Answer all your burning questions (and your patients’ burning questions) about the different COVID-19 vaccines currently authorized in the US. Infectious diseases / HIV expert, Dr Monica Gandhi @MonicaGandhi9 (UCSF) joins us to cover: the Pfizer-BioNTech and Moderna novel mRNA vaccine mechanisms, trial data, and practicalities of who should receive them. We discuss data around the Oxford-AstraZeneca adenovirus vaccine, which is authorized in the UK and India, and may be available in the US later this year. Feel confident recommending COVID-19 vaccines to your patients!
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There are two currently authorized vaccines under Emergency Use Authorization by the FDA in the US (as of this recording 1/2021): Pfizer-BioNTech and Moderna.
These use a novel mechanism of messenger RNA (mRNA) coding for the coronavirus spike protein encapsulated in a lipid nanoparticle. When injected into the body, the lipid nanoparticles allow the mRNA to easily enter our cells. The genetic coding is picked up by our ribosomes and endoplasmic reticulum, causing our cells to make large amounts of the coronavirus spike proteins which then triggers immune response to activate T cells and create antibodies. The mRNA quickly degrades and is not incorporated into the nucleus thus does not stay around in the host’s body (Almeh 2020, Sahin 2020).
The Pfizer and Moderna vaccines each require two shots each, typical for many vaccines to stimulate lasting immunity.
As genetic material is unstable, mRNA degrades quickly and needs to be kept extremely cold which impacts the ability to distribute. For reference, a typical refrigerator is 4℃. The Pfizer-BioNTech vaccine needs to be kept at -70℃, typical of a research laboratory refrigerator. The Moderna vaccine can be stored at -20℃ for 6 months and in a typical refrigerator (2-8℃) for 30 days allowing for a little more flexibility with mass distribution (FDA 2020, FDA 2020).
The Pfizer-BioNTech and Moderna COVID-19 vaccines phase 3 trials were designed to evaluate rates of symptomatic COVID-19 infection and assess the presence of severe disease. The trade-off for getting data from these trials as quickly as possible was that asymptomatic disease detection with routine swabbing was not an outcome studied. Both of the mRNA vaccines showed around a 95% efficacy in preventing symptomatic infection and significantly reduced rates of severe disease. Unfortunately, we don’t know yet if they stopped asymptomatic spread and we need to wait for the data to be published. Dr. Gandhi thinks it would make sense, biologically speaking, that it would stop the asymptomatic spread of COVID-19 infection. These large phase 3 trials showed no sign of serious safety concerns (Baden 2020, Polack 2020).
These vaccines have come to market very quickly by overlapping phases of the vaccine trials, as opposed to being carried in a subsequent manner. Additionally, the interval of time between the first and second vaccine administrations was shortened to 21 days for the Pfizer-BioNTech and 28 days for Moderna (many other vaccines may be spaced by months). Dr. Gandhi mentioned it may be efficacious to separate the doses by a wider interval since it helps create greater immunogenicity. The outcomes were assessed starting just 2 weeks following the second dose (Baden 2020, Polack 2020).
Since these vaccines are so new, we don’t know how long they will offer protection. Dr. Gandhi is hopeful these vaccines will provide lasting immunity for at least 5 years, from extrapolating existing data. She says they may require periodic boosters, but will not likely be yearly.
A number of mutated strains of coronavirus have spread, including an earlier D614G, the recent UK Variant B.1.1.7 lineage, and South African variant B.1.351 lineage. These strains seem more transmissible because of increased viral load. At this point, research suggests the current vaccines should still be highly effective. (CDC 2021, Conti 2021)
Dr. Gandhi suggests basically everyone should get the vaccine.
While pregnant and breastfeeding women were excluded from trials, Dr. Gandhi feels there should not be a scientific reason for vaccination to be unsafe. The mRNA degrades very quickly and the spike protein is very specific to coronavirus thus there is little risk of autoimmunity. Current guidance is that we should offer the vaccine to pregnant patients since the risk of COVID-19 infection in pregnancy is serious; women should discuss their concerns with their medical providers and weigh the risks and benefits (Rasmussen 2020, CDC 2021).
Only a small number of patients with HIV or immunosuppression were included in the Pfizer-BioNTech trial. Dr. Gandhi suggests that vaccination should be safe in immunosuppressed patients though we do not have specific data on this matter.
