks long-term safety studies
- How Dr. Fauci has overseen and captured a huge drug incubation laboratory, the NIAID, where he has produced profitable, patentable drugs for the pharma cartel
The Real Anthony Fauci provides an in-depth behind-the-scenes portrait of “America’s Doctor” detailing his experiments not only on animals but also on young Black and Hispanic children trapped in the welfare system. “This book presents a shocking, nightmare-inducing history of failed public health programs, not to mention the huge waste of taxpayer dollars that funded horrific and inhumane studies,” said CHD executive director Laura Bono. “The use of vulnerable, and sometimes orphaned, children as guinea pigs needs to be investigated to the fullest extent.”
For more information, please contact Rita Shreffler or call 202-599-1461.
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Children’s Health Defense is a 501(c)(3) non-profit organization. Its mission is to end childhood health epidemics by working aggressively to eliminate harmful exposures, hold those responsible accountable, and establish safeguards to prevent future harm. For more information, visit ChildrensHealthDefense.org.
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SYNOPSIS
Ivermectin is an effective treatment for COVID-19. Treatment is more effective when used early. Meta analysis using the most serious outcome reported shows 66% [53‑76%] and 86% [75‑92%] improvement for early treatment and prophylaxis, with similar results after exclusion based sensitivity analysis and restriction to peer-reviewed studies or Randomized Controlled Trials.
TITLE
Ivermectin for COVID-19: real-time meta analysis of 65 studies
CITATION
(2021). Ivermectin for COVID-19: real-time meta analysis of 65 studies, Covid Analysis, Oct 4, 2021, Version 127. Retrieved from https://ivmmeta.com/
SUMMARY
We analyze all significant studies concerning the use of ivermectin for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for mortality results, for COVID-19 case results, for viral clearance results, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
We also perform a simple analysis of the distribution of study effects. If treatment was not effective, the observed effects would be randomly distributed (or more likely to be negative if treatment is harmful). We can compute the probability that the observed percentage of positive results (or higher) could occur due to chance with an ineffective treatment (the probability of >= k heads in n coin tosses, or the one-sided sign test / binomial test). Analysis of publication bias is important and adjustments may be needed if there is a bias toward publishing positive results.
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SYNOPSIS
The COVID-19 pandemic caused increased mortality in nursing homes due to its quick spread and the age-related high lethality.
TITLE
Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
CITATION
Cangiano, B., Fatti, L. M., Danesi, L., Gazzano, G., Croci, M., Vitale, G., Gilardini, L., Bonadonna, S., Chiodini, I., Caparello, C. F., Conti, A., Persani, L., Stramba-Badiale, M., & Bonomi, M. (2020). Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests. Aging, 12(24), 24522–24534. https://doi.org/10.18632/aging.202307.
SUMMARY
Results: We observed two-month mortality of 40%, compared to 6.4% in the previous year. This increase was seen in both COVID-19 positive (43%) and negative (24%) residents, but 8 patients among those testing negative on the swab, tested positive on serological tests. Increased mortality was associated with male gender, older age, no previous vitamin D supplementation, and worse “activities of daily living (ADL)” scores, such as Barthel index, Tinetti scale, and S.OS.I.A. classification.
Conclusion: Our data confirm a higher geriatric mortality due to COVID-19. Negative residents also had higher mortality, which we suspect is secondary to preanalytical error and low sensitivity of the swab test in poorly compliant subjects. Male gender, older age, and low scores on ADL scales (probably due to immobility) are risk factors for COVID-19 related mortality. Finally, mortality was inversely associated with vitamin D supplementation.
Design: In this observational study, we described the two-month mortality among the 157 residents (age 60-100) of a nursing home after Sars-CoV-2 spreading, reporting the factors associated with the outcome. We also compared the diagnostic tests for Sars-CoV-2.
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The high proportion of asymptomatic COVID-19 patients and independent factors for mortality suggest that early diagnosis and treatment of COVID-19 patients in LTCFs may be effective in saving lives.
