Coronavirus Research Tracking - 1 March
Viral evolution, years of life lost, societal culture & outcomes, "underdog" therapies, transmission and quarantine risks, prior infections and vaccination responses
This Research Tracker covers evolution of the virus, transmission and quarantine risks, years of life lost, persistent symptoms, cultural influences on outcomes, disproving “underdog” therapy stories, and how previous infections influence the immune response to the Pfizer/BioNTech vaccine. There will also be a regular Friday Tracker.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
FDA says there is no evidence for food-borne transmission
The FDA announced that there is no evidence of Covid-19 transmission from food or food packaging. They note that it is a respiratory illness not a foodborne illness like norovirus. Most studies of viral presence on food do not test for viability or transmissibility.
One year of SARS-CoV-2 evolution
A paper published in Cell Host & Microbe summarises the changes and mutations that have been observed in the SARS-CoV-2 genome over the last year. 130 mutations have been identified, of which 75 change amino acids. Ten important mutations in the spike protein’s receptor-binding domain have been identified. The authors predict that more infectious and pathogenic variants are likely to emerge over the next year.
The Economist provides a readable account of mutations that have independently appeared in different variants. The article includes a very good illustration of the evolution of some of the recent variants of concern.
Dominance of the D614G mutation linked to increased infectivity
An experimental study, published in Nature, demonstrates that the increasing frequency of viral genomes with the 614G mutation is due to greater transmissibility, rather than chance due to founder effects.
Two viral variants that differ only at the 614 site were created. The 614G variant bound more strongly to the human ACE2 receptor than 614D. The 614G variant also outcompeted the other variant when both were introduced into small numbers of syrian hamsters and ferrets. These competition experiments agree with experiments reported last year using naturally occurring variants that had the 614D and 614G mutations.
Emergence of variants within a person may correlate with increasing antibody levels
In the 12th Feb Tracker we included a study of how the virus evolved in an immunocompromised patient given convalescent plasma. A more recent paper, not yet peer reviewed, examined the changing variant population in an individual as their own immune system responded.
Four variants in the N-terminal domain of the spike protein emerged and became common about 2 weeks after infection. These had mutations at sites targeted by a potent neutralising antibody. The increasing dominance of these variants’ correlated with increased levels of N-terminal domain-specific antibodies, suggesting selective pressure.
These variants subsequently disappeared or declined, probably due to other antibodies neutralising the variants.
Years of life lost to COVID-19
An analysis, published in Scientific Reports, estimated the years of life lost due to Covid-19 in 81 countries so far. In countries where there are large outbreaks, years of life lost are between two and nine times higher than seen for seasonal flu, and 1/4 to 1/2 of years lost due to heart diseases.
There is considerable variability between countries in years of life lost due to Covid-19. Globally they calculated that 20.5 million years of life had been lost due to Covid-19.
Three quarters of the years of life lost are borne by people under 75 dying. In higher income countries the greatest proportion of years of life lost has occurred in the oldest age groups, but in low and middle income countries younger age groups account for the larger proportion of years of lives lost.
Persistent symptoms
Research published in JAMA Network Open found that 30% of 172 people still reported Covid-19 symptoms up to 9 months after being infected. Fatigue and loss of the sense of smell or taste were the most common persistent symptoms. The study relied on self-reporting of symptoms.
How culture may affect outcomes
Research published in The Lancet Planetary Health reports that nations with “tight cultures” had proportionally fewer infections and deaths than those characterised as having a “looser” culture (at least in the first 10 months of 2020).
Tight cultures were defined as those having strict norms and “punishments for deviance”, while looser cultures are more permissive. The analyses indicated that “looser” cultures had about five times more cases and eight times more deaths than “tighter” cultures.
However, variability increased as cultural tightness increased, and the looseness vs tightness classification is a spectrum rather than well defined either/or categories.
Fifty seven countries were included, New Zealand was not one of them.
