Recent Developments
Merck and Ridgeback’s Investigational Oral Antiviral Molnupiravir
"Merck (NYSE: MRK), known as MSD outside the United States and Canada,
and Ridgeback Biotherapeutics today announced that molnupiravir
(MK-4482, EIDD-2801), an investigational oral antiviral medicine,
significantly reduced the risk of hospitalization or death at a planned
interim analysis of the Phase 3 MOVe-OUT trial in at risk,
non-hospitalized adult patients with mild-to-moderate COVID-19. At the
interim analysis, molnupiravir reduced the risk of hospitalization or
death by approximately 50%; 7.3% of patients who received molnupiravir
were either hospitalized or died through Day 29 following randomization
(28/385), compared with 14.1% of placebo-treated patients (53/377);
p=0.0012. Through Day 29, no deaths were reported in patients who
received molnupiravir, as compared to 8 deaths in patients who received
placebo. At the recommendation of an independent Data Monitoring
Committee and in consultation with the U.S. Food and Drug Administration
(FDA), recruitment into the study is being stopped early due to these
positive results. Merck plans to submit an application for Emergency Use
Authorization (EUA) to the U.S. FDA as soon as possible based on these
findings and plans to submit marketing applications to other regulatory
bodies worldwide."
Dr John Campbell discusses current knowledge of Molnupiravir (Nov 4, 2021) following approval by UK government, the first government to approve this treatment (it has EAU in the US). He says that the drug seems effective given what we know about it but the actual data has not been made available for independent revue. There is a concern that this drug, which works by causing the virus to mutate in ways that make it less able to mount a serious infection, could also cause mutations in human DNA. Currently we are being asked to "take their word for it" that this is not a problem but again the actual data is not available for revue. This med is also quite expensive at around $700 per course.
the Panel’s statement on prioritizing the use of outpatient therapies when there are logistical or supply constraints.
The COVID-19 Treatment Guidelines Panel's Statement on Potential Drug-Drug Interactions Between Ritonavir-Boosted Nirmatrelvir (Paxlovid) and Concomitant Medications
"Ritonavir-boosted nirmatrelvir (Paxlovid) has significant and complex
drug-drug interaction potential, primarily due to the ritonavir
component of the combination. Boosting with ritonavir, a strong
cytochrome P450 (CYP) 3A inhibitor, is required to increase the exposure
of nirmatrelvir to a concentration that is effective against
SARS-CoV-2. Ritonavir is an FDA-approved drug that has been used for
more than 2 decades as a pharmacologic boosting agent for certain
anti-HIV medications; therefore, there is a large body of literature
describing its use with other drugs and its potential for serious and
sometimes life-threatening drug-drug interactions."
FACT SHEET FOR HEALTHCARE PROVIDERS:
EMERGENCY USE AUTHORIZATION FOR PAXLOVID
Liverpool COVID 19 Drug Interaction Website
Treatment Targets
Pathogenesis-directed therapy of 2019 novel coronavirus disease
COVID-19: Characteristics and Therapeutics
"In this review, we present a succinct overview of the SARS-CoV-2 virus
structure, molecular mechanisms of infection, COVID-19 epidemiology,
diagnosis, and clinical manifestations. We also systematize different
treatment strategies and clinical trials initiated after the pandemic
outbreak, based on viral infection and replication mechanisms.
Additionally, we reviewed the novel pharmacological intervention
approaches and vaccine development strategies against COVID-19. We
speculate that the current pandemic emergency will trigger detailed
studies of coronaviruses, their mechanism of infection, development of
systematic drug repurposing approaches, and novel drug discoveries for
current and future pandemic outbreaks."
Treatment of Multisystem Inflammatory Syndrome in Children
"We found no evidence that recovery from MIS-C differed after primary
treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids
alone, although significant differences may emerge as more data accrue."
SARS-CoV-2 Antiviral Therapy
"The development of effective antiviral therapy for COVID-19 is critical
for those awaiting vaccination, as well as for those who do not respond
robustly to vaccination. This review summarizes 1 year of progress in
the race to develop antiviral therapies for COVID-19, including research
spanning preclinical and clinical drug development efforts, with an
emphasis on antiviral compounds that are in clinical development or that
are high priorities for clinical development. The review is divided
into sections on compounds that inhibit SARS-CoV-2 enzymes, including
its polymerase and proteases; compounds that inhibit virus entry,
including monoclonal antibodies; interferons; and repurposed drugs that
inhibit host processes required for SARS-CoV-2 replication. The review
concludes with a summary of the lessons to be learned from SARS-CoV-2
drug development efforts and the challenges to continued progress."
