Coronavirus Research Tracking - 25 March
Omicron and immune responses, effectiveness of three vaccine doses, diabetes and long Covid risks, infections in children
This week, weaker immune responses following Omicron infections, and a randomised trial assessing the effectiveness of a third vaccine dose.
White blood cells may provide an indication of the course of an infection, diabetes risk may increase after infection, a meta-analysis of the incidence of long Covid, and impacts of infections on children.
The tracker is shared with the COVID-19 Vaccine Media Hub.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine-related papers
Omicron infection doesn’t generate as strong an immune response as previous variants
Lab experiments indicate that an Omicron infection after vaccination does not generate as strong a neutralising antibody response as a Delta infection. This may mean that a breakthrough Omicron infection may generate a lower level of lower protection against a subsequent infection than a Delta infection.
Part of this lower immunogenicity may be due to the greater frequency of asymptomatic or mild Omicron infections compared with the Delta variant, and an associated lower level of neutralising antibodies.
The experiments used virus-like particles to test immune responses. The paper was published in Cell.
Another study reports that an infection involving the Omicron variant may not provide protection against other variants. Neutralising antibodies generated by an Omicron infection in unvaccinated people did not cross-react with other variants.
However, being vaccinated before an Omicron infection did subsequently produce antibodies that were able to neutralise other variants, demonstrating an Omicron infection without vaccination does not generate strong immunity. The results are based on serum samples from 59 people. The paper was published in the New England Journal of Medicine.
Vaccinations provide similar protection against Omicron and the BA.2 subvariant
Further research from Qatar found that immunity against BA.2, based on prior infection and/or vaccination, was the same as for BA.1 (Omicron). Symptomatic infections were assessed, as were hospitalisations.
Strongest protection against symptomatic infection (about 80%) was seen for a prior infection and three vaccine doses. Both mRNA vaccines were used in Qatar. Protection against severe Covid-19 was over 70% for two or three vaccine doses, with or without a prior infection.
One limitation in the study was that vaccine effectiveness after two or three doses were not assessed at the same time point after the last dose. The Qatari population is relatively young, so some results may not apply in other populations. The paper has not yet been peer reviewed.
Effectiveness of a third Pfizer dose in a randomised trial
A randomised controlled trial of the effects of a third Pfizer/BioNTech dose found it provided 95.3% effectiveness against infection. The third dose was given about 10 months after the second, and effectiveness was assessed about two-and-a-half months later. The Delta variant was the main circulating variant at that time. The paper was published in the New England Journal of Medicine.
Non-vaccine-related papers
Differences in white blood cell types associated with severity of Covid-19
A study of cell types in hospitalised patients with and without Covid-19 found differences in immune cells over time linked to disease severity and clinical improvement. Both infected and uninfected participants had similar numbers of neutrophils but differed in what proteins were expressed on the surfaces of them. Neutrophils are one type of white blood cells associated with early immune responses.
Frequencies of different monocytes (another type of white blood cell) also varied between the two groups. In Covid patients who improved relatively quickly the cell types and proteins expressed changed relatively quickly, in contrast to those with more serious illness.
However, as more serious cases started to improve their cell profiles became similar to the faster recovered patients. This indicates differences in cell signalling between more severe and less severe Covid-19 states. The results may be able to inform treatments that help shift the immune response to more effective control. The paper has not yet been peer reviewed.
Heightened risk of developing diabetes after Covid-19
A US study found that the risk and burden of diabetes increases in veterans who develop long Covid. Risk was about 40% higher in patients with long Covid, compared with patients without Covid-19. Antihyperglycemic use was also much higher in patients who previously had Covid-19. The increased risk was seen even in patients with relatively mild Covid symptoms, but was higher in those who exhibited more severe symptoms initially.
The risk and burden of diabetes was assessed 12 months after infection. The cause for the link between Covid and diabetes was not identified. Participants in the study were mostly older white males. The paper was published in The Lancet Diabetes and Endocrinology.
A German study also found an increased risk of type 2 diabetes after relatively mild Covid-19. The risk was estimated to be 28% higher relative to patients who had other acute upper respiratory infections, with assessments made around 4 months after infection.
The authors suggest that high levels of cytokines after Covid-19 may lead to beta cell dysfunction and insulin resistance The paper was published in Diabetologia.
Longer term effects from Covid-19
A meta-analysis concluded that over one third of those hospitalised with Covid-19 suffered from subsequent fatigue. One third also reported breathing difficulties up to four months after being discharged from hospital. Many hospitalised patients required additional sick leave months after being discharged.
For non-hospitalised cases, nearly half of women and a third of the men reported more than one symptom associated with long Covid four months after being infected.
Forty nine studies were included in the analysis. Results varied considerably between individual studies due to different methods and populations. The paper has not yet been peer reviewed.
Covid-19 in children
An article in the Proceedings of the National Academy of Sciences discusses why children usually develop less serious Covid-19 than adults. A key reason appears to be the high levels of some interferons in children’s mucosal surfaces in airways. This helps generate a rapid immune response in the early stages of infection.
Young people also have a much higher proportion of naive T-cells (not specific to one pathogen) that can also quickly attack the virus. Due to the potential of a high proportion of asymptomatic or very mild cases in children it is uncertain if infection rates in children are lower.
BA.2 subvariant can be more pathogenic in unvaccinated children than earlier variants
A review of clinical cases in Hong Kong concludes that BA.2 Omicron subvariant infections in unvaccinated children (under 12 years old) can lead to moderate or even severe Covid-19 symptoms. This variant appears to be more pathogenic in children than earlier variants, and other common respiratory infections in children. The Omicron variant is associated with a higher frequency of seizures and croup.
The paper has not yet been peer reviewed.
Long lasting neutralising antibody and T-cell responses after infection
Persistence of SARS-CoV-2-specific neutralising antibody and T-cell response for at least a year were found following infections. T-cell responses were still detectable in participants whose neutralising antibody responses were no longer detectable (usually those over 60). The study was undertaken before the emergence of the Omicron variant. The paper was published in The Lancet Microbe.