Dr. Dora Anne Mills

By Dr. Dora Anne Mills

This weekend I enjoyed a wonderful movie experience with my daughter. Two of the theaters at a local cinema are reserved so you can rent them for a private showing of any of the featured movies. She’s been wanting to see “Wonder Woman 1984” on the big screen, so we splurged. Not having seen a movie in an indoor theater for a year, it was quite a treat and reminded me of how much you experience a movie in the theater, with the big screen, big sound, and this one topped with reclining heated seats. What a contrast to watching movies on a tv, or worse yet, my laptop screen, as we’ve been doing. The limited audience and need for reservations were perhaps a glimpse into a new normal. And it was a good cap to the week.

COVID news

It was definitely a week with a lot of mixed news. Let’s start with the variants. The fact that SARS-CoV-2 is mutating is a reflection that it’s part of the natural world. Viruses mutate faster and more significantly when they are replicating more, which they do when there is more transmission. In other words, during surges, when more people contract and transmit COVID-19, there is more viral replication, and therefore the virus is likely to mutate as well as to spread new and existing mutations.

The major concern about the B.1.1.7 (UK), B.1.351 (South African), and P.1 (Brazilian) variants is that they appear to be about 50% more highly transmissible. I hear a sense of relief from people that these variants may not be more virulent, i.e., they may not have a higher fatality rate. Actually, I am more concerned about their likely increase in contagiousness.

Dr. Mill’s concern

Here are the reasons. If you have a virus that sickens 1,000 people per day and has a 1% fatality rate, then if all other things are equal, if you increase the fatality rate by 50%, instead of 10 people per day dying, this increases to 15 per day. The key is, it’s a linear increase, and the 15 per day stays steady.

If instead, you increase the contagiousness by 50%, then after about 5 days (the generation interval for COVID-19), there are 1,500 cases per day, then after 5 more days, there are 2,250 cases per day, and so forth. With a steady 1% fatality rate, that means there are 10 people dying per day the first 5 days (1,000 x 1%), then there are 15 deaths per day the next 5 days (1,500 x 1%), then 22.5 deaths per day the following 5 days (2,250 x 1%). This is exponential growth (versus linear), and after only 60 days, there are 1,277 people dying every day and growing. By contrast, with a fatality rate increase of 50% without an increase in contagiousness, there are still 15 people dying per day after 60 days. (If these statistics are hard to follow, see the graph that is linked to in the resources below.)

Preventing surges

Especially since these new variants seem to be more contagious, it is imperative we get ahead of these mutations and stop them from causing surges here in the U.S. Although we are seeing some plateauing and even reductions in people dying, being hospitalized, and being diagnosed with COVID-19 in much of the U.S., it is only a matter of time before these variants take a bigger hold and tighten the disease’s grip on us again.

What can we do to prevent surges from these new variants? First, we can vaccinate as many as possible and as quickly as possible. Vaccination will reduce transmission, which will reduce further mutations. Since the vaccines thus far appear to be effective against the new variants, even if somewhat diminished, vaccine is likely to reduce transmission as well as severe disease among those infected with the variants. Similar to influenza, even when a season’s vaccine is not a great match against the circulating variants, vaccine most often reduces transmission and provides some levels of protection, especially against severe disease.

Second, to prevent surges with the new variants, we need to double down on non-pharmaceutical interventions, e.g., masking, distancing, hand hygiene, and ventilation (especially important during these winter months). And I mean literally a double down; we can double mask, especially if you don’t have a mask with at least 2 layers of tightly woven different fabrics. I have a two-layer polyester mask that I like wearing, but now I wear a surgical mask under it in order to add a different fabric and another layer of protection. And if I’m headed into a store or other indoor place with people outside of my household, then I’ll add a face shield or goggles.

The third action step – and this is a major concern – is the U.S. needs to conduct genetic sequencing on far more COVID-19 viruses than we are now. This isn’t a matter of building the plane while flying it; we are basically flying blind. The U.S. sequences about 0.3% of all samples. By contrast, Australia and New Zealand sequence about half of all samples, and a number of other countries, such as the U.K., Denmark, Iceland, and Taiwan, test between 10 – 20% of all samples.

What Denmark is doing about COVID

Denmark provides an interesting example. They experienced a surge earlier this winter, and for the last month, their cases, hospitalizations, and deaths have been dropping. They would normally be reopening the country. However, they’re in as strict a lockdown as they were in March. Even though last winter they were one of the first countries to reopen schools (reopening elementary schools after only three weeks), those schools are closed now. Why? Because their genetic sequencing of COVID-19 viral samples is showing an alarming increase in frequency of the B.1.1.7 variant, of nearly a doubling per week, to now about 8% of all cases. Because they recognize the growth is exponential, they realize now is the time to keep lockdown measures in place, in order to prevent a major surge and to buy time while aggressively vaccinating the public.

