Tweet
The Lancet: The Durability of Immunity Against SARS-CoV-2
GAO: A Herd Immunity For COVID-19 Primer
#16.234
Eighteen months ago - in the opening months of the COVID-19 pandemic - many people's hopes for a quick resolution to this crisis were pinned on society achieving `Herd Immunity', either through natural infection, or eventually from a vaccine.
The flaw in this ointment was that we'd previously seen evidence of frequent human reinfection with other coronaviruses.
In Fenner and White's Medical Virology (Fifth Edition - 2017), the authors describe the clinical features of seasonal human coronaviruses (hCoVs) in Chapter 31:
The typical coronavirus “common cold” is mild and the virus remains localized to the epithelium of the upper respiratory tract and elicits a poor immune response, hence the high rate of reinfection. There is no cross-immunity between human coronavirus-229E and human coronavirus-OC43, and it is likely that new strains are continually arising by mutation selection.
In 2016's EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, we looked at a study that tested 9 Health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), that found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.
Those who experienced a milder pneumonia had shorter lived antibody responses (1 out to 10 months, 2 out to 3 months), while the URTI and asymptomatic cases tested negative at 3 months post infection.
We explored these barriers to `herd immunity' frequently in the spring and summer of 2020 (see COVID-19: From Here To Immunity and GAO: A Herd Immunity For COVID-19 Primer) while we awaited signs of confirmed reinfection with SARS-CoV-2.
By the end of summer, reinfections - and waning immunity - were becoming increasingly apparent.
By late 2020, with the emergence of several COVID variants (Alpha, Beta, P.1., etc.) we began to see unexpected surges of the pandemic virus - even among populations with a presumed high degree of acquired immunity (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence).
While appealing, the notion that COVID-19 would be a `one-and-done' infection (like measles or chickenpox) - and `the pandemic would quickly burn itself out' - was a bit naive, and probably based more on hope than on science. The same could be said for the durability of the vaccine.
As we discussed nearly two months ago, in COVID: From Here To Endemicity, SAR-CoV-2 is more likely to become another in the panoply of seasonal ILI (Influenza-like-illnesses) that return each winter, than to fade away entirely.
To better understand its threat of recurrence, we've a new open-access study, published in The Lancet, that looks at the spectrum of known human-infecting coronaviruses, and attempts to calculate how long immunity lasts from each infection.
First the link, and abstract to the paper (the full article is available, and worth reading), followed by a press release and summary from the University of North Carolina at Charlotte. I'll have a brief postscript after the break.
Summary
Background
Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63.
Methods
We conducted phylogenetic analyses of the S, M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses.
Findings
We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset.
Interpretation
The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality.
UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE
CHARLOTTE, N.C. - Oct. 1, 2021 - Throughout the COVID-19 pandemic, there has been much uncertainty about how long immunity lasts after someone who is unvaccinated is infected with SARS-CoV-2.
Now a team of scientists led by faculty at Yale School of Public Health and the University of North Carolina at Charlotte have an answer. Strong protection following natural infection is short-lived.
“Reinfection can reasonably happen in three months or less,” said Jeffrey Townsend, the Elihu Professor of Biostatistics at the Yale School of Public Health and a lead author of the study. “Therefore, those who have been naturally infected should get vaccinated. Previous infection alone can offer very little long-term protection against subsequent infections.”
The study, published in the journal The Lancet Microbe, is the first to determine the likelihood of reinfection following natural infection and without vaccination.
Townsend and his team analyzed known reinfection and immunological data from the close viral relatives of SARS-CoV-2 that cause “common colds” — along with immunological data from SARS-CoV-1 and Middle East Respiratory Syndrome. Leveraging evolutionary principles, the team was able to model the risk of COVID-19 reinfection over time.
Reinfections can and have happened, even shortly after recovery. And they will become increasingly common as immunity wanes and new SARS-CoV-2 variants arise.
“We tend to think about immunity as being immune or not immune. Our study cautions that we instead should be more focused on the risk of reinfection through time,” said Alex Dornburg, assistant professor of bioinformatics and genomics at the University of North Carolina at Charlotte, who co-led the study with Townsend. “As new variants arise, previous immune responses become less effective at combating the virus. Those who were naturally infected early in the pandemic are increasingly likely to become reinfected in the near future.”
