NSAIDs and Kelleni’s protocol as potential early COVID-19 treatment game changer: could it be the final countdown?

Inflammopharmacology, Journal Year: 2021, Volume and Issue: 30(1), P. 343 - 348

Published: Nov. 25, 2021

We have previously published several papers illustrating numerous immunomodulatory and anti-inflammatory potential benefits when we repurposed safe, generic non-steroidal drugs (NSAIDs)/nitazoxanide/azithromycin (Kelleni's protocol), to early manage our COVID-19 pediatric, adult, pregnant patients. In this manuscript, discuss some recently meta-analysis clinical studies supporting practice a molecular study that might be interpreted as an academic proof protocol also prevent SARS-CoV-2 replication. Moreover, after aspirin has been suggested independently associated with reduced risk of mechanical ventilation, ICU admission in-hospital mortality COVID-19, claim the interpretation results led suggestion was not scientifically accurate, provide confirming low-dose is least likely improve through anticoagulation suggested. Furthermore, describe other related aspirin-triggered lipoxins resolvins while how NSAIDs interfere COX-1, COX-2, SARS-CoV-2/ ORF protein-dependent activation caspases their subsequent mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis necroptosis which were complications. Similarly, are known caspase inhibitors thus they inhibit caspase-related COVID-19-associated downstream pathological signaling mechanisms. Finally, postulated CARD-14, recruitment domain-containing protein, polymorphisms play role in development severe critical confirmed old call adopt NSAIDs, integral part Kelleni's protocol, choice its management aiming end pandemic.

Language: Английский

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The AndroCoV Clinical Scoring for COVID-19 Diagnosis: A Prompt, Feasible, Costless, and Highly Sensitive Diagnostic Tool for COVID-19 Based on a 1757-Patient Cohort

Cureus, Journal Year: 2021, Volume and Issue: unknown

Published: Jan. 7, 2021

Introduction A major barrier for successful therapeutic approaches COVID-19 is the inability to diagnose during viral replication stage, when drugs with potential antiviral activity could demonstrate efficacy and preclude progression more severe stages. Reasons that hamper an earlier diagnosis of include unspecific mild symptoms first delay in specific management caused by requirement a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) SARS-CoV-2 COVID-19, insufficient sensitivity RT-PCR-SARS-CoV-2, converse what recommended screening test outbreak. More sensitive diagnostic tools should be unraveled as key strategy breakthrough change disease course response therapies, particularly those target blockage shedding. We aimed create accurate, sensitive, easy-to-perform, intuitive clinical scoring without need RT-PCR-SARS-CoV-2 (termed The AndroCoV Clinical Scoring Diagnosis), resulting from 1,757 population cohort, eventually encourage patients high pre-clinical likelihood presenting independent RT-PCR-SARS-COV-2 test, avoid delays loss appropriate timing therapies. Methods This post-hoc analysis data prospectively collected Pre-AndroCoV AndroCov Trials, which resulted scorings based on actual according number symptoms, presence anosmia, known positive household contact. Sensitivity, specificity, predictive value, negative ratio, accuracy were calculated subjects screened two different periods both together, females, males, both, total nine scenarios, combinations one, two, or three anosmia contacts, no ageusia contacts. Scorings yielded highest pre-test probability, sensitivity, selected. Results Of screened, 1,284 diagnosed COVID-19. required: (1) alone, contact; (2) one including contacts presented (80.4%) among all attempted, higher (85.7%) than commercially available kit tests. Conclusion was demonstrated feasible, easy, costless, tool Because avoids treatments, high-risk populations, prevents false-negative diagnosis, reduces costs, this considered option at least while prevailing circulating virus vaccination rate below required herd immunity.

Language: Английский

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Ivermectin and the Integrity of Healthcare Evidence During COVID-19

Frontiers in Public Health, Journal Year: 2022, Volume and Issue: 10

Published: March 1, 2022

The COVID-19 pandemic has been characterized by a lack of clear evidence to guide healthcare professionals, the public and policymakers. resulting uncertainty, coupled with changing guidelines as additional became available, added stress anxiety reported decision-makers. Research results are key providing decisions. Important questions have arisen about whether various interventions safe effective. found guides those making treatment decisions, influences selecting for further evaluation in research studies. As intensified, effectiveness safety many pharmaceuticals was queried. Ivermectin will be used explore ethics how must critically appraised, even, or especially, during pandemic. This drug is alleged effective treating COVID-19, studies systematic reviews finding supportive evidence. Some these now linked concerns fraud poor reporting. article focus on scientific literature apparently fraudulent were published influenced on-going health guidelines. critical emergencies like pandemics, but urgency should not overtake ethical responsibilities appraise (or evaluate) they become available. These apply ways editors, peer-reviewers, news media reporters, including clinicians, policymakers general public. While authors primary responsibility reject inaccurate claims, readers carefully evaluate all publications. To detect need appraisal skills that match their level engagement articles. core principles described article, can adapted different types readers. Exemplar tools develop noted, ivermectin's efficacy explored examples. stakeholders increasingly able identify well-conducted simultaneously spot reports prevent them from influencing

