11th September - the COVID-19 coronavirus compendium

The early outbreak in the US and Europe, the Russian vaccine, and severe COVID-19 in young adults

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This week we learnt that initial introductions of the virus into Washington State and Bavaria were effectively controlled, that the already-licensed Russian vaccine induced immune responses in a small trial, and that young adults with pre-existing health conditions such as obesity have similar mortality rates as older adults without these conditions.

Transmission

The slow mutation rate of coronaviruses, combined with the risk of small sequencing errors, make tracking the current outbreak through genetics much more challenging than for other RNA viruses, such as influenza. A new study therefore combines sequencing data with mathematical modelling to infer how the early outbreak arrived in Europe and the US. Using this approach the researchers find that initial outbreaks in Washington State and Bavaria were effectively controlled, and that later outbreaks in Italy and New York State caused widespread transmission. This suggests that the global pandemic could have been averted through better surveillance, testing, and quarantine.

A separate study of the outbreak in Washington State found that the virus was circulating there undetected for a month before active community surveillance. Whether there was a single introduction into WA (as this study asserts), or multiple introductions (as the above article finds), is a subject of some disagreement.

A mathematical model estimated that more than 6 million in the US have been infected with SARS-CoV-2, representing 1.9% of the population, and much higher than official estimates of around 700,000. The predicted differences were mainly due to incomplete testing.

Stay at home orders in the US reduced mobility, which led to reduced transmission of the virus, according to a study using mobility data from more than 45 million mobile phones.

Vaccines

A phase 1/2 trial of a Russian vaccine, which has already been licensed for use, was published. 76 participants received either a single recombinant adenovirus vector expressing the spike protein, based on Ad5 or Ad26, or both vectors in a prime-boost. All participants produced a robust humoral and cellular immune response. The trial was too small to test for uncommon side effects, and there was no measurement of efficacy, both of which would normally be needed before widespread use in the population.

Treatments

Two existing drugs, one for hepatitis C virus, and another for feline infectious peritonitis virus (a cat coronavirus) both inhibited the SARS-CoV-2 protease in cell culture, with added efficacy when used in combination with remdesivir.

A panel of single domain humanised antibodies against the spike protein of SARS-CoV-2 were generated, which block interaction with the ACE-2 receptor. An alpaca-derived single domain antibody fragment, known as a nanobody, was generated that binds and neutralised the spike protein. Another study generated a human antibody VH domain and found that it neutralised the virus in animal models.

Protein inhibitors, termed minibinders, that blocked the interaction between the coronavirus spike protein and ACE-2 were rationally designed, and may provide a starting point for new therapeutics.

One may wonder how many studies are needed to prove that hydroxychloroquine with azithromycin does not improve the quality of care for patients with COVID-19, but more data on this was published from a multi-centre Brazilian study. In this study, the treatment arm was azithromycin, as hydroxychloroquine is still part of the standard treatment package, despite its lack of efficacy.

Testing

An automated testing platform for SARS-CoV-2 was created using a combination of RT-qPCR, CRISPR-Cas13a, and RT-LAMP. This Biofoundry approach allowed an increase in testing of 1000 samples per day for a local NHS hospital, and could be scaled up further.

Risk factors

The first major study of COVID-19 in young adults (18-34 years) was carried out in the US, and found that the majority were Black or Hispanic, and had underlying conditions such as obesity, diabetes, and hypertension.  2.7% of these hospitalised young adults died, much lower than for older age groups, but higher than for other serious conditions, such as acute myocardial infarction. Young adults with morbid obesity, diabetes, or hypertension had a similar risk of death from COVID-19 as older adults without these pre-existing conditions.

A mortality risk prediction model was developed using existing risk factors for severe respiratory infection or sepsis, and then calibrated to known risk factors for COVID-19. The model is now being used in hospitals to assess incoming patients.

Healthcare

Only 2 hospital-acquired cases of COVID-19 were detected in a large US hospital with almost 700 COVID-19 patients, showing the effectiveness of infection control measures.

Immunology

The immunology of Multisystem Inflammatory Syndrome in Children (MIS-C) differs from the immune response in adult COVID-19, and is also different to Kawasaki disease, with which it has superficial similarities.

The ORF3b protein of SARS-CoV-2 is an interferon antagonist, and is more potent that the equivalent from SARS-CoV. A mutation in ORF3b was identified in some severe cases.

COVID-19 patients with severe disease had a stronger overall T cell response than those with mild disease, although in mild cases the CD8 T cell response was higher. Many T cell epitopes are in proteins other than the spike, suggesting that vaccines should include other antigens. Another study found that COVID-19 patients develop diverse antibody responses, but with convergent responses to specific antigens, many of which are shared with SARS-CoV.

Mental health

A new panic buying scale was developed by psychologists, which found that panic buying behaviour was associated with being male, impulse buying, and risk perception, and negatively correlated with optimism and age.

Clinical findings

Children with COVID-19 or seasonal influenza virus had similar rates of hospitalisation and ICU admission, according to a small retrospective study from a single children’s hospital in the US. Deaths in children are rare.

Ben Johnson

Head of Communities & Engagement, Springer Nature

I gained my first degree in virology from the University of Warwick and a PhD in influenza virus immune evasion from Public Health England and the University of Reading, UK. My research interests then moved on to smallpox vaccines, viral ion channels, and cell adhesion, while a postdoc at Imperial College London. I joined open access publisher BioMed Central in 2011 as an Acquisitions Editor and then Associate Publisher, and was responsible for launching new journals, including Microbiome, Zoological Letters, and Movement Ecology. I have been Head of Communities & Engagement at Springer Nature since 2016, running our online community blogs, and a Consulting Editor at Nature Medicine since June 2020, handling COVID-19 papers. I am based in our London office.

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