The team’s data-driven model reveals striking similarities to the reinfection risks over time between SARS-CoV-2 and endemic coronaviruses.
“Just like common colds, from one year to the next you may get reinfected with the same virus. The difference is that, during its emergence in this pandemic, COVID-19 has proven to be much more deadly.” said Townsend.
“Due to the ability of SARS-CoV-2 to evolve and reinfect, it, too, is likely to transition from pandemic to an endemic disease,” added Dornburg.
“A hallmark of the modern world is going to be the evolution of new threats to human health,” said Townsend. “Evolutionary biology — which provided the theoretical foundations for these analyses — is traditionally considered a historical discipline. However, our findings underscore its important role in informing decision-making, and provide a crucial stepping stone toward robust knowledge of our prospects of resistance to SARS-CoV-2 reinfection.”
Co-authors include researchers from Temple University. Funding for the research was provided by the U.S. National Science Foundation.
Unless some new scientific breakthrough changes the equation - or the SARS-CoV-2 virus mutates into a much less `biologically fit' pathogen - COVID appear to be here to stay.
For those who eschew the vaccine because they've `had COVID', and therefore believe themselves to be now and forever immune, this study should raise some red flags.
While contracting the virus every 6 to 18 months is arguably the most `natural' way to gain temporary immunity, there are some decided downsides (death, hospitalization, disability, etc.) to consider.
Vaccines (including boosters) can provide similar - or likely even better - protection, with far less risk.
Neither option is ideal, but those - for now, at least - are the two we have to choose from. At least for those of us who are lucky enough to live in a country where the vaccines are readily available.
GAO: A Herd Immunity For COVID-19 Primer
#16.234
Eighteen months ago - in the opening months of the COVID-19 pandemic - many people's hopes for a quick resolution to this crisis were pinned on society achieving `Herd Immunity', either through natural infection, or eventually from a vaccine.
The flaw in this ointment was that we'd previously seen evidence of frequent human reinfection with other coronaviruses.
In Fenner and White's Medical Virology (Fifth Edition - 2017), the authors describe the clinical features of seasonal human coronaviruses (hCoVs) in Chapter 31:
The typical coronavirus “common cold” is mild and the virus remains localized to the epithelium of the upper respiratory tract and elicits a poor immune response, hence the high rate of reinfection. There is no cross-immunity between human coronavirus-229E and human coronavirus-OC43, and it is likely that new strains are continually arising by mutation selection.
In 2016's EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, we looked at a study that tested 9 Health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), that found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.
Those who experienced a milder pneumonia had shorter lived antibody responses (1 out to 10 months, 2 out to 3 months), while the URTI and asymptomatic cases tested negative at 3 months post infection.
We explored these barriers to `herd immunity' frequently in the spring and summer of 2020 (see COVID-19: From Here To Immunity and GAO: A Herd Immunity For COVID-19 Primer) while we awaited signs of confirmed reinfection with SARS-CoV-2.
By the end of summer, reinfections - and waning immunity - were becoming increasingly apparent.
By late 2020, with the emergence of several COVID variants (Alpha, Beta, P.1., etc.) we began to see unexpected surges of the pandemic virus - even among populations with a presumed high degree of acquired immunity (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence).
Hopes gradually shifted from naturally acquired immunity, to vaccination. But as we now know - while they offer good initial protection - their protective effect appears to wane over 6 to 8 months, requiring booster shots.
While appealing, the notion that COVID-19 would be a `one-and-done' infection (like measles or chickenpox) - and `the pandemic would quickly burn itself out' - was a bit naive, and probably based more on hope than on science. The same could be said for the durability of the vaccine.
As we discussed nearly two months ago, in COVID: From Here To Endemicity, SAR-CoV-2 is more likely to become another in the panoply of seasonal ILI (Influenza-like-illnesses) that return each winter, than to fade away entirely.
