Coronavirus Research Tracking - 31 December
Coronavirus Research Tracking - 31 December
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This week, papers on the reduced incubation period of Omicron, its lower severity, and benefits of three vaccine doses. However, there are indications of third dose effectiveness declining over a few months. Other papers look at the widespread distribution of SARS-CoV-2 throughout the body, cell fusion as a means of spread, and broad spectrum inhibitors that can be inhaled. The Research Tracker is prepared by Dr Robert Hickson for the NZ Science Media Centre.
This week, papers on the reduced incubation period of Omicron, its lower severity, and benefits of three vaccine doses. However, there are indications of third dose effectiveness declining over a few months. Other papers look at the widespread distribution of SARS-CoV-2 throughout the body, cell fusion as a means of spread, and broad spectrum inhibitors that can be inhaled. The Research Tracker is prepared by Dr Robert Hickson for the NZ Science Media Centre.
Publication
What our experts say
Context and background
Resources
Omicron variant papers
Three day incubation period possible for Omicron
The median incubation period for a household Omicron outbreak in the US was 3 days. This compares to four days between infection and symptom development for the Delta variant. The report was published in the Morbidity and Mortality Weekly Report.
Further studies are required to confirm the incubation time for this variant. However, three days was also the incubation time for an Omicron outbreak in Norway.
Indications that Omicron infections are less severe
Preliminary data from Scotland indicates that infection with the Omicron variant is less likely to result in hospitalisation, compared with a Delta infection. The estimated reduction in risk was 75%.
The rate of a reinfection was 10 times higher for Omicron than Delta. A third vaccine dose was associated with a 57% reduction in the risk of a symptomatic infection, relative to the risk at least 25 weeks after a second dose. This reduction was seen for the Pfizer/BioNTech, AstraZeneca/Oxford, and the Moderna vaccines.
The results are based on over 150,000 positive symptomatic cases in Scotland between 1 November and 19 December. Results may change as additional data is collected. Full genome sequence data was not used to precisely identify variants, but most cases were assumed to involve Delta and Omicron variants. The paper has not yet been peer reviewed.
The proportion of Covid-19 patients hospitalised in South Africa’s Omicron wave was also lower than for earlier infection waves. About 5% were hospitalised in the most recent, Omicron dominant, period, compared with 19% and 14% for the third and second waves earlier in the year. Severe Covid-19 cases were also less common in the most recent wave. The paper has not yet been peer reviewed.
T cell responses from prior infections and vaccinations still effectively recognise the Omicron variant, a South African study reports. The paper has not yet been peer reviewed.
Omicron shows reduced pathogenicity in hamsters
Unlike other variants, the Omicron variant does not replicate well in Syrian hamsters. Viral loads of Omicron in their lungs in this study were low and there was little tissue damage, indicating poor replication.
The authors speculate that the variant may be better adapted to binding to the human ACE2 receptor now than to the hamster receptor, but this hasn’t yet been tested. Alternatively, the Omicron variant may be better adapted to infection of the upper respiratory tract than the lungs. This too needs further research. The paper has not yet been peer reviewed.
Another study also found less severe disease in hamsters from Omicron, and also in mice with the human ACE2 receptor. The paper has not yet been peer reviewed.
Three vaccine doses provide much stronger neutralisation against Omicron
Consistent with previous studies, two doses of the Pfizer/BioNTech vaccine do little to neutralise the Omicron variant, but three doses significantly improved neutralisation, by about 100-fold. After two doses only 30-37% of serum samples showed neutralisation activity against Omicron. The study involved sera collected at several time points from 30 vaccinated people. The paper has been accepted by Nature Medicine.
Similar results are published in Cell. People who had a third mRNA vaccine dose had a level of neutralising activity against Omicron only 4-6-fold lower than that seen for the early Wuhan strain.
Sera from those who had a prior infection followed by one or two vaccine doses had higher levels of neutralising activity against wild type, Delta and Omicron variants than samples from people with two vaccine doses without an infection. However, three vaccine doses provided the strongest levels of neutralising activity.
The mRNA vaccines stimulated greater humoral immune responses than the Johnson & Johnson/Janssen vaccine.
The authors suggest that the improved effectiveness of a third dose may be due to it amplifying existing antibodies that bind to more conserved regions of the spike protein, improving the binding affinity of antibodies, or a combination of both of these.
Two doses of the Pfizer/BioNTech vaccine provided around 70% effectiveness against hospitalisation in the Gauteng province of South Africa during the period Omicron was spreading. Prior to that vaccine effectiveness was 93% in the province. The paper was published in the New England Journal of Medicine.
Early indication of waning effectiveness of third vaccine dose
An analysis by the UKHSA (not peer reviewed) reports a 15-25% decline in effectiveness against infection 10 weeks after a third vaccine dose. Waning effectiveness against Omicron was greater for the Pfizer vaccine than Moderna, when assessed at 9-10 weeks. For Pfizer, effectiveness declined from 70% to 45%, whereas effectiveness of the Moderna vaccine remained around 70%. The AstraZeneca/Oxford vaccine was less effective against Omicron even when an mRNA vaccine was used as the third dose.