Superspreading
A news article in Nature summarises what is known about superspreading, and how that helps reduce transmission. Research indicates that differences in viral loads between people is less important than behaviours (such as sociability, physical distancing, mask wearing, singing, shouting and exercise) and venues (crowded indoor events with poor ventilation). The most risky period of transmission is in the pre-symptomatic and early symptomatic stages.
Reducing quarantine risks
A paper (not yet peer-reviewed) compares the risks of community outbreaks linked to hotel quarantine facilities in New Zealand and Australia. It identified seven outbreaks or border control failures in Australia and nine in New Zealand up until the end of January.
The authors calculated that there were 15.5 failures per 1000 SARS-CoV-2 positive cases transiting quarantine in NZ, compared to 2.0 per 1000 SARS-CoV-2 positive cases in Australia. These estimates are subject to chance variations due to the small number of events, while on the other hand not all breaches of quarantine may have been detected. Seventeen policy and operational options are suggested that could further reduce the risks of failures.
Zinc, Vitamin C and Vitamin D are ineffective treatments
A randomized clinical trial, published in JAMA Network Open, found that zinc and vitamin C supplements did not help recovery of people with mild cases of Covid-19. of 214 patients with confirmed SARS-CoV-2 infection receiving outpatient care, there was no significant difference in the duration of symptoms among the 4 groups.
A separate study (not yet peer-reviewed) examined the efficacy of vitamin D. It did not find that vitamin D supplementation reduced the severity of Covid-19 symptoms.
An article on Medscape referencing the zinc and vitamin C study discusses why such potential remedies can be attractive. They have biological plausibility, but also an “underdog story” - long familiar simple agents that could bring down a dangerous virus. The article advocates the approach of “Keep hope, but bring data” .
Comparing vaccines
A useful table comparing nine Covid-19 vaccines accompanies an article in JAMA Insights. Efficacy data for some of the vaccines is included. The article only describes similarities and differences rather than picks the “best” vaccines.
A news article in Nature discusses why the vaccines are difficult to compare. Currently there is insufficient data to make useful comparisons as to which vaccines may be most suitable for different groups or situations. More informed decisions may be possible in the next month or so.
T-cell responses to the Pfizer/BioNTech vaccine
Most research so far on immune responses to vaccinations has focused on the humoral (antibody) aspect. A short study published in The Lancet reports that T-cell responses in 21 people who had previously been infected with SARS-CoV-2 infections generated strong T-cell (and antibody) responses after one dose of the Pfizer/BioNTech vaccine.
In contrast, most individuals who were not previously infected produced weak T-cell responses and low titres of neutralising antibodies after receiving the first vaccine dose. This indicates that this vaccine (and probably others) could help boost several parts of the immune response generated by earlier infections, and that both doses of the Pfizer vaccine are desirable if people haven’t previously been infected.
Antibody responses to first and second doses of Pfizer/BioNTech
Another paper in The Lancet reports that the first dose of the Pfizer vaccine may generate significantly higher levels of anti-spike protein antibodies in people who were previously infected compared to vaccination of uninfected people.
However, a different result is reported in a paper not yet peer reviewed. Those with no prior infection exhibited strong immune response increases after both vaccine shots (when tested one week after the second shot). Participants with a previous infection showed strong antibody and antigen-specific antibody-secreting cell responses after receiving the first vaccine dose, but relatively little change was seen after the second dose.
The differences between the studies may be due to the small number of participants in each, or other factors. It highlights the current limits in knowledge about the immune impacts of prior infections on vaccinations.
Evidence of reduction in infections following vaccination with Pfizer/BioTech vaccine
A four-fold reduction in asymptomatic infections was found in a study of healthcare workers when they were tested at 12-14 days after being given the first dose of the Pfizer vaccine. The research, not yet peer reviewed, also reports reductions in symptomatic cases, and more substantial reductions six weeks after vaccination.