"When you think about diseases that have an R0 of eight or nine—there aren't that many. [SARS-CoV-2 Delta variant] is one of the most transmissible viruses we know about. Measles, chickenpox, this—they're all up there."
- Dr. Rochelle Walensky, director, Center for Disease Control and Prevention
“Vaccines and antibiotics have made many infectious diseases a thing of the past; we've come to expect that public health and modern science can conquer all microbes. But nature is a formidable adversary.”
- Dr. Tom Frieden, former director, Center for Disease Control and Prevention
Recently, Dr. Rochelle Walensky, the director of the Center for Disease Control and Prevention (CDC), used chickenpox as a point of reference for explaining how fiercely contagious the Delta variant of SARS-CoV-2 is. While this variant continues to capture everyone’s attention, in this week’s Germ Gems post I discuss how we’ve accommodated living with varicella zoster virus (VZV), the etiologic agent of chickenpox, to provide some perspective on dealing with SARS-CoV-2.
VZV and SARS-CoV-2: a comparison. Unlike the case for SARS-CoV-2, which is an RNA-based coronavirus, the genome of VZV is composed of DNA. This is good news for humans because DNA, unlike RNA, is stable and far less prone to mutations.
When Dr. Walensky recently compared the Delta variant of SARS-CoV-2 to VZV in terms of its contagiousness, the CDC added that Delta is about twice as contagious as other SARS-CoV-2 variants and is more transmissible than several other viruses, including, the coronaviruses that cause Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS-CoV), as well as Ebola virus, and viruses that cause the common cold and seasonal flu. When transmissibility is expressed as a reproductive number (R0 or R “naught”), which is the number of susceptible people who become infected by a person transmitting the virus, the R0 of the SARS-CoV-2 Delta variant is between 5-9.5. The R0 of VZV is close, about 8.5. This is why Delta is sweeping the world at such a dizzying pace. But it could be worse—consider the R0 of the measles virus, i.e., 12-18.
Both VZV and SARS-CoV-2 are airborne pathogens spread by aerosols containing the virus. Aerosols generated by coughing and sneezing of infected people is the primary route of transmission of SARS-CoV-2, whereas VZV is acquired by inhalation of aerosols as well as from contact with vesicular fluid of skin lesions of chickenpox or a directly related infection, herpes zoster.
The incubation period of VZV (10-21 days) is somewhat longer than that of SARS-CoV-2. According to the CDC, symptoms of COVID-19 develop about 5 days after the initiation of infection, but the incubation period can extend to 14 days (this is the reason for 14 days of quarantine after exposure to an a SARS-CoV-2-infected person).
Chickenpox: vaccine and treatment. In 1995, a vaccine for VZV was licensed. Before the vaccine, about 2,200 American children died of chicken pox per year. Chances are that some readers of my Germ Gems posts are old enough to have had chickenpox and developed natural immunity to VZV before a vaccine was licensed. These readers may remember getting sick with the telltale itchy, small blisters (“pox”). But even if you don’t recall actually getting sick with chickenpox, you almost certainly were infected because a large percentage of VZV infections are asymptomatic. (Sound familiar? Asymptomatic COVID-19 infection was recognized as a big problem in the early months of the pandemic in 2020.)
Varicella affects nearly all children worldwide who do not have immunity. The annual worldwide incidence is now estimated at 80-90 million cases. Most developing countries have low immunization rates because of the cost involved. Moreover, the COVID-19 pandemic has caused major disruptions to childhood immunization throughout the world. It is not yet clear how this has impacted the numbers of cases and deaths due to chickenpox.
Itchy blisters (“vesicles”) are a hallmark of chickenpox. But other symptoms such as fever, fatigue, loss of appetite, and headache, are shared by both chickenpox and COVID-19. Another clinical feature that is common to both viral infections is the impact of patient age on the course of illness. Older age is by far the biggest risk factor for developing severe COVID-19. In the case of chickenpox, the illness is almost always mild or asymptomatic in early childhood, whereas chickenpox in adults can be severe, including complications such as involvement of the lungs or nervous system. (Before a vaccine became available, recognition of this age-related feature of chickenpox led to a practice called “pox parties,” where young children would purposively be invited to the homes of children with active chickenpox “to get it over with.”)
Another important distinguishing feature of chickenpox versus COVID-19 is the availability of a highly effective and safe antiviral drug for treatment of chickenpox, namely acyclovir. When it first became available, acyclovir was often reserved for adults, given their predilection for more complicated infections, or for those with herpes zoster (shingles). Acyclovir can be administered orally or intravenously. Development of such an antiviral equivalent for COVID-19 is recognized as a very high priority.
What is shingles? Shingles, also known as herpes zoster, gets its name from both the Latin and French words for belt, or girdle, and refers to girdle-like skin eruptions on the torso or trunk of the body. Anyone who had chicken pox can develop shingles because the same virus that causes chicken pox, that is, VZV, causes herpes zoster. Like all the DNA viruses that belong to what’s called the “herpes group,” including, herpes simples virus, cytomegalovirus, Epstein Barr virus, and human herpes viruses-6, 7, and 8, VZV has the ability to become latent or dormant. And if one’s immune defenses become compromised, VZV can come out of hiding, that is, reactivate.
Most commonly in adults, it is “immunosenescence” associated with aging that allows VZV to reactivate. About one out of every three people who had chickenpox will develop shingles at some point, usually after age 50 (one-half of those over 85 years-of-age are at risk). Because latent VZV hangs out in nerves, the vesicular skin eruption of zoster often tracks along nerves. These skin lesions can be extremely painful, and although they usually heal in several weeks, they can sometimes last months to years. Of greatest concern is herpes zoster in persons with severely compromised immunity, such as, hematological malignancy or HIV infection. In these patients, VZV can disseminate to internal organs and cause life-threatening disease.
To prevent reactivation of VZV, vaccination is recommended for everyone over 50 years-of-age with Shingrix, an inactivated form of VZV that was approved by the Federal Drug Administration in 2017. It is given in two shots 2 to 6 months apart and is about 90% effective. The CDC estimates that about 1 million Americans develop shingles per year and that the incidence is going up for unknown reasons. So this is a vaccine all American adults should know about.
The good news, however, is that VZV is a virus whose impact is fading, at least here in America. There is an effective chickenpox vaccine for kids and Shingrix for adults. In addition, there is a highly effective antiviral drug, acyclovir, for treating chickenpox and shingles. My hunch is that SARS-CoV-2 will follow a similar history. We already have highly effective vaccines to fight this virus, and more are soon to come. Moreover, I believe it won’t be long before we’ll have antiviral drugs for oral as well as intravenous administration to counter this nasty coronavirus.