Language: Английский

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Central Effects of Ivermectin in Alleviation of Covid-19-induced Dysauto-nomia

Current Drug Targets, Journal Year: 2022, Volume and Issue: 23(13), P. 1277 - 1287

Published: Aug. 11, 2022

Covid-19 may be associated with various neurological disorders, including dysautonomia, a dysfunction of the autonomic nervous system (ANS). In Covid-19, hypoxia, immunoinflammatory abnormality, and deregulation renin-angiotensin (RAS) increase sympathetic discharge dysautonomia development. Direct SARS-CoV-2 cytopathic effects inflammatory reaction lead to neuroinflammation, affecting different parts central (CNS), center in hypothalamus, causing dysautonomia. High circulating AngII, oxidative stress, high pro-inflammatory cytokines, emotional stress can also provoke outflow development storm. During infection neuro-invasion, GABA-ergic neurons nicotinic acetylcholine receptor (nAChR) are inhibited hypothalamic pre-sympathetic leading storm Different therapeutic modalities applied treat infection, like antiviral anti-inflammatory drugs. Ivermectin (IVM) is robust repurposed drug widely used prevent manage mild-moderate Covid-19. IVM activates both nAChRs mitigate infection- induced Therefore, this brief report, we try identify potential role managing Covid-19-induced

Language: Английский

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Oxytocin, the panacea for long-COVID? a review

Hormone Molecular Biology and Clinical Investigation, Journal Year: 2022, Volume and Issue: 43(3), P. 363 - 371

Published: May 16, 2022

Abstract Objectives In this hypothesis paper we explore the underlying mechanisms for long-COVID and how oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, aim review relevance of OXT hypothalamic function recovery from symptoms pathology, through exploring pro-health effects neuropeptide. Methods A published literature was surveyed using Google Scholar PubMed. Results Numerous experimental data can shown correlate with conditions, thus providing strong circumstantial evidence support our hypothesis. It is postulated that due acute post-viral damage hypothalamus contributes variable multi-system, remitting relapsing nature long-COVID. The intranasal route application determined most appropriate clinically relevant restoration post COVID-19 infection. Conclusions We believe it imperative further investigate whether alleviates prolonged suffering patients Succinctly, may much-needed post-pandemic panacea.

Language: Английский

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Meta-Analyses Do Not Establish Improved Mortality With Ivermectin Use in COVID-19

American Journal of Therapeutics, Journal Year: 2021, Volume and Issue: 29(1), P. e87 - e94

