COVID-19 Update—Vaccines, Variants and Rollout: A Puzzlement

“Our national strategy is comprehensive, it’s based on science not politics. It’s based on truth not denial and it’s detailed.” - President Joe Biden

“Is a danger to be trusting one another; One will seldom do what other wishes; But unless someday somebody trust somebody; There’ll be nothing left on earth excepting fishes!” - “A Puzzlement” sung by King Mongkut in “The King and I,” music by Richard Rogers, lyrics by Oscar Hammerstein II

As an infectious diseases specialist and medical journal junkie, I can barely stay abreast of all the new information about COVID-19. Each week new questions are posed. What new vaccines are in the pipeline? Are the current vaccines effective against the variants? If eligible, where can I get vaccinated? In this Germ Gem post, I’ll try to boil down some of the massive amount of new information about COVID-19 vaccines for those readers who are in a quandary.

Current status of vaccines. Researchers are presently testing 67 COVID-19 vaccines in clinical trials. But to date the U.S. Food and Drug Administration (FDA) has given emergency use authorization for only the Pfizer/BioNTech and Moderna COVID-19 vaccines. As discussed in my December 23rd Germ Gem post, both of these highly effective vaccines are mRNA-based and require two doses. (In clinical trials both vaccines showed exceptional efficacy of about 95%.) The storage of these vaccines is a challenge, however, as they must be stored at extremely low temperatures (minus 70 degrees Celsius and minus 20 degrees Celsius respectively.)

The FDA is likely to approve additional vaccines soon. Three that are on the horizon are:

· AstraZeneca’s vaccine (AZD1222) consists of the replication-deficient chimpanzee adenovirus vector ChAdOx1 that expresses the SARS-CoV-2 spike protein. It requires two doses and can be stored at normal refrigerator temperatures. The vaccine was reportedly 85% effective in preventing severe/critical COVID-19 across all geographical regions. It’s also relatively cheap, making it an attractive vaccine for low-income countries. It was recently approved by the European Medicines Agency.

· Johnson & Johnson’s vaccine is also adenovirus vector-based and requires only one dose. It was found to be 66% effective against moderate to severe COVID-19 in a multinational phase III clinical trial (72% effective in the US cohort). Moreover, it is stable at normal refrigerator temperatures. The US government purchased 100 million doses of this vaccine to be delivered by the end of June, and the company committed to producing up to one billion doses of the vaccine by year-end.

· Novavax, a Maryland-based biotech firm, has developed NVX-CoV2373, a single-dose protein-based vaccine. The company created this vaccine using their recombinant nanoparticle technology to generate antigen derived from the coronavirus spike protein with an adjuvant patented by the company that enhances the immune response. In clinical trials in the UK it was reported to be 89.3% effective against the UK SARS-Co-V-2 variant. It requires only normal refrigeration.

Are the SARS-CoV-2 variant strains vaccine spoilers? A brief refresher of some general information about viruses might be helpful before discussing the SARS-CoV-2 mutants. It is suggested by some evolutionary biologists that viruses have been around for as long as the Earth’s first recognized form of life, namely, bacteria. Bacteria emerged about 3.8 billion years ago, and it appears viruses got their start around the same time. Bacteria and viruses have been coevolving ever since. Viruses are masters at getting themselves into host cells—first into bacteria and only recently (300,000 years ago) into human cells. SARS-CoV-2 uses its spike protein like a key to gain entry into cells via ACE2 receptors (for a discussion of how this works see my April 1st Germ Gem post: “COVID-19: Know your enemy…and your troops”). While viruses are extremely tiny creatures (an estimated 500 million can fit on the head of a pin), their ability to mutate can cause very big trouble for their hosts. This is especially true for RNA viruses like influenza virus, HIV, and coronaviruses.

Enter the elephant into the room, the SARS-CoV-2 mutants. These variants have spike proteins that are no longer recognized by antibodies and T lymphocytes produced by the immune system in response to a vaccine. The major concerns regarding all SARS-CoV-2 variants are: (1) increased transmissibility or contagiousness, (2) greater virulence (more deaths), and (3) enhanced evasiveness of the immune system. The evidence to date suggests that there are three “variants of concern” that all share the property of increased transmissibility.

The UK variant (B.1.1.7) was the first, and it emerged with a large number of mutations. This variant has since been detected in numerous countries around the world, including the US where it was discovered at the end of 2020. In January 2021, scientists from the UK reported evidence suggesting that the B.1.1.7 variant may be associated with an increased risk of death compared with other variants. (More studies are needed to confirm this finding.) And it appears to be about 50% more contagious than the more common strain in the US.

In South Africa, another SARS-CoV-2 variant (known as B.1.351) emerged independently of B.1.1.7 but does share some mutations with B.1.1.7. Cases attributed to this variant have been detected in multiple countries outside of South Africa. It was first reported in the US at the end of January 2021. As mentioned earlier, the Novavax vaccine is highly effective against the UK variant, but its efficacy slipped to 60% against the South African variant. Novavax is therefore working on a “booster and/or combination bivalent vaccine.” Also, the efficacy of the Johnson & Johnson vaccine that was 72% in the US dropped to 57% in South Africa due to the variant.

