COVID-19 Alaska Clinical Update: November 21, 2020

COVID-19 Alaska Weekly Update

COVID-19 Alaska Clinical Update
November 21, 2020

AK cases

There are 26,044 cases recorded in AK total, and the state is in its eighth week in a row of accelerating cases. There have been 600 hospitalizations and 101 deaths among Alaskans. 111 Alaskans are currently hospitalized, with 14 requiring mechanical ventilation.

What you really need to know about the COVID-19 vaccine

  • Safety and efficacy data from COVID-19 vaccine trials will be reviewed by the FDA as well as an independent review board before a vaccine is authorized or approved
  • The companies making the leading vaccine candidates (Moderna and Pfizer) have taken the unusual step of releasing their protocols for public review to ensure transparency
  • Both Moderna and Pfizer announced promising results from initial planned analyses and plan to file for EUAs shortly, meaning the first distribution of vaccines may be weeks away
  • Healthcare workers are top priority for the vaccine
  • There are no plans to mandate a vaccine
  • The State of Alaska is preparing to distribute the vaccine as soon as late November, although the date when the first doses will be available is not yet known
  • Distribution may be challenging, since one of the two leading vaccine candidates is stored at an extremely cold temperature
  • You can help distribute vaccine to your community! See the Alaska COVID-19 Vaccine Information Page for Healthcare Workers to sign up. DHSS is actively seeking providers to enroll in vaccine distribution in all communities.

A refresher on vaccine development: part 2 of 2

As conversation on vaccines ramps up, clinicians may get more and more questions from patients. DHSS developed a multi-part series reviewing the vaccine development process, delving in depth on the different types of vaccines being tested for COVID-19 and where they are in the pipeline, and addressing common questions about vaccines to help clinicians have answers at their fingertips. The first part will discuss the process for approval, while the second part discusses specific vaccine candidates, risks and FAQs. For more information, see the DHSS website on vaccines. Please also join us on the DHSS Vaccine ECHO, Thursdays at 2PM: register here

Types of COVID-19 vaccines being proposed 

Some vaccines are built on adapted older technology, while other vaccines use new technology. As of late October, there were 48 vaccines in clinical trials on humans, and at least 88 vaccines are currently undergoing preclinical testing in animals. 

Two of the vaccines that are furthest along in clinical trials are messenger RNA (mRNA) vaccines, which work by helping the body produce proteins similar to the proteins the virus uses. If the immune system recognizes those proteins already, it can be ready to fight off a virus that has those proteins if it encounters the virus later. Other vaccines use engineered viruses (mainly adenoviruses, which normally cause colds and other common infections) to warn the immune system by allowing it to recognize viral proteins that SARS-CoV-2 uses. Another type of vaccine puts SARS-CoV-2 proteins directly in the body, either whole, in part, or attached to a larger molecule. The last category of vaccines are made from coronaviruses themselves that have been killed or weakened so as to not cause illness (live attenuated vaccines).

COVID-19 Alaska Weekly Update

How are the phase 3 trials going?

As of late October, there were 4 vaccines in phase 3 trials in the United States. 

The Moderna/NIH mRNA-based vaccine started US Phase 3 trials in July. Moderna has enrolled over 30,000 participants, including 42% with higher risk medical conditions and more than 8,000 aged 65 or older. Half will receive the two-part vaccination, 28 days apart, and half will receive a shot of saline; neither the volunteers nor the doctors know who gets which. Moderna’s study design is to wait until a certain number of people become sick with COVID-19 before allowing an independent review board to look at their records to see if they were vaccinated or not. On November 16, 2020, Moderna announced results of its first interim preliminary analysis: of 95 cases of symptomatic COVID-19 occurring in their Phase 3 trial, 90 were in the control arm and received a placebo, corresponding to 94% efficacy. These data were reviewed by independent experts. Moderna plans to apply for an EUA within the next few days. After the trial, participants would still be able to report any adverse effects through the national vaccine monitoring system. The US has purchased 100 million doses of this vaccine, development of which was funded through the US government. 