Repurposed Antiviral Drugs for Covid-19 — Interim WHO Solidarity Trial Results
"These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens
had little or no effect on hospitalized patients with Covid-19, as
indicated by overall mortality, initiation of ventilation, and duration
of hospital stay."
Monoclonal Antibody Treatments
Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab
"Among high-risk patients with mild-to-moderate Covid-19, sotrovimab
reduced the risk of disease progression. No safety signals were
identified."
Regeneron is a monoclonal antibody cocktail. Antibodies were
taken from recovered patients and reproduced, and combines two different
antibodies. Helps keep the disease more mild, intended to reduce need for
hospitalization and intensive care. Needs to be used early in disease to
help.
Remdesivir,
Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis
Beracitinib is an anti-inflammatory medicine. Is used in
combination with Remdesivir. This combo helps people who are already on
oxygen avoid more serious complications of the disease.
Tocilizumab in Hospitalized
Patients with Severe Covid-19 Pneumonia
"In this randomized trial involving hospitalized patients with severe
Covid-19 pneumonia, the use of tocilizumab did not result in significantly
better clinical status or lower mortality than placebo at 28 days."
"Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19–related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501)"
Dexamethasone in Hospitalized Patients with Covid-19
Convalescent Plasma
Convalescent plasma and COVID 8/24/20
Today the FDA granted emergency use authorization for convalescent plasma as a
treatment for COVID 19. Plasma is a part of the blood that includes antibodies
to diseases that the donor has immunity to or has at least fought off recently.
This treatment has been use for over 100 years, so it is not a new technology.
It has been tried as a treatment in many diseases during that time and has been
shown to be only moderately effective, and in many cases completely
ineffective. It is not considered standard of care for any specific inspection.
The problem here is that the FDA granted this authorization on minimal evidence and evidence that does not meet even the lowest requirements for setting medical policy. The FDA based their decision on one open-label study of 35,000 patients which was evaluating the outcomes of the patients based on how soon in the disease process they received the treatment and how high or low the level of antibodies was in the plasma that they received. The study was not blinded or randomized, there was no control group and no placebo, no peer review, many patients who were given the plasma were also enrolled in other similar studies looking at Remdesivir, Hydroxychloraquine, and other treatments that differed from each other and may not have even been known by the studies authors. It has been given to about 100,000 Americans so far.
A Randomized Trial of Convalescent Plasma
in Covid-19 Severe Pneumonia
"No significant differences were observed in clinical status or overall
mortality between patients treated with convalescent plasma and those who
received placebo."
Early Convalescent Plasma for High-Risk Outpatients with Covid-19
"Convalescent plasma may still play a role if it is
administered before the development of native antibodies. The treatment
may also be efficacious in preventing symptomatic Covid-19 after
exposure. This trial was designed to detect an absolute risk difference
of 10 percentage points in disease progression. However, we cannot
exclude smaller effect sizes with less clinical importance. Data
regarding viral genotypes were not collected during this trial, and new
variants emerged during the period of enrollment. Future studies may
also consider whether convalescent plasma that is collected during
different epochs and from different geographic locations during a
pandemic will have different therapeutic potentials. Donations that are
temporally and geographically proximate to their point of use may be
more effective. Since convalescent plasma may be the only available
therapeutic agent during the early phases of a pandemic, understanding
how and when it is useful is important for public health. It is also
important to consider that host factors and other aspects of the host
response to the infection may be more important than humoral immunity
for determining the natural history of the illness.
In
this randomized, controlled trial, infusion of high-titer Covid-19
convalescent plasma within 7 days after symptom onset did not prevent
the progression of Covid-19 in patients at high risk for severe disease."
Treatments and Therapies Not Approved by the FDA for use in Treating COVID 19
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
"In critically ill patients with Covid-19, an initial strategy of
therapeutic-dose anticoagulation with heparin did not result in a
greater probability of survival to hospital discharge or a greater
number of days free of cardiovascular or respiratory organ support than
did usual-care pharmacologic thromboprophylaxis."
Naltrexone a potential therapeutic candidate for COVID-19
"SARS-CoV-2 infection induces a profound downstream pro-inflammatory
cytokine storm. This release of the pro-inflammatory cytokines is
underpinning lung tissue damage, respiratory failure, and eventually
multiple organ failure in COVID-19 patients. The phosphorylation status
of ERK1/2 is positively correlated with virus load and ERK1/2 inhibition
suppressed viral replication and viral infectivity. Therefore,
molecular entities able to interfere with binding of the SARS-CoV-2
Spike protein to ACE2, or damping hyperinflammatory cytokines storm,
blocking ERK1/2 phosphorylation have a great potential to inhibit viral
entry along with viral infectivity. Herein, we report that the
FDA-approved non-peptide opioid antagonist drug, naltrexone suppresses
high fat/LPS induced pro-inflammatory cytokine release both from
macrophage cells and Adipose Tissue Macrophage. Moreover, Low Dose
Naltrexone (LDN) also showed its activity as an ERK1/2 inhibitor.
