Evidence Based Medicine

Monkeypox virus is similar to variola (smallpox virus) first isolated in Monkeys in 1958...hence the name. This name is soon to be changed by the WHO ( World Health Organization). It has been endemic in Africa since 1970s but in the last few months has spread to over 70 countries. Now, that’s the problem! Currently in the US, cases are increasing, with over 830 cases in New York. As of July 22, there are 110 documented cases in Texas.

How does it SPREAD?
Typical: Contact through infected animal bite.
Human to human transmission: Large respiratory droplets, direct contact with infected skin lesions/saliva/body fluids/contaminated clothing.

Typical SYMPTOMS: 97 % Rash (usually starts 1-5 days after onset of symptoms, over face, hands, feet, ge****ls, stages vesicle→pustule→ ulceration→crusting→scab), 85% fever, 71 % lymphadenopathy, 56% body aches, 65% headaches

At risk population for serious infection: Immunocompromised, homosexuals, children

Another variant already? I mean we just heard of omicron few weeks back (10 weeks to be exact) and here we are! BA.2.

Here is my blog link (it's much easier to read there and has figures/graphs):
https://zaurezkhanmd.wixsite.com/evidencebasedmed/post/another-variant-ba-2-do-not-panic

*Where was it found first?

November 2021- South Africa
Early December 2021– positive samples from Philippines, Denmark, India, UK and now spreading across the globe.

*Where is it now?

As of last week, it is found in 57 countries (Source:WHO)

*How is it different?

Omicron has 3 sub variants – 1.1.529.1 (original), 529.2 (BA.2) and 529.3
Common mutations with omicron (BA.1): 32
Unique mutations in BA.2: 28
Some perspective: Delta had 9 mutations in S protein and omicron had over 30, this BA.2 has even more mutations. That does not necessarily make it more dangerous.
However with that number of mutations it might as well get a new name!

*Sibling rivalry?

Well this new sibling is outcompeting the original omicron or BA.1 in terms of high transmission. We certainly do not wish to see any further achievements.
FIGURE (in blog)

*Can it be detected by antigen tests?
Yes, but less sensitivity is being reported. As in my previous post, if symptomatic and antigen test is negative follow by a PCR test.

*Can it be detected by PCR?
Yes. But it has more mutations it can make it difficult to detect by certain PCR tests that have single gene target. PCR tests with multiple gene targets will not be affected. You can find the approved tests at fda.gov.
Omicron 529.1 has SGTF (S gene target failure)
Omicron 529.2 (BA.2) does NOT have SGTF. That is why it is also called the “stealth variant.”
What is S gene target failure?
S gene is one of the target genes used by PCR tests to detect Covid-19. The S gene target is not identified in the original omicron, so it’s called S gene drop out or S gene target failure. That is because of the S69-70 gene deletion, which is not present in the new BA.2 variant.
For proper identification of this variant (or any variant)– genomic sequencing needs to be done.

*More transmissible?
Yes. There is a preprint Danish study showing higher transmission (posted January 30,2022, link: https://www.medrxiv.org/content/10.1101/2022.01.28.22270044v1). There is a possibility that it can replace the original omicron (BA.1) globally. In fact, it has already become the predominant strain in Denmark.

*Can we get omicron if we had delta infection?
Yes. There is an Imperial College London study that shows that risk of infection is 5.4 times more likely with omicron than with delta.

*Can we get omicron twice?
Yes, there is a strong possibility. Why am I using the word possibility?... because we don’t have published data yet. There have been reports of people getting re-infected after omicron, which may very well be this variant??

*Is it more dangerous?
No published data yet. South Africa and Denmark cases so far do NOT show more severe disease than delta. Scientists are not expecting it to be worse than omicron (which is less severe than delta) but it’s too early to say for sure.

*Immune escape? Or will vaccines be effective?
Yes. There is however one mutation linked to immune escape that was in the original omicron is missing - G446S. This is making scientists think that it may have less immune escape compared to BA.1, but not necessary. You can check an immune escape calculator developed by jbloomlab here: https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/
Vaccines are still effective. The efficacy may be lower, but as I mentioned in my previous post, there is clear evidence that vaccines reduce risk of severe disease (graphs in my previous post). Vaccines also reduce transmission and emergence of newer strains. Having said that, if this continues we will need more strain specific vaccines. And yes..masks are still very important. Even if the virus is not as severe, you never know how your body will react to it.

