Respiratory syncytial virus, flu, and COVID-19 — the “tripledemic”


I rarely write about the respiratory syncytial virus (RSV), but the number of people infected by the virus, especially children, is leading to a fear of a tripledemic that includes RSV, the seasonal flu, and our constant nemesis, COVID-19. I guess this is the time I start writing more about the respiratory syncytial virus because everyone needs to be aware of this infectious disease.

This post will review what respiratory syncytial virus is, why it is so dangerous to children and seniors, and whether a vaccine is available.

What is the respiratory syncytial virus?

The respiratory syncytial virus is a common, contagious virus that causes infections of the respiratory tract. It is a single-stranded RNA virus, and its name is derived from the large cells known as syncytia that form when infected cells fuse.

It usually causes mild, cold-like symptoms. But it can cause serious lung infections, especially in infants, seniors, and people with serious comorbidities. For seniors, RSV infections are dangerous as immune systems weaken.

RSV spreads from person to person through:

  • The air by coughing and sneezing.
  • Direct contact, such as kissing the face of a child who has RSV.
  • Touching an object or surface with the virus on it, then touching your mouth, nose, or eyes before washing your hands.

(I don’t mean to keep repeating myself, but all the measures you take to reduce your risk for COVID-19 seem to be helpful in preventing RSV.)

RSV can sometimes lead to pneumonia (infection of the lungs) and congestive heart failure (when the heart can’t pump blood and oxygen to the body’s tissues).

According to the CDC, each year in the United States, RSV leads to approximately—

  • 2.1 million outpatient visits among children younger than 5 years old
  • 58,000-80,000 hospitalizations among children younger than 5 years old
  • 100–300 deaths in children younger than 5 years old.
  • 60,000-120,000 hospitalizations among adults 65 years and older
  • 6,000-10,000 deaths among adults 65 years and older

I know these numbers pale next to COVID-19, but before the pandemic, an RSV vaccine was often at the top of the wish list for a new vaccine. And those who had children or parents who had to deal with a serious RSV case, probably wish there was a vaccine too.

Hopefully, these vaccines will soon become available, as new research is quantifying their need:

  • The JAMA Network published an article on 29 December 2021 that suggests RSV poses a greater risk to infants than influenza, while both are associated with substantial mortality among elderly individuals.
  • The journal PNAS published research on 14 March 2022, which found that administering an RSV vaccine to pregnant mothers reduced antimicrobial prescribing among their infants by 12.9% over the first three months.  
Growth of RSV cases since August 6, 2022.

Why is everyone scared about RSV?

Just take a look at that graph above — the number of cases of RSV has skyrocketed by over 6X in just two months in the USA. Add RSV to new (and scary) COVID-19 variants and a potentially rough season for the seasonal flu, I’m hoping that you haven’t thrown out your masks, because you should be wearing them this fall.

According to an ABC News analysis, as of 24 October 2022, pediatric bed occupancy in the U.S. is the highest it’s been in two years with 75% of the estimated 40,000 beds filled with patients. Though we can’t be sure what is causing this, COVID-19, RSV, or the flu (or possibly all three), that is troubling.

There is a lack of pediatric ICU beds in the USA, so if these children require an ICU bed, there may not be any available (especially since hospitals are cutting pediatric ICU beds across the nation). This could lead to higher mortality rates from respiratory diseases, like RSV, COVID-19, and flu.

Respiratory syncytial virus kind of disappeared during the COVID-19 pandemic (which hasn’t disappeared) because mitigation efforts, like masks, distance learning, and social distancing, kept both the flu and RSV at remarkably low levels.

After two years of isolation, we’ve also not built up immunity to flu and RSV, so we are all more vulnerable to these diseases. And for children, this is an even worse situation. All of this could lead to a much worse situation in the USA (and across the world) where more than 100-300 children die from the virus.

Right now, there is no vaccine for RSV, but there is some good news going forward on that front. Let’s take a look at the four candidates for an RSV vaccine.

RSV vaccine candidates

Since the four candidates are in phase 3 clinical trials, there’s not a lot to write about their safety and effectiveness. However, if they are in phase 3, it’s probably a good assumption that they have met the standards of safety.

So here is the list of vaccine candidates:

  • Moderna — yes, Moderna who brought us an mRNA vaccine for COVID-19 has developed a new mRNA vaccine for RSV. Moderna has developed one RSV vaccine candidate for seniors, mRNA-1345, and two for pediatrics, mRNA-1345 and mRNA-1365. At this point, the mRNA-1345 candidate is in phase 1 trials for pediatrics and phase 2/3 trials for seniors. Both trials are recruiting subjects, so you have a chance to join in. The US FDA has granted Fast Track designation for the senior version of the mRNA-1345 — this does not mean that the FDA makes it easy to get approval, it just means that the new drug application goes to the “top of the pile,” so it might get a quicker review.
  • Pfizer — another COVID-19 vaccine manufacturer is developing an RSV vaccine, PF-06928316. However, unlike the COVID-19 vaccine, this is not an mRNA vaccine. It is based on the crystal structure of prefusion F, a key form of the viral fusion protein (F) that RSV uses to attack human cells. There are two forms of the F-protein, and this vaccine targets both. It is undergoing phase 3 trials for seniors and two phase 3 trials for adults. They also have a phase 3 trial that is examining the effectiveness of the vaccines in infants who were born to vaccinated mothers — results showed that the vaccine was safe and effective in preventing RSV infections in newborn babies. The trial for the maternal vaccine has been completed and Pfizer will submit their application for FDA review before the end of 2022. This is great news.
  • GSK — the GSK vaccine, RSVPreF3 OA, is a single-dose vaccine that contains a recombinant subunit RSV antigen combined with GSK’s proprietary AS01 adjuvant. Four phase 3 clinical trials are currently recruiting subjects — non-pregnant women, pregnant women, pregnant women and infants born to vaccinated women, and booster vaccination after pregnancy.
  • Bavarian Nordic — their MVA-BN RSV vaccine candidate incorporates five different RSV antigens to stimulate a broad immune response against both RSV subtypes (A and B). It theoretically mimics the immune response that is observed following a natural reaction to RSV. They are recruiting for a phase 3 clinical trial in seniors.

Back before COVID-19, I would assume that once a vaccine candidate entered phase 3 clinical trials, we were still four or five years away from getting approval for the vaccine. But today, with the experience some of these companies got developing the COVID-19 vaccines, it could be much faster.

The RSV vaccine is probably one of the most important vaccines, outside of COVID-19, of course, under development. And I wish it were here today.

Summary

Over the past two years, most of the country had strong COVID-19 mitigation efforts, such as masks, social distancing, school closures, and capacity limits at large events. With most of those restrictions being lifted, we are all going to be exposed to the trifecta of serious viruses — flu, RSV, and COVID-19.

I don’t want to be that guy, but I am — this tripledemic could make for a terrible winter for a lot of families. I am particularly worried about pediatric cases because they are one of the most vulnerable groups to flu and RSV and because of pediatric beds in hospitals nearing capacity, and it’s just November.

Get the COVID-19 vaccine. Get the seasonal flu vaccine. And pretend it’s 2020, wear a mask, and try to stay away from crowds. Maybe you can avoid RSV — because you don’t want to pass it on to your children or your grandmother.

Citations

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