TITLE
Pattern of SARS-CoV-2 infection among dependent elderly residents living in long-term care facilities in Marseille, France, March–June 2020
CITATION
Ly, T., Zanini, D., Laforge, V., Arlotto, S., Gentile, S., Mendizabal, H., Finaud, M., Morel, D., Quenette, O., Malfuson-Clot-Faybesse, P., Midejean, A., Le-Dinh, P., Daher, G., Labarriere, B., Morel-Roux, A. M., Coquet, A., Augier, P., Parola, P., Chabriere, E., Raoult, D., … Gautret, P. (2020). Pattern of SARS-CoV-2 infection among dependant elderly residents living in long-term care facilities in Marseille, France, March-June 2020. International journal of antimicrobial agents, 56(6), 106219. https://doi.org/10.1016/j.ijantimicag.2020.106219
SUMMARY
Objectives: This study aimed to report the results of SARS-CoV-2 PCR-based screening campaigns conducted on dependent elderly residents (compared with staff members) in long-term care facilities (LTCFs) in Marseille, France, and the follow-up of positive cases.
Methods: Data from 1691 elderly residents and 1000 members of staff were retrospectively collected through interviewing the medical teams in 24 LTCFs and using the hospitals’ electronic health record systems.
Results: Elderly residents were predominantly female (64.8%) with a mean age of 83.0 years. SARS-CoV-2 detection among residents (226, 13.4%) was significantly higher than among staff members (87, 8.7%) (P < 0.001). Of the 226 infected residents, 37 (16.4%) were detected on a case-by-case basis due to their COVID-19 symptoms and 189 (83.6%) were detected through mass screening. Most (77.0%) had possible COVID-19 symptoms, including respiratory symptoms and signs (44.5%) and fever (46.5%); 23.0% were asymptomatic. A total of 116 (51.4%) patients received a course of oral hydroxychloroquine and azithromycin (HCQ-AZM) for ≥ 3 days; 47 (20.8%) died. Through multivariate analysis, the death rate was positively associated with being male (30.7% vs. 14.0%, OR = 3.95, P = 0.002), aged > 85 years (26.1% vs. 15.6%, OR = 2.43, P = 0.041) and receiving oxygen therapy (39.0% vs. 12.9%, OR = 5.16, P < 0.001) and negatively associated with being diagnosed through mass screening (16.9% vs. 40.5%, OR = 0.20, P= 0.001) and receiving HCQ-AZM treatment ≥ 3 days (15.5% vs. 26.4%, OR = 0.37, P = 0.02).
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SYNOPSIS
The clinical experience of this case series indicates DOXY-HCQ treatment in high-risk COVID-19 patients is associated with a reduction in clinical recovery, decreased transfer to hospital, and decreased mortality were observed after treatment with DOXY-HCQ.
TITLE
Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities
CITATION
Imtiaz Ahmad, Mohammud Alam, Ryan Saadi, Saborny Mahmud, Emily Saadi. (2020). Doxycycline and Hydroxychloroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities, medRxiv: 20066902. doi: https://doi.org/10.1101/2020.05.18.20066902
SUMMARY
Importance: Patients in long-term care facilities (LTCF) are at a high risk of contracting COVID-19 due to advanced age and multiple comorbidities. Without effective treatments, outbreaks in such facilities will become commonplace and will result in severe morbidity and mortality. The effectiveness of doxycycline (DOXY) and hydroxychloroquine (HCQ) combination therapy in high-risk COVID-19 patients in long-term care facilities are not yet understood.
Objective: The goal of this analysis is to describe outcomes after the use of DOXY-HCQ combination in high-risk COVID-19 patients in LTCF.
Design: Case-series analysis.
Setting: Three (3) LTCFs in New York.
Participants: From March 19 to March 30, 2020, fifty-four (54) patients, residents of three (3) LTCFs in New York and diagnosed (confirmed or presumed) with COVID-19, were included in this analysis.
Exposure: All patients who were diagnosed (confirmed or presumed) with COVID-19 received DOXY-HCQ combination therapy along with the standard of care.
Main Outcomes and Measures: Patients characteristics, clinical recovery, radiological improvements, medication side-effects, hospital transfer, and death were assessed as outcome measures.
