South Africa’s battle against Covid-19 is intensifying, and another invisible enemy is fast approaching. As temperatures change and long summer days turn into cold winter nights, more and more people will get sick with influenza.

The government’s chief advisor on Covid-19, Professor Salim Abdool Karim, earlier encouraged people to get a flu vaccine as a way to lessen the burden on the country’s healthcare system.

With the Department of Health facing a shortage of these seasonal vaccines, Spotlight spoke to leading Professor in Vaccinology Shabir Madhi about how the vaccine works, who should get it and what it means for the Covid-19 pandemic. Madhi is also Director of the South African Medical Research Council’s Respiratory and Meningeal Pathogens Research Unit.

Two million doses

“In the past, South Africa has usually procured about 1.2 million doses of the [flu] vaccine and often they haven’t even been able to use all of the doses, says Madhi. “This year they procured two million doses and because of SARS-CoV-2 and all the hype around it, many people, myself included, were strongly recommending that people at least get the flu vaccine to mitigate some of the full effects of the coronavirus, especially people at high-risk of severe disease.”

He explains that each year during flu season, capacity in hospitals goes up to 80 and 90 percent in terms of bed occupancy, and if people got flu vaccines, this pressure could be severely reduced. “It’s a good thing that we’ve ended up having a shortage because it shows that people have really been buying into that message, and they did get out to actually get vaccinated. “Hopefully,” he says, “this is a positive legacy of the coronavirus.”

How the flu vaccine works

The flu vaccine, simply put, works by giving our bodies the necessary tools it needs to fight off flu. More specifically, Madhi explains, the vaccine is training the immune system to produce antibodies to the head of a specific protein on the surface of the flu virus, called hemagglutinin. The head of this hemagglutinin is what our immune system is responding to, says Madhi.

When the virus infects a cell and makes us sick, the hemagglutinin binds the virus on to our cells, sort of like a glue. The flu vaccine is providing us with antigens, which results in our bodies producing antibodies – strong proteins that help our cells fight the head of the hemagglutinin. If the head of the hemagglutinin can be defeated by these antibodies, we won’t become sick with the flu because the virus has no way of binding and infecting our cells.

“The mutations in the head portion of [the hemagglutinin] is what actually drives the diversity of strains,” says Madhi. “We have gradual changes that take place in the head of the protein, which makes for a slight drift [change] in the genetic composition of the virus which makes the predictability of the virus difficult. If there’s too much drift away from what [strains were] anticipated then [the vaccine] becomes less effective, and if there wasn’t too much mutation, then the vaccine itself will be more effective – it depends on the extent of the mix-match from what’s in the vaccine and what ends up circulating in the country,” says Madhi.

How the flu vaccine is made

New flu vaccines have to be made every year in order to reflect the mutations and different strains of the virus around the world. A key element of these vaccines is what specific antigens they contain. Broadly defined, an antigen is a molecule that causes an immune response in the body.

Madhi explains that each year the World Health Organisation (WHO) reference laboratories collect flu virus samples and submit them for genetic sequencing at central facilities. Once the samples are sequenced, using a predictive model, scientists work to predict which are the most likely strains that will circulate in the next flu season in a specific region. (Read here about how genetic sequencing works, and how it’s helping scientists fight COVID-19.)

“The selection of the strains is done through predictive modelling based on historical data looking at mutations that are occurring in the different strains of virus. There are three important strains – H1N1, H3N2 and Flu B. With Flu B, there’s two major dominant lineages which are Victoria and Yamagata strains,” says Madhi.

He explains that flu vaccines can either be trivalent, meaning they provide antigens for three strains, or quadrivalent, which provides antigens for all four. The difference between them is that a quadrivalent vaccine offers antigens for two Flu B strains [one from both lineages] instead of one.

“Most of the vaccines in South Africa are trivalent but this year there has been an imported quadrivalent vaccine as well. What we do know of the trivalent vaccine, especially in adults, is that there is cross-protection between the lineages [like Flu B lineages Yamagata and Victoria]. So even though the lineage included in the flu vaccine might be [different] from the lineage which eventually starts circulating in a country, there is some protection between the lineages. It’s not an absolute requirement to have a quadrivalent vaccine to have protection against a lineage which is not included in a vaccine, for Flu B specifically.”

How much protection it offers

While a flu vaccine’s purpose is to equip our bodies to fight influenza, a specific year’s vaccine’s effectiveness depends on whether the circulating strains match what was predicted in the vaccine. Madhi says that in a good year, the vaccine could be roughly 72 to 75 percent effective, but should there be a mix-match of circulating strains and what is offered in the vaccine, this effectiveness could drop to 20%.