Published: Dec. 7, 2021

Ivermectin has been identified as an inexpensive, readily available drug with the potential to be repurposed a treatment for COVID-19, especially in countries limited access vaccines. Although multiple studies have published attempt evaluate its usefulness many are small and not constructed appropriately detect differences important clinical outcomes (ie, death). For this reason, researchers turned meta-analyses combine study results draw summary conclusions regarding ivermectin's effectiveness. Two such recently American Journal of Therapeutics concluded that ivermectin decreased mortality improved other surrogate end points COVID-19.1–4 A withdrawn article caused both authors rework their without altering main conclusions.1–5 We feel shortcomings within sets limitations component significant enough invalidate finding reduces mortality. review on same subject, containing individual studies, were similarly by poor design. KORY AND MARIK META-ANALYSES In updated meta-analysis, missed opportunity improve methodologic weaknesses original study.1,2 follow-up meta-analyses, did list standard methodological items (eg, Preferred Reporting Items Systematic Reviews-Metanalysis) had no description statistical techniques.6 Absence these descriptors makes nonreproducible nonreplicable, thereby limiting external validity.7 Their absence automatically classifies meta-analysis having critically low quality.8,9 The implied was performed exclude retracted study. However, explanation, deleted second while adding 2 others.10 One newly added unblinded enrolled patients negative PCR tests control underling comorbid risks.11,12 larger omission, include 3 double-blind placebo-controlled trials showing effect mortality—biasing favor ivermectin.13–15 follow-up, correct errors from overstated benefit. Ravikirti et al, described “improved” compared controls “0% versus 6.9%, P = 0.019.”1,16 there difference (0/55 vs. 4/57, Fisher exact value 0.12). benefit severely ill stated “of borderline significance, 0% (0/11) 27.3% (6/22), 0.052” Hashim's study.1,17 This incorrect, test, is 0.08. phrases “borderline significant,” “approached” “nearly statistically significant” used inappropriate misleading “results do movement cannot approach significance because dichotomous definition” significant.1,18,19 Inclusion unblinded, single-blinded, nonrandomized authors' ability calculate reliable, reproducible, pooled estimates effects. largest reworked comprising 39% all cases 48% deaths chart where only 3.5% given ivermectin.20 Patients also received treatments uncontrolled manner steroids, tocilizumab) comparison disease severity or comorbidity between groups. Khan nonrandomization resulted sicker population (46% 10% oxygen requirement).21 Nonrandomization led different (39.8% dexamethasone 19.6% group) retrospective Rajter al.22 inappropriately adjusted baseline risk groups constructing prediction model using binary logistic regression overfitted data 13 variables create predicted 53 outcomes.22 ratio studied outcome should be, at most, 1:10 1:20.23 double-blind, randomized controlled (RCTs), differed. Niaee al,24 fewer positive tests, lower saturations, higher body mass indices (BMI), more initial CT scans patients. miscalculated values when comparing positivity performance <0.001 comparisons 0.421, 0.527 reported.24 Vital sign appear error diastolic blood pressure median interquartile range 80 mm Hg (80–80) reported 4 6 It unlikely half (60/120 patients) first pressure. Mahmud 32 lost (LTFU).25 Study validity affected LTFU >5% (9% study), LTFUs exceed (32 deaths) worst-case scenario imputation alters adverse outcome).26–28 would result 8.2% 1.7% (P < 0.01) render overall nonsignificant [odds ratio, 0.48; 95% confidence interval (CI) 0.21–1.07, RevMan 5.4; MedCalc 19.7, Osteen Belgium] meta-analysis. BRYANT Bryant's corrected set including Reviews-Metanalysis items. authors, however, register critical item categorizes registration improves transparency minimizes selective reporting bias. Selection bias may introduced previous pro-ivermectin (or pro ivermectin) contacted aid identifying additional articles analysis. inclusion exclusion criteria methods stating they searched RCTs. final included double blind, open label, quasi-RCTs. Some experts believe quasiexperimental RCTs, thus, requiring true randomization absent.29,30 Many undersized sample size calculations any calculating samples sizes points: recovery (n 5), viral clearance (2), CIs around combined group (1).3,4 No Eleven (<100 increasing likelihood findings false inflating effects treatments.31,32 Further misinterpretation can occur make corrections. example, Okumus al Shahbaznejad conducted 69 58 60 total patients, respectively.11,12 Nine 14 adequate random sequence generation allocation concealment.3 Failed randomization/allocation occurred “adequate” cycle threshold plus polymerase chain reaction (PCR) positivity, BMI, saturation groups.24,33 5 allocation, one SOFA scores analyze groups.11,13,14,17,34 These confounding biases alter describe unclear high inadequate blinding.3 They state blinding “less important” evaluating evidence related mortality.3 disagree. Inadequate treatments, aggressiveness care, actions taken manage potentially resulting outcomes. Five lacked placebo controls,11,12,17,33,35 contained nonplacebo (ritonavir/lopinavir, doxycycline, chloroquine, hydroxychloroquine),12,13,33,35 doxycycline