Results: A series of fifty-four (54) high-risk patients, who developed a sudden onset of fever, cough, and shortness of breath (SOB) and were diagnosed or presumed to have COVID-19, were started with a combination of DOXY-HCQ and 85% (n=46) patients showed clinical recovery defined as the resolution of fever and SOB, or a return to baseline setting if patients are ventilator-dependent. A total of 11% (n=6) patients were transferred to acute care hospitals due to clinical deterioration and 6% (n=3) patients died in the facilities. Naive Indirect Comparison suggests these data were significantly better outcomes than the data reported in MMWR (reported on March 26, 2020) from a long-term care facility in King County, Washington where 57% of patients were hospitalized, and 22% patients died.
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SYNOPSIS
Male gender, low Barthel index, and lymphocytopenia are independent risk factors for COVID-19 mortality in institutionalized older patients in long-term care nursing homes. Treatment with hydroxychloroquine and azithromycin was associated with lower mortality in these patients.
TITLE
COVID-19 mortality risk factors in older people in a long-term care center
CITATION
Heras E, Garibaldi P, Boix M, Valero O, Castillo J, Curbelo Y, Gonzalez E, Mendoza O, Anglada M, Miralles JC, Llull P, Llovera R, Piqué JM. (2021). COVID-19 mortality risk factors in older people in a long-term care center. Eur Geriatr Med. 12(3):601-607. doi: 10.1007/s41999-020-00432-w. Epub 2020 Nov 27. PMID: 33245505; PMCID: PMC7693854.
SUMMARY
Purpose: Despite high rates of COVID-19 infection and increased related mortality have been reported among older adults admitted in long-term care facilities, a limited amount of information is available about the natural course of this pandemic and prognostic factors in such population. In the current study, we aimed to investigate the epidemiologic, demographics, clinical, or therapeutic factors that may predict the prognosis in a cohort of COVID-19 infected institutionalized older in a nursing home.
Methods: We conducted a retrospective analysis of all COVID-19 confirmed institutionalized older in a nursing home from March 15 to June 5, 2020. Epidemiological, demographic, and frailty status before infection, and clinical, laboratory, treatment, and outcome data during infection were collected. We used bivariate analysis and multivariate logistic regression to identify risk factors for mortality.
Results: The analysis comprised all 100 COVID-19 confirmed cases during the study period. The median age was 85 years; 62% were female. The case fatality rate was 20%. In the bivariate analysis, male gender, fever, respiratory symptoms, severe cognitive decline, a low Barthel index, and lymphocytopenia were significantly associated with mortality. Patients treated with hydroxychloroquine plus azithromycin were related to a higher chance of survival than those without pharmacological treatment. Multivariate logistic regression analysis identified male gender, low Barthel index, no pharmacological treatment, and lymphocytopenia as independent risk factors associated with mortality.
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SYNOPSIS
A coordinated on-site MP of nursing homes with COVID-19 outbreaks achieved a higher SOPC rate, and a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents.
TITLE
Effectiveness of a On-site Medicalization Program for Nursing Homes With COVID-19 Outbreaks
CITATION
M Bernabeu-Wittel, MD, PhD, J E Ternero-Vega, MD, M D Nieto-Martín, MD, PhD, L Moreno-Gaviño, MD, PhD, C Conde-Guzmán, MD, PhD, J Delgado-Cuesta, MD, PhD, M Rincón-Gómez, MD, PhD, P Díaz-Jiménez, MD, L Giménez-Miranda, MD, J M Lomas-Cabezas, MD, PhD, M M Muñoz-García, MD, S Calzón-Fernández, MD, PhD, M Ollero-Baturone, MD, PhD. (2021). Effectiveness of a On-site Medicalization Program for Nursing Homes With COVID-19 Outbreaks, The Journals of Gerontology: Series A, Volume 76, Issue 3, Pages e19–e27. https://doi.org/10.1093/gerona/glaa192. Epub ahead of print. PMID: 32738140; PMCID: PMC7454360.
SUMMARY
Nursing homes are highly vulnerable to the occurrence of COVID-19 outbreaks, which result in high lethality rates. Most of them are not prepared to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
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SYNOPSIS
Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2 and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.
