13th November - the COVID-19 coronavirus compendium

Superspreader locations, pre-existing antibodies, and prevalence in Kenya
Published in Microbiology
13th November - the COVID-19 coronavirus compendium
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This is a summary of the last three weeks’ research highlights on SARS-CoV-2 and COVID-19. The main news of the past week is not covered here, as it has not yet been published or peer-reviewed – that is the news that the BioNTech mRNA vaccine made in collaboration with Pfizer is 90% effective. We are all keen to see this data for ourselves, but it certainly sounds promising.

In the past few weeks we learnt that a small number of locations are responsible for the majority of cases - so-called superspreading events; that some young adults have pre-existing antibodies to COVID-19, from common cold coronaviruses; and that the prevalence of COVID-19 in Kenya is much higher than expected.

Transmission

A mobility map of 10 US metropolitan districts, based on mobile phone data, was used to model the outbreak, and predicted that a small number of superspreader locations were responsible for the majority of infections. The model predicted that places visited by low income families and some ethnic groups were more crowded, making social distancing more difficult. Another study found that residents of low income neighbourhoods in the US spent more time outside the home, particularly for work, and that stay at home orders did not reduce this.

A detailed study of every COVID-19 case in Singapore found that household contacts were most likely to be infected by an index case, with work contacts and social contacts less likely to be infected. Sharing a bedroom and being spoken to for more than 30 minutes increased the risk, whereas indirect contact and sharing a bathroom did not increase the risk. Symptom-based PCR testing missed 62% of cases, partly because more than 1/3 were without symptoms.

A study of lockdown in France found that it was highly effective at reducing movement, again based on mobile phone data. US counties that voted for Donald Trump and watch conservative media such as Fox News were less likely to physically distance, as measured by 15 million smartphones.

Modelling the outbreak in Australia found that closing schools did not bring decisive benefits, unless coupled with a high level of social distancing. Another study tracked the outbreak in two communities in Wisconsin. Travellers from the US were responsible for most infections in Israel. Cases in Beijing before May 2020 were due to Wuhan exposure, local transmission, or overseas imports, according to a genomic analysis. A website that allows prediction of risk from certain indoor events was developed.

Farmed mink have become infected with SARS-CoV-2 and then transmitted the virus back to humans, with 68% of mink farm residents, employees and contacts testing positive.

Treatments

A monoclonal antibody therapy, LY-CoV555, was tested in a phase 2 clinical trial, and accelerated the decline of viral load. Baricitinib supressed the pro-inflammatory response to COVID-19 in rhesus macaques. A soluble ACE-2 decoy receptor was generated that bound to the coronavirus spike protein and protected Syrian hamsters from a lethal challenge.

At-risk groups

The infection-fatality rate in different age groups across 45 countries was estimated and found to be consistent for younger age groups, with differences between countries for the over 65s. Overall infection-fatality rates were generally between 0.24% and 1.49%, depending on the country, but ranged from 0.001% in those aged 5-9, to around 0.01% in those between 20-45, and 0.1% in those aged 45-60. The fatality rate in those over 65 varied by country, but was between 1% and 20%.

US Marine Corps are now tested for COVID-19 upon arrival, but 2% of those who tested negative had a positive test 14 days later, almost all of whom were asymptomatic. More than one quarter of the USS Theodore Roosevelt, an aircraft carrier, tested positive for COVID-19 during an outbreak, 45% of whom had no symptoms, and one of whom died.

Healthcare workers in the UK, and their households, comprised a sixth of COVID-19 cases admitted to hospital, with a 2 to 3–fold increased risk of admission. Construction workers in Texas were 5-fold more likely to be hospitalised with COVID-19 than other occupations. Older adults in Sweden who lived with working age adults were more likely to have a fatal COVID-19 infection, as were those living in care homes. Higher viral load was associated with a worse outcome in a study of hospitalised patients in the US. The severity of the initial COVID-19 outbreak in Wuhan was similar to the 1918 influenza pandemic.

Immunology

Pre-existing humoral immunity against both SARS-CoV and SARS-CoV-2 was detected, especially in children and young adults, presumably from past infection with common cold seasonal coronaviruses. It is not known what protection from infection this may provide, if any.

Antibody responses were triggered in 95% of COVID-19 patients in a small UK study, but most saw these responses decrease over time. However, a larger study of 30,000 people in New York City found that titres remained stable for 5 months. A third study observed considerable heterogeneity in antibody responses, with some short lived, and others long lived.

A case study of families found that children can mount an immune response to the virus without any evidence of infection. Another study characterised the immune response in children versus adults.

The T cell response to infection was characterised, and found that people who do not produce antibodies often do produce CD8+ T cells that target the virus. Another study found that severe COVID-19 patients produce a unique serological signature, with increased likelihood of IgG1 with afucosylated Fc glycans.

Model systems

K18-hACE2 mice developed for SARS can be infected with SARS-CoV-2 and develop anosmia, amongst other symptoms. Convalescent plasma protected the mice from severe disease.

Lung and colonic organoids were developed and infected with SARS-CoV-2, allowing new drugs to be tested in this model system. Imatinib, mycophenolic acid, and quinacrine dihydochloride all had anti-viral activity, although they would need to be tested in clinical trials before any effects were proven.

Genomics

Two studies found that the D614G mutation in the coronavirus spike protein enhanced viral replication in tissue culture and in mice and hamsters, with the virus transmitting faster, although these animals also developed stronger antibody responses.

Diagnostics

20% of New York City tested positive for past infection with SARS-CoV-2, according to serology testing of more than 10,000 people. Antibodies remained stable from May to July, suggesting lasting immune responses. The earliest positive tests were taken in February, earlier than previously thought.

4.3% of Kenyans were estimated to have been infected with SARS-CoV-2, based on a screen of blood donors, much higher than expected based on case-based surveillance. Prevalence was higher in cities, reaching up to 8%.

A serosurvey of blood donors in the Netherlands found that 2.7% were positive for a past infection with SARS-CoV-2. Blood is not infectious, but this gives an indication of the spread of the virus there, and shows that the majority of people are still susceptible to infection.

Personal data from wearable sensors improved diagnosis of COVID-19, when combined with symptom information, according to a study of 30,000 participants. A point-of-care test, AbC-19, had a high rate of false positives when used in healthcare settings.

Clinical findings

66 babies have been infected with COVID-19 in the UK, one of whom died, but of a cause unrelated to SARS-CoV-2 infection. A high proportion were from Black, Asian, or ethnic minority backgrounds.

COVID-19 survivors are at an increased risk of psychiatric symptoms, and those with pre-existing psychiatric conditions may be at greater risk of COVID-19, according to a study of almost 70 million patients across the world, as well as a separate study using UK Biobank.

A single case of an immunocompromised cancer patient with COVID-19 found that the patient continued to shed live virus for up to 70 days after diagnosis, with continuous viral replication during this time. Convalescent plasma was not effective, although the patient eventually cleared the virus.

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