To better understand its threat of recurrence, we've a new open-access study, published in The Lancet, that looks at the spectrum of known human-infecting coronaviruses, and attempts to calculate how long immunity lasts from each infection.
First the link, and abstract to the paper (the full article is available, and worth reading), followed by a press release and summary from the University of North Carolina at Charlotte. I'll have a brief postscript after the break.
Prof Jeffrey P Townsend, PhDHayley B Hassler, MS, Zheng Wang, PhD, Sayaka Miura, PhD, Jaiveer Singh, Prof Sudhir Kumar, PhD, et al.
Open Access
Published : October 01, 2021 DOI:https://doi.org/10.1016/S2666-5247(21)00219-6
Published : October 01, 2021 DOI:https://doi.org/10.1016/S2666-5247(21)00219-6
Summary
Background
Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63.
Methods
We conducted phylogenetic analyses of the S, M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses.
Findings
We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset.
Interpretation
The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality.
UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE
CHARLOTTE, N.C. - Oct. 1, 2021 - Throughout the COVID-19 pandemic, there has been much uncertainty about how long immunity lasts after someone who is unvaccinated is infected with SARS-CoV-2.
Now a team of scientists led by faculty at Yale School of Public Health and the University of North Carolina at Charlotte have an answer. Strong protection following natural infection is short-lived.
“Reinfection can reasonably happen in three months or less,” said Jeffrey Townsend, the Elihu Professor of Biostatistics at the Yale School of Public Health and a lead author of the study. “Therefore, those who have been naturally infected should get vaccinated. Previous infection alone can offer very little long-term protection against subsequent infections.”
The study, published in the journal The Lancet Microbe, is the first to determine the likelihood of reinfection following natural infection and without vaccination.
Townsend and his team analyzed known reinfection and immunological data from the close viral relatives of SARS-CoV-2 that cause “common colds” — along with immunological data from SARS-CoV-1 and Middle East Respiratory Syndrome. Leveraging evolutionary principles, the team was able to model the risk of COVID-19 reinfection over time.
Reinfections can and have happened, even shortly after recovery. And they will become increasingly common as immunity wanes and new SARS-CoV-2 variants arise.
“We tend to think about immunity as being immune or not immune. Our study cautions that we instead should be more focused on the risk of reinfection through time,” said Alex Dornburg, assistant professor of bioinformatics and genomics at the University of North Carolina at Charlotte, who co-led the study with Townsend. “As new variants arise, previous immune responses become less effective at combating the virus. Those who were naturally infected early in the pandemic are increasingly likely to become reinfected in the near future.”
The team’s data-driven model reveals striking similarities to the reinfection risks over time between SARS-CoV-2 and endemic coronaviruses.
“Just like common colds, from one year to the next you may get reinfected with the same virus. The difference is that, during its emergence in this pandemic, COVID-19 has proven to be much more deadly.” said Townsend.
“Due to the ability of SARS-CoV-2 to evolve and reinfect, it, too, is likely to transition from pandemic to an endemic disease,” added Dornburg.
“A hallmark of the modern world is going to be the evolution of new threats to human health,” said Townsend. “Evolutionary biology — which provided the theoretical foundations for these analyses — is traditionally considered a historical discipline. However, our findings underscore its important role in informing decision-making, and provide a crucial stepping stone toward robust knowledge of our prospects of resistance to SARS-CoV-2 reinfection.”
Co-authors include researchers from Temple University. Funding for the research was provided by the U.S. National Science Foundation.
Unless some new scientific breakthrough changes the equation - or the SARS-CoV-2 virus mutates into a much less `biologically fit' pathogen - COVID appear to be here to stay.
For those who eschew the vaccine because they've `had COVID', and therefore believe themselves to be now and forever immune, this study should raise some red flags.
While contracting the virus every 6 to 18 months is arguably the most `natural' way to gain temporary immunity, there are some decided downsides (death, hospitalization, disability, etc.) to consider.
Vaccines (including boosters) can provide similar - or likely even better - protection, with far less risk.
Neither option is ideal, but those - for now, at least - are the two we have to choose from. At least for those of us who are lucky enough to live in a country where the vaccines are readily available.
Comment