But neutralisation activity may improve over time
A South African study reports that neutralisation ability of the Omicron variant improved in infected people about 14-fold in the two weeks after initial testing. In addition, those who were infected by Omicron had a 4.4-fold increase in the ability to neutralise the Delta variant, which may prevent (re-)infection.
The authors suggest that this cross-neutralisation ability may be associated with either Omicron-elicited antibodies being able to neutralise Delta too, or the Omicron infection activating a broader variety of antibodies generated by a previous infection or vaccination. This requires further research. The study is based on only 15 participants. The paper has not yet been peer reviewed.
Similar cross-reactivity results are reported from Hong Kong. The paper has not yet been peer reviewed.
Vaccine-related papers
Three CoronaVac doses can lead to better neutralisation of a range of variants
Three doses of the CoronaVac vaccine can generate potent antibodies that are able to neutralise all current variants of concern. After a third dose 24 of 163 monoclonal antibodies were able to neutralise all current variants of concern. These potent antibodies were found in four of 60 people. The third dose was given six months after the second. The paper has not yet been peer reviewed.
Non-vaccine-related papers
An inhibitor shows promise against all variants of concern
An intranasal inhibitor appears to be effective at blocking all variants of concern, preventing infection. The inhibitor mimics a small antibody and targets a conserved region of the spike protein. When tested on small numbers of mice there was no evidence that the SARS-CoV-2 virus spread to the lungs. The paper has not yet been peer reviewed.
SARS-CoV-2 can be widely distributed in the body
Autopsies on 44 people with Covid-19 indicate that the SARS-CoV-2 virus can be widely distributed in the body, even in mild or asymptomatic cases. However, inflammation and tissue damage was largely restricted to the lungs. The virus may persist for more than two weeks in tissues and organs in some people. The paper has not yet been peer reviewed.
Cell-to-cell fusion is an important means of spread for SARS-CoV-2 within the body
Cell-to-cell fusion helps the SARS-CoV-2 virus spread within an infected person. This is also known to occur in some other viruses. This means of spread allows the virus to avoid neutralising antibodies.
The SARS-CoV-2 virus is more effective at spreading by cell fusion than the SARS-CoV virus, and this is partly attributed to differences in their spike proteins. However, very high levels of cell-to-cell fusion lead to cell death so reducing spread by this means. The ACE2 receptor can help cell fusion, but it is not essential. The paper was published in the Proceedings of the National Academy of Sciences.
However, the Omicron variant appears to have a reduced ability for cell-cell fusion, which may be a trade-off from a better cell infection ability. (See the 23 December Tracker).
Improving testing strategies
A review published in The Lancet looks at the advantages and disadvantages of three main types of Covid diagnostic tests - PCR tests, rapid antigen tests, and antibody tests. It identifies three areas of improvement in national and global testing strategies as the uses of these tests change during the pandemic, and beyond.
Omicron variant papers
Three day incubation period possible for Omicron
The median incubation period for a household Omicron outbreak in the US was 3 days. This compares to four days between infection and symptom development for the Delta variant. The report was published in the Morbidity and Mortality Weekly Report.
Further studies are required to confirm the incubation time for this variant. However, three days was also the incubation time for an Omicron outbreak in Norway.
Indications that Omicron infections are less severe
Preliminary data from Scotland indicates that infection with the Omicron variant is less likely to result in hospitalisation, compared with a Delta infection. The estimated reduction in risk was 75%.
The rate of a reinfection was 10 times higher for Omicron than Delta. A third vaccine dose was associated with a 57% reduction in the risk of a symptomatic infection, relative to the risk at least 25 weeks after a second dose. This reduction was seen for the Pfizer/BioNTech, AstraZeneca/Oxford, and the Moderna vaccines.
The results are based on over 150,000 positive symptomatic cases in Scotland between 1 November and 19 December. Results may change as additional data is collected. Full genome sequence data was not used to precisely identify variants, but most cases were assumed to involve Delta and Omicron variants. The paper has not yet been peer reviewed.
The proportion of Covid-19 patients hospitalised in South Africa’s Omicron wave was also lower than for earlier infection waves. About 5% were hospitalised in the most recent, Omicron dominant, period, compared with 19% and 14% for the third and second waves earlier in the year. Severe Covid-19 cases were also less common in the most recent wave. The paper has not yet been peer reviewed.
T cell responses from prior infections and vaccinations still effectively recognise the Omicron variant, a South African study reports. The paper has not yet been peer reviewed.
Omicron shows reduced pathogenicity in hamsters
Unlike other variants, the Omicron variant does not replicate well in Syrian hamsters. Viral loads of Omicron in their lungs in this study were low and there was little tissue damage, indicating poor replication.
The authors speculate that the variant may be better adapted to binding to the human ACE2 receptor now than to the hamster receptor, but this hasn’t yet been tested. Alternatively, the Omicron variant may be better adapted to infection of the upper respiratory tract than the lungs. This too needs further research. The paper has not yet been peer reviewed.
