Ivermectin and Covid-19

By Dhia Aldoori November 22, 2021 

I have updated my knowledge and stance on ivermectin use in humans for treating the SARS-CoV-2 viral infection to where I consider it to have potential benefit in treating severe cases of COVID 19. I may endorse (not yet though) its regular use in severe cases after randomized controlled trials are carried out on it.[1]–[6][7],[8] 

Bibliography: 

[1] S. Ahmed et al., “A five-day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness,” Int. J. Infect. Dis., vol. 103, no. 0, pp. 214–216, Feb. 2021, doi: 10.1016/j.ijid.2020.11.191. 

[2] N. Okumuş et al., “Evaluation of the effectiveness and safety of adding ivermectin to treatment in severe COVID-19 patients,” BMC Infect. Dis., vol. 21, no. 1, 2021, doi: 10.1186/s12879-021-06104-9. 

[3] S. Lehrer and P. H. Rheinstein, “Ivermectin docks to the SARS-CoV-2 spike receptor-binding domain attached to ACE2,” In Vivo (Brooklyn)., vol. 34, no. 5, 2020, doi: 10.21873/invivo.12134. 

[4] J. C. Rajter, M. S. Sherman, N. Fatteh, F. Vogel, J. Sacks, and J.-J. Rajter, “Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019,” Chest, vol. 159, no. 1, pp. 85–92, Jan. 2021, doi: 10.1016/j.chest.2020.10.009. 

[5] F. Heidary and R. Gharebaghi, “Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen,” Journal of Antibiotics, vol. 73, no. 9. 2020, doi: 10.1038/s41429-020-0336-z. 

[6] L. Caly, J. D. Druce, M. G. Catton, D. A. Jans, and K. M. Wagstaff, “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro,” Antiviral Res., vol. 178, 2020, doi: 10.1016/j.antiviral.2020.104787. 

[7] G. Momekov and D. Momekova, “Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens,” Biotechnol. Biotechnol. Equip., vol. 34, no. 1, pp. 469–474, Jan. 2020, doi: 10.1080/13102818.2020.1775118. 

[8] “Ivermectin | COVID-19 Treatment Guidelines.” [Online]. Available: https://www.covid19treatmentguidelines.nih.gov/therapies/antiviral-therapy/ivermectin/. [Accessed: 22-Nov-2021]. 

 

Notes about Vaccinating With the Covid-19 Janssen/Biotech Vaccine Given the Recent CVST Pause

 By Dr. Dhia Aldoori April 16, 2021

 As of today I am aware of 6 patients with the diagnosis of cerebral venous sinus thrombosis (CVST) who have received the Johnson & Johnson (Janssen/Biotech Vaccine) within three weeks of manifestations emanating from CVST.¹ One sadly passed away, one currently in hospital and all are female.

 Pending further analysis of the safety of administering this vaccination, a ‘pause’ has been advised by the CDC (Centers for Disease Control) and Food and Drug Administration (FDA). A pause doesn’t mean stopping this vaccine and a caregiver may discuss administration of it with her/his patient and go ahead and advise its receipt.¹

A limited literature search revealed there has been the association of cerebral venous sinus thrombosis (CVST) with prior medical conditions. Examples are thrombophilias (blood platelet abnormalities), inflammatory bowel disease, transient situations (e.g., pregnancy, dehydration, and infection), some medications (e.g., oral contraceptives), substance abuse, and unpredictable events (e.g., head trauma).²

Considering above and pending clarification of the situation I would say you should avoid getting the Janssen Biotech, Inc. (a pharmaceutical company of Johnson & Johnson) vaccine if you have any of the above conditions mentioned in paragraph 3 above.

Furthermore I would not critique those who do not have a possible predisposing condition and wish to avoid this vaccine until the dust is settled. Bear in mind this is a vaccine that is not fully vetted study/safety wise (like the Pfizer and Moderna vaccines), and hence being administered by virtue of the Emergency Use Authorization (EUA) pathway.

Bibliography

1.         Joint Media Call: FDA & CDC to Discuss Janssen COVID-19 Vaccine - 4/13/2021 - YouTube. Accessed April 16, 2021. https://www.youtube.com/watch?v=_ELXnGYgsJY

2.         Saposnik G, Barinagarrementeria F, Brown RD, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42(4):1158-1192. doi:10.1161/STR.0b013e31820a8364

 

Notes about Vaccinating against COVID-19 (Pfizer/BioNtech, Moderna and Janssen/Biotech vaccines)

 

By Dr. Dhia Aldoori March/2021

(Orange font text targets other caregivers or indicates that  that text is my conclusion.)

