Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

McCullough, P. R.

doi:10.31083/j.rcm.2020.04.264

Cited by 63 publications

(50 citation statements)

References 46 publications

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“…We refer here to therapeutics that are provided under clinician/health expert/provider supervision and in a sequenced manner with carefully considered dosing and timing and direct the reader to Reviews in Cardiovascular Medicine for complete details on the suggested early outpatient ambulatory SMDT dosing and treatment algorithm with combinations of well-known, safe, cheap, and effective drugs. These drugs include ivermectin, hydroxychloroquine, colchicine, azithromycin, doxycycline, and favipiravir (outside the US), along with inhaled steroids such as budesonide and oral steroids including dexamethasone and prednisone, and anti-thrombotic anti-clotting drugs such as heparin 12 ). We also present the relative reduction in mortality risk (Figure 1) where data from certain selected studies described below allowed such computations.…”

Section: Resultsmentioning

confidence: 99%

“…These findings, although derived from independent investigations, were externally consistent and in most instances, clinical improvements as well as reduced rates of mortality were shown to be statistically significant and clinically significant. While the reports focused on HCQ and anti-infectives, as indicted in a prior early outpatient SMDT study, 12 early treatment can potentially include other antivirals/anti-infectives, corticosteroids, and anti-thrombotic/platelet drugs based on clinically valid decision-making. Our data imply that early medical therapy in addition to several other interventions in nursing homes when combined could reduce hospitalization rates dramatically and improve survival.…”

Section: Discussionmentioning

confidence: 99%

“…However, based on the reporting and clinical experience, the early therapeutics that we advocate for such as HCQ, ivermectin, and doxycycline etc. 12,17, 18, 38, 39 ) may potentially function by working to inhibit viral replication while also dampening the host innate immune response thereby reducing oxidative stress, matrix-metalloproteinase-mediated inflammation/tissue damage, as well as the production of a wider array of inflammatory cytokines. In the meantime then and given the dearth of such randomized evidence that would provide clarification, and given the present emergency crisis, the observational non-randomized data we reviewed which we judged as acceptable to informing this report (and in line with expert arguments for observational study evidence use especially when RCT evidence is not available or is in many cases, of poor methodological quality), 43 suggest a treatment mandate is present and should replace therapeutic nihilism for nursing home residents with acute COVID-19.…”

Section: Discussionmentioning

confidence: 99%

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Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents

Alexander

Armstrong²,

Fareed

et al. 2021

Preprint

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The outbreak of COVID-19 from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world with tremendous morbidity and mortality in the elderly. In-hospital treatment addresses the multifaceted nature of the illness including viral replication, cytokine storm, and endothelial injury with thrombosis. We identified nine reports of early treatment outcomes in COVID-19 nursing home patients. Multi-drug therapy including hydroxychloroquine with one or more anti-infectives, corticosteroids, and antithrombotic agents can be extended to seniors in the nursing home setting without hospitalization. Data from nine studies found multidrug regimens relying on the use of hydroxychloroquine as well as other agents including doxycycline were associated with a statistically significant and >60% reductions in mortality. Going forward, we theorize and based on the evidence, that early empiric treatment for the elderly with COVID-19 in the nursing home setting (or similar congregated settings with elderly residents/patients) has a genuine probability of success and acceptable safety. This group remains our highest at-risk group and warrants acute treatment focus that will prevent the development and/or worsening of problems associated with COVID-19, most particularly isolation, hospitalization, and death. In fact, with the rapidity and severity of SARS-CoV-2 outbreaks in nursing homes, in-center treatment of patients with acute COVID-19 is possibly the most rational and importantly feasible strategy to reduce the risks of hospitalization and death. If the approach remains ‘wait-and-see’ and elderly high-risk patients in such congregated nursing room type settings are allowed to worsen with no early treatment, they may be too sick and fragile to benefit from in-hospital therapeutics and are at risk for pulmonary failure, life-ending micro-thrombi of the lungs, kidneys etc. We put forth the notion that the most important factor in this regard, is making available early therapeutic intervention as described here. These drugs include and under supervision by skilled doctors, combination/sequenced ivermectin, hydroxychloroquine, colchicine, azithromycin, doxycycline, bromhexine hydrochloride, and favipiravir (outside the US), along with inhaled steroids such as budesonide and oral steroids including dexamethasone and prednisone, and anti-thrombotic anti-clotting drugs such as heparin). As the clinical trials data on treatments for COVID-19 mature, this early treatment therapeutic option deserves serious, urgent, and sober consideration by the medical establishment and respective decision-makers.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents

