Coronavirus Research Tracking - 26 March
Vaccine effectiveness, reinfection, variants, super-carriers, flu and cold impacts, pet infections, social sciences, viral origins
This Research Tracker covers reports on vaccine effectiveness, vaccinating pregnant women, reinfection risks, immune evasion by variants, unusual symptoms in pets from new variants, how the flu and colds affect infection, the roles of social sciences, humanities and the arts in pandemic recovery, and viral origins.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Vaccine effectiveness
Three studies in the New England Journal of Medicine report on vaccine effectiveness in health care workers in situations where there were high levels of community infections. They don’t all report their results in the same way, but there is a consistent pattern, with vaccinations reducing infections.
A study of 23,000 employees at a Texas medical centre found that 2.6% of unvaccinated workers became infected, compared with 1.8% for partially vaccinated and 0.05% (four out of 8,121 people) for staff fully vaccinated with either the Pfizer/BioNTech or Moderna vaccine.
A study of Californian health care workers calculated that the absolute risk of becoming infected after vaccination with either the Pfizer or Moderna vaccine was around 1%. The majority of infections after vaccination occurred in the first two weeks after receiving the first dose. New infections two weeks after the second dose were very low (seven out of 14,990 employees).
A study of previously uninfected staff at an Israeli medical centre found that the incidence of infection decreased significantly two weeks after workers received the first dose of the Pfizer/BioNTech vaccine. Nearly all (98.9%) who had received the first dose of vaccine had not become infected 21 days after receiving the second dose.
A UK study, not yet peer reviewed, found that vaccination of health care workers (with the Pfizer/BioNTech or AstraZeneca/Oxford vaccines) reduced cases of infections in their household contacts, compared to the contacts of unvaccinated staff.
A study, also in the New England Journal of Medicine, found that antibody levels three weeks after receiving the first dose of the Pfizer/BioNTech vaccine were higher in health care workers who had previously been infected, compared to uninfected colleagues. This supports previous findings. It is unknown whether this boost provides the infected people with a higher level of protection.
AstraZeneca explainer
A news explainer in Nature discusses what is known, and not known, about the effectiveness of the AstraZeneca/Oxford vaccine. It points out that compared to Pfizer’s and Moderna’s vaccines it is much cheaper, and is the only vaccine available in large quantities in many less developed countries.
Chance of reinfection within six months is relatively low for those under 65
A Danish study published in The Lancet investigated infection and reinfection rates in 4 million people. It calculated that protection against repeat infection after six months for those under 65 was around 80%. Those over 65 were more likely to become reinfected, with protection against repeat infection was 47%. The study was done before the emergence of the newer variants of concern. It did not assess if symptoms differed between first and second infections.
Herd immunity
A modelling study in the UK indicates that vaccination alone will not be able to control the pandemic. The results, published in The Lancet Infectious Diseases, indicated that even with all adults being vaccinated and 85% of infections being prevented, the virus’ reproduction rate would still be greater than one. A slow phase out of non-pharmaceutical interventions (like masks and distancing) over several months is recommended as immunity slowly increases.
Testing of nearly 10,000 people for antibodies in Wuhan between April & December indicated that herd immunity had not been achieved, a paper in The Lancet reports. The study calculated that 6·92% of the population developed antibodies against SARS-CoV-2, with 39·8% of this group developing neutralising antibodies. Concentrations of neutralising antibodies were relatively stable for at least 9 months.
Evidence that mRNA vaccines are safe and effective for pregnant women
A small study, not yet peer reviewed, has shown that immune responses to vaccination in pregnant and lactating women is the same as non-pregnant women of similar ages. There were also no differences in reactions to the vaccine. Vaccine-generated antibodies were present in umbilical cord blood and breast milk. The study involved 84 pregnant, 31 lactating, and 16 non-pregnant women in the USA.
A case report in BMC Pediatrics describes the presence of SARS-CoV-2 antibodies in the cord blood of a baby whose mother had received the first dose of the Moderna vaccine three weeks before the birth.
Vaccine developments
Vaccine developments continue. While prospects for several of the initial Covid-19 vaccines remain high, research and development on new vaccines continue. These may be used as either booster shots or longer lasting vaccines. An example, published in Science Advances, is one based on self-assembling protein nanoparticles that present a small part of the spike protein.
A perspective published in the New England Journal of Medicine gives a brief general history of vaccines. It suggests that equitable and efficient distribution of vaccines could be as great an achievement as the development of some of the recent new types of vaccines.
P.1 variant is more transmissible
A study, not yet peer reviewed, estimates that the P.1 variant is 2.6 times more transmissible than earlier variants in Brazil. This is similar to the estimate reported in last week’s tracker, and is higher than that calculated for B.1.1.7.
Analysis in Nature calculates that the B.1.1.7 variant has a 50-100% higher reproduction number in the UK than earlier strains.
Immune evasion by variants
A study published in Cell Host & Microbe found that while there was reduced antibody binding and neutralisation of B.1.351 from sera of infected or vaccinated people the variant could still be neutralised. The paper suggests that antibodies that target sites away from the receptor binding domain of the spike protein (where many, but not all of the mutations occur) are also important.
