History of Coronavirus: How Will It End?

On December 11, the U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization to the first COVID-19 vaccine in the U.S., making the Pfizer-BioNTech injection the first to be administered.

Yesterday, the FDA also approved the second candidate from Moderna-BioNTech.

While having a vaccine is a necessary ingredient, it alone is not sufficient to end the pandemic.

What will it take to arrest the progress of COVID-19 that has already killed 1.6 million people worldwide?

Since the beginning of the COVID-19 lockdown, people have been wondering that very question.

“If we only had a vaccine. Then it would all be over, we’d be back to normal!”

Not so fast.

There are several additional steps we must take correctly, learning from the way past pandemics ended, as I wrote about here.

The Good News

Make no mistake; the U.S. authorization of these initial vaccination candidates is good news. Indeed, it is the best news on the COVID-19 front this year, at a time when the U.K. is experiencing a third wave of infections.

But this is only the first step:

Is it the beginning of the end, or just the end of the beginning?

The U.K. was the first to deploy the initial Pfizer-BioNTech COVID-19 vaccination.

Margaret Keenan, 90, is the first person in the U.K. to receive the Pfizer-BioNtech COVID-19 vaccine.

Developing a vaccine in less than a year is remarkable (see History of Vaccines.) Until now, the fastest vaccine developed was for Measles; it took 4 years. How long did it take for others?

• Typhoid fever vaccination took 13 years to be developed by US Army physician Frederick F. Russell. But it was not widely available to the American public for another 5 years.
• Yellow fever vaccination was developed by Max Theiler, who received a Nobel Prize for his work. Research began in 1918, but Theiler did not release the first safe and effective vaccination until 1937… 19 years later.
• The Great Influenza of 1918 prompted scientists to look for a vaccine. They began in the 1930s, but it wasn’t until 1945, over a decade later, that the first vaccine was approved in the U.S. for use. But rapid mutations require scientists to tweak the vaccine each year.
• Polio vaccination research began in the first few decades of the 20th century, but a vaccine was not attempted until 1935. However, it yielded poor results. It was not until 1953 that Jonas Salk developed an effective vaccine, and in 1956 Albin Sabin developed another.
• Hepatitis B vaccination was developed in 1965, but it took another 12 years for the FDA to approve the first commercially available vaccination.

But, as one of my readers has pointed out about my previous article on How Pandemics End:

I did not describe how all of the half-dozen major historical pandemics ended.

That’s because most of them did not end. Some of them mutated, changing to less-lethal versions. But others came back: some a couple of years later, others a couple of decades later, still others centuries later.

Some of these diseases became endemic, from the Greek roots in + demos, meaning “in the population.” Endemics can be regionally persistent or present among a population and may result in another outbreak. Examples:

• Chickenpox is endemic in the UK.
• HIV is endemic in many parts of Africa.
• Malaria is endemic in parts of Africa, Asia, Latin America, and the Middle East.
• Hepatitis B is endemic throughout the world.
• Common Cold (influenza) is endemic in America.

Nevertheless, there is cause for excitement with the release of COVID-19 vaccinations.

President Eisenhower honors Jonas Salk at the White House

When Jonas Salk developed the first Polio vaccine in the 1950s, all of America was excited. I remembered standing in line to receive it. Polio had touched the lives of people I knew. The disease had killed over 1,300 Americans (a large percentage were children) and crippled more than 18,000 in 1954 alone. Within a year of vaccination, polio deaths were cut in half.

Salk was invited to the White House. President Eisenhower publicly praised Salk as a “benefactor of mankind,” and then took him aside and tearfully thanked him for protecting the lives of his grandchildren.

So, what is the next step with COVID-19 vaccines?

The clinical trial portion of the Moderna drug development tested 30 thousand people. Now vaccinations will need to scale to the U.S. population of 330 million.

That’s a difference of over 10,000 times the population of the original trial!

When hundreds of millions of people are vaccinated, rare adverse effects may become apparent, either from the mRNA vaccines that I’ll describe below — which are the first out of the gate, that have never been used on people — or the AstraZeneca-Oxford’s vaccine which uses a virus that usually affects chimpanzees.