The Danish prime minister wrote an excellent Facebook post in mid-January, explaining why they were taking such aggressive steps, despite dropping numbers of overall cases. She gave the example of a stadium filling up with water, starting with one drop per minute, and increasing by a doubling of the drops every minute (1, then 2, then 4, then 8 drops each of the first 4 minutes). At that rate, the stadium will fill up in 44 minutes, but it will seem almost empty for the first 42 minutes. She explained that the more contagious variants are just like the drops of water, spreading silently and exponentially. By the time a surge in hospitalizations is detected, it is often too late to flatten the curve.

Continue to be vigilant

Since the U.S. knows these variants exist but not the extent at which they do, it is imperative we continue to be vigilant – masking (including double masking), distancing, ventilation, hand hygiene, and vaccination.

The good news

There is also good news this week. Actually, the J[ohnson]&J[ohnson] vaccine is fantastic news. Although much was made of its reported lower efficacy rates, the preliminary results are still stunning. We cheer in a year when the influenza vaccine is 60% effective, yet the reports on the J&J vaccine are much better. Considering this is a new virus and this vaccine has arrived only about a year into this pandemic, its reported efficacy is truly remarkable.

The J&J vaccine is stated to protect against severe disease and provides some protection against the worrisome B.1.351 (South African) strain. Although in vitro data (i.e., data generated in a lab) shows the mRNA vaccines (Pfizer and Moderna) to be effective against the emerging variants, though less so against B.1.351, the J&J vaccine data were generated in people in several different countries, including South Africa. Their clinical trials there report that even in South Africa, where the variant now dominates, the vaccine prevented severe disease (e.g., hospitalization and death) a month after the shot, including among those with chronic diseases. That’s excellent news.

The J&J vaccine uses a different technology than mRNA (Pfizer and Moderna). It uses an attenuated adenovirus (also attenuated so it cannot replicate) that works much the same way as mRNA vaccines, by harnessing our cells to produce the spike protein. It is this spike protein that is found on the surface of the COVID-19 virus and is responsible for generating our immune responses and binding to cells in different organs in our body.

This technology is used by J&J in its Ebola vaccine, which is licensed in the EU for use in parts of Africa. Using the same technology, J&J also has vaccines in development against HIV, RSV, and Zika. Over 100,000 people have received a form of adenovirus vaccines in clinical trials for these four diseases. What’s exciting is that these vaccines elicit both B (humoral) and T (cellular) immune responses, and for the latter, both CD4+ and CD8+ responses. These are robust immune responses.

Interestingly, this is the same technology used in an oral rabies vaccine for wildlife, including in Maine. For years, planes have dropped an oral rabies vaccine across the woods of northern Maine, to be eaten by wildlife in order to prevent rabies from progressing further, including into Canada.

Pre-clinical and phase one and two clinical trials of the J&J vaccine against COVID-19 conducted last spring and summer indicated strong immune responses, including after one dose. I look forward to reading the phase three clinical trials data when they are released, hopefully, this week.

However, the biggest news from J&J is that this vaccine is effective after one dose and can be kept in a regular refrigerator for three months. This makes it much more like influenza vaccine. As we ramp up large throughput clinics over the next several weeks (many of which are ramped up, but just lack vaccine), there will also need to be other vaccine strategies in order to be successful. That includes what I call a sprinkling strategy of administering vaccine in smaller places where people are gathered (albeit distanced), e.g., worksites, community health centers, small office practices, houses of worship, grange halls, and corner pharmacies. The current mRNA vaccines (Pfizer and Moderna) are challenging to administer in such small venues.

COVID variants and vaccines

Even with the difficult news about the variants, the vaccines also provide good news on this front. These vaccines – mRNA (Pfizer and Moderna) and adenovirus (J&J) – can be modified to work specifically against the new variants. Moderna is already working on one and says it could develop a vaccine booster that incorporates the new variants in about six weeks.

This pandemic in some ways is evolving as influenza does. Influenza mutates at a faster rate than the COVID-19 virus since it lacks some of the proofreading in its replication process that the COVID-19 virus has. Each year the multiple strains of circulating influenza viruses evolve, and so must the vaccines. The good news is that we now have new vaccines that can be modified much more quickly than our traditional influenza vaccines. Perhaps we’ll have mRNA vaccines against influenza as well.

So, although this week’s news is mixed, none of it is unexpected. Sometimes we wish the clocks would strike thirteen, and the dystopia we have lived through will be questioned and erased. However, as my daughter and I experienced a movie in a theater again this weekend, perhaps providing us with glimpses into our future, I realized that just like post-9/11, we never returned to September 10th. But we did evolve to a new normal. And it was fine. Indeed, we have reasons for optimism.

Dora Anne Mills, MD, MPH, FAAP, Chief Health Improvement Officer, MaineHealth

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