***What you need to know is that it is somewhat similar to the original omicron, vaccines are still helping and there is no need to panic.***

Article by,
Dr. Zaurez Khan

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We have a vaccine for the world!

Below is a 'copy and paste' from my blog (easier to read here):
https://zaurezkhanmd.wixsite.com/evidencebasedmed/post/a-vaccine-for-the-world

It’s true that there is vaccine inequity in the world. The rich countries have access to mRNA vaccines like Pfizer and Moderna but what about the rest of the world?

We have had a solution for quite sometime but unfortunately this game changing vaccine did not get the attention it deserved. I’m talking about Corbevax .This is one of the cheapest and effective vaccines out there against Covid-19.

Wondering how come you didn’t hear about it? Probably because it doesn’t involve big Pharmaceutical giants. This was developed by scientists at Baylor Houston, Texas with the intention of ‘an affordable vaccine for all’. They prepared a vaccine for the SARS outbreak in 2003 as well. Based on the same technology, they redesigned a Covid-19 vaccine.
Another US based company Novavax has similar vaccine using sf9-baculovirus technology instead of yeast.
It will be available under the trade name Nuvaxovid in Europe and Covovax in India.

How do they work?

In Corbevax, the Covid-19 spike protein gene is inserted into yeast, which produces spike proteins (In contrast, in an mRNA vaccine like Pfizer and Moderna, the mRNA is introduced into the body and the spike protein is produced by the body). These spike proteins (made in the yeast) are then introduced into the body. The body then produces antibodies against these spike proteins.

In Novavax, the spike protein gene is inserted into baculoviruses which then infect sf9 insect cells. The sf9 cells produce the spike protein which is then purified as nanoparticles and introduced into the body.

The good news is that the recombinant technology can be scaled up, making it easy to provide at a global scale.
This is the same technology as hepatitis B vaccine.

So if you are still hesitant about mRNA vaccines, this is your vaccine!

What age? 18years and up.

Safe for pregnancy? Yes

How is it stored? 2- 8 degrees Celsius. That means that it can be stored in a regular refrigerator.
Therefore, easy to transport.

Dosage: 2 doses (0.5ml intramuscular) 3-4 weeks apart.

The phase 3 clinical trial of Corbevax with over 3000 participants showed over 90% efficacy against the original Covid-19 virus( source: texaschildrens.org, published study pending)

The phase 3 clinical trial data for Novavax with over 15000 participants is published in NEJM(summarized in my blog link)

Efficacy: 90% effective against original Covid-19 virus.

Efficacy against delta variant: 51% (a study by Shinde V et al on 4387 participants)
(N Engl J Med 2021;384:1899-1909).

Side effects: Mostly local reactions like injection site pain/tenderness, systemic adverse effects (fever, headache, body aches). Below is a graphical summary of side effects from the phase 3 clinical trial published in NEJM. (figure in my blog link)

Big question: Is it effective against Omicron?

The trials that were done did not include Omicron…. hmm…. I know …disappointing right( but omicron wasn’t in circulation at the time of the studies). We will have that data soon. It would be best to have more prevalent strain specific vaccines. We do know however, based on previous studies, that vaccination prevents severe disease. Even the current vaccines that have lower efficacy against omicron reduce risk of hospitalization.

“Oh I’m waiting for my immune system to make antibodies after getting infected…my natural immunity” … “Sure, but did you know? Over 4 million people(unvaccinated) never got to their ‘natural immunity’ after getting infected because they made it to the grave first.” Look at this recent data from New York and Seattle!
(see figures in my link)
This week in the US, hospitalizations increased dramatically (as you see in the graphs; majority unvaccinated)and we are seeing the highest Covid death rate we have seen yet since the start of the pandemic.
Should I say anything further?
Vaccination also helps reduce transmission and emergence of newer variants. I mean aren’t we all just exhausted of these variants!

Whichever vaccine you choose, get vaccinated:)

Article by
Dr. Zaurez Khan


Disclaimer: I have NO financial disclosures. This article is for education purpose only.