groups.17,25,36 Studies active controls, add drugs groups, allow isolated those drugs. Moreover, it possible might worsen outcomes, falsely skewing toward Several aspects each limits conclusions. Variable doses, duration use, admission status, variable testing COVID-19 testing, timing administration during course obscure interpretation results. Mixing varying definitions further enrolling children differs dramatically adults children.12,17 Bryant al3 sensitivity analyses assess robustness performing trial sequential analysis confirm reduced Reanalysis showed recategorized excluded analysis.24 previously PCR-negative between-group saturation, performance, indicating failure. our opinion, issues require removal Importantly, mortality.4 Removal single so now exists (risk 0.73; CI, 0.45–1.18). OTHER literature search (EMBASE, PubMed, Web Science, bioRxiv, medRxiv, Google Scholar, January 12,020 October 15, 2021) found 18 (now 20 total) evaluated (Table 1).37–54 There substantial overlap meta-analyses. Fourteen majority Marik 1). prevented Removing Elgazzar left 9 removing concluding effective Marik's (previously critiqued), Kow Nardlli whose completely Karale subsets RCTs 3-study Padhy quality evidence, Cochrane GRADE, rated very low.2,4,5,24,44,46–48 Table 1. - Meta-analyses Ivermectin's association COVID-19. Author* publication date Mortality (without Elgazzar) Number (%) revised Bryant† Marik† mortality‡ excluding Elgazzar§ Elgazzar/Niaee§ AMSTAR quality¶ Siemeniuk51July 30, 2020Living updates periodically 8 (7) 7/7 (100%) 3/7 (43%) Network relative estimate0.31 (0.14 0.72) RR, 0.33 0.77) 0.54 (0.21 1.36) Mod/high Padhy48November 23, 2020 0 2/3 (67%) OR, 0.53 (0.29 0.96) NA Critically Kim45December 2/2 Moderate/severeOR, 0.76 (0.25 2.33)Critical (one study)OR, 0.15 (0.04 0.57) Castenada-Sabogal#,37January 27, 2021 (75%) 0.7 (0.31 2.28) Kow46March 29, (5) 5/5 0.21 (0.11 0.42) 0.27 0.55) 0.37 (0.16 0.89) Nardelli47May 8, 7 (6) 6/6 5/6 (83%) 0.19 (0.1 0.34) Hariyanto41June 6, 5/7 (71%) 0.31 (0.15 0.62)** 0.42 (0.24 0.74) 0.55 (0.3 1) Zein53June (8) 7/8 (88%) 5/8 (63%) 0.39 (0.2 0.56 (0.34 0.93) 0.6 1.05) Low Roman50June 28, 2/5 (40%) (0.12 1.13) 0.62 1.65) Hill42July 11 (10) 9/10 (90%) 6/10 (60%) 0.44 0.57 (0.35 0.95) 0.77 (0.51 1.16) Popp49Jul 4/4 1/4 (25%) Moderate–severe 2.51) mild (0.01 8.05) Izcovich43August 21, 12 (11) 9/11 (82%) 6/11 (55%) 0.5 (0.28 0.88); 0.96†† (0.58 1.96) 0.64 (0.4 0.84 (0.57 1.24) Bryant4August 14/14 6/14 0.51 (0.27 0.73 (0.45 1.18) Marik2September 2, 10 10/10 0.6) 0.71) Deng40September 9/13 (69%) 4/13 (31%) OR (0.5 1.19) Cruciani39September 4/7 (57%) RD 0.02 (−0.05 0.01)‖ −0.01 (−0.04 Cheng38September 16, 1/3 (33%) 2.61) Karale44September 17, 29 11/29 (38%) 10/29 (34%) 0.86) 0.58 (0.36 0.92) Zhang‡‡,54September 4/10 0.61 (0.37 0.87 1.49) Singh52October 10, 0.45 (0.17 0.18) *Dates inaccurate preprint server changes online print journal publication. Within listed differed Cepelowicz Rajter, Fonseca Bermijo Galan Galan, Shahbazneiad Rezai, Kirti, Beltran-Gonzales Gonzales).†Number meta-analyses.‡RD, parenthesis.§Recalculated RD, RR deletion Elgazzar/Niaee studies,5,24 Multiple studies. When available, numbers re-calculation. columns indicatesnot applicable 5.4 osteen Belgium repeating technique study.¶Two reviewers (by consensus, disagreements settled third reviewer–unnecessary) independently assessed presence classify low, moderate/high.8,9 If present, moderate quality. categorize (kappa 0.72, interval, 0.49–0.94 reviewer agreement).‖Cruciani off group, back −0.03 (−0.06 0.01).#These treated Cepelowicz-Rajter [preprint (Cepelowicz) (Rajter)] separate Thus, incorrect. Deleting version calculated 0.68 (0.24–1.97).**The mislabeled transposed Forest plots article. Figure (a) (b) descriptions transposed.††Excluding bias.‡‡The S3 (Detailed Trial Characteristics) S5 [Evaluation (mortality)].OR, odds ratio; difference; (relative risk). appraisal AMSTAR-2 tool 15 after exclusions quality2,44,46–48 Others noted similar large number recommended remediation following best-practice guidelines anonymized patient (IPD) obtained directly authors.55–57 Using IPD increase transparency, quality, offset better subgroup analysis, standardizing common measures, avoid In-depth assessment “other” indicates transparent, inclusion/exclusion criteria, proper assessments, across assessments analyses. failures combination flawed techniques rendered unreliable useless decision making. Unfortunately, improperly confusion inside outside medical community. August 26, health advisory, Centers Disease Control Prevention 24-fold prescriptions per week since prepandemic period, physicians prescribing COVID-19.58 July 2021, 5-fold calls US poison centers increased emergency department visits effects.58 recent report Oregon detailed 21 center developing seizures, hypotension, confusion, ataxia intensive care unit ingestion. Seventeen purchased veterinary formulations, 1 unknown source drug.59 reports indicate despite NIH lack United States Food Drug Administration approval, off-label use lay people continued throughout pandemic.58 inconclusive contributed activity. NEXT STEPS Ultimately, imperfect need replaced larger, adequately powered, trials, ideally IPD, based Assuming case fatality rate 2%, 4638 (2319 arm) needed 80% power (alpha 0.05, 1:1 enrollment) 1% 50% drop intervention ivermectin).60 (7% mortality, meta-analysis), 1274 (637 (50% relative) await before decrease subset