TITLE
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
CITATION
Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, International Journal of Antimicrobial Agents, Volume 56, Issue 1, 105949. ISSN 0924-8579. https://doi.org/10.1016/j.ijantimicag.2020.105949. Epub 2020 Mar 20. PMID: 32205204; PMCID: PMC7102549.
SUMMARY
Patients and Methods
French Confirmed COVID-19 patients were included in a single-arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. The presence and absence of virus at Day6-post inclusion was considered the endpoint.
Results
Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms.
Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and a much lower average carrying duration than reported in the literature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Conclusion
Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
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SYNOPSIS
This natural trial showed that the COVID-19 regimen containing both HCQ and azithromycin can be helpful to promote the recovery of most patients and reduced their signs and symptoms significantly.
TITLE
Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A natural clinical trial
CITATION
Abbas HM, Al-Jumaili AA, Nassir KF, Al-Obaidy MW, Al Jubouri AM, Dakhil BD, Abdulelah MM, Al Khames QA. (2021). Assessment of COVID-19 Treatment containing both Hydroxychloroquine and Azithromycin: A natural clinical trial. Int J Clin Pract. 75(4):e13856. doi: 10.1111/ijcp.13856. Epub 2020 Dec 5. PMID: 33231925; PMCID: PMC7744890.
SUMMARY
The goal of this study was to assess the clinical effectiveness and safety profile of the COVID-19 treatment protocol (containing both hydroxychloroquine (HCQ) and azithromycin) in an Iraqi specialised hospital.
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SYNOPSIS
Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.
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Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review
CITATION
Bhowmick S, Dang A, Vallish BN, Dang S. (2021). Safety and Efficacy of Ivermectin and Doxycycline Monotherapy and in Combination in the Treatment of COVID-19: A Scoping Review. Drug Saf. 44(6):635-644. doi: 10.1007/s40264-021-01066-y. Epub 2021 Apr 16. PMID: 33864232; PMCID: PMC8051548.
SUMMARY
Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.
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SYNOPSIS
Ivermectin is an FDA-approved antiparasitic agent, being currently investigated in COVID-19 patients.
TITLE
Ivermectin: an award-winning drug with expected antiviral activity against COVID-19
CITATION
Formiga FR, Leblanc R, de Souza Rebouças J, Farias LP, de Oliveira RN, Pena L. (2021). Ivermectin: an award-winning drug with expected antiviral activity against COVID-19. J Control Release. 329:758-761. doi: 10.1016/j.jconrel.2020.10.009. Epub 2020 Oct 7. PMID: 33038449; PMCID: PMC7539925.
SUMMARY
Ivermectin is an FDA-approved broad-spectrum antiparasitic agent with demonstrated antiviral activity against a number of DNA and RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite this promise, the antiviral activity of ivermectin has not been consistently proven in vivo. While ivermectin’s activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges. Here, we discuss challenges surrounding the use of ivermectin in the context of coronavirus disease-19 (COVID-19) and how novel formulations employing micro- and nanotechnologies may address these concerns.
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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?
CITATION
Jans DA, Wagstaff KM. (2021). The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2? Biochem Biophys Res Commun. 538:163-172. doi: 10.1016/j.bbrc.2020.10.042. Epub 2020 Oct 21. PMID: 33341233; PMCID: PMC7577703.
SUMMARY
FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) α/β1 heterodimer, and recently demonstrated its ability to bind directly to IMPα to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
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SYNOPSIS
The authors declare that there are no known competing financial interests or personal relationships that could have appeared to influence the work described in this paper.
TITLE
A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
CITATION
Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA. (2021). A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis. 103:214-216. doi: 10.1016/j.ijid.2020.11.191. Epub 2020 Dec 2. PMID: 33278625; PMCID: PMC7709596.
