Brief Notes:
This week there is a further downgrading of CDC alert levels in many locations, especially in Africa, but also in Philippines, Mexico, UAE and some others.
(The alert levels were raised to the highest levels for Hong Kong, Thailand, and New Zealand because of high and rising case numbers.)
This commentary on travel measures from the London School of Hygiene and Tropical Medicine is interesting, and well worth reading – Kucharski et al:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00366-X/fulltext
A very large nationwide French study looking at effectiveness of the Janssen vaccine compared with the Pfizer, was published by Botton et al: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789572
“This study found that the Ad26.COV2.S [Janssen] vaccine is less effective against COVID-19–related hospitalization than the BNT162b2 [Pfizer] vaccine. These results strengthen the evidence supporting a second dose in people who received the [Janssen] vaccine by an mRNA vaccine as recommended in both France and the US.”
According to BlueDot, in Ukraine, in addition to the current violent conflict, only 34% of eligible people are fully vaccinated (ranging from 65% in Kyiv to about 20% in Donetsk and Luhansk).
A Canadian study across 73 workplaces confirming the effectiveness of workplace antigen testing amongst asymptomatic workers is here – Rosella et al: https://www.science.org/doi/10.1126/sciadv.abm3608
Impressively, only 1:4300 RATs was presumptive positive but later tested PCR negative, and thus, false positives did not meaningfully disrupt workplace operations.
In a recent paper Pulliam (one of the very first authors on Omicron in South Africa) et al identify that the reinfection rate with Omicron is 70-75% higher than previous variants, and attribute the difference to immune escape: https://www.medrxiv.org/content/10.1101/2021.11.11.21266068v3
Quite a good little Nature article “How Omicron overtook Delta in three simple charts” – mainly looking at household transmission, is here: https://www.nature.com/articles/d41586-022-00632-3 citing Allen et al from UKHSA: https://www.medrxiv.org/content/10.1101/2022.02.15.22271001v1
Omicron is around twice as likely to be passed to household members than Delta. People who had received a booster shot were 38% less likely to spread a Delta infection to their household members, and 22% less likely to pass on an Omicron infection than were those who had had just two shots.
Also looking at secondary attack rates is this one from Denmark - Jorgensen et al: https://jamanetwork.com/journals/jama/fullarticle/2789920
And this small study from Harvard/MIT and the Mass Gen Hospital shows that those with Omicron continued to shed live virus for an average of 6 days after the start of symptoms, with over a quarter of them shedding for more than 8 days. Boucau et al: https://www.medrxiv.org/content/10.1101/2022.03.01.22271582v1
In this Qatar study, the BA.2 subvariant appears substantially more infectious than the BA.1 subvariant. This may reflect higher viral load and/or longer duration of infection.
(see above) – Qassim et al: https://www.medrxiv.org/content/10.1101/2022.03.02.22271771v1
Further Reading:
You may be interested in this discussion of a Peer-Reviewed Publication from Bristol University: “SARS-CoV-2-infected individuals could have different variants hidden in different parts of the body - New research shows virus plays ultimate game of ‘hide and seek’ with immune system.
…..In new research, comprising two studies published in parallel in Nature Communications, an international team led by Professor Imre Berger at the University of Bristol and Professor Joachim Spatz at the Max Planck Institute for Medical Research in Heidelberg … show how the virus can evolve distinctly in different cell types, and adapt its immunity, in the same infected host. The team sought to investigate the function of a tailor-made pocket in the SARS-CoV-2 spike protein in the infection cycle of the virus. The pocket, discovered by the Bristol team in an earlier breakthrough, played an essential role in viral infectivity.
“An incessant series of variants have completely replaced the original virus by now, with Omicron and Omicron 2 dominating worldwide.” said Professor Imre Berger. “We analysed an early variant discovered in Bristol, BrisDelta. It had changed its shape from the original virus, but the pocket we had discovered was there, unaltered”. Intriguingly, BrisDelta, presents as a small subpopulation in the samples taken from patients, but appears to infect certain cell-types better than the virus that dominated the first wave of infections.
Dr Kapil Gupta, lead author of the BrisDelta study, explains: “Our results showed that one can have several different virus variants in one’s body. Some of these variants may use kidney or spleen cells as their niche to hide, while the body is busy defending against the dominant virus type. This could make it difficult for the infected patients to get rid of SARS-CoV-2 entirely.”
The team applied cutting-edge synthetic biology techniques, state-of-the-art imaging and cloud computing to decipher viral mechanisms at work. To understand the function of the pocket, the scientists built synthetic SARS-CoV-2 virions in the test tube, that are mimics of the virus but have a major advantage in that they are safe, as they do not multiply in human cells. Using these artificial virions, they were able to study the exact mechanism of the pocket in viral infection. They demonstrated that upon binding of a fatty acid, the spike protein decorating the virions changed their shape. This switching ‘shape’ mechanism effectively cloaks the virus from the immune system.”
The researchers are seeking to exploit this “pocket” feature to develop an antiviral that recognises and blocks it.