COVID-19 testing - confused ? When to get tested ? What kind of test? Rapid test or PCR?
Read about it here (much easier to read):
https://zaurezkhanmd.wixsite.com/evidencebasedmed/post/covid-testing

Below is a 'copy and paste' from my website/blog (see link above):

Confused about testing ? When to get tested? What kind of test? Rapid test? PCR test? Which one is more accurate? Saliva or nasal swab? When to get retested?

First off, what's the difference between an antigen test and PCR test?

In PCR (polymerase chain reaction) test, we amplify the genetic material so that even a small amount of virus can be detected. The sample taken from patient (nasal swab or saliva) is treated with an enzyme called reverse transcriptase to make the RNA into DNA. The DNA is then mixed with polymerase and heated , it separates into two strands. Then it is cooled and the primer copies it so we get a double from each strand. Now keep repeating the process. It goes through many such cycles and we get billions of copies in about an hour. Fluorescein dye enables the copies to generate fluorescence which is measured by a machine.

Antigen tests are much faster (15-20 minutes), easy to perform and can be done at home but have some drawbacks. First, you mix the sample with a solution and then apply that to the test strip which has antibodies. If there are Coronavirus antigens in the sample, they will bind to the antibodies and change color on the strip. They don't amplify so that means there needs to be enough amount of virus to make the test positive. That makes them less sensitive.

What do antigen tests detect?

If you are thinking it is testing the famous spike protein…then you guessed it wrong. Antigen tests detect the N or nucleocapsid protein of coronavirus.
Where omicron has 32 mutations of spike protein, there are only 4 mutations on the N protein. So that answers your next question.

Can antigen tests detect Omicron?

Yes, but how sensitive are they? I’ve discussed that later.

What are some antigen tests available?
You can find all the FDA approved antigen kits using this link:
https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euas-antigen-diagnostic-tests-sars-cov-2

Throat or nasal swab?
Some experts recommend swabbing the throat and then the nose.
It is a bit difficult to do on your own and then there is risk of using the wrong technique. Best if a professional does it or someone else.
To avoid a false positive test, it is recommended that there is no food/ drink/ gum/ to***co use 30 minutes prior to throat swab.

The FDA and CDC have warned against doing throat swabs at home by yourself. Some factors here – because they didn’t approve it that way. They can give a green light only after they have tested something…since they approved nasal swabs initially and didn't test otherwise, plus there are safety concerns.
You can get false negatives with antigen tests.
Here's why: Firstly, antigen tests lag behind PCR tests.
Secondly, they are likely not as sensitive as depicted by manufacturing companies. Now, is that due to the assay quality or because we are not testing saliva?? We don't have published data yet.

If you are thinking about screening for students or workplace, antigen testing is not the right option because you will likely miss the asymptomatic phase and first 2-3 days of symptomatic phase.

Test timing

For omicron the antigen test has a lag of ~3 days after a positive PCR test according to a study later mentioned. There is a pre-omicron era graph from a Lancet study ( see in my blog) which gives you an idea of the infective period and when to expect a positive test

High risk individuals need to test early!

The first few days are important for the antivirals to be effective. You may still be in the monoclonal window but you may miss the antiviral window.
Read my previous post on antivirals:
https://www.facebook.com/100076599069559/posts/108726791690623/?d=n

Individuals who are immunocompromised need to get tested early so they can benefit from the treatment options we have.
According to a preprint study (small population) posted Jan 5, 2022, the antigen test lags behind the PCR by 3 days for omicron. See the graph on my blog (link shared in the beginning)

What's the use of antigen tests?

They are useful when done correctly and if the test is positive especially when symptomatic and the fact that wait times are longer for PCR tests.
Some may say that if an antigen test is negative it means you are not infectious because you did not have enough viral load to spread. But was the timing right ? ...and did you use the right technique to swab? We don’t have published data on current antigen tests and omicron sensitivity except for the preprint study I shared with you.
To me a negative PCR test is more reassuring.
Ummm... you still have to wear a mask!

Can PCR test be done at home?
There are FDA approved molecular self test kits available like Lucira and Cue Health. They are more costly compared to antigen tests but more sensitive and accurate.

You don't have access to PCR testing?
Use serial antigen testing and discuss with your physician about the best way to proceed.

Next post is about Covid Exposure Guidelines for 2022.
If you would like to show support, please follow this page and so that you don't miss new posts.

Article by
Dr.Zaurez Khan

Disclaimer: I have no financial disclosures.