The most worrisome variant so far emerged in 2020 in Brazil. This variant, known as P.1, was first identified in four travelers from Brazil, who were tested during routine screening at Haneda airport outside Tokyo, Japan. P.1 has 17 unique mutations, including three in the receptor binding domain of the spike protein. This variant was a wakeup call, especially for Minnesotans as it was first detected in the US in a traveler arriving in Minnesota from Brazil at the end of January 2021. P.1 is most worrisome because it recently spread explosively in an area of Brazil where 75% of people had been infected in the spring of last year, suggesting previous infection with another viral strain provided little or no protection against P.1. And P.1. has been found to be dramatically resistant to antibodies that ordinarily confer immunity.

Researchers in public health laboratories, such as the CDC, and pharmaceutical companies are working tirelessly to track and define the nuances of each of these three variants (as well as being on the lookout for others). The presence of these mutations is a wake-up call for all of us. It clearly serves notice that the public must be vaccinated as quickly as possible to prevent further evolution of the virus.

Vaccine hesitancy. The world needs an estimated 75% of the population to develop immunity via vaccination and natural infection in order to stop this virus in its tracks. This is referred to as “herd immunity” or "community immunity". And, vaccination is the key to preventing the further evolution and spread of SARS-CO-V-2. Nonetheless, at the end of December 2020, the Journal of the American Medical Association published the results of a study where the authors found that the percentage of people who said they were somewhat or very likely to get vaccinated had declined over the course of the year from 74% to 56%. This news is particularly surprising as the current vaccines have been shown to be safe, as well as highly effective.

The FDA has approved both Pfizer and Moderna vaccines not only for their efficacy but, more importantly, for their safety. When the FDA reviews applications for new therapies (including vaccines) its most important consideration is safety. In fact, only after the safety data are convincing, does the FDA pay attention to efficacy. The CDC follows the same protocol.

As you may recall from the December 23rd Germ Gem post, “COVID-19 Vaccines: Take One for the Team,” the administration of both the Pfizer and Moderna vaccines was associated with side effects, such as, pain at the injection site, fatigue, headache, muscle pain, fever, and chills. While these side effects are common with many vaccines, a very small number of patients in both the Pfizer and Moderna clinical trials experienced an anaphylactic reaction, with an incidence between 1 per 100,000 to 1,000,000 patients. (The risk of getting an anaphylactic reaction to the vaccine is comparable to the odds of being struck by lightening in a given year.)

Now that both vaccines are being given to large numbers of subjects, the FDA and CDC are gathering a voluminous amount of data on reactions. On January 27, the CDC reported there had been no rise in anaphylaxis rates associated with either of the vaccines. (The constituent of the vaccines that is responsible for severe allergic reactions is unknown, but it could be polyethylene glycol. Also, it’s unclear why the risk of anaphylaxis is higher in women.)

If we are ever to reach herd immunity, people need to be vaccinated. The misinformation about the vaccines that abounds on the Internet may account for some of the waning interest that people have in getting vaccinated. It is evident therefore that the general public needs additional encouragement regarding the benefits and safety of the current COVID-19 vaccines. To that end, the CDC and other public health institutions throughout this country have renewed their commitment to providing clear, simple messages to the public about the safety and efficacy of the vaccines. It is time for us to trust science. And, if we are to win this war, we must urge everyone who is eligible to get vaccinated.

Vaccine rollout. Unfortunately, President Biden’s goal to get 100 million doses of vaccines into the arms of 100 million Americans within 100 days of his inauguration is looking a little shaky. The vaccine rollout to the individual states has been extremely slow. And if that were not enough, the strategy of states for getting the vaccines into the arms of people is, to put it bluntly, a mess.

Contrast our vaccination rate with those of Israel and Britain. On January 27, 2021, Israel boasted (quite appropriately) that it had surpassed 1 million fully vaccinated citizens (12.45% of the population). On that same day the CDC reported that only about 3.8 million people have been fully vaccinated (about 1% of the American population). Britain is another global leader in vaccinating its people. Britain set up dozens of vaccination centers in sports stadiums, churches, mosques, and museums so that by January 29, 11.7% of the UK population had received their first vaccine shot (called a “jab” in the UK).

The delivery and administration of vaccines in the US is a “systems issue.” Our federal government plays an overarching role in the distribution of vaccines to the states. On January 27, President Biden announced a substantial increase in COVID-19 vaccine distribution. This is good news and, hopefully, it includes an increase in the final step in the rollout, that is, vaccinations.

But it is up to states and their departments of health to ensure that the delivery of the vaccines is efficient and equitable. For those who receive their medical care via a Health Care Organization, it is the responsibility of that health care system to notify its members when and where they can get jabbed.

It’s been frustrating for me to see how the COVID-19 vaccinations have been rolled out in the US. Obviously, it is an enormous logistical challenge. But we have the technology and manpower and now apparently sufficient vaccine available to reach President Biden’s immunization goal. And, history tells us that it can be done.

Facing a small pox outbreak in 1946, the City of New York sought to vaccinate all its citizens. At that time, there was no Internet or other means of mass communication readily available to the general public. Nonetheless, in less than one month six million New Yorkers had been inoculated! This was an outstanding public health achievement and one that we should strive to replicate in this pandemic.

I meet all of Minnesota’s eligibility requirements for getting vaccinated. Nonetheless, over the past few weeks I’ve spent a few frustrating days trying to locate adequate information about when and where I might be able to be vaccinated. Last Thursday, the organization where I receive my health care finally announced via “My Chart” that it was taking appointments for eligible patients to receive their first “jab.” I went online, scheduled an appointment and on Saturday was vaccinated. I have to admit that I was delighted to finally get the vaccine. It brings me one step closer to seeing my children and grandchildren!