Alexander

Armstrong²,

Fareed

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Due to the multifaceted pathophysiology of the SARS-CoV-2 virus, no single proven therapeutic agent exists to date. An ideal early therapeutic option in this group of patients may be the one that can address the principal components of infection severity that are shared between schizophrenia and COVID-19, such as cardiometabolic factors (e.g., obesity and prediabetes), hypercoagulable state, and inflammation (110). In this context, accruing evidence from pilot RCTs and observational studies have reported mortality benefits for antiplatelet and anticoagulant agents such as aspirin and heparin, non-steroidal anti-mitotic drug such as colchicine and oral hypoglycaemic agents such as metformin, in a diverse population with COVID-19 (110)(111)(112).…”

Section: Treatment For Early Covid-19 In Schizophrenia-a Critical Needmentioning

confidence: 99%

COVID-19 in People With Schizophrenia: Potential Mechanisms Linking Schizophrenia to Poor Prognosis

et al. 2021

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As the global burden of mortality from COVID-19 continues to rise, an understanding of who is most at risk of adverse outcomes is of paramount importance. Pre-existing cardiometabolic, renal and respiratory diseases as well as old age are well-established risk factors associated with disease severity and mortality among patients with COVID-19. However, mounting evidence also indicates an increased susceptibility to, and risk of adverse outcomes from COVID-19 in people with schizophrenia, independent of age and comorbidity. Therefore, elucidating the underlying pathophysiological mechanisms which may increase the risk of poor outcomes in people with schizophrenia is of crucial importance. Here, we provide a narrative on the current understanding of COVID-19 in patients with schizophrenia and propose potential mechanisms which may link schizophrenia with an increased susceptibility to, and greater risk of adverse outcomes from COVID-19. Given the existing knowledge gaps, robust clinical and biological studies are required to further our understanding of some of these underlying mechanisms, so that effective prevention and treatment strategies for COVID-19 in patients with schizophrenia can be developed.

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“…Since COVID-19 was declared a pandemic in March 2020, over 150 million cases and 3 million cases of deaths from or with SARS-CoV-2 have been reported worldwide. Despite progress on early ambulatory, multidrugtherapy for high-risk patients, resulting in 85% reductions in COVID-19 hospitalization and death [1], the current paradigm for control is mass-vaccination. While we recognize the effort involved in development, production and emergency authorization of SARS-CoV-2 vaccines, we are concerned that risks have been minimized or ignored by health organizations and government authorities, despite calls for caution [2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers

Acevedo‐Whitehouse¹,

Bruno²,

McCullough

et al. 2021

Preprint

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Since the start of the COVID-19 outbreak, the race for testing new platforms designed to confer immunity against SARS-CoV-2, has been rampant and unprecedented, leading to conditional emergency authorization of various vaccines. Despite progress on early multidrug therapy for COVID-19 patients, the current mandate is to immunize the world population as quickly as possible. The lack of thorough testing in animals prior to clinical trials, and authorization based on safety data generated during trials that lasted less than 3.5 months, raise questions regarding vaccine safety. The recently identified role of SARS-CoV-2 Spike glycoprotein for inducing endothelial damage characteristic of COVID-19, even in absence of infection, is extremely relevant given that most of the authorized vaccines induce endogenous production of Spike. Given the high rate of occurrence of adverse effects that have been reported to date, as well as the potential for vaccine-driven disease enhancement, Th2-immunopathology, autoimmunity, and immune evasion, there is a need for a better understanding of the benefits and risks of mass vaccination, particularly in groups excluded from clinical trials. Despite calls for caution, the risks of SARS-CoV-2 vaccination have been minimized or ignored by health organizations and government authorities. As for any investigational biomedical program, data safety monitoring boards (DSMB) and event adjudication committees (EAC), should be enacting risk mitigation. If DSMBs and EACs do not do so, we will call for a pause in mass vaccination. If DSMBs and EACs do not exist, then vaccination should be halted immediately, in particular for demographic groups at highest risk of vaccine-associated death or serious adverse effects, during such time as it takes to assemble these boards and commence critical and independent assessments. We urge for pluralistic dialogue in the context of health policies, emphasizing critical questions that require urgent answers, particularly if we wish to avoid a global erosion of public confidence in science and public health.

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Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19)

Cited by 63 publications

References 46 publications

Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents

Early Multidrug Outpatient Treatment of SARS-CoV-2 Infection (COVID-19) and Reduced Mortality Among Nursing Home Residents

COVID-19 in People With Schizophrenia: Potential Mechanisms Linking Schizophrenia to Poor Prognosis

SARS-CoV-2 mass vaccination: Urgent questions on vaccine safety that demand answers from international health agencies, regulatory authorities, governments and vaccine developers

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