Based Medicine

The Covid Antivirals pills are here !! This is excellent news!

COVID-19 Antiviral pills are here!

Definitely a breakthrough !!

Let’s start with Paxlovid

This is a promising anti-viral that got FDA approved for emergency use authorization on December 22, 2021.
Manufacturer: Pfizer
Composition: Nirmatrelvir + Ritonavir
Dose: 300mg Nirmatrelvir + 100mg Ritonavir twice a day for 5 days.

How does it work?

Nirmatrelvir is a protease inhibitor. Antivirals target the RdRp( RNA-dependent RNA polymerase)or Mpro (main protease). Main target for Nirmatrelvir is Mpro. This is required for virus replication.
In simple words, it slows viral replication. It is active against all known coronaviruses.

Clinical Trial (EPIC-HR study) phase 3 trial summary: High risk Covid positive patients were randomized into 2 groups. Individuals who had received monoclonal antibodies(6%) were excluded from analysis. 697 received 5 days of paxlovid versus 682 who received placebo and monitored over 28 days. 5 out of 697 were hospitalized in paxlovid group, out of which 0 died. Whereas, 44 out of 682 were hospitalized in placebo group, out of which 9 died.
I have made an easy to understand table ( scroll down to the pictures).
So it is 89% effective if given in the first 3 days and 88% effective if given in the first 5 days. Amazing isn’t it!
This data has been confirmed by an independent study (not conducted by Pfizer).
EPIC-SR is an ongoing trial on non-high risk patients. We do not have complete results yet.

Why ritonavir has been added?
Yes ritonavir is an anti HIV drug. This has been added to slow the clearance (breakdown/removal) of nirmatrelvir from the system so higher level of medicine can be achieved. It acts by blocking an enzyme (CYP3A) made by the liver that breaks down medicines like Nirmatrelvir(main drug in paxlovid).

Molnupiravir is another antiviral
Manufacturer: Merck, Ridgeback Biotherapeutics
This got FDA Authorization in December 2021 as well.

Personally, I do not recommend this one. Here’s why?
Clinical Trial Data (MOVe-OUT study) Summary: 1433 Covid positive patients (May –July 2021) were randomized into 2 groups.28/385 were hospitalized, out of which 0 died. Whereas in the placebo group 53 out of 377 were hospitalized out of which 8 died. That’s 50% efficacy but study from August to October 2021 found only 3% reduced hospitalization or deaths.
Dose: 800 mg twice a day for 5 days. Start within 5 days of symptoms.
Age? 18 years and up
It is NOT safe for pregnancy/lactation
It has reproductive toxicity for men and women and has low efficacy.

Not so glamorous? I don’t want to bore you guys with molnupiravir. So let’s move on.

Remdesivir is also another good option. It has been used in hospitalized patients for some time but you can now prescribe it for outpatient treatment. A 3 day IV(intravenous) course. 200 mg on day 1, followed by 100 mg on day 2 and 3. The oral version will be out soon as well.
Don’t forget that monoclonal antibodies are quite useful tools. Explained at length in my previous post.

Are antivirals an option for you?

Like Tamiflu for influenza, you have to take it within the first few days (preferably 3 days) of mild-moderate symptoms for these to be effective.
What ages ? 12 years and up and weight 40 kg and up.
Pregnancy: Paxlovid is safe.
Molnupiravir is NOT safe for pregnancy.
What are the most common side effects?
Muscle pains, diarrhea, high blood pressure, change in taste.

Can patients with kidney disease take it?
If your GFR is below 30 mL/min, then the answer is no. But if it is between 30-60 mL/min, it can be taken at a lower dose: 150 mg Nirmatrelvir + 100 mg ritonavir at your physician’s discretion.

Can patients with liver disease take it?
Your physician can decide to use with caution if there is liver disease but do not take if you have severe disease like Child-Pugh Class 3.

Can you get an anti-viral if you are vaccinated?
Yes, if you fulfill the conditions listed above.

What’s the cost?
Currently, they are being provided for free to the US population by the Government. However, there is limited stock…like 65000 doses only .Now distribute that over 50 states of USA. The entire state of Texas got like 4240 doses. You get the idea! But they are rolling out more like over 300000 in less than 2 months.

How to find a pharmacy near you (USA residents)?