Language: Английский

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Can Anti-Parasitic Drugs Help Control COVID-19?

Future Virology, Journal Year: 2022, Volume and Issue: 17(5), P. 315 - 339

Published: March 21, 2022

Novel COVID-19 is a public health emergency that poses serious threat to people worldwide. Given the virus spreading so quickly, novel antiviral medications are desperately needed. Repurposing existing drugs first strategy. Anti-parasitic were among be considered as potential treatment option for this disease. Even though many papers have discussed efficacy of various anti-parasitic in treating separately, far, no single study comprehensively these drugs. This reviews some recommended treat COVID-19, terms function and vitro well clinical results. Finally, we briefly review advanced techniques, such artificial intelligence, been used find effective COVID-19.

Language: Английский

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Ivermectin: A Controversial Focal Point during the COVID-19 Pandemic

Life, Journal Year: 2022, Volume and Issue: 12(9), P. 1384 - 1384

Published: Sept. 6, 2022

The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. challenge world is facing of trying to find a possible treatment, and viable expedient option addressing this repurposing drugs. However, in some cases, although these drugs are approved use humans, mechanisms action involved unknown. In sense, justify its therapeutic application new disease, it ideal, but not necessary, know basic drug’s biological effects. This review compiled available information regarding various effects attributed Ivermectin. controversy over treatment COVID-19 demonstrated by report considers proposal unfeasible because doses proposed achieve effect cannot be achieved. due urgent need an exhaustive impartial necessary order integrate knowledge exists, date, through which may helpful defining safe schedules

Language: Английский

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Nanostructures for the Prevention, Diagnosis, and Treatment of COVID‐19: A Review

Particle & Particle Systems Characterization, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Abstract Viral infections are a significant cause of death globally, resulting in substantial ethical, social, and economic costs. In recent years, the world has experienced worst epidemic current millennium, caused by Coronavirus 2019, severe acute respiratory syndrome. This infection can complications various organs, such as stomach, heart, liver, kidney, brain. Antimicrobial drugs or vaccines be practical approach to combating these pathogens. However, there drug‐resistant emerging that do not have effective vaccines. Therefore, it is necessary explore new approaches for early diagnosis, prevention, therapies. So, nanomaterials widely considered due their unique properties. review employs elucidate role nanostructures against COVID‐19. Also, effects benefits types discussed been used diagnose, prevent, treat COVID‐19 years. Furthermore, evaluating different nanostructures, utilization biocompatible nanoparticles consisting selenium chitosan derivatives suggested promising candidate industrial use fight Ultimately, this study offer insight into potential applications microbial infections.

Language: Английский

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To Risk or Not to Risk? Evaluating Self-medication Practices among Ecuadorian Adults During COVID-19 Lockdown

The Open Public Health Journal, Journal Year: 2024, Volume and Issue: 17(1)

Published: Nov. 7, 2024

Background Self-medication involves using drugs to treat self-diagnosed disorders or symptoms. According WHO, it is associated with a high risk among the general population, exacerbated by COVID-19 pandemic. Objective This study aimed assess self-medication practices, risks, and severity index Ecuadorian adults during first lockdown period in April 2020, descriptive non-experimental research design hazard assessment score analysis. Material Methods A was used risk, 364 2020. The utilized an online survey Hazard-Risk-Assessment-Score (HRAS) analysis of clinically relevant questions. Descriptive statistics were mainly used, integrating Chi-square ANOVA R. Results Despite level education surveyed there significant medication-related problems, 63.1% 26.72% respondents at third fourth levels, respectively. Furthermore, 55% severe self-medication, while 35% opted for medication therapies recommended on television, social media, influencers instead consulting health professionals. Another 39% took before receiving recommendations from doctor pharmacist. Conclusion highlights need improve image pharmaceutical chemists as part multidisciplinary teams, monitor prescriptions doctors, reduce drug side effects mitigate risks self-medication.

Language: Английский

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