The Pfizer vaccine, which is an mRNA vaccine given in two doses 21 days apart, started US Phase 3 trials in July and has enrolled more than 43,000 Americans. They are using a similar strategy for their trial as Moderna, including an independent review board for early efficacy checks. In October, they got permission to start testing the vaccine in children, starting with older teenagers and eventually in children as young as 12. This is the only vaccine currently being tested in children in the US. In early November, they announced that a preliminary review conducted more than halfway to their final analysis was more than 90% effective in preventing COVID-19 and that no serious safety concerns have been seen. The company applied for an EUA on November 20, 2020. The US has purchased 100 million doses of this vaccine with the option to acquire 500 million more. One limitation of this vaccine is it must be stored at negative 80 Celsius (-112F), although can be stored and/or transported in dry ice containers for up to 5 days. 

Both Moderna and Pfizer have published the full protocols for their Phase 3 trials.

Johnson & Johnson have a one-dose adenovirus vector vaccine that started a Phase 3 trial in September. They hope to enroll up to 60,000 participants by the end of the year. The US has agreed to buy 100 million doses if approved. Data is not available yet for phase 3 trials of this vaccine, but a similar technology has been used to make vaccines for Ebola virus, HIV, RSV and Zika virus.

AstraZeneca, in partnership with Oxford University, has a two-dose chimpanzee adenovirus vector vaccine in Phase 3 trials in the UK and Brazil and announced plans in September to enroll 30,000 American adults in a US-based trial. This trial was paused after a case of transverse myelitis was found in a study participant, but was restarted in late October after safety data was reviewed by the FDA and an independent monitoring board. The trial’s registration on notes that they expect preliminary results as early as the beginning of December. 

Of note, most phase 3 trials are not currently testing vaccines in children or pregnant women. As of late October, Pfizer is now testing its vaccine in older teenagers and plans to expand testing to younger teenagers soon, but no company has announced plans to test a COVID-19 vaccine in young children in the near future. Testing vaccines in these populations requires additional safety studies. Because none are currently being tested in young children or in women who are pregnant, the first offerings of vaccines likely will not include eligibility for these groups. 

Risks that vaccines can pose

The main contraindications to vaccines in general are that anyone with severe egg allergy should avoid vaccines made in eggs (for example, the yellow fever vaccine) because they may react to egg proteins in the vaccine. This is not an allergy to the vaccine itself. People with compromised immune systems should avoid live attenuated vaccines because the virus that has been altered to not cause disease may find a way to cause disease in a person without a functioning immune system. Pregnant women should avoid MMR vaccines and certain other live vaccines due to (mainly theoretical) concerns that live attenuated virus may produce illness in the fetus. Women who are breastfeeding may receive live attenuated vaccines, however. Live attenuated virus vaccines cannot pass to infants via breastmilk. 

The CDC says that any vaccine can cause side effects, but typically these are minor and go away within a few days- for instance, a sore arm or swelling at the injection site. 

All vaccines are tracked through the Vaccine Adverse Event Reporting System, which started in 1990. Anyone can report a health problem they suspect might be related to a vaccine through this system, and then the CDC investigates the health problem to see if it was caused by the vaccine. While many health problems reported through this system turn out to not be related to the vaccine at all (many just occurred around the same time) several rare vaccine side effects have been found using this system. For example, a rare intestinal side effect of an older version of the rotavirus vaccine was found because of this system. 

If a clinical trial finds worrying symptoms in participants, the trial can be paused while more information is gathered. Once there is more information, the decision about whether the trial can continue will be made. If unexpected side effects occur after approval, the FDA has the ability to take a vaccine off the market temporarily or permanently.

Want to enroll to provide Covid-19 vaccine?

DHSS is seeking Alaska providers to help make the vaccine available in their community will enroll in a CDC COVID-19 Vaccination Program administered by the Alaska Department of Health and Social Services. As an enrolled provider, your facility will be eligible to order COVID-19 vaccine through the department’s immunization program and receive shipments of COVID-19 vaccine from the distributor.

