Archives 2021

What is Omicron? The new B.1.1.529 variant (Omicron) clade 21K, which harbors many mutations, particularly in the spike protein, was first detected in South Africa. Unlike the other variants of concern, B.1.1.529 has emerged independently from mid-2020 strains of SARS-CoV-2.

Why South Africa? It is possible, but unlikely, that this variant emerged in South Africa. South Africa has excellent scientists, a great surveillance program, transparency, and sharing of data!

Anytime there’s a new variant of SARS-CoV-2, there are at least 4 concerning things to consider: 1) Is it more transmissible than currently circulating strains? 2) Does it evade neutralization by antibodies (i.e., antibodies from natural infection, immunization, or monoclonal antibodies)? 3) Does it evade immunity due to vaccination (i.e., antibodies, T cell response)? 4) Does it cause a more severe (or milder) disease?

1) Is it really more transmissible than Delta? It’s too soon to tell. Superspreader events, which are outliers, get noticed early and can result in a very high estimation of basic reproduction number (R0). However, it does seem like B.1.1.529 (Omicron) is outcompeting B.1.617.2 (Delta) in South Africa.

2) Does it evade neutralization by antibodies? Omicron seems to have many more S1 mutations than previously circulating variants, which might be very problematic. While we don’t know for sure yet, its mutation profile predicts significant immune evasion.

3) Does it evade immunity due to vaccination (i.e., antibodies, T cell response)? We don’t know yet.

4) Does it cause a more severe (or milder) disease? We don’t know yet.

We need more studies to understand this variant and its impact more. In the meantime, please get vaccinated and wear a mask!

[All images from IDTwitter]

Last night (8/12/21), the FDA extended the emergency use authorizations (EUA) for Pfizer-BioNTech’s BNT162b2 (currently for age 12 years and older) and Moderna’s mRNA-1273 (currently for age 18 years and older) to allow for the use of an additional dose in certain immunocompromised individuals, such as solid organ transplant recipients or those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise (https://bit.ly/37DWxk3).

Today (8/13/21), the CDC’s ACIP voted 11-0 to approve a 3rd dose following a primary 2-dose series in immunocompromised people. Of note, whenever possible, vaccination should be given at least 2 weeks prior to initiation of immunosuppressive therapies. Who’s considered immunocompromised? Here’s a slide from ACIP meeting:

What about individuals who received a single dose of Johnson & Johnson’s Ad26.COV2.S vaccine? No recommendations yet due to lack of data, but probably best to get at least one mRNA vaccine booster.

The good news is that influenza was very scarce last year (2020-21) in the Northern Hemisphere and remained scarce this summer in the Southern Hemisphere. As well described by Uyeki et al (doi:10.1001/jama.2021.6125), this could generally be attributed to three factors: 1) community mitigation measures (e.g., masking, social distancing, workplace closures, school closures, virtual school instruction, indoor dining restrictions), 2) behavioral changes (e.g., staying at home, working from home, reduced domestic and international travel, or international travel with subsequent quarantine upon arrival, and 3) influenza vaccination. Last flu season set a record for vaccine distribution (194 million doses), with more than 55% of adults getting immunized in the U.S. What to expect this year? Anything from a repeat of last season’s numbers to an explosion of cases is possible.

Let’s look at the first factor, community mitigation measures. Schools are open, which means that children are in a position to accelerate the transmission of influenza in the community. Many people who are vaccinated against COVID-19 have eased masking and social distancing, increasing their exposure to influenza. Indoor dining is almost back to normal, where social distancing and masking are difficult to follow. Let’s look at the second factor, behavioral changes. People are more comfortably resuming normal activities because they are vaccinated against COVID-19, including international and domestic air travel. All of these make factor three, influenza vaccination, more important than ever. The CDC released the new Prevention and Control of Seasonal Influenza with Vaccines recommendations for the 2021-22 influenza season last week. Here are a few takeaways:

https://www.cdc.gov/mmwr/volumes/70/rr/rr7005a1.htm

• Routine annual seasonal influenza immunization is recommended for all persons aged ≥6 months who do not have contraindications
• No preferential recommendation is made for one influenza vaccine product over another
• Vaccination should be offered by the end of October and continued through flu season
• For nonpregnant adults, early vaccination (i.e., in July and August) should be avoided unless there is concern that later vaccination might not be possible
• Revaccination later in the season of persons already vaccinated is not recommended
• COVID-19 vaccines can be co-administered with influenza vaccines

Influenza vaccine formulations available:

New recommendations regarding severe allergy to influenza vaccines:

• Can consider 3 different groups: egg-based vaccines, cell-cultured, and recombinant
• Precaution use should occur in an inpatient or outpatient medical setting under the supervision of a provider who can recognize and manage a severe allergic reaction

Influenza season typically peaks between Christmas and Valentine’s day, most often closer to Valentine’s day. Get your flu vaccine by November and be ready for Christmas and Valentine’s day!

