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Coronavirus Research Tracking - 11 March

Coronavirus Research Tracking - 11 March

This article was published on
March 11, 2022

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This week, a series of reviews on the pandemic, and more evidence of effectiveness of three doses against Omicron, and of mRNA vaccine safety. In non-vaccine papers, a large study of the effects of Covid on the brain, incidence of long Covid, and genetic indicators of increased risk of developing more severe symptoms. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

This week, a series of reviews on the pandemic, and more evidence of effectiveness of three doses against Omicron, and of mRNA vaccine safety. In non-vaccine papers, a large study of the effects of Covid on the brain, incidence of long Covid, and genetic indicators of increased risk of developing more severe symptoms. The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Publication

What our experts say

Context and background

Resources

Vaccine-related papers

The vaccine road ahead

As part of a special issue review in Science on the pandemic, an article discusses the road ahead for vaccines. It describes the challenges ahead, due to both the evolving nature of the pandemic and the diverse landscape of vaccines becoming available. A re-evaluation of vaccination strategies is recommended.

Three mRNA doses improve protection against Omicron

A US study found three mRNA vaccine doses provide much better protection against hospitalisation following an Omicron infection than two doses. Effectiveness was 86% for three and 65% for two doses. In comparison, three doses provided 94% protection against the Delta variant, and two doses 85%.

Compared with the Delta variant less severe disease was seen for Omicron, although infections could still result in significant health effects and death, especially in unvaccinated people. The paper was published in the BMJ.

A Qatari study found that third doses of either the Pfizer/BioNTech or Moderna vaccines nearly halved the incidence of symptomatic Omicron infections, compared with two doses.The incidence of Covid-related hospitalisations and deaths after three doses was very low.

Effectiveness was calculated approximately one month after the second or third dose. The third dose was given on average 8 months after the second. The paper was published in the New England Journal of Medicine.

mRNA vaccines have very low incidence of adverse effects

An analysis of reports to the US Vaccine Adverse Event Reporting System and v-safe during the first six months of mRNA vaccinations found 92% were non-serious. Nearly 300 million vaccine doses were administered, with only 340,522 adverse effects reported. There were 4,496 deaths associated with the vaccine, mostly in those over 60.

The VAERS suffers from underreporting and variable or incomplete reporting, so does not provide a comprehensive picture of reactions to vaccines. The v-safe system requires access to a smartphone, so data from it may not be representative of all who were vaccinated.The paper was published in The Lancet Infectious Diseases.

Masks still an important factor after vaccination

A modelling study concluded that wearing face masks for several weeks after vaccination programmes were completed improved reduction in transmission. The masks were also cost effective, and could save money, for the health system. The model used US data. Different levels of mask effectiveness and levels of compliance were modelled. The paper was published in The Lancet Public Health.

Non-vaccine-related papers

Covid effects on the brain

Brain scans before and after people became infected with SARS-CoV-2 found that infection can cause damage to some brain tissues, especially those associated with the olfactory system. Infected participants, particularly older ones, also showed larger declines in cognitive tests than uninfected participants. Those with mild symptoms took longer to complete some of the tests.

The study included 401 adults who developed Covid-19, mostly aged in their late 50’s or older, and of European ancestry. Whether the effects on the brain lead to permanent or further cognitive decline is unknown. Most had relatively mild to moderate Covid-19 symptoms. However, full clinical details about symptoms were not available.

The research was undertaken in the first half of 2021. The Omicron variant does not appear to affect the sense of smell, but it is not yet known if it may affect the olfactory system in the same way as earlier variants. The paper was published in Nature.

Long Covid can be relatively common

Another study has found that symptoms associated with long Covid can be common. The Danish study found that about 30% of infected people had at least one physical post-acute Covid symptom 6-to-12 months after their infection. Over half (53%) of those infected reported concentration difficulties, sleep issues, or physical exhaustion.

Some symptoms can also occur in uninfected people, with 13% of uninfected people reported at least one symptom.. However, the risk of developing a range of symptoms was higher in those who had Covid-19, compared with those who hadn't.

Those aged 15 or older were included in the study, with over 60,000 people having an infection. Women between 30 & 59 were more likely to report symptoms. Symptoms were self-reported. The paper has not yet been peer reviewed.

Genetic factors associated with increased risk of more severe Covid-19

Analysis of more than 3,000 blood proteins found that five were associated with greater risk of hospitalisation, serious illness or death due to Covid-19. One of the proteins is associated with determining blood type.

Increased or decreased susceptibility based on specific blood type was not investigated in this study, although earlier studies have found an association with type A blood and a greater infection risk. Some of the other proteins help mediate interactions between immune cells and blood vessels.

The study did not assess associations of proteins in tissues or intracellular spaces, so further research is needed to see if they correlate with blood concentrations. While the study is based on samples from nearly 10,000 Covid patients, the people were mostly of European ancestry. The paper was published in PLOS Genetics.