SUMMARY
Ivermectin, a US Food and Drug Administration-approved anti-parasitic agent, was found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in vitro. A randomized, double-blind, placebo-controlled trial was conducted to determine the rapidity of viral clearance and safety of ivermectin among adult SARS-CoV-2 patients. The trial included 72 hospitalized patients in Dhaka, Bangladesh, who were assigned to one of three groups: oral ivermectin alone (12 mg once daily for 5 days), oral ivermectin in combination with doxycycline (12 mg ivermectin single dose and 200 mg doxycycline on day 1, followed by 100 mg every 12 h for the next 4 days), and a placebo control group. Clinical symptoms of fever, cough, and sore throat were comparable among the three groups. Virological clearance was earlier in the 5-day ivermectin treatment arm when compared to the placebo group (9.7 days vs 12.7 days; p = 0.02), but this was not the case for the ivermectin + doxycycline arm (11.5 days; p = 0.27). There were no severe adverse drug events recorded in the study. A 5-day course of ivermectin was found to be safe and effective in treating adult patients with mild COVID-19. Larger trials will be needed to confirm these preliminary findings.
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SYNOPSIS
After COVID-19 emerged on U.S shores, providers began reviewing the emerging basic science, translational, and clinical data to identify potentially effective treatment options. In addition, a multitude of both novel and repurposed therapeutic agents were used empirically and studied within clinical trials.
TITLE
Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19
CITATION
Pierre Kory, Gianfranco Umberto Meduri, Joseph Varon, Jose Iglesias, Paul E. Marik. (2021). Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19. American Journal of Therapeutics. 2021 May-Jun; 28(3): e299–e318. doi: 10.1097/MJT.0000000000001377
SUMMARY
Areas of Uncertainty:
The majority of trialed agents have failed to provide reproducible, definitive proof of efficacy in reducing the mortality of COVID-19 with the exception of corticosteroids in moderate to severe disease. Recently, evidence has emerged that the oral antiparasitic agent ivermectin exhibits numerous antiviral and anti-inflammatory mechanisms with trial results reporting significant outcome benefits. Given some have not passed peer review, several expert groups including Unitaid/World Health Organization have undertaken a systematic global effort to contact all active trial investigators to rapidly gather the data needed to grade and perform meta-analyses.
Data Sources:
Data were sourced from published peer-reviewed studies, manuscripts posted to preprint servers, expert meta-analyses, and numerous epidemiological analyses of regions with ivermectin distribution campaigns.
Therapeutic Advances:
A large majority of randomized and observational controlled trials of ivermectin are reporting repeated, large magnitude improvements in clinical outcomes. Numerous prophylaxis trials demonstrate that regular ivermectin use leads to large reductions in transmission. Multiple, large “natural experiments” occurred in regions that initiated “ivermectin distribution” campaigns followed by tight, reproducible, temporally associated decreases in case counts and case fatality rates compared with nearby regions without such campaigns.
Conclusions:
Meta-analyses based on 18 randomized controlled treatment trials of ivermectin in COVID-19 have found large, statistically significant reductions in mortality, time to clinical recovery, and time to viral clearance. Furthermore, results from numerous controlled prophylaxis trials report significantly reduced risks of contracting COVID-19 with the regular use of ivermectin. Finally, the many examples of ivermectin distribution campaigns leading to rapid population-wide decreases in morbidity and mortality indicate that an oral agent effective in all phases of COVID-19 has been identified.
TAGS
SYNOPSIS
Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro. A single treatment able to effect ~5000-fold reduction in virus at 48 h in cell culture.
TITLE
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
CITATION
Leon Caly, Julian D. Druce, Mike G. Catton, David A. Jans, Kylie M. Wagstaff. (2020). The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Research, Volume 178, 104787.ISSN 0166-3542. https://doi.org/10.1016/j.antiviral.2020.104787.
SUMMARY
Abstract: Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
TAGS
SYNOPSIS
We examined whether existing licensed pharmacotherapies could reduce the spread of coronavirus disease 2019 (COVID-19).
TITLE
Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial
CITATION
Seet RCS, Quek AML, Ooi DSQ, et al. Int J Infect Dis. 2021;106:314-322. doi:10.1016/j.ijid.2021.04.035 https://pubmed.ncbi.nlm.nih.gov/33864917/
SUMMARY
Chemoprophylaxis with either oral hydroxychloroquine or povidone-iodine throat spray was superior to oral vitamin C in reducing SARS-CoV-2 infection in young and healthy men.