Notably, virtual docking and simulation data also suggest LDN may
disrupt the interaction of ACE2 with RBD. LDN may be considered as a
target as the treatment and (or) adjuvant therapy for coronavirus
infection. Clinical toxicity measurements may not be required for LDN
since naltrexone was previously tested and is an approved drug by the
FDA."
"These preclinical findings support clinical investigation of the repurposing of CPZ, a drug with mild side effects, in the treatment of patients with COVID-19. "
Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro
"Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 μM and 400 μM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine."
Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro (chinese skullcap)
"We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredients. We found that the ethanol extract of S. baicalensis and its major component, baicalein, inhibit SARS-CoV-2 3CLpro activity in vitro with IC50's of 8.52 µg/ml and 0.39 µM, respectively. Both of them inhibit the replication of SARS-CoV-2 in Vero cells with EC50's of 0.74 µg/ml and 2.9 µM, respectively. While baicalein is mainly active at the viral post-entry stage, the ethanol extract also inhibits viral entry. We further identified four baicalein analogues from other herbs that inhibit SARS-CoV-2 3CLpro activity at µM concentration. All the active compounds and the S. baicalensis extract also inhibit the SARS-CoV 3CLpro, demonstrating their potential as broad-spectrum anti-coronavirus drugs."
Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CL pro (pomegranate extract)
"Here we examined the inhibitory abilities of two broad-spectrum
antiviral natural products chebulagic acid (CHLA) and punicalagin (PUG)
against SARS-CoV-2 viral replication. Both CHLA and PUG reduced
virus-induced plaque formation in Vero-E6 monolayer at noncytotoxic
concentrations, by targeting the enzymatic activity of viral
3-chymotrypsin-like cysteine protease (3CLpro) as allosteric regulators. Our study demonstrates the potential use of CHLA and PUG as novel COVID-19 therapies."
Hydroxychloraquine
A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19
"Results were similar in the hydroxychloroquine and usual-care groups
with respect to the incidence of PCR-confirmed, symptomatic Covid-19
(5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval,
0.52 to 1.42]). In
addition, hydroxychloroquine was not associated with a lower incidence
of SARS-CoV-2 transmission than usual care (18.7% and 17.8%,
respectively). The incidence of adverse events was higher in the
hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%),
but no treatment-related serious adverse events were reported."
Ivermectin in the Prevention and Treatment of COVID 19
How Ivermectin works – and how this plays out in practice
(This is an interview with Dr Jackie Stone who is a primary care physician in Zimbabwe)
Ivermectin works against SARS Cov 2 in multiple ways. It prevents the virus from connecting to the receptor sites on host cells (both ACE 2 and CD 147) by coating it and binding to the spike protein. It also inhibits viral replication in several ways. It inhibits RNA polymerase and is also a zinc ionophore (meaning it transports zinc across the cell membrane) and zinc also inhibits RNA polymerase (in a dose-dependent way). It also binds to RNA helicase which may explain why it is effective against all RNA viruses including West Nile Virus and Yellow Fever. Her protocol also includes the use of doxycycline, a drug which has the same anti-viral properties listed above for Ivermectin.
She emphasizes the need to treat patients early on, before they reach
the inflammatory stage, the thrombotic stage, and before oxygen sat
levels drop. If patients receive treatment for COVID 19 according to this protocol early on they are spared the later stages. If the patients present already in a later stage the protocol is effective by breaking up the blood clots. The spike proteins on the virus cross link blood cells together causing the blood to become "sludgy" and to have clots. By coating the virus' spike proteins the cross-linking of cells is interrupted and inhibited. She noted that in patients receiving Ivermectin at this stage their levels of d-dimer (a marker associated with blood clotting) shoots up very high which actually indicates that the clots are coming apart. Their blood also re-perfuses with oxygen relatively quickly.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
"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."
Strong Evidence of Ivermectin's Effectiveness From Japan
The drug Ivermectin was approved for use (with some limitations) during a major surge of Coronavirus cases in Japan. Several weeks later the number of cases began to plummet to an extremely low number. It is important to note that Ivermectin use is not the only thing that contributed to this decline. Vaccination has played some role, but vaccination uptake was already high in Japan. Limiting measures including mask-wearing and social distancing have also been practiced more consistently in Japan than they have been in many other countries, but again this behavior was already occurring before the surge. I will post more about this when I find more.
