Coronavirus Research Tracking - 21 August
Emerging evidence for at least short term immunity, and revealing the dynamic cellular and genetic immune responses to infection.
In this week’s Research Tracker we look at pandemic history, antibody mediated immunity, and the dynamics of immune responses in the blood.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
A history of pandemics
Anthony Fauci and a colleague have written an excellent overview of the history of pandemics, and the determinants involved in their emergence. They also summarise what we know about SARS-CoV-2. The paper is published, somewhat unusually, in the specialist journal Cell.
Herd immunity
There is considerable discussion about what levels of infection or vaccination are required to create herd immunity - meaning the virus is no longer able to spread effectively. See the New York Times and Quanta Magazine.
Standard calculations usually predict that at least 60% of the population would need to be infected, or vaccinated, to establish herd immunity. However, two recent modelling studies calculate that lower proportions, under 50%, may be sufficient if variability in exposure and susceptibility is accounted for.
A paper in Science estimated that a population-wide infection level of about 40% may be sufficient. However, the intent of the paper is to illustrate how heterogeneity affects assumptions, rather than identify a precise level.
A pre-print paper indicates levels down to 20% could theoretically provide immunity if there is considerable community variation. However, this low level isn’t supported by evidence from other respiratory viruses.
Both papers emphasise the need for further research and more sophisticated models. Vaccination rather than natural infection is regarded as the more efficient and ethical way to achieve herd immunity.
Evidence of longer lasting antibody responses and neutralising activity
Several studies are reporting that IgG antibodies specific to the virus persist for over 2 months, and that this is usually associated with neutralisation of the virus. A stronger antibody response can also often be related to more severe Covid-19 symptoms. This is consistent with other viral infections.
A pre-print paper found that IgG antibodies that target the virus’ receptor-binding domain in the spike protein were highly correlated with neutralisation of the virus. The antibodies could be detected for at least 75 days, and patients who had more severe conditions tended to produce these antibodies earlier.
SARS-CoV-2-specific IgG antibodies, neutralizing plasma, and activated T and B cells were found in another study, and these were detectable for at least 3 months. This paper is also not yet peer reviewed.
A third study (also in pre-print) found a correlation between antibody and neutralising activity and the severity of Covid-19. Antibodies targeting the spike protein were more long lasting than those targeting the virus’ nucelocapsid, and could be detected 2-3 months after symptom onset.
A paper just published in Cell Reports Medicine found that SARS-CoV-2 specific CD4+ and CD8+ T cells were produced for at least two months in patients with mild symptoms.
Evidence that these responses confer protection
The studies noted above don’t demonstrate that those infected are immune to re-infection, or have less severe symptoms. However, other studies are providing evidence.
Testing of a fishing boat crew shows that there seems to be a post-infection immune period. A pre-print paper describes finding three crew had antibodies and neutralising activity against the virus before a trip. The boat returned 18 days later following an outbreak, with 104 of the 122 crew infected. None of the three with pre-existing antibodies were re-infected.
As we’ve previously noted in Highlights, a trial (published in Science) found that re-infecting macaques with the virus didn’t prevent infection, but did reduce symptom severity.
A news article in Nature points out that it is too soon to know if there will be lasting immunity, but also notes that immune responses to SARS-CoV-2 don’t appear to be acting differently from other respiratory viruses.
Understanding the dynamic nature of the immune response
A very good overview of what is currently known about the immune response to Covid-19 was published in The Atlantic. A more technical description of recent research is in this commentary in Nature.
Studies of innate immune responses to infection are becoming increasingly sophisticated. Researchers are looking at the dynamics of different immune cell types and specific gene transcription activity following infection.
These studies are showing that severe cases of Covid-19 can be due, at least in part, to different aspects of the immune response becoming “unbalanced”, or responding inappropriately.
A commentary in Science notes that suppression of peripheral innate immunity (through reduced levels of type I interferon) and increased pro-inflammatory responses is often reported in those who develop severe Covid-19.
Four recent papers report on immune response dynamics in the peripheral blood or plasma of small numbers of Covid-19 patients and healthy subjects who were tested over several weeks. The results don’t always provide similar immune response profiles, but this can be due to different methods, sample sizes, and the patients studied.
A paper in Nature Immunology found that those with less severe cases of Covid-19 disease had a moderate and broad activation of innate immune signals, including greater cytotoxic T cell activity. In contrast, patients with severe clinical conditions showed a “deranged” interferon response and immune exhaustion.
A paper in Science found that patients with severe Covid-19 produced specific cytokines and had much stronger inflammatory immune responses than those with milder conditions. These authors propose that bacterial fragments, possibly flushed from the lungs due to severe infection, may enhance the cytokine, and subsequent immune, reactions.
A Nature paper identified four “immune signatures” early in disease development. Patients who developed moderate Covid-19 had an immune profile enriched in tissue reparative growth factors, along with low levels of inflammatory molecules. Those who subsequently developed more severe disease had, in addition, high levels of various specific cytokines.
However, research published in Cell found reduced inflammatory cytokines in patients with severe Covid-19. They had impaired monocyte and neutrophil cells, and increased numbers of immature blood cells, which are associated with immunosuppression.
The dynamics of immune responses in organs and other tissues are less well known at the moment.