Meanwhile, a paper in Cell reports that previously infected people may only be partially protected from subsequent infections by B.1.351 or P.1 variants. Sera from people vaccinated with the Pfizer vaccine also showed reduced inhibition of these two variants. The B.1.1.7 variant did not demonstrate escape from antibody-mediated control. The experiments involved convalescent sera and cell-based assays using only the spike protein in pseudoviruses.
A paper in the New England Journal of Medicine summarises recent evidence of the effectiveness of several vaccines against the B.1.1.7, B.1.351, and P.1 variants.
“Super-carriers”
An analysis of viral loads in 1,400 people calculated that about 50% of those testing positive using PCR probably don’t have live viruses or aren’t infectious because their viral levels are very low. The researchers also identified “super-carriers” who have very high viral loads. They estimate that any given time just 2% of infected people carry 90% of the virus in a community. The paper has not yet been peer reviewed.
The flu may increase Covid-19 infection risk …
A paper published in February in Cell Research reported that SARS-CoV-2 infection is enhanced when cells are already infected with the influenza A virus. This was based on lab studies, using a pseudovirus containing the SARS-CoV-2 spike protein.
Infection with the influenza A virus was shown to increase mRNA levels of the ACE2 and TMPRSS2 genes, which are known to be involved in SARS-CoV-2 infection. Other respiratory viruses did not enhance SARS-CoV-2 infection.
The study also showed that mice co-infected with both the influenza virus and SARS-CoV-2 had higher levels of the latter virus and greater lung damage compared to mice only infected with SARS-CoV-2
A subsequent paper in Cell Research proposes that these results should stimulate the development of a combined vaccine that can protect against both a spectrum of influenza A strains and Covid-19.
A paper published in the American Journal of Infection Control found that the odds of getting Covid-19 was 24% lower if the person had the flu vaccine in 2019. Patients vaccinated against the flu who had Covid-19 were also less likely to be hospitalised or require mechanical ventilation.
The authors suggest that “trained immunity” may account for the reduced risk of infection. However, those who chose to get the flu vaccine may behave in ways that reduce their risk of becoming infected with SARS-CoV-2. Further research is necessary.
… while a cold may provide some protection
A paper published in the Journal of Infectious Diseases reports that infection with a cold virus (human rhinovirus) blocks SARS-CoV-2 infection. The experiments were done using cell lines and complete viruses. The protection was shown to be due to interferons produced in response to the rhinovirus infection.
Asymptomatic transmission of respiratory viruses in general is poorly understood
A perspective published in Science notes that the biological basis for transmission without symptoms in respiratory viruses is poorly understood. Poor levels of infection surveillance for SARS-CoV-2 makes it difficult to understand the risk of transmission for asymptomatic infections. This in turn could prevent complete elimination of the virus.
Effects of new variants on other animals
Dogs and cats can be infected by the B.1.1.7 variant reports a paper not yet peer reviewed. Instead of developing respiratory problems, these pets developed heart problems, indicating more recent variants may cause different pathologies in pets (and people). Eight cats and three dogs were treated, and all recovered. Their owners often developed Covid-19 symptoms 3-6 weeks beforehand.
An article in Science reporting on this study notes that the risk of people catching the virus from their pets is very low based on current evidence.
A paper, not yet peer reviewed, reports that the B.1.351 and P.1 variants are able to infect laboratory mice. Previously SARS-CoV-2 could only infect mice that had been modified to carry the human ACE2 receptor. The ability of the mice to infect other mice was not tested, but the results raise the possibility of larger non-human reservoirs for some SARS-CoV-2 variants.
White-tailed deer are also able to be infected, and pass the infection on to other white-tailed deer according to a paper in the Journal of Virology. Whether they can infect people or other animals is unknown.
Policy responses affect health and economic impacts
A simulation study, not yet peer reviewed, examined the health and economic impacts of four policy responses to the pandemic in the state of Victoria. The four options were “aggressive elimination”, “moderate elimination”, “tight suppression” and “loose suppression.”
It found that the outcomes of policy responses are very uncertain due to both stochastic uncertainty and uncertainty about the impact of non-pharmaceutical interventions. Median GDP losses across all four policies were similar, although loose suppression was more likely to see the highest GDP losses.
The “best” strategy depends on what outcomes are measured. Aggressive elimination was the best option from the perspective of impact on the health system, while greater societal benefits were seen under the moderate elimination policy.
Social sciences, humanities and arts matter too
A commentary in Nature highlights the need for policy makers to consider social sciences, humanities and the arts for people and the economy (“SHAPE”), alongside science and technology, in recovering from the pandemic. This summarises the findings of a report by The British Academy.
Viral origins
A paper published in PLOS Biology suggests that bat Sarbecoviruses developed a generalist phenotype long ago, leading to their ability to infect a range of other mammals.This implies that a variety of coronaviruses in species other than bats could be the source of the next human SARS pandemic.
A paper in Science suggests that the first case of Covid-19 possibly occurred in October or November 2019, one or two months before the first reported case. This was based on phylogenetic analyses and epidemiological modelling.
Using simulations it also found that in only about 30% of the simulations led to self-sustaining epidemics. The authors conclude that “humans are constantly being bombarded with zoonotic pathogens”, most of which don’t spread. However, they also note that the period of time before a pandemic develops is very short, so the window for intervention is small.
Fill your Covid boots
Nature Communications has identified its 50 most popular Covid-19 papers from 2020, based on downloads
The top paper, with 1.32 million accesses, was about screening 10 million people in Wuhan.