In another study, whole genome sequencing identified 23 independent sets of mutations associated with more severe Covid-19. Five of these genetic markers are associated with interferon signalling, so support the hypothesis that severe Covid can result from poor early control of viral replication.

Other mutations are associated with poorer development of lymphocytes and disruption of molecules associated with inflammatory responses. Screening for these mutations can help identify more appropriate clinical care options. The paper was published in Nature.

Higher viral loads seen in BA.2 subvariant infections

A Qatari study found that the BA.2 subvariant resulted in higher viral loads than BA.1 (Omicron) infections. Lowest viral loads were seen in those vaccinated within four weeks prior to an infection, with loads increasing as time from vaccination increased. Older people also tended to have higher viral loads.

Viral loads were measured using quantitative PCR. The results are based on tests from 156,000 infected people, mostly working-age adults. The paper has not yet been peer reviewed.

BA.2 subvariant has a shorter generation time and higher transmissibility than BA.1

A Japanese study of the BA.1 and BA.2 infections in Denmark calculated that their effective reproductive numbers are 2 and 2.5 times higher, respectively, than the Delta variant. The analyses also indicated that the generation time for BA.2 is about half as long as Delta, with BA.1 about 40% quicker than Delta.

Consequently, the authors suggest that the isolation times for people infected with the BA.1 and BA.2 variants can be reduced proportionately. But that isolation controls need to be stronger. The paper has not yet been peer reviewed.

Arthritis drug can help reduce Covid-19 deaths

The oral drug Baricitinib, originally used to treat rheumatoid arthritis, is also effective at reducing the risk of death in hospitalised Covid-19 patients. The risk reduction was 13% when assessed at 28 days after the treatment commenced. Baricitinib was given for 10 days. Similar results were seen when Baricitinib was given along with several other drugs.

The reduction in risk of death was smaller than reported by previous trials, but they were much smaller trials. The study is part of the UK’s RECOVERY trial, which is testing a variety of Covid-19 treatments. The paper has not yet been peer reviewed. An article in Science discusses the results of this study.

Monitoring viral mutations in immunocompromised people can provide an early warning of new variants

A study of viral mutations in immuno-compromised people with chronic Covid-19 infections found that the mutations generally mirrored those seen in variants of concern.  In particular mutations aiding antibody evasion were more frequent than those that may increase transmissibility. The authors suggest that this may indicate a trade-off between immune evasion and transmissibility.

The authors recommend closely monitoring people with chronic infections to identify potential future mutations of concern. Twenty seven people with chronic infections were involved in the study. The paper has not yet been peer reviewed.

Looking back at the changing epidemiological questions during the pandemic

Another review in Science examines how the key epidemiological issues and questions about the pandemic have changed over the last two years. It notes that we shouldn’t assume viral evolution towards lower virulence.

Vaccine-related papers

The vaccine road ahead

As part of a special issue review in Science on the pandemic, an article discusses the road ahead for vaccines. It describes the challenges ahead, due to both the evolving nature of the pandemic and the diverse landscape of vaccines becoming available. A re-evaluation of vaccination strategies is recommended.

Three mRNA doses improve protection against Omicron

A US study found three mRNA vaccine doses provide much better protection against hospitalisation following an Omicron infection than two doses. Effectiveness was 86% for three and 65% for two doses. In comparison, three doses provided 94% protection against the Delta variant, and two doses 85%.

Compared with the Delta variant less severe disease was seen for Omicron, although infections could still result in significant health effects and death, especially in unvaccinated people. The paper was published in the BMJ.

A Qatari study found that third doses of either the Pfizer/BioNTech or Moderna vaccines nearly halved the incidence of symptomatic Omicron infections, compared with two doses.The incidence of Covid-related hospitalisations and deaths after three doses was very low.

Effectiveness was calculated approximately one month after the second or third dose. The third dose was given on average 8 months after the second. The paper was published in the New England Journal of Medicine.

mRNA vaccines have very low incidence of adverse effects

An analysis of reports to the US Vaccine Adverse Event Reporting System and v-safe during the first six months of mRNA vaccinations found 92% were non-serious. Nearly 300 million vaccine doses were administered, with only 340,522 adverse effects reported. There were 4,496 deaths associated with the vaccine, mostly in those over 60.

The VAERS suffers from underreporting and variable or incomplete reporting, so does not provide a comprehensive picture of reactions to vaccines. The v-safe system requires access to a smartphone, so data from it may not be representative of all who were vaccinated.The paper was published in The Lancet Infectious Diseases.

Masks still an important factor after vaccination

A modelling study concluded that wearing face masks for several weeks after vaccination programmes were completed improved reduction in transmission. The masks were also cost effective, and could save money, for the health system. The model used US data. Different levels of mask effectiveness and levels of compliance were modelled. The paper was published in The Lancet Public Health.