When the vaccines looked like they were going to hit the stage somewhere in December 2020, I started looking for the data related to its testing. I was looking at efficacy, safety, how many people were vaccinated, how many controls (individuals given sham vaccinations to compare) were employed, mechanism of action, etc.

The numbers we were hearing were the stellar efficacy of 95% and 94.5% for the Pfizer/BioNtek and Moderna vaccines, respectively.

Starting with ingredients:

The Pfizer-BioNTech COVID-19 Vaccine includes the following ingredients: mRNA (messenger ribonucleic acid), lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol), potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate dihydrate, and sucrose.[1]

The Moderna COVID-19 Vaccine contains the following ingredients: messenger ribonucleic acid (mRNA), lipids (SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG], cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]), tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and sucrose.[2]

Both Pfizer/BioNtech and Moderna vaccines do NOT contain live virus and therefore can NOT cause infection in recipients. They also do NOT interact with our own DNA in any way, but rather use mRNA (messenger ribonucleic acid). How it works: the ‘instructions’ (mRNA) enter immune cells, who ‘listen’ to the instructions and make the spike protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them. Next, the cell displays the protein (spike) piece on its surface which trigger an immune response with cytokines and ultimate antibody production which can defend against severe disease caused by SARS-CoV-2. (I do not know yet to what extent it prevents against actual infection – science pending).

The next thing here I want to look at is, what do they mean by ‘efficacy’?

The Moderna vaccine phase 3 trial had 30,351 participants. The primary efficacy end point relied on manifestation of symptoms suggestive of COVID-19 with a positive SARS-CoV-2 by RT-PCR. In those aged 65 and older the efficacy was 100% (meaning no symptoms), and in ages 18 to under 65 the efficacy was 93.4% with an overall participant average efficacy of 94.5%. None vaccinated had severe illness or were admitted to a hospital. [3]

The Pfizer/BioNtech vaccine phase 3 trial had 44,000+ participants. Here also the primary efficacy end point relied on manifestation of symptoms suggestive of COVID-19 with a positive SARS-CoV-2 by RT-PCR or in some cases a local nucleic acid amplification test (NAAT) result. There was 1 severe COVID-19 occurrence from 14 days after Dose 2 out of 18,175 vaccinated. In the placebo group of 18,261 there were 3 severe cases.[4] (I thought there would be more in the placebo group.) The other efficacy endpoint I looked at was based on the first COVID-19 occurrence based on CDC defined symptoms from 7 days after dose 2.  See table 22 in reference [4].  The number of vaccinated participants was 19,965 and the placebo group was 20,172.  The number of cases in the vaccinated group was 9, and the number of cases in the placebo group was 172 ending with a vaccine efficacy of 94.7%. (I am assuming the different numbers of vaccinated and placebo seen, results from the different times at which data was extracted for analysis, or because of their status regarding whether or not they were infected previously. I could not tell which.)

Given that both methods relied on reporting symptoms, I surmise an unknown number of participants must have gotten COVID-19 without being detected, as they were symptom free subjectively. (I wish all the participants would have had periodic, e.g. weekly testing for the virus, which would have given us more accurate numbers overall.)

The safety issues: (I have relied on the CDC - Centers for Disease Control - which I do trust at this time for safety information.) COVID-19 vaccines appear relatively safe to date (March 28, 2021) after millions of people in the United States have received COVID-19 vaccines, and these vaccines will continue to undergo safety monitoring. Some people have no side effects. Others have reported common side effects after COVID-19 vaccination like swelling, redness and pain at injection site, fever, headache, tiredness, muscle pain, chills, and nausea. A small number of people have had a severe allergic reaction (called “anaphylaxis”) after vaccination, but this is extremely rare.[5] That said, the word ‘rare’ takes on a different meaning when you know that the actual reports of death through March 22, 2021 have been 2,216. That’s a very unfortunate loss of life representing 0.0018% of 126 million doses of COVID-19 vaccines administered in the United States from December 14, 2020.[6] So I recommend getting the vaccine in a venue that has the capacity to deal with a possible severe allergic reaction. Also stay for 15–30 minutes after your injection for observation, which becomes even more important if you are an allergy prone person.

The third vaccine I would like to talk about is the vaccine from Janssen Biotech, Inc. (a pharmaceutical company of Johnson & Johnson). The related Emergency Use Authorization (EUA) application is dated February 26, 2021 and since has been granted by the Food and Drug Administration (FDA).  This vaccine is administered in 1 shot with similar side effects to the two dose vaccines (Pfizer/BioNtech, Moderna).