Another study also found less severe disease in hamsters from Omicron, and also in mice with the human ACE2 receptor. The paper has not yet been peer reviewed.
Three vaccine doses provide much stronger neutralisation against Omicron
Consistent with previous studies, two doses of the Pfizer/BioNTech vaccine do little to neutralise the Omicron variant, but three doses significantly improved neutralisation, by about 100-fold. After two doses only 30-37% of serum samples showed neutralisation activity against Omicron. The study involved sera collected at several time points from 30 vaccinated people. The paper has been accepted by Nature Medicine.
Similar results are published in Cell. People who had a third mRNA vaccine dose had a level of neutralising activity against Omicron only 4-6-fold lower than that seen for the early Wuhan strain.
Sera from those who had a prior infection followed by one or two vaccine doses had higher levels of neutralising activity against wild type, Delta and Omicron variants than samples from people with two vaccine doses without an infection. However, three vaccine doses provided the strongest levels of neutralising activity.
The mRNA vaccines stimulated greater humoral immune responses than the Johnson & Johnson/Janssen vaccine.
The authors suggest that the improved effectiveness of a third dose may be due to it amplifying existing antibodies that bind to more conserved regions of the spike protein, improving the binding affinity of antibodies, or a combination of both of these.
Two doses of the Pfizer/BioNTech vaccine provided around 70% effectiveness against hospitalisation in the Gauteng province of South Africa during the period Omicron was spreading. Prior to that vaccine effectiveness was 93% in the province. The paper was published in the New England Journal of Medicine.
Early indication of waning effectiveness of third vaccine dose
An analysis by the UKHSA (not peer reviewed) reports a 15-25% decline in effectiveness against infection 10 weeks after a third vaccine dose. Waning effectiveness against Omicron was greater for the Pfizer vaccine than Moderna, when assessed at 9-10 weeks. For Pfizer, effectiveness declined from 70% to 45%, whereas effectiveness of the Moderna vaccine remained around 70%. The AstraZeneca/Oxford vaccine was less effective against Omicron even when an mRNA vaccine was used as the third dose.
But neutralisation activity may improve over time
A South African study reports that neutralisation ability of the Omicron variant improved in infected people about 14-fold in the two weeks after initial testing. In addition, those who were infected by Omicron had a 4.4-fold increase in the ability to neutralise the Delta variant, which may prevent (re-)infection.
The authors suggest that this cross-neutralisation ability may be associated with either Omicron-elicited antibodies being able to neutralise Delta too, or the Omicron infection activating a broader variety of antibodies generated by a previous infection or vaccination. This requires further research. The study is based on only 15 participants. The paper has not yet been peer reviewed.
Similar cross-reactivity results are reported from Hong Kong. The paper has not yet been peer reviewed.
Vaccine-related papers
Three CoronaVac doses can lead to better neutralisation of a range of variants
Three doses of the CoronaVac vaccine can generate potent antibodies that are able to neutralise all current variants of concern. After a third dose 24 of 163 monoclonal antibodies were able to neutralise all current variants of concern. These potent antibodies were found in four of 60 people. The third dose was given six months after the second. The paper has not yet been peer reviewed.
Non-vaccine-related papers
An inhibitor shows promise against all variants of concern
An intranasal inhibitor appears to be effective at blocking all variants of concern, preventing infection. The inhibitor mimics a small antibody and targets a conserved region of the spike protein. When tested on small numbers of mice there was no evidence that the SARS-CoV-2 virus spread to the lungs. The paper has not yet been peer reviewed.
SARS-CoV-2 can be widely distributed in the body
Autopsies on 44 people with Covid-19 indicate that the SARS-CoV-2 virus can be widely distributed in the body, even in mild or asymptomatic cases. However, inflammation and tissue damage was largely restricted to the lungs. The virus may persist for more than two weeks in tissues and organs in some people. The paper has not yet been peer reviewed.
Cell-to-cell fusion is an important means of spread for SARS-CoV-2 within the body
Cell-to-cell fusion helps the SARS-CoV-2 virus spread within an infected person. This is also known to occur in some other viruses. This means of spread allows the virus to avoid neutralising antibodies.
The SARS-CoV-2 virus is more effective at spreading by cell fusion than the SARS-CoV virus, and this is partly attributed to differences in their spike proteins. However, very high levels of cell-to-cell fusion lead to cell death so reducing spread by this means. The ACE2 receptor can help cell fusion, but it is not essential. The paper was published in the Proceedings of the National Academy of Sciences.
However, the Omicron variant appears to have a reduced ability for cell-cell fusion, which may be a trade-off from a better cell infection ability. (See the 23 December Tracker).
Improving testing strategies
A review published in The Lancet looks at the advantages and disadvantages of three main types of Covid diagnostic tests - PCR tests, rapid antigen tests, and antibody tests. It identifies three areas of improvement in national and global testing strategies as the uses of these tests change during the pandemic, and beyond.
