Paul E Alexander’s research while affiliated with McMaster University and other places

PUBLISHED IN: Science, Public Health Policy and the Law (https://publichealthpolicyjournal.com/a-systematic-review-of-autopsy-findings-in-deaths-after-covid-19-vaccination/) Background: The rapid development of COVID-19 vaccines, combined with a high number of adverse event reports, have led to concerns over possible mechanisms of injury including systemic lipid nanoparticle (LNP) and mRNA distribution, Spike protein-associated tissue damage, thrombogenicity, immune system dysfunction, and carcinogenicity. The aim of this systematic review is to investigate possible causal links between COVID-19 vaccine administration and death using autopsies and post-mortem analysis. Methods: We searched PubMed and ScienceDirect for all published autopsy and organ-restricted autopsy reports relating to COVID-19 vaccination up until May 18th, 2023. All autopsy and organ-restricted autopsy studies that included COVID-19 vaccination as an antecedent exposure were included. Because the state of knowledge has advanced since the time of the original publications, three physicians independently reviewed each case and adjudicated whether or not COVID-19 vaccination was the direct cause or contributed significantly to death. Results: We initially identified 678 studies and, after screening for our inclusion criteria, included 44 papers that contained 325 autopsy cases and one organ-restricted autopsy case (heart). The mean age of death was 70.4 years. The most implicated organ system among cases was the cardiovascular (49%), followed by hematological (17%), respiratory (11%), and multiple organ systems (7%). Three or more organ systems were affected in 21 cases. The mean time from vaccination to death was 14.3 days. Most deaths occurred within a week from last vaccine administration. A total of 240 deaths (73.9%) were independently adjudicated as directly due to or significantly contributed to by COVID-19 vaccination, of which the primary causes of death include sudden cardiac death (35%), pulmonary embolism (12.5%), myocardial infarction (12%), VITT (7.9%), myocarditis (7.1%), multisystem inflammatory syndrome (4.6%), and cerebral hemorrhage (3.8%). Conclusions: The consistency seen among cases in this review with known COVID-19 vaccine mechanisms of injury and death, coupled with autopsy confirmation by physician adjudication, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death. Further urgent investigation is required for the purpose of clarifying our findings.

Background: The rapid development of COVID-19 vaccines, combined with a high number of adverse event reports, have led to concerns over possible mechanisms of injury including systemic lipid nanoparticle (LNP) and mRNA distribution, Spike protein-associated tissue damage, thrombogenicity, immune system dysfunction, and carcinogenicity. The aim of this systematic review is to investigate possible causal links between COVID-19 vaccine administration and death using autopsies and post-mortem analysis. Methods: We searched PubMed and ScienceDirect for all published autopsy and necropsy reports relating to COVID-19 vaccination up until May 18th, 2023. All autopsy and necropsy studies that included COVID-19 vaccination as an antecedent exposure were included. Because the state of knowledge has advanced since the time of the original publications, three physicians independently reviewed each case and adjudicated whether or not COVID-19 vaccination was the direct cause or contributed significantly to death. Results: We initially identified 678 studies and, after screening for our inclusion criteria, included 44 papers that contained 325 autopsy cases and one necropsy case. The mean age of death was 70.4 years. The most implicated organ system among cases was the cardiovascular (49%), followed by hematological (17%), respiratory (11%), and multiple organ systems (7%). Three or more organ systems were affected in 21 cases. The mean time from vaccination to death was 14.3 days. Most deaths occurred within a week from last vaccine administration. A total of 240 deaths (73.9%) were independently adjudicated as directly due to or significantly contributed to by COVID-19 vaccination, of which the primary causes of death include sudden cardiac death (35%), pulmonary embolism (12.5%), myocardial infarction (12%), VITT (7.9%), myocarditis (7.1%), multisystem inflammatory syndrome (4.6%), and cerebral hemorrhage (3.8%). Conclusions: The consistency seen among cases in this review with known COVID-19 vaccine mechanisms of injury and death, coupled with autopsy confirmation by physician adjudication, suggests there is a high likelihood of a causal link between COVID-19 vaccines and death. Further urgent investigation is required for the purpose of clarifying our findings.

This is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines. Guideline developers and authors of systematic reviews and other evidence syntheses use randomized controlled studies (RCTs) and non-randomized studies of interventions (NRSI) as sources of evidence for questions about health interventions. RCTs with low risk of bias are the most trustworthy source of evidence for estimating relative effects of interventions because of protection against confounding and other biases. However, in several instances, NRSI can still provide valuable information as complementary, sequential, or replacement evidence for RCTs. In this article we offer guidance on the decision regarding when to search for and include either or both types of studies in systematic reviews to inform health recommendations. This work aims to help methodologists in review teams, technology assessors, guideline panelists, and anyone conducting evidence syntheses using GRADE.

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 hydroxychloroquine-based multidrug regimens were associated with a statistically significant >60% reduction in mortality. Going forward, we conclude 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 reasonable probability of success and acceptable safety. This group remains our highest at-risk group and warrants acute treatment focus prior to symptoms worsening. Given the rapidity and severity of SARS-CoV-2 outbreaks in nursing homes, in-center treatment of acute COVID-19 patients is a reasonable strategy to reduce the risks of hospitalization and death. If 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. The issue is timing of therapeutics, and we argue that early treatment before hospitalization, is the right time and can potentially save lives, especially among our higher-risk elderly populations hit hardest by severe illness and death from COVID-19. We must reiterate, we are talking about ‘early’ treatment before the disease is far along in the disease sequelae where the patient needs hospitalization and aggressive interventions. This early therapeutic option deserves serious and urgent consideration by the medical establishment and respective decision-makers. Doctors must be allowed their clinical discretion in how they optimally treat their patients. We therefore hypothesize that early outpatient ambulatory treatment, once initiated as soon as symptoms begin in high-risk positive persons, would significantly reduce hospitalizations and prevent deaths. Specifically, the provision of early multi-drug therapy with repurposed drugs will reduce hospitalization and death in elderly patients being cared for in long-term-care facilities. The most important implications of our hypothesis are: 1) hospitalizations and deaths would be reduced 2) transmission would be reduced due to the mitigation of symptoms and 3) recovery following infection and treatment provides for natural exposure immunity that is broad, durable, and robust (helping towards natural immunity in the population). The end result is reduced strain on hospitals and systems that would allow for other non-COVID illnesses to receive care.

Objective: To provide practical principles and examples to help GRADE users make optimal choices regarding their ratings of certainty of evidence using a minimally or partially contextualized approach. Study design and setting: Based on the GRADE clarification of certainty of evidence in 2017, a project group within the GRADE Working Group conducted iterative discussions and presentations at GRADE Working Group meetings to refine this construct and produce practical guidance. Results: Systematic review and health technology assessment authors need to clarify what it is in which they are rating their certainty of evidence (i.e. the target of their certainty rating). The decision depends on the degree of contextualization (partially or minimally contextualized), thresholds (null, small, moderate or large effect threshold), and where the point estimate lies in relation to the chosen threshold(s). When the 95% confidence interval crosses multiple possible thresholds (i.e. including both large benefit and large harm), it is not worthwhile for authors to determine the target of certainty rating. Conclusion: GRADE provides practical principles to help systematic review and health technology assessment authors specify the target of their certainty of evidence rating.

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.

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.