What are our COVID-19 vaccination options?

Here are the vaccine candidates:

• Pfizer-BioNTech — already approved by the FDA.
• Moderna-BioNTech — just approved by the FDA.
• AstraZeneca-Oxford — tested in the UK, with unclear results.
• Johnson & Johnson — perhaps months away, but requiring only one dose and no refrigeration.

In an unusual step, China and Russia authorized their own vaccines in July and August, before they’d been fully tested. Including those, a total of five vaccines are now available in limited quantities in at least six countries.

Pfizer and Moderna are the first available, unsurprisingly, because they both bet on the new and hitherto unproven idea of using mRNA (messenger Ribonucleic Acid), which has the long-promised advantage of speed. According to testing so far, this novel idea has now survived a trial by the pandemic and emerged triumphantly. If mRNA vaccines help end the pandemic and restore normal life, they may also usher in a new era for vaccine development in the future.

The mRNA vaccines are meant to get the immune system to react to only a portion of the coronavirus, the so-called “spike protein,” which would seem to offer fewer targets.

But the spike protein has the potential to generate a broad immune response because there are multiple sites on the spike protein where potent neutralizing antibodies can bind.

What are the major milestones we must pass to arrest COVID-19?

US COVID-19 Deaths

Especially at a time in our history when we’re experiencing a spike in cases and a subsequent increase in deaths, we need to examine the specific milestones required to address this.

Sufficient Doses

Pfizer allocated an initial supply of 6.4 million doses. Each recipient must get two doses, about three weeks apart. But it requires refrigeration to -94 degrees Fahrenheit. After thawing, it only has a shelf-life of 5 days.

Moderna’s mRNA-1273 vaccine requires refrigeration, but just above freezing: 36-46 degrees Fahrenheit. That’s a normal fridge or an ice-filled cooler. It should last for 30 days. Moderna has 6 million doses ready to ship.

These numbers of doses are insufficient to immunize the population of the country. Back during the days of the H1N1 outbreak, the head of the CDC at that time, Tom Frieden, had to inform the public that insufficient doses were available. It is expected that it will be many months before we have enough of the vaccines to address COVID-19.

Minimal Side Effects

Side effects are inevitable, especially as the distribution of the vaccination extends beyond the trial population. Are those side effects minimal and temporary? Part of the answer depends on who was included in the vaccine trial.

For example, the early trial phase for the AstraZeneca-Oxford vaccine in the U.K. excluded people who had a history of severe adverse reactions. Later phase trial incidents that included that population turned up people who had adverse reactions to the vaccine.

Other tests did not include children under 18. The question then is: what other populations were excluded from the clinical trials, and how will that impact those vaccinated?

Persistent Immunity Response

We want a vaccination that will produce immunity in people for at least some period of time. But how long will that immunity last? We don’t know yet how long.

“In people who are only mildly ill, the immune protection that can prevent a second infection may wane within a few months. Those people might benefit more from the vaccine than others would,”

said Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.

Effective Distribution Nodes

There are, at least, three ways of distributing the vaccine:

1. Hospitals and clinics: some of these are already receiving the first vaccinations for the first audience — health workers.
2. Doctor offices: they have expertise in administering vaccinations, but don’t yet know when they’ll get doses.
3. Pharmacies: flu and shingles shots have been administered by pharmacies for years; they know how to deliver vaccinations, but don’t yet know when they’ll get doses.

For the Pfizer and Moderna vaccinations, they will require two doses, weeks apart.

Stable strains of the virus

The coronavirus is not a shapeshifter like the flu virus, but it could become vaccine-resistant over time.

Neither bacteria nor viruses evolve resistance to vaccines as easily as they do to antibiotic drugs. The two key differences are that vaccines generally act earlier than drugs — before the virus begins to proliferate and change inside the body — and that the natural immune response they promote is usually more varied, with more lines of attack. A drug may be narrowly targeted, sometimes attacking one metabolic pathway or biochemical process.

Vaccination-accepting population

COVID-19 was the first disease to have an anti-vaccine movement before there was a vaccine. Sometimes called “anti-vax,” the sentiment has been growing of late.