Out of the 21,000 Pfizer and 16,000 Moderna trial participants, there were no hypersensitivity reactions noted. Anaphylaxis was seen among healthcare workers who were vaccinated early during the roll out. The CDC issued a caveat for patients to wait 15 minutes after vaccination and wait for 30 minutes if they have a history of anaphylaxis. Dr. Gandhi feels this is probably overkill and people who know what to look for with anaphylaxis should likely self monitor for symptoms. At this point, it seems the reaction may be to PEG (polyethylene glycol). Someone with a peanut or seafood allergy is likely at very low risk. Since our recording, the CDC/MMWR released data that only 21 cases of anaphylaxis have been recorded in the 1.8 million doses of Pfizer-BioNTech vaccine given so far (11 cases per million).
Patients who had COVID-19 infection have immunity, and vaccines should ideally be saved for others when we still have vaccine shortages. The CDC/ACIP recommend waiting 90 days after COVID-19 infection for vaccination, not because of any risk, but because the risk of reinfection is very low. A recent NEJM study showed that immunity lasts at least 6 months, so this recommendation may be extended (Lumley 2020).
The Pfizer-BioNTech mRNA vaccine is authorized for age 16 and up (FDA 2020). The Moderna vaccine is only approved for age 18+ (FDA, 2020). There are active pediatric vaccine trials enrolling for younger children. Dr Gandhi is hopeful we can achieve herd immunity without needing to vaccinate very young children, but it is likely the vaccines may be available to older children over the coming months.
Dr. Gandhi states the main point to remember is that most of the effects were not too serious. Injection site reactions were reported in over 90% of the participants, with pain being the most common side effect. A fair amount of people reported fatigue, headaches, and fever; these reactions are a reassuring sign of an active immune stimulation. Dr. Gandhi notes those with fever could be managed with antipyretics. Serious side effects were rare, and similar between vaccine and placebo groups (Baden 2020, Polack 2020).
The main goals laid out by the CDC are to protect the vulnerable populations and focus on reopening society. It should be noted that the vaccine distribution groups vary from state to state in the US.
Phase 1a: Health care and nursing home residents and staff (done in Jan)
Phase 1b: Age 75+, teachers, grocery store, transit workers, meat processors, etc (Late Jan-Feb)
Phase 1c: Ages 65-74 or 16+ if you have a pre-existing condition, or others who cannot work from home (CDC timeline said March-June)
Phase 2: Anyone age 16+
Dr Gandhi suggests herd immunity might be at 70% of the population. She is hopeful we will reach this by the time we complete phase 2 which should be helpful with protecting the pediatric population since there will not be high priority to immunize young children.
As of this recording (1/2021), the University of Oxford-AstraZeneca vaccine is only approved in the UK and India. This vaccine uses an adenovirus from a primate as the vector for DNA that codes for the coronavirus spike protein. This DNA is taken up within our cells and coded into mRNA which then triggers our cells to create the spike protein. This primate adenovirus does not reproduce or cause pathology in humans. This is also a two-dose vaccine. Unlike the mRNA vaccines available, this vaccine can be stored in a regular refrigerator for at least 6 months which allows for more flexibility with mass distribution such as rural settings. According to trial data, no severe outcomes were found in the vaccine group.
Unlike the mRNA vaccine trial, the participants in the Oxford-AstraZeneca vaccine trial self-swabbed every week to watch for asymptomatic infection. Phase 3 data showed a 59% reduction in asymptomatic infection. There were some irregularities in these study protocols. Some participants were accidentally given a lower first dose then received the standard dose for the second shot (LD/SD). The LD/SD arm of the trial was found to be more effective at 90% compared to 62% effectiveness for individuals in the standard dose/standard dose (SD/SD) arm. Participants in the LD/SD arm were mostly under the age of 55 and received the doses of their vaccines with an interval of 12-weeks, which could explain the higher immunogenicity. The LD/SD participants also experienced fewer side effects. The total effectiveness at reducing sympathetic disease was reported to be 70%, with no hospitalizations or COVID-19 deaths seen in the vaccinated arm (Voysey 2020). As of the time of the recording, the AstraZeneca trial is still ongoing in the US.
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Listeners will understand the currently available and likely soon to be released COVID-19 vaccines.
After listening to this episode listeners will…
Dr Gandhi reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures.
Heublein M, Gandhi M, Chiu C, Okamoto E, Karginov T, Williams P. “#253 COVID-19 Vaccines with Dr Monica Gandhi”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. January 27, 2021.
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