Coronavirus Research Tracking - 27 November
Iceland, surfaces, transmission patterns, host genes, immunity, treatments, genomes
This week’s Research Tracker covers a broad range of topics from Iceland’s approach to the pandemic through to the fluid dynamics of sneezes.
The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.
Iceland’s approach
A news feature in Nature describes Iceland’s (population 364,000) approach to pandemic control. It notes that it did not close its border, instead focussing on isolation, quarantining and contact tracing. Tele-health and the company deCODE genetics are crucial parts of their response. Fifty five percent of the population have been tested so far. New Zealand researchers are also interviewed as part of the article.
SARS-CoV-2 on food
A review article published in Frontiers in Nutrition examined studies of SARS-CoV-2 survival in food, on food contact materials, and on food packaging. There is no evidence that SARS-CoV-2 is a food safety risk, meaning that infection does not occur by eating food contaminated with the virus.
Refrigeration of food does not appear to inactivate the virus. It is believed that viability will not be significantly reduced by freezing, though there is less evidence to support this. However, cases of infection from surface contact are very rare compared with person to person contact.
SARS-CoV-2 on surfaces
A short report in The Lancet Infectious Diseases looked at six studies that tested surfaces for SARS-CoV-2. Five studies did not detect infectious viral particles, while the sixth found less than 10% of samples infectious (and usually associated with an infected person with a persistent cough). In these studies infectiousness is often inferred based on the number of PCR cycles needed for detection. In one study of 5500 surfaces only 44 (0·8%) had detectable virus.
Infectiousness lasts only 9 days
A review in The Lancet Microbe examined studies of the dynamics of SARS-CoV-2, SARS-CoV and MERS infections. The three viruses have slightly different post-infection dynamics. SARS-CoV-2 RNA can be shed or found at high levels in people for more than 80 days, but the virus is infectious only up to nine days after symptoms develop. Viral loads in asymptomatic and symptomatic cases are similar, although asymptomatic carriers usually clear the virus more quickly. There is insufficient evidence to conclude whether there are differences in infectiousness between asymptomatic and symptomatic people.
80% of infections from less than 20% of cases
A study published in Science traced and tested 1,178 SARS-CoV-2 infected individuals and their 15,648 close contacts in Hunan, China, between January and April. It found that 80% of secondary infections traced back to just 15% of the primary infections. This is strongly related to the number of contacts a person has. Children 12 years were significantly less susceptible to infection. The paper has a good visual representation of transmission clusters.
Chains of transmission are also described during the early stages of the pandemic in France (not yet peer reviewed). 6,082 contacts of 735 confirmed cases were traced. Transmission between family members was the most common path. Eighty percent of secondary cases were linked to 10% of the primary cases.
Transmission dynamics are sometimes different in India
A report in Science describes transmission in the Indian states of Tamil Nadu and Andhra Pradesh. Compared to observations in more affluent countries, and taking account for demographic differences, reported cases were concentrated in younger age groups. Greater transmission risks were found among children and young adults, who accounted for one-third of cases. However, most deaths occurred in those aged between 50 and 64, with men being more likely to die.
A similarity with affluent countries is that 80% of secondary cases were linked to 5% of the primary cases.
Antibodies associated with protection against reinfection
A UK study (not yet peer reviewed) followed 12,000 health care workers for six months. Twelve hundred had spike protein antibodies at the start. Only three of those with antibodies became re-infected during the study, and they were asymptomatic. This provides evidence that antibodies provide protection from re-infection for several months.
Immune memory persists after mild COVID-19
This study, published in Cell, followed antibody and T cell responses over three months in the blood of 15 people with mild Covid-19 symptoms. All of them produced SARS-CoV-2-specific IgG antibodies, neutralizing plasma, memory B and memory T cells that persisted during the study. IgG memory B cells increased over time. The results are indicative, but not definitive, that immunity develops after milder infections.
Another, not yet peer-reviewed, paper reports persistence of SARS-CoV-2-specific memory B cells for at least 8 months.
Convalescent plasma ineffective for severe Covid-19
A randomized trial of convalescent plasma to treat people with severe pneumonia is reported in the New England Journal of Medicine. Two hundred and twenty eight patients received the plasma, and there were no significant differences in mortality compared to those receiving the placebo.
The paper also notes other research that demonstrated convalescent plasma was an ineffective treatment for moderate Covid-19 as well.
The New England Journal of Medicine also has a paper that reports hydroxychloroquine failed to prevent infections.
Miniprotein inhibitors
Research published in Science describes designing small proteins (56 to 64 amino acids) that bind very strongly to the spike protein receptor binding site. These are much easier and cheaper to produce than antibodies, and are stable at room temperature.
The New York Times reports research on similar molecules underway in other labs, including animal trials. Research in this field is starting to use artificial intelligence to inform small molecule design. Other “nanodecoys” were reported in the 23 October issue of the Tracker.
Research on human genes is biased
A paper published in eLife points out that while genome-wide studies identify a range of genes associated with SARS-CoV-2 infection or disease, most published papers focus on a small set of previously well studied genes. This is similar to other research biases on human genes. As a consequence, some genes of biological significance for Covid-19 may be poorly studied.
Identifying human genes that interact with the virus
As a counterpoint, research published in Cell systematically disabled genes in cultured human cells to identify which ones interacted with SARS-CoV-2. Thirty genes were found to be involved in assisting viral infection. These were usually associated with a group of proteins that have a role in transporting other proteins across cell membranes. Increased cholesterol production was often when these genes were disabled.
The study also tested 26 small molecule inhibitors that have the potential to target these genes. Seven increased resistance to the virus by more than 100 fold in cell tests. Three of these drugs are already on the market for treating other conditions.
Duelling analyses
A paper in Nature Communications analysed 46,000 SARS-CoV-2 genomes to see if any of the repeated mutations found in different genomes are associated with increased infectiousness. They did not find evidence that any were, including the 614G lineage.
However, a paper in Cell that analysed 25,000 genes from the UK reports that there is evidence for selection of the 614G lineage, although they note “the signal is difficult to detect”. The New York Times discusses some earlier evidence and the Cell paper, and comes down on the selective advantage side.
The conflicting conclusions possibly arise because any selective advantage is slight, and different methods and data sets are used in different papers. Chance and circumstance still have important roles in transmission.
Still searching for the ancestral virus
A news item in Nature reports that a research group may have found a coronavirus in a Cambodian horseshoe bat closely related to SARS-CoV-2. The bat was collected in 2010. Only about 70% of the virus’s genome has been sequenced, so it is still unclear how closely related it is to SARS-CoV-2. The results have not yet been submitted for publication.
To be a likely direct ancestor the sequences will need to be 99% identical. The closest ancestor to SARS-CoV-2 identified so far is the virus RaTG13, which has 96% sequence similarity (representing 40-70 years divergence).
Another coronavirus found in a Japanese horseshoe bat has 81% sequence similarity to SARS-CoV-2, so it is much more distantly related.
Extreme geek zone
A paper in One Earth reviews the factors that affect the filtration performance of masks that filter out particulate matter below 2.5 μm (such as viruses). It also describes how such masks are made and identifies research areas that can further improve performance and reduce costs.
A paper in Physics of Fluids describes the fluid dynamics and physiology that determine the size of droplets produced by a sneeze. Bless you.