A paper published yesterday in the journal Nature Medicine starts with this understatement of the week:

“A  key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity.”

Immunity — the fact that recovery from infection confers an almost magical ability to fight off the same pathogen in the future — is one of the most fascinating areas of biology and underlies many hopes for containing SARS-CoV-2 (the virus that causes Covid-19). Immunity can be obtained from either infection or vaccination, or even from infection with a related virus, in which case it’s called cross-immunity.

We still don’t know the answer to this “key unsolved question” but now we’re a little closer. Specifically, we now know that the answer for some very closely related viruses is “not very long”.

The new paper by Arthur Edridge and colleagues is the first to estimate the duration of protective immunity in four closely related coronaviruses, known as HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1. (The “HCoV” stands for “human coronavirus”.) These viruses are similar to SARS-CoV-2 in several ways. Each causes respiratory tract infections. They all cycle seasonally. Symptoms are typically mild.

3d visualization of coronaviruses GETTY

It was previously known that reinfection with seasonal coronaviruses is possible. Two experimental studies from the 1980s with people who were voluntarily reinfected after their first bout with one of these viruses (HCoV-229E) had shown this. What we didn’t know was how frequently reinfection occurred or how quickly immunity was lost.

To estimate the duration of protective immunity in these four viruses, Edridge and colleagues went back to blood serum samples that had been collected from ten apparently healthy individuals in 1985 and 1986 as part of the Amsterdam Cohort Studies on HIV and AIDS. By testing the archived samples with a method called ELISA, the investigators were able to quantify the waxing and waning of each person’s antibody response — a pattern that traced the person’s sequence of infection and reinfection.

The upshot was that reinfection with seasonal coronaviruses is actually very common. In one case, 17 total infections were counted in one patient over a period of just 19 years. Moreover, reinfection with the same virus was found to occur in as little as six months for the three most common viruses, although reinfection more typically occurred around three years. 

There is a problem with extrapolating this result to SARS-CoV-2, namely that these four seasonal coronaviruses — the ones that circulate naturally among humans and are one of the causes of common colds — are only distantly related to SARS-CoV-2. SARS-CoV-2 is most closely related to SARS-CoV, which caused a very serious global outbreak of SARS in 2003, and MERS-CoV, which has caused sporadic outbreaks of Middle East Respiratory Syndrome (MERS) since 2012. SARS-CoV, SARS-CoV-2 (the virus that causes Covid-19), and MERS-CoV are all betacoronaviruses in the so-called “B” and “C” subgroups. HCoV-HKU1 and HCoV-OC43 are in the more distantly related “A” subgroup while HCoV-NL63 and HCov-229E are in the even more distantly related alphacoronaviruses.

human coronaviruses
Genetic relationships among human coronaviruses JOHN M. DRAKE

In contrast to the seasonal coronaviruses, antibodies from infection with SARS-CoV have been shown to last for as long as three years (although it’s not known whether these longer-lasting antibodies are fully protective). The key question, then, is whether SARS-Cov-2 will follow the pattern of the viruses that are most genetically similar to SARS-CoV and MERS-CoV or most functionally similar to the seasonal human coronaviruses? Answering that unsolved question will tell us if immunity can be expected to last years or just a few months.



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