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2020 ; 143
(ä): 109851
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Three novel prevention, diagnostic, and treatment options for COVID-19 urgently
necessitating controlled randomized trials
#MMPMID32534175
Horowitz RI
; Freeman PR
Med Hypotheses
2020[Oct]; 143
(ä): 109851
PMID32534175
show ga
PURPOSE: Asymptomatic or minimally symptomatic infection with COVID-19 can result
in silent transmission to large numbers of individuals, resulting in expansion of
the pandemic with a global increase in morbidity and mortality. New ways of
screening the general population for COVID-19 are urgently needed along with
novel effective prevention and treatment strategies. HYPOTHESIS: A hypothetical
three-part prevention, diagnostic, and treatment approach based on an up-to-date
scientific literature review for COVID-19 is proposed. Regarding diagnosis, a
validated screening questionnaire and digital app for COVID-19 could help
identify individuals who are at risk of transmitting the disease, as well as
those at highest risk for poor clinical outcomes. Global implementation and
online tracking of vital signs and scored questionnaires that are statistically
validated would help health authorities properly allocate essential health care
resources to test and isolate those at highest risk for transmission and poor
outcomes. Second, regarding prevention, no validated protocols except for
physical distancing, hand washing, and isolation exist, and recently ivermectin
has been published to have anti-viral properties against COVID-19. A randomized
trial of ivermectin, and/or nutraceuticals that have been published to support
immune function including glutathione, vitamin C, zinc, and immunomodulatory
supplements (3,6 Beta glucan) could be beneficial in preventing transmission or
lessening symptomatology but requires statistical validation. Third, concerning
treatment, COVID-19 induced inflammation and "cytokine storm syndrome" with
hemophagocytic lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS)
have resulted in extreme morbidity and mortality in those with certain
comorbidities, secondary to "acute respiratory distress syndrome" (ARDS) and
multiorgan dysfunction with disseminated intravascular coagulation (DIC).
Deficiency in red blood cell, serum and alveolar glutathione has been published
in the medical literature for ARDS, as well as viral and bacterial pneumonias,
resulting from increased levels of free radical/oxidative stress. A randomized
controlled trial of blocking NF-?B and cytokine formation using glutathione
precursors (N-acetyl-cysteine [NAC] and alpha lipoic acid) and PO/IV glutathione
with associated anti-viral effects should be performed, along with an evaluation
of Nrf2 activators (curcumin, sulforaphane glucosinolate) which have been
scientifically proven to lower inflammation. Since high mortality rates from
sepsis induced DIC due to COVID-19 infection has also been associated with
thrombotic events and elevated levels of D-dimer, randomized controlled trials of
using anticoagulant therapy with heparin is urgently required. This is especially
important in patients on ventilators who have met certain sepsis induced
coagulopathy (SIC) criteria. The use of acetazolamide with or without sildenafil
also needs to be explored with or without heparin, since increased oxygen
delivery to vital organs through prevention of thrombosis/pulmonary emboli along
with carbonic anhydrase inhibition may help increase oxygenation and prevent
adverse clinical outcomes. CONCLUSION AND IMPLICATIONS: A three-part prevention,
diagnostic, and treatment plan is proposed for addressing the severe
complications of COVID-19. Digital monitoring of symptoms to clinically diagnose
early exposure and response to treatment; prevention with ivermectin as well as
nutritional therapies that support a healthy immune response; treatment with
anti-inflammatory therapies that block NF-?B and activate Nrf2 pathways, as well
as novel therapies that address COVID-19 pneumonia and ARDS with DIC including
anticoagulation and/or novel respiratory therapies with or without acetazolamide
and sildenafil. These three broad-based interventions urgently need to be
subjected to randomized, controlled trials.
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