Coronavirus Research Tracking - 20 November
T cells, non-vaccine treatments, human coronavirus effects, mask effectiveness
This week’s Research Tracker has a focus on T cells and immunity. It also provides a reminder that there are many non-vaccine treatments in the works and masks are still an effective intervention. Caution is required with antigen tests, as well as with inferring Covid-19 protection from previous coronaviruses infections. The virus also appears to be adapting to mink.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Useful questions for vaccine trial results
Stat News has a good article on what to look for when vaccine trial data are released.
Other treatments
Lest we forget amid the vaccine enthusiasm there are a large number of other treatments being explored. See the NY Times’ drug and treatment tracker.
Inhalation of Interferon-beta showed promise in a randomised controlled phase 2 trial. Covid-19 patients given interferon were more likely to improve, and recovered more quickly, than those who were given a placebo. The results were published in The Lancet Respiratory Medicine.
A viewpoint, published in JAMA, discusses the challenges with testing, approving, and using monoclonal antibodies. It notes that clinical trials of monoclonal antibodies to treat Covid-19 (such as Regeneron’s) are incomplete, and that available stocks are limited. Some could run out within two weeks of being approved.
Providing adequate and equitable access to monoclonal antibodies will be a considerable challenge. They are very expensive, and monoclonal antibodies need to be given soon after infection, with patients going home afterwards. Infusion of the antibodies may take an hour or more. This means that healthcare centres are likely to be put under considerable pressure if monoclonal antibodies are widely used, and it may be difficult to follow up all those treated.
Further indications of longer lasting immunity
Most immunity research has focussed on longevity of separate components of the immune response - antibodies or T cells. A recent pre-print paper looked at both. It examined antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory in blood samples from 185 people with Covid-19. Some of the participants had been infected more than eight months earlier.
Spike protein-specific IgG antibodies usually persisted for more than five months. Memory B and T cells (which produce the antibodies and activated T cells, respectively) appear to have long half-lives, showing little or slow rates of decline over months. This has been observed for some other infectious diseases as well.
The results suggest that relatively long lasting immunity to the virus is likely, at least in some people. However, there was considerable variation in immune responses between patients, so it is probable that some may lose immunity more quickly. The reasons for variation need further research.
Long lasting memory B cells were also reported in another study (in pre-print). The virus may also be long lasting after infection. The same study found that the virus was detected in the small bowel of 7 out of 14 patients three months after they developed Covid-19 symptoms.
Interferon-producing T cells may correlate with protection
An as yet unreviewed paper describes a correlation between the abundance of interferon-gamma secreting T cells that react to the virus and the presence of SARS-CoV-2 antibodies. Only about half of those with high reactive T cell levels had antibodies, so just using antibody presence to assess immunity may over-estimate susceptibility to infection.
In the study high levels of these T cells were associated with protection from symptomatic Covid-19. However, most people with low levels didn’t become infected either, so assessments about protection aren’t simple.
Two cytokines acting together cause cell death
A paper published in Cell reports that while many cytokines that stimulate inflammation are produced following SARS-CoV-2 infection, only two appear to cause the tissue damage commonly seen with Covid-19. These are Tumour necrosis factor alpha and Interferon-gamma. Treating SARS-CoV-2-infected mice with antibodies that neutralise these two cytokines prevented serious tissue damage and mouse death.
Known unknowns of T cell immunity
A review of what is and isn’t known about T cell responses to Covid-19 was published in Science Immunology. It states that there is still much to learn about the roles that T cells play in immune responses to SARS-CoV-2. Most of the research so far has focussed on T cell responses in blood, because they are easier to study, and less is known about immune responses in lungs. Further research using animals and more longitudinal studies in people are desirable to better understand T cell effects and dynamics.
Are previous human coronavirus infections protective?
In last week’s Tracker we noted a paper in Science indicating SARs-CoV-2 cross-reactivity with human coronavirus antibodies, though it was unknown if they prevented infection.
A study (not yet peer-reviewed) found that nearly one quarter of people with previous human coronavirus infections had non-neutralizing antibodies that cross-reacted with SARS-CoV-2 proteins. These did not provide protection against infections or appear to reduce disease severity. Curiously however, the levels of these antibodies did increase after the person was infected with SARS-CoV-2.
A study published in the Journal of Clinical Infection found that people who had previously had human coronavirus infections developed less severe Covid-19 (they mostly didn’t require intensive care). An earlier coronavirus infection did not appear to affect the likelihood of becoming infected with SARS-CoV-2.
A point to note in this study is that many more (17 times) of those involved had no evidence of human coronavirus infections than those that did, so further studies are necessary.
Evidence of rapid host adaptation of SARS-CoV-2 in mink
Analysis of viral mutations that occur only in SARS-CoV-2 collected from mink found 23 mutations that occurred independently several times (not yet peer-reviewed). Seven may indicate adaptation to mink as hosts. These occur in the receptor binding site of the spike protein, as well as regions that affect viral replication and host inflammatory response. There is no evidence that these mutations enhance transmission or disease in people.
Comparing antigen tests
Thanks to Elon Musk, the accuracy of antigen tests have been in the news this week. Antigen tests detect viral proteins which are common early in the infectious period. Antigen tests are less specific and sensitive than PCR tests, but they are easier and cheaper, provide quicker results, and identify who is infectious rather than simply infected. There are concerns though that regulators may be approving such tests too quickly without proper evaluations or guidelines.
A pre-print paper compared the performance of seven commercially available antigen tests that can be used at point of care (such as homes, hospitals, work places). The seven tests showed variation in specificity, but five exceeded 98%, and specificities are likely to improve as new versions are produced.
The authors recommend that results from antigen tests should be regarded as a momentary assessment of infectiousness, not a firm diagnosis about infection.
Mask effectiveness
A study (not yet peer-reviewed) of the effectiveness of different face coverings measured how well they blocked the dispersal of cough-generated aerosols.
It found that an N95 respirator blocked 99% of the aerosol and a medical grade mask 59%. A 3-ply cotton cloth face mask blocked 51%, while a single layer polyester neck gaiter blocked 47% (but 60% when it was doubled up). In contrast, a face shield blocked only 2%. These were lab tests, so results are likely to vary between individuals and outside of controlled conditions.
The New York Times provides a good interactive visualization of how face masks work.
Extreme geek zone
With much of the coronavirus research about genetic sequences, binding, and blocking, and the fixed images we see of the virus, its easy to view SARS-CoV-2 and how it infects as largely a rigid mechanical process. That’s not the case. For structural biology fans an elegant study in Cell Host & Microbe shows how the conformation of the spike protein changes during the infection process.