After a COVID-19 infection, whether it’s our first, second or even third, many of us wonder how long we might be protected from re-infection and whether we will be sensitive to new variations.
Also, if we catch COVID-19 again, will the immunity we gained from that infection reduce the severity of the next one?
A new study published in The Lancet set out to answer these questions, examining the strength and duration of natural immunity by the COVID-19 variant.
The authors collected data from 65 studies in 19 countries, making this the largest review on this topic to date.
These studies compared the risk of COVID-19 in people who had previously been infected and those who did not have a previous infection. Studies investigating natural immunity in combination with vaccination (hybrid immunity) were excluded.
The researchers aimed to assess whether infection induced similar protection against reinfection with different variants, and whether this declined differently over time.
The analyzes covered studies from the start of the pandemic until September 2022 and focused primarily on the alpha, beta, delta and omicron BA.1 variants.
Protection against reinfection
The authors assessed protection against reinfection, symptomatic disease, and severe disease (defined as hospitalization or death) separately.
They found that prior infection was highly protective against reinfection with alpha, beta, and delta variants, but less so against omicron BA.1.
Previous infection provided moderate protection against reinfection with omicron BA.1 (45%), compared to stronger protection against pre-omicron variants (82%). This was also the case for symptomatic infection.
Data from long-term studies showed that protection against reinfection for pre-omicron variants dropped to 78.6% over 40 weeks, while for omicron BA.1 it dropped faster to 36.1 %.
When assessed for severe disease, however, all variants showed greater than 88% sustained protection for 40 weeks.
This does not mean that protection decreases significantly after 40 weeks. Rather, there appears to have been little data available that followed people long enough for the authors to draw strong conclusions beyond that time.
The results also revealed that protection against severe disease after natural infection was comparable to that obtained with two doses of vaccine, for the pre-omicron and omicron BA.1 variants.
Giving meaning to discoveries
A few years is a long time for highly contagious respiratory viruses, and SARS-CoV-2 (the virus that causes COVID-19) was no different.
It generated worrying sequential variants, with increased transmissibility and ability to evade our immune responses compared to the ancestral virus.
The study’s findings, which address protection against pre-omicron variants and omicron BA.1 separately, make sense when considering how omicron variants differ from their predecessors.
As a background, neutralizing antibodies generated after previous viral infection are important in preventing further entry of the virus into susceptible cells.
These Y-shaped molecules recognize intact proteins from outside the virus and attach themselves to them, preventing the virus from latching onto the cellular receptor needed for infection.
But to persist, viruses like SARS-CoV-2 introduce random mutations into their genome as they replicate, aiming to permanently alter their proteins to evade immune recognition.
The Omicron lines have enough mutations to be significantly different from previous variants, and therefore evade existing antibodies. Evasion of neutralizing antibodies explains our inability to control reinfection with omicron variants.
Fortunately, we don’t just rely on antibodies to protect us. A type of immune cells called T cells recognize extracts of viral proteins rather than intact proteins. This means that it would take many more mutations in the virus genome to completely evade T-cell immunity.
Unlike antibodies, T cells do not search for viruses. Instead, they recognize infected cells and quickly eliminate them to reduce virus factories in the body. T cells therefore act where neutralizing antibodies may have failed, after infection. A robust T-cell response to coronaviruses is crucial for preventing serious disease and, fortunately, harder for omicron to avoid.
SARS-CoV-2 specific T cells decline more slowly than antibodies. In fact, people infected with the similar SARS coronavirus in 2003 still had T cells that recognize SARS-CoV-2 17 years after infection.
Infection versus vaccination
Although a natural infection may offer equivalent protection to vaccination, this does not mean that you should seek to infect yourself. SARS-CoV-2 remains a dangerous and unpredictable virus that can, in some cases, cause a host of adverse effects that persist long after recovery.
The authors suggest that the state and timing of a person’s prior infection should be considered alongside their booster vaccinations to predict protection.
However, this may be difficult to implement as infection surveillance has decreased in most countries compared to the start of the pandemic. In any case, COVID certificates are less used now.
They also suggest that their results could be used to determine the optimal timing of booster vaccination strategies. That is, there’s probably merit in waiting a while after an infection before getting a booster.
Further high-quality long-term follow-up studies will be important to supplement these findings, as the authors acknowledge that there are not as many studies of natural infection versus protection after vaccination.
There were also few studies mapping protection against the new omicron sublines. As the pandemic continues, much remains to be learned about immune protection against this evolving virus.
Zania Stamataki, Associate Professor in Viral Immunology, University of Birmingham
This article is republished from The Conversation under a Creative Commons license. Read the original article.