Learn more about enrolling in the program at the Alaska COVID-19 Vaccine Information Page for Healthcare Workers.

Other frequently asked questions:

Will the COVID-19 vaccine make me test positive on a PCR test?

No, it will not. The vaccines work by causing your immune system to recognize the virus. The PCR test looks for specific parts of the genetic material contained in the virus, which vaccines do not have. 

Some of the vaccine trials have been paused after a participant became ill. Does this raise safety concerns?

Vaccine trials closely monitor all participants for health effects. If a participant has a new health problem, it can sometimes take time to determine if the health problem was because of the vaccine or related to something else, and to make sure nobody else in the trial has had that type of health problem. Pausing a trial while this investigation happens is a routine part of vaccine trials and does not necessarily mean the vaccine is causing a health problem- it is a built-in safety measure. Typically, trials are restarted if no link is found between a health problem and the vaccine, for example because a health problem was found to be in a patient who received a placebo vaccine or related to a previous health problem the patient had had, so the restarting of several of the trials that were paused is good news. 

How do we know the vaccine will be safe?

An independent panel called a data-safety monitoring board analyzes the results of all trial data at several points during any Phase 3 trial conducted in the US. So, all data will be reviewed not just by the company and by the FDA but by an independent group of scientists to make sure that the vaccine is not just safe but effective before authorization or approval is granted. Both of the companies making the vaccines leading in phase 3 trials have also released their study protocol, an unusually transparent move, so that anyone can review how their studies are designed. 

Are these trials moving too fast to make sure a new vaccine is safe?

These trials build off years of vaccine knowledge and in many cases are similar to other vaccines or use technology already used in other vaccines. Research has moved at an unprecedented speed in large part because of the vast number of labs and companies that have turned their efforts to a COVID-19 vaccine. Information such as the genetic sequence of SARS-CoV-2 has been shared openly, speeding collaboration, and trials have been conducted in parallel with manufacturing at great financial risk, rather than waiting for results before beginning a lengthy manufacturing process. It is important to note that vaccines for COVID-19 must still undergo the same safety checks and safety monitoring as any other vaccine, and that safety data is still being collected on an ongoing basis from anyone who received the vaccine in Phase 1 and 2 trials as well as Phase 3.

Can a mRNA vaccine change my genetic code?

The mRNA vaccines are designed to allow mRNA to make its way into the cytoplasm of a cell, where the cellular machinery present there (e.g. ribosomes) can translate the mRNA to proteins. The mRNA in both vaccines codes for spike proteins, which cells can build and install on the outside of their membranes for the immune system to come by and react to. Spike proteins were chosen because it is the spike proteins on the outside of the SARS-CoV-2 virion that the immune system recognizes and reacts to. No virus is involved in the vaccine so there is not a concern for viral replication. No DNA is involved, and mRNA does not pass readily from the outside to the inside of a nucleus (or use the same coding system), so there isn’t a good way for mRNA outside the nucleus to change the DNA inside the nucleus.

Will these vaccines cause long term/autoimmune side effects?

With vaccines, adverse effects typically present in the first week after administration, and nearly all adverse effects occur in the first two months. At this point, both of the leading companies have announced that more than half of their trial participants received the second dose of their series more than two months ago, meaning that the data submitted to the independent review board and the EUA should reflect the side effects observed in the most likely period of time to experience side effects.

Part 1 of 2 covered how vaccines work, are developed and are tested and is available here. For more information and to stay up to date on the most current information on vaccine data and distribution plans, join us on the DHSS weekly vaccine ECHO on Thursdays at 2PM.

References and further information

Alaska COVID-19 Vaccine Information
CDC general vaccine information
FDA statement on vaccine approval and guidance document for COVID-19 vaccine development
FDA definition of an EUA and EUA guidelines for a COVID-19 vaccine
CDC guidance for vaccination during a pandemic
The New York Times maintains a vaccine tracker for updates on vaccine status
The Moderna vaccine’s study protocol
The Pfizer vaccine’s study protocol