Non-vaccine-related papers

Covid effects on the brain

Brain scans before and after people became infected with SARS-CoV-2 found that infection can cause damage to some brain tissues, especially those associated with the olfactory system. Infected participants, particularly older ones, also showed larger declines in cognitive tests than uninfected participants. Those with mild symptoms took longer to complete some of the tests.

The study included 401 adults who developed Covid-19, mostly aged in their late 50’s or older, and of European ancestry. Whether the effects on the brain lead to permanent or further cognitive decline is unknown. Most had relatively mild to moderate Covid-19 symptoms. However, full clinical details about symptoms were not available.

The research was undertaken in the first half of 2021. The Omicron variant does not appear to affect the sense of smell, but it is not yet known if it may affect the olfactory system in the same way as earlier variants. The paper was published in Nature.

Long Covid can be relatively common

Another study has found that symptoms associated with long Covid can be common. The Danish study found that about 30% of infected people had at least one physical post-acute Covid symptom 6-to-12 months after their infection. Over half (53%) of those infected reported concentration difficulties, sleep issues, or physical exhaustion.

Some symptoms can also occur in uninfected people, with 13% of uninfected people reported at least one symptom.. However, the risk of developing a range of symptoms was higher in those who had Covid-19, compared with those who hadn't.

Those aged 15 or older were included in the study, with over 60,000 people having an infection. Women between 30 & 59 were more likely to report symptoms. Symptoms were self-reported. The paper has not yet been peer reviewed.

Genetic factors associated with increased risk of more severe Covid-19

Analysis of more than 3,000 blood proteins found that five were associated with greater risk of hospitalisation, serious illness or death due to Covid-19. One of the proteins is associated with determining blood type.

Increased or decreased susceptibility based on specific blood type was not investigated in this study, although earlier studies have found an association with type A blood and a greater infection risk. Some of the other proteins help mediate interactions between immune cells and blood vessels.

The study did not assess associations of proteins in tissues or intracellular spaces, so further research is needed to see if they correlate with blood concentrations. While the study is based on samples from nearly 10,000 Covid patients, the people were mostly of European ancestry. The paper was published in PLOS Genetics.

In another study, whole genome sequencing identified 23 independent sets of mutations associated with more severe Covid-19. Five of these genetic markers are associated with interferon signalling, so support the hypothesis that severe Covid can result from poor early control of viral replication.

Other mutations are associated with poorer development of lymphocytes and disruption of molecules associated with inflammatory responses. Screening for these mutations can help identify more appropriate clinical care options. The paper was published in Nature.

Higher viral loads seen in BA.2 subvariant infections

A Qatari study found that the BA.2 subvariant resulted in higher viral loads than BA.1 (Omicron) infections. Lowest viral loads were seen in those vaccinated within four weeks prior to an infection, with loads increasing as time from vaccination increased. Older people also tended to have higher viral loads.

Viral loads were measured using quantitative PCR. The results are based on tests from 156,000 infected people, mostly working-age adults. The paper has not yet been peer reviewed.

BA.2 subvariant has a shorter generation time and higher transmissibility than BA.1

A Japanese study of the BA.1 and BA.2 infections in Denmark calculated that their effective reproductive numbers are 2 and 2.5 times higher, respectively, than the Delta variant. The analyses also indicated that the generation time for BA.2 is about half as long as Delta, with BA.1 about 40% quicker than Delta.

Consequently, the authors suggest that the isolation times for people infected with the BA.1 and BA.2 variants can be reduced proportionately. But that isolation controls need to be stronger. The paper has not yet been peer reviewed.

Arthritis drug can help reduce Covid-19 deaths

The oral drug Baricitinib, originally used to treat rheumatoid arthritis, is also effective at reducing the risk of death in hospitalised Covid-19 patients. The risk reduction was 13% when assessed at 28 days after the treatment commenced. Baricitinib was given for 10 days. Similar results were seen when Baricitinib was given along with several other drugs.

The reduction in risk of death was smaller than reported by previous trials, but they were much smaller trials. The study is part of the UK’s RECOVERY trial, which is testing a variety of Covid-19 treatments. The paper has not yet been peer reviewed. An article in Science discusses the results of this study.

Monitoring viral mutations in immunocompromised people can provide an early warning of new variants

A study of viral mutations in immuno-compromised people with chronic Covid-19 infections found that the mutations generally mirrored those seen in variants of concern.  In particular mutations aiding antibody evasion were more frequent than those that may increase transmissibility. The authors suggest that this may indicate a trade-off between immune evasion and transmissibility.

The authors recommend closely monitoring people with chronic infections to identify potential future mutations of concern. Twenty seven people with chronic infections were involved in the study. The paper has not yet been peer reviewed.

Looking back at the changing epidemiological questions during the pandemic

Another review in Science examines how the key epidemiological issues and questions about the pandemic have changed over the last two years. It notes that we shouldn’t assume viral evolution towards lower virulence.

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