The Janssen COVID-19 Vaccine includes the following ingredients: recombinant, replication-incompetent (i.e. can NOT cause infections) adenovirus type 26 expressing the SARS-CoV-2 spike protein, citric acid monohydrate, trisodium citrate dihydrate, ethanol, 2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, sodium chloride.[7]

How it works: after administration of Ad26.COV2.S, binding of the Ad26 vector to cellular receptors is mediated by fibers on the Ad26 capsid. After transduction of the cell, episomal vector DNA drives cellular production of the transgene encoded S protein. The S protein is then expressed on the cell membrane where it is sensed by the host immune system, resulting in humoral and cellular immune responses directed against the SARS-CoV-2 S protein.[8]

The J&J/Janssen vaccine was 66.3% effective in clinical trials (efficacy) at preventing laboratory-confirmed COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. The vaccine had high efficacy at preventing hospitalization and death in people who did get sick. No one who got COVID-19 at least 4 weeks after receiving the J&J/Janssen vaccine had to be hospitalized.[9]

The efficacy numbers will change as more people are vaccinated.

So, what is the actual benefit from these vaccines? They help prevent serious illness and death from SARS-CoV-2. Also, of vital import is it will help end the pandemic by increasing herd immunity (assuming enough individuals get it) and by virtue of lessening manifestations of COVID-19 which spread the virus such as coughing and resultant aerosolization of virus particles.

To get or not to get: GET. The risk/benefit ratio is very convincing to me in favor of getting one of the  vaccines above. I personally received my first Moderna shot December 29, 2020 and the second one January 26, 2021. (The second shot laid me out in bed the next day with significant achiness, headache, and chills – so allegedly my immune system is still intact J.)

 

Bibliography

[1]       Pfizer, “PFIZER-BIONTECH COVID-19 VACCINE.” https://www.fda.gov/media/144414/download (accessed Mar. 29, 2021).

[2]       Moderna TX and Inc, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online]. Available: www.modernatx.com/covid19vaccine-eua.

[3]       FDA and Cber, “Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Briefing Document - FDA,” 2020.

[4]       Pfizer, “Vaccines and Related Biological Products Advisory Committee December 10, 2020 Meeting Briefing Document- Sponsor,” 2020.

[5]       CDC, “Safety of COVID-19 Vaccines | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html (accessed Mar. 28, 2021).

[6]       CDC, “Selected Adverse Events Reported after COVID-19 Vaccination | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html (accessed Mar. 28, 2021).

[7]       D. Administration, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online]. Available: www.janssencovid19vaccine.com.

[8]       JANSSEN BIOTECH, “Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Briefing Document- Sponsor,” 2021. Accessed: Mar. 29, 2021. [Online]. Available: https://www.fda.gov/media/146219/download.

[9]       “Information About Johnson & Johnson’s Janssen COVID-19 Vaccine | CDC.” https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html (accessed Mar. 29, 2021).

 

COVID-19: The Jury is OUT again on Hydroxychloroquine

The jury is out again on hydroxychloroquine (HCQ) and chloroquine (CQ) as a result of refusal of Surgisphere Corporation (the analyzing agency of the database elements presented in the paper) to divulge the full dataset, client contracts, and the full ISO audit report to peer review for analysis. The claim was that such transfer would violate client agreements and confidentiality requirements.
This retraction is appropriate in my view as the full scientific evaluation wasn't completed.
In spite of the retraction, the information and data didn't appear flawed to me and therefore I would hesitate in endorsing use of HCQ and CQ pending further elucidation of this quandary. 

Frustrating stuff.

D. Aldoori

[Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet]
[COVID-19 Running Notes]

COVID-19: The Jury is Back on Hydroxychloroquine

At this time, I recommend against using chloroquine or hydroxychloroquine to prevent or treat COVID-19 infection. This recommendation is mostly based on the study published in the Lancet online, May 22, 2020.[1]

Included in this study were 96,032 hospitalized patients from 671 hospitals who were diagnosed with COVID-19 between Dec 20, 2019, and April 14, 2020 and met the inclusion criteria for said study. It was convincingly a large multinational real-world analysis.

The authors (who I agree with), did not observe any benefit of hydroxychloroquine or chloroquine (when used alone or in combination with a macrolide) on in-hospital outcomes, when initiated early after diagnosis of COVID-19. Each of the drug regimens of chloroquine or hydroxychloroquine alone or in combination with a macrolide was associated with an increased hazard for clinically significant occurrence of ventricular arrhythmias and increased risk of in-hospital death with COVID-19.[1]

[1]       M. R. Mehra, S. S. Desai, F. Ruschitzka, and A. N. Patel, “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis,” Lancet, vol. 0, no. 0, 2020. Link to study.