This month, a recent Gallup poll indicated that only 63% of those polled were ready to take the vaccine. This is up from August when 35% said they would not get a free, FDA-approved vaccine if it were ready then.

This leaves the country somewhat short of the 75-85% of the population to get to the “herd immunity” that Dr. Anthony Fauci says is needed to arrest COVID-19.

What can we learn from the Spanish Flu of 1918?

“Mask Slackers” arrested, San Francisco

Ironically, so-called anti-vax sentiment, based on either partisan or ideological reasons, is similar to the ani-mask sentiment we’ve seen throughout the COVID-19 lockdown. During the 1918 Spanish Flu outbreak, there were similar anti-mask disputes, reactions, and protests.

Most notable was in San Francisco. In October 1918, mass arrests — with people sent to jail for “disturbing the peace” — required a $10 bail. On November 21, the ordinance was dropped, and excited citizens threw off their masks. But the jubilation was short-lived as influenza cases spiked. City officials asked that masks be worn voluntarily, but no business restrictions were put back in place.

U.S. Second wave of Spanish Flu, November 1918

Cases began spiking again in November with 600 new daily cases in San Francisco. By the end of the winter of 1919, in a city of 500,000, San Francisco had 45,000 cases and 3,000 deaths from influenza. Country-wide, this highly fatal second wave was responsible for most of the U.S. deaths attributed to the pandemic.

Our early efforts to combat COVID-19 by “flattening the curve” may have been inspired by this historical event, though the clear virologic differences between the influenza of 1918 and the SARS-CoV-2 virus of COVID-19 mean that their courses are not perfectly matched. Nevertheless, troop movements at that time during World War I provided an ideal situation, well-suited to influenza dispersal, similar to today’s air travel. Presently, the U.S. has experienced about half the number of deaths as the Spanish Flu of 1918-1920.

Anti-Mask Meeting, San Francisco

Back in January 1919, as Spanish Flu case numbers dropped, the call for repealing the mask ordinance reappeared. There was even an Anti-Mask League. San Francisco was one of the most vocal on this topic, where enforcement was the most strict and criticism about the masks’ effectiveness and their negative impact on civil liberties were the most intense.

They were often called “mask slackers” or “sanitary spartans.” A rally at Dreamland Roller Rink attracted 4,500 protesters demanding that the mask ordinances be repealed.

Vaccine certifications?

I wonder… unless and until universal vaccination is attained, or at least to sufficient numbers to achieve herd immunity, will some form of vaccination certification or immunity certificate be developed? I anticipate this may be required for some types of travel, say cruise ships or trains, possibly even air travel. This would introduce a new level of legal issues and operational and logistical challenges far beyond today’s TSA regulations.

Today “temperature checks” are required to enter medical facilities; what if an official COVID-19 vaccination certification is required? Many questions come immediately to mind:

• Does vaccination ensure immunity? For how long?
• Does immunity mean you cannot transmit the disease and infect others?
• Is one vaccine better than another? Will Moderna’s provide different results than Pfizer’s?
• How difficult will it be to counterfeit a certification? Will there be a black market for fake certifications?
• Will one country recognize the certifications of another country?

Are we ready for the next global pandemic?

There will be one, that we know from our examination of the History of Pandemics. Will we remember the lessons we learned from this one? Did we remember the lessons from the Spanish Flu?

Societies and organizations are notoriously poor at retaining institutional memory. Within our lifetime, we have a glaring example.

Fifteen years ago, in the summer of 2005, President George W. Bush read the popular 2004 book “The Great Influenza: The Story of the Deadliest Plague in History” about the Spanish Flu of 1918. He was so struck by how poorly the U.S. was prepared for that influenza pandemic that he announced that November the National Strategy for Pandemic Influenza with $7.1B of funding. He put in place emergency plans to address the next pandemic, asking for even more funding to train medical personnel in other nations.

If this was our level of preparedness 15 years ago, what happened?

Regrettably, subsequent administrations have ignored the challenge and have not continued funding the initiative.

May we learn from the lessons of history.

Bill Petro, your friendly neighborhood historian

www.billpetro.com

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