The gene that codes for an enzyme called APOBEC3A, produced in human cells that attacks RNA viruses including coronaviruses, is more common in people of Japanese decent. There is another enzyme, nsp14, that is produced by the SARS Cov2 virus to correct errors made in transcription and replication that has developed a mutation called A394V that renders the enzyme ineffective. The A394V mutation has been found in viral samples from 24 other countries. It is hypothesized that this mutation may have played a role in the extinction of the SARS CoV1 virus that occurred earlier. Research is being done to see if there is an interplay between these 2 mutations that has contributed to the dramatic reduction in COVID 19 cases in Japan. There is also research being done to produce a drug that inhibits the nsp14 enzyme.
A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
"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."
"Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection.
Two-dose ivermectin prophylaxis at a dose of 300 μg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic."
Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines
"Moderate-certainty evidence finds that large reductions in COVID-19 deaths are possible using ivermectin. Using ivermectin early in the clinical course may reduce numbers progressing to severe disease. The apparent safety and low cost suggest that ivermectin is likely to have a significant impact on the SARS-CoV-2 pandemic globally."
"Given the evidence of efficacy, safety, low cost, and current death rates, ivermectin is likely to have an impact on health and economic outcomes of the pandemic across many countries. Ivermectin is not a new and experimental drug with an unknown safety profile. It is a WHO “Essential Medicine” already used in several different indications, in colossal cumulative volumes. Corticosteroids have become an accepted standard of care in COVID-19, based on a single RCT of dexamethasone.1 If a single RCT is sufficient for the adoption of dexamethasone, then a fortiori the evidence of 2 dozen RCTs supports the adoption of ivermectin.
Ivermectin is likely to
be an equitable, acceptable, and feasible global intervention against
COVID-19. Health professionals should strongly consider its use, in both
treatment and prophylaxis."
Ivermectin and COVID-19: Keeping Rigor in Times of Urgency
"First, ivermectin, which targets glutamate-gated chlorine channels in
invertebrates, may cross-target the GABA-gated chlorine channels present
in the mammalian central nervous system (CNS) and cause neurotoxicity.
This is normally prevented by an intact blood–brain barrier (BBB), but
in patients with a hyperinflammatory state, endothelial permeability at
the BBB may be increased and cause leaking of drugs into the CNS,
potentially causing harm."
INDIAN BAR ASSOCIATION SERVES LEGAL NOTICE UPON
DR. SOUMYA SWAMINATHAN, THE CHIEF SCIENTIST,
WORLD HEALTH ORGANISATION
Indian Bar Association sues WHO scientist over Ivermectin
Doctors Prescribing Ivermectin
Ivermectin Dose For COVID (Prophylaxis, Acute Disease, Long Haulers)
There are many different protocols being used to treat and/or prevent COVID 19 infection with very good results. This video discusses several protocols.
Ivermectin is usually dosed by giving 150-200mcg/kg, so by multiplying the patients weight in kgs with 0.15mg or 0.2mg. Example – for 70kg person 70 x 0.15mg = 10.5mg round up to 12mg. Ivermectin comes in 3mg or 6mg tablets so take that into account when rounding up to calculate the dose. When taken on empty stomach, more of the drug stays in the GI tract and kills parasites there. When taken with food more of it gets absorbed and is available to fight COVID.
For prophylaxis, a common dosing schedule is to take the full dose on day 1, the full dose again on day3, and nothing more for the rest of the month. At this point some protocols suggest taking one full dose each week after this and another common protocol suggests taking a full dose every two weeks. For treating active infection one approach is to give the patient one full dose per day, divided into AM and PM, until the patient
stabilizes (oxygen sat is 97 or above and symptoms begin to reduce). Another common approach is to give the patient one full dose per day (once a day, not divided) for 5 days, taken with food. Long haulers are usually told to follow the same regimen used for prophylaxis.
Side effects- can cause diarrhea, nausea, and allergic
reactions. It can cross the BBB in
people whose BBB is compromised or less strong (young children under 2 or under
15kg, people with meningitis, acute brain inflammation, pregnant women) and may
cause permanent brain damage. Claims
circulate about Ivermectin leading to liver damage but there is only one case
reported where it was linked to hepatitis.
It may cause inflammation in rat testes that can reduce amount and
quality of sperm but this is countered by taking anti-oxidants. Vit C, NAC, vit E selenium, vit A.