The COVID vaccination campaign has been extremely successful in the United States, with highly effective mRNA vaccines from Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273), as well as an Adenovirus-vectored vaccine from Janssen (Ad26.COV2.S). There are at least 2 questions to be answered. 1) While the vaccines seem to continue to work up to 6 months, how long will the efficacy last (hence the need for a booster)? and 2) how effective are these vaccines against the emerging variants (particularly against problematic B.1.351 and P.1 variants)? While antibodies produced from 2 doses of mRNA-1273 still seem to neutralize B.1.351 (first identified in South Africa) and P.1 (first identified in Brazil) variants, the neutralization capacity is reduced by 6.4- and 3.5-fold, respectively, which is concerning due to the possibility of breakthrough infection and waning efficacy.

There are 2 approaches to tackle this problem: 1) Administer a third booster of the original vaccine to increase the neutralization capacity and overcome the waning of antibodies, or 2) Administer a booster vaccine that matches the variant of concern (not the original vaccine).

In a pre-print paper (not peer-reviewed yet), Moderna shares the preliminary safety and immunogenicity results of a third booster shot in a phase 2 trial (http://doi.org/10.1101/2021.05.05.21256716). They enrolled adult participants from previous phase 2 or 3 trials who had received a 2-dose series of the original mRNA-1273 about 6-7 months before enrollment (no pregnant individuals). A booster dose of 50 mcg mRNA-1273 was given to 20 participants from the previous phase 2 trial. A booster dose of 50 mcg mRNA-1273.351 was given to 20 participants from the previous phase 3 trial. A 20 mg dose of mRNA-1273.351 is also being evaluated in 20 participants (results not published yet).

Boosting with mRNA-1273 resulted in a 23-, 32-, and 44-fold increase in neutralization against D614G (considered wild-type), B.1.351, and P.1 variants, respectively. Boosting with mRNA-1273.351 resulted in a 12-, 35-, and 27-fold increase in the neutralization of each variant, respectively. Of note, mRNA-1273.351 resulted in significantly higher titers against B.1.351 compared to mRNA-1273 boost. Because a correlate of protection from neutralizing antibodies has not been established yet, it remains to be seen if these boosted titers result in protection against B.1.351 and P.1 variants. The trial is ongoing and is currently evaluating a multivalent vaccine (50 mcg mRNA-1273.211) comprising of a 1:1 mix of the original mRNA-1273 (25 mcg) and mRNA-1273.351 (25 mcg). Will I personally get a third shot if authorized by the FDA? You bet! mRNA-1273.351.

Back in January 2021, I had a patient who had experienced a delayed edematous plaque (very large and painful) at the site of injection several days after she received her first dose of Moderna’s mRNA-1273. It lasted 5 to 6 days and then resolved. She was concerned about the second shot. She was still willing to get it in the same non-dominant arm but wanted to make sure that it is okay to do so. I told her it would be okay but advised her to get the jab in the other arm.

First of all, neither local injection-site reactions nor delayed-type hypersensitivity reactions are contraindications to subsequent vaccination. As reported by Dr. Blumenthal and colleagues in NEJM today, in a sample of 12 patients with delayed large local reactions to mRNA-1273, half the patients did not have a recurrence of large local reactions, a quarter had recurrent reactions that were of a lower grade than the initial dose, and the remaining quarter had recurrent reactions similar to the initial dose. Skin biopsy revealed that these were in fact type IV delayed T-cell mediated hypersensitivity reactions. The symptoms lasted a median of 6 days (range 2 to 11 days).

What can help with these severe skin reactions? Ice packs, oral antihistamines, and topical glucocorticoids. For antihistamine, it is best to use second-generation H1-receptor antagonists like loratadine 10 mg PO daily, fexofenadine 180-360 mg PO daily or even twice a day, or cetirizine 10 mg (this one might cause drowsiness). You can also use first-generation H1-receptor antagonists like diphenhydramine 25-50 mg every 4 hours as needed (max 300 mg/day) if you want to cause drowsiness. H2-receptor antagonists might help in combination with H1-receptor antagonists, like famotidine 20 mg twice a day. Common topical corticosteroids include hydrocortisone 1%, clobetasol propionate 0.05%, or triamcinolone 0.1%.

https://www.nejm.org/doi/full/10.1056/NEJMc2102131