“Most of the years South Africa has seen more than one vaccine strain circulating. It might be H1N1 and some H3N2, or it might be H1N1 and Flu B, and that might come at different times of the winter season,” he says.

However, the vaccine’s effectiveness also depends on age group. While the general population may experience 72 to 75 percent effectiveness, those over the age of 65 need what’s called a high-dose of the vaccine, which is about three times the strength of the standard vaccine, says Madhi.

“[The effectiveness of the standard flu vaccine] probably drops to around 45 to 50 percent in the elderly, which is obviously a concern because the elderly is one of the high-risk groups for severe disease.”

Young children and the elderly

“The highest burden for severe disease from flu occurs in the two extremes of age – under the age of one and above the age of 65. That’s where the highest burden of severe influenza occurs, which would require hospitalisation,” says Madhi.

South Africa sees around 11,000 deaths and 40,000 hospitalisations for flu each year. According to Madhi, each year one third of South Africans will become infected, but only one to three percent of those people will have symptomatic illness, meaning they experience fever, headache and/or sore throat.

“After [people] become infected, the risk groups for [developing severe disease] is the extremes of age, people with chronic lung disease [including TB], chronic heart disease, people living with HIV and pregnant women, especially pregnant women in the second and third trimester of pregnancy,” he says. So far, these risk groups and healthcare workers have been prioritised to receive flu vaccines by the Department of Health.

Currently there is no licensed vaccine for children under the age of six months, and the only way to protect those children is to vaccinate their mothers during pregnancy. “We’ve shown in our studies that when you do that you get similar protection in the babies in the first three months of their lives, compared to the mothers. In the first three months of life, babies [whose mothers have been vaccinated] are 85% less likely to develop illness than babies who are born to mothers who haven’t received a flu vaccine,” adds Madhi.

Madhi says the adult vaccine only worked about half as well for children aged six months to nine years, and children who had not previously received the vaccine would need two doses one month apart. He adds that children in this age group were not considered a priority or at-risk group for the vaccine.

Flu vaccines and Covid-19

While the flu vaccine won’t protect people from becoming infected with SARS-CoV-2 and developing Covid-19, scientists are concerned that should an individual become co-infected with Covid-19 and flu, they might develop a more severe illness. “But, that is purely hypothetical,” says Madhi. “What we don’t know at this point is that when there’s two viruses co-circulating, at the same time, whether co-infection results in more severe disease or not. There’s no data to support that.”

While there is no current data to support this, Madhi says studies were underway in both China and North America. “If there’s a synergy between these two viruses in terms of how they cause disease, then it can end up that someone who didn’t receive a flu vaccine might be susceptible to developing more severe Covid-19, which could have been mitigated by receiving a flu vaccine as an indirect effect.” But he repeats that this is hypothetical.

How Covid-19 is changing the behaviour of other diseases

“Even without annual flu, our healthcare systems are going to be split beyond capacity when we get an upsurge in Covid-19 cases irrespective of what plan we do, and how much we’re planning to delay the epidemic. That’s the unfortunate reality,” says Madhi. “Having [the Covid-19 epidemic] concurrently with flu will just compound the situation.”

As a result of the lockdown, Madhi says that the natural epidemiology of SARS-CoV-2 was changing, in that the peak in case numbers has been delayed by six to eight weeks. “Rather than peaking in May, we will start to peak in the middle of July or August. Hopefully by then… usually the flu virus starts disappearing in South Africa, but it might be that the lockdown and closure of schools has also affected the behaviour of the flu virus this year,” he said.

What Madhi emphasises, reiterates what Karim previously said; that the lockdown has bought South Africa time. “South Africa is not on a unique trajectory with what’s going to occur from Covid-19, we have only changed the epidemiology by sort of delaying it,” he says. 

“Certainly, everyone should [get a flu vaccine] but in the context of there being a shortage, we do highly recommend for the prioritisation of who receives the vaccine and included in those are specifically individuals who are at high-risk of Covid-19 people over the age of 65, healthcare workers, pregnant women, people living with HIV and people with chronic lung and heart disease.”

People in South Africa can get the flu vaccine at their local public clinic and private facilities through medical aid or out of pocket. Spotlight has also seen the vaccine, both trivalent and quadrivalent, available at some private sector pharmacies. DM/MC

*This article was produced by Spotlight – health journalism in the public interest. Like what you read? Sign up for our newsletter and stay informed.