Several leads and ideas for finding and paying for Ivermectin. There is a coupon on GoodRx that can reduce the cost by as much as 90%. Another source is Internationaldrugmart.com (100 6mg tabs of Ivermectin for $300, took 6 weeks for delivery). It's good to take anti-oxidants with Ivermectin, this doctor takes daily 20,000 IU vit D, with K2, calcium, copper, magnesium, selenium, curcumin, CoQ10, quercetin, zinc, fish oil, black seed oil (1 tsp), sometimes honey. Hot hydrotherapy is good for viruses in general, including sauna and hot baths. A similar anti-parasitic drug called Nitazoxanide has been found to lessen viral load but not reduce severity of disease in COVID 19.
U.S. Poison Control Ivermectin Data Analyzed by TrialSite – Some Surprises
The above press release cites a huge rise in prescriptions for Ivermectin and a 3-fold increase in calls to poison control centers, with no context or data. Media reports about the use of ivermectin for COVID 19 tend not to differentiate between the lawful prescription of the drug Ivermectin for human use and the non-sanctioned use of veterinary forms of the drug, including a paste used for horses and other livestock. TrialSite News got ahold of the data behind the above press release warning from the AAPCC (American Association of Poison Control Centers) and the National Poison Data System (NPDS) Bulletin. From January through August of 2021 there were a total of 1143 cases involving Ivermectin. The baseline data, from the previous year, was 435 cases. The increase in prescriptions for Ivermectin rose 2,344% over the same time period. In the 1143 cases mentioned above there were no deaths, 11 major effects, 91 moderate effects, and 148 minor effects. 22% of the calls indicate that there was any effect at all. 78% of calls are classified as "no problem" or "an aggregate label of "not sure" meaning no follow up was needed. 754 of the total of 1143 cases were classified as no effect, non-toxic, or minimal. 137 were potentially toxic but there was no follow-up. None of the 11 cases of "severe" effects were labeled as resulting from abuse of veterinary forms of the medicine. The number of prescriptions for Ivermectin rose from 3600 per week before the pandemic to 88,000 per week during the pandemic.
For comparison, calls to poison control regarding hand sanitizer rose 58% from the baseline before the pandemic in 2019 to during the pandemic in 2020. 3,320 of these calls were classified as major, moderate, or minor effects while 4 people died according to this report. The data from poison control centers indicates that methanol-based hand sanitizers pose far more of a risk to the population than does Ivermectin. It has been suggested that the media, who conflate the off-label use of the FDA-approved human form of the medicine with veterinary versions- in particular "horse paste"- are doing this to intentionally cast doubt on the use of Ivermectin for COVID 19 at all.
AMA, APhA, ASHP statement on ending use of ivermectin to treat COVID-19
Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol — Arizona and New Mexico, May–June 2020
Increase in Outpatient Ivermectin Dispensing in the US During the COVID-19 Pandemic: A Cross-Sectional Analysis
Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis
"There is insufficient evidence to conclude on the safety profile of ivermectin during pregnancy. Treatment campaigns should focus additional efforts on preventing inadvertent treatment of pregnant women."
Preventative Measures (can reduce the number and severity of cases):
MMR Vaccine May Confer Non-Specific Immune Protection Against COVID 19
Melatonin potentials against viral
infections including COVID-19: Current evidence and new findings
"This study has provided a comprehensive overview of numerous beneficial
properties of melatonin in different viral complications even viral respiratory
disorders associated with oxidative stress, inflammation, and immune
dysfunction. Literature evidence supports that the management of oxidative
stress and inflammatory responses, as well as the regulation of immune
responses may be critical to target respiratory virus infections such as
SARS-CoV-2."
Cleveland Clinic Identifies Melatonin asCOVID-19 Treatment
"Analysis of patient data from Cleveland Clinic’s COVID-19 registry also
revealed that melatonin usage was associated with a nearly 30 percent reduced
likelihood of testing positive for SARS-CoV-2 (the virus that causes COVID-19)
after adjusting for age, race, smoking history and various disease
comorbidities. Notably, the reduced likelihood of testing positive for the
virus increased from 30 to 52
percent for African Americans when adjusted for the same variables."
Can Melatonin Help Treat COVID-19?
More discussion and interpretation of the study mentioned above.
Predictors of Severity of Illness
Biomarker
Detects Severe COVID-19 Early On
"A team led by Professor Burkhard Becher at the Institute of Experimental
Immunology at the University of Zurich has... discovered a biomarker – the
number of natural killer T cells in the blood. These cells are a type of white
blood cell and part of the early immune response. “The number of natural killer
T cells in the blood can be used to predict severe cases of COVID-19 with a
high degree of certainty – even on a patient’s first day in hospital,” says
Burkhard Becher."