‘Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2’ by K Gupta et al in Nature Communications
‘Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein’ by O Staufer et al in Nature Communications
‘Free fatty acid binding pocket in the locked structure of SARS CoV-2 spike protein’ by C Toelzer et al in Science
Further reading continued:
This text is from a good, well-referenced summary from BlueDot on the state of knowledge regarding waning of long-term immunity, and boosters.
It has previously been established that a booster dose of a COVID-19 vaccine increases neutralizing antibodies in the body and is more effective at preventing infection compared to the immune response observed after two doses or after an acquired infection. However, the duration and level of protection against infection offered by vaccination and infection has declined in the current context of the Omicron variant in comparison with previous variants of concern. It is important to recognize that the primary purpose of the COVID-19 vaccines is to protect against severe COVID-19 disease, for which they remain highly effective. Given a relatively lower rate of hospitalizations attributed to the Omicron variant, recent research has accumulated regarding other aspects of the immune system that contribute to increased protection against severe disease – immune cells, i.e., B and T cells. The primary role of B cells, specifically memory B cells, is to produce antibodies when exposed to an antigen (i.e., specific proteins on the surface of pathogens that are recognized by the body’s immune system), while T cells help coordinate the immune response by helping B cells generate a stronger and longer-lived antibody response (CD4+ T cells) as well as killing infected host cells (CD8+ cells). Together, this part of the body’s immune response may be providing long-lasting immunity and protection against severe disease.
What does the most recent research inform us about long-term immunity to severe COVID-19?
Several recent studies have explored the role of the B and T cell response to a SARS-CoV-2 infection. One study found that a third dose of the COVID-19 vaccine resulted in the diversification and expansion of the memory B cell compartment, leading to an increase in memory B cells that are specific to the receptor binding domain (RBD) in the spike protein of the virus. These memory B cells produced large quantities of antibodies within 3-5 days of exposure to the SARS-CoV-2 antigen via a vaccine or infection, and the response was strengthened after the booster dose. The antibodies produced by these cells were higher in neutralizing potency against the virus, compared to antibodies produced after the 2nd dose. The antibodies produced by these B cells were also found to have a higher breadth of response, compared to the antibodies produced after the 2nd dose, making them better at responding to infection from variants such as Omicron, even though the vaccine was designed against the ancestral strain.
T cells are important components of the immune system as well. While they don’t prevent infection or help to neutralize the virus like antibodies do, CD8+ T cells help clear the infection by recognizing and killing infected host cells, and CD4+ T cells coordinate the host immune response by influencing other necessary immune components. Hence, although antibody levels produced after infection or vaccination may be waning after a certain time period, both B and T cell responses to SARS-CoV-2 antigens remain robust. The responses in these components of the immune system likely contribute to long-term vaccine efficacy against severe disease, and support findings of more rapid clearance of the virus upon infection among the vaccinated as well as lower rates of long-term health impacts (i.e., Long COVID).
A study was conducted on T-cell response aimed to measure cross-reactivity of T cells towards the Omicron variant. Cross-reactivity measures the extent of T-cell response to different antigens, such as different spike proteins in different SARS-CoV-2 variants; higher ability for cross-reactivity indicates a potentially increased immune response to new variants. The study concluded that 85% of individuals in the study who were vaccinated (i.e., had received either two doses of the Pfizer/BioNTech vaccine or one or two doses of the Johnson and Johnson vaccine) generated a T-cell response after being vaccinated. Additionally, the vaccination induced robust CD4+ and CD8+ T -cell responses, with 70-80% of the T-cell response being cross-reactive. T cells were able to recognize many more sites on the spike protein of the SARS-CoV-2 virus compared to antibodies, making them more likely recognize variants with mutations on its spike protein (such as Omicron). Another study conducted on T cell response to SARS-CoV-2 infections concluded similar results. The authors of the study reported that 91% of CD4+ T cells and 92% of CD8+ T cells cross-recognized the Omicron variant in individuals that received two doses of the Pfizer-BioNTech vaccine, indicating that the T-cell response remains robust against the Omicron variant.
A study conducted before the emergence of the Omicron variant also reported similar findings – that B-cell and T-cell response remains strong despite waning levels of antibodies. This study found that the frequency of memory B cells continued to increase from three to six months post-vaccination (two doses), and over 50% of these cells displayed cross-reactivity with the Alpha, Beta, and Delta variants after six months.
These studies emphasize the role B and T cells play in coordinating the immune response upon exposure to an antigen, and highlight the relevance of the robust response maintained by these cells despite waning antibody response, suggesting effective protection against severe COVID-19.
What may be the long-term vaccination strategy for COVID-19?
As many countries across the world are ramping up booster coverage, some countries are also beginning to administer 4th doses (or 2nd booster shots) for high-risk groups, and many people have now encountered the virus. It is unclear how many boosters may be required or what the optimal time interval may be between doses for current vaccines in use. However, given the research on sustained long-lasting immunity conferred by B and T cells, it is likely that a third shot (or one booster dose) may be enough to prevent severe disease for most of the population.
(Source: BlueDot).
Best wishes,
David Powell
IATA Medical Advisor