Copy and paste the following URL in another browser to open:
https://healthdata.gov/Health/COVID-19-Public-Therapeutic-Locator/rxn6-qnx8

A patient is in the hospital, can it be prescribed to them?

Depends. They can be used at the physician’s discretion, if they are admitted for other reasons besides Covid or have mild-moderate Covid symptoms and at high risk of progression to severe disease.

It is important to check for drug-drug interactions before prescribing this drug.
How to check for drug interactions?

Copy and paste the following URL in another browser to open and then type in the co-medications:

https://www.covid19-druginteractions.org/checker

Are they effective against Omicron?

Yes! Great news isn’t it. Omicron has over 30 mutations in the spike protein but only 1 of those that are being targeted by paxlovid. The target proteins of these antivirals are conserved.

Look at the graph below. It is from a preprint study (28 December 2021). It shows the in vitro efficacy of remdesivir, Nirmatrelvir (paxlovid), molnupiravir and some other drugs against SARS-COV 2 variants of concern including omicron.

Antivirals are definitely good news! But remember prevention is better than cure. Wear masks and get vaccinated. We need mass scale production of these antivirals. Now that’s the problem .We are close to ending this pandemic but not just yet. Covid-19 is a moving target and our dedicated researchers are keeping up. Happy new year!

Article by
Dr. Zaurez Khan

DISCLAIMER: This post is NOT sponsored by any company or organization and I have NO financial disclosures. This is free evidence-based medical/health education. For medical advice, contact your physician.
.Zaurez Khan

Should you get your antibody titers checked after Covid-19 infection or vaccination ?

The FDA ( U.S. Food and Drug Administration) in a statement (May 2021) has advised against titer testing . The CDC (Centers for Disease Control and Prevention) doesn’t recommend either. I don’t represent any institution but based on my experience and interpretation of studies with omicron you simply need a booster. Some studies suggest the booster to be effective for 10 weeks.

Here is what we know with prior variants : The nature study moderna and Pfizer with 95% efficacy goes down to 77% by 90 days and keeps waning, but a vaccine with a 70% efficacy to start with will be 32% effective only. Lancet study ( Oct 2021): Moderna reduces hospital admissions uptil 6 months after vaccination. Overall effectiveness drops from 88% during first month to 47% after 5 months / 53% for delta after 4 months.
For omicron : A December 2021 non-peer reviewed Denmark study shows Pfizer effectiveness against omicron 55% after a month, 36% with moderna, 16% after 2 months with Pfizer and 30% with moderna ,9% after 3 months with Pfizer and 4% with moderna.

People on immunosuppressive therapy esp. antiCD20 won’t get good titres. So there are many factors here.

If you are to get your titers checked, it has to be IgG to S spike protein because that’s what Pfizer and moderna are targeting and I would say at least 54 for neutralising antibodies and 400 for S ELISA 400 ( Nature study). Another nature study ( different units) at least 0.25 mcg/ ml will provide complement activation , Fc Receptor and neutrophil phagocytosis.

So what do we know about people who got their titers checked ?

There is a November 2021 JAMA study - anti spike IgG antibody titers before and after third Pfizer dose in 97 individuals above age 60 were assessed. The median level increased from 440 IU/mL to 25468 AU/mL after third dose.
Another JAMA study of 1960 health care workers who provided serum samples at least 14 days after second vaccine dose revealed 3.7% had evidence of previous infection. Individuals with history of infection and vaccination had higher titers than vaccination alone.

Remember antibodies titres are checking one limb of immune response. T cell immunity is there to help as well. Some people may have low titres but are protected due to good T cell response ,CD8 in particular . So that can be tested as well .

Covid-19 is a moving target and our researchers are keeping up !

Article by Dr. Zaurez Khan

Based Medicine

What is the new Covid variant Omicron? How is it different from Delta? Explained in 5 minutes - Latest updates on Omicron in video description box
Click on the link below to watch

New Covid-19 variant Omicron - Should we be concerned? Latest update about the new Covid variant .We have cases now in UK, Germany, Australia, Denmark etc . It is spreading rapidly .. wear masks for your own and ...

Monoclonal antibodies are one of the tools against Covid-19. How are they made and which ones are effective against omicron? There is a new monoclonal with long lasting immunity!
Click on the link below. Please take a few minutes to learn!
https://youtu.be/KC7yC1V5YmE