10th July - the COVID-19 coronavirus compendium

Serology studies in Spain and Brazil, deprivation as a risk factor for fatal COVID-19, and paediatric inflammatory syndrome associated with SARS-CoV-2

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This week we learnt that less than 5% of the Spanish population and less than 1% of the southern Brazilian population have antibodies against SARS-CoV-2, that deprivation is a risk factor for fatal COVID-19 in the UK, and that there has been an 11-fold increase in paediatric inflammatory syndrome, coinciding with the outbreak.

Risk factors

The largest study so far of risk factors for severe disease was published in Nature, based on the electronic health records of 17 million NHS patients in the UK, including more than 10,000 who  died of COVID-19. Being male, older age, deprivation, diabetes, severe asthma, and other medical conditions were associated with an increased risk of death, as was black or South Asian ethnicity. The increased risk for black and South Asian people was only partially due to increased deprivation and the prevalence of medical problems, such as diabetes; similarly, the increased risk for deprivation was partly, but not wholly, due to other clinical risk factors, suggesting that social factors have a role in disease severity.

Chronic lymphocytic leukaemia patients taking antileukaemic treatment had less severe COVID-19 than those who were not on treatment, according to a retrospective, international, multi-centre study.

Pollution

Lockdown in China reduced air pollution, including PM2.5, with greater effects in cities that observed lockdown, but some effects even in those cities that did not. However, the levels of PM2.5 were still four times the recommended levels.

Transmission

Household serology surveys of more than 4000 people in Rio Grande do Sul, in the south of Brazil, found that the proportion of the population with antibodies against SARS-CoV-2 has steadily increased through April and May, albeit at low levels, from 0.045% to 0.222%. 4 out of the 10 positive cases were from the city of Passo Fundo, where there was a recent outbreak in a meat-processing plant. Contact tracing found that 35% of family members of positive individuals also tested positive. The authors note that social distancing has been well observed in this region, unlike some other parts of Brazil.

A study of more than 60,000 people in Spain found that 5% of the population had evidence of a past infection by serology testing. There was considerable regional variation, with more than 10% infected around Madrid, and less than 3% in coastal areas. More than 90% of those who were shown to be infected by RT-PCR had evidence of antibodies, showing good rates of seroconversion, and around one third of positive cases were asymptomatic.

A combination of sequencing of viral isolates and a computational agent-based model, based on census data, was used to track the outbreak in Australia, and showed that there were multiple introductions from other countries, with some local transmission in individual institutions. This shows the value of genomic sequencing to aid epidemiology.

The case rate of COVID-19 in prisons was 5.5 higher than the rate in the general US population, with 42,000 cases and 510 deaths amongst 1.3 million prisoners. The death rate was also higher, at 39 deaths per 100,000 prisoners, despite the prison population being younger.

246 COVID-19 cases were associated with nightclubs in Seoul, South Korea. Of the more than 5000 people who attended the clubs, 1.7% tested positive, with 60% of positive tests identified in contacts. Anonymous testing was allowed after discussion with LGBTQ+ groups in the city, to help encourage participation amongst residents who may not wish their sexuality to be revealed, as some of the outbreaks were in gay venues.

Screening of respiratory samples in California from 2019 found no evidence of SARS-CoV-2, suggesting, as expected, that the virus was not in the US before 2020.

Increases in temperature or relative humidity reduced the half-life of the virus on a variety of surfaces.

Masks

Cloth masks and surgical masks both varied considerably in particle filtration, with cloth masks removing 28-90% of particles, compared to 99% removal by an N95 respirator. A nylon overlayer improved the filtration efficiency of many masks by improving the fit and minimising gaps.

Vaccines

A novel vaccine design comprising a self-amplifying RNA, encoding the SARS-CoV-2 spike protein, encapsulated within a lipid nanoparticle, was developed and induced robust immune responses in mice.

Infection of vaccine trial participants with live SARS-CoV-2, to test the efficacy of the vaccine, may be acceptable to the public, according to a structured public consultation with 57 individuals in the UK.

Immunology

T cell activation is altered in COVID-19 patients with pneumonia, and production of IL-17 was elevated, suggesting that blocking this could alleviate symptoms. Another study has shown immune dysregulation in COVID-19 patients, especially in those with severe disease, including lymphopenia and aberrant T cell activation.

Five major classes of neutralising antibodies against SARS-CoV-2 were identified, based on reactivity to the spike protein, and their cross-reactivity with SARS virus. Neutralising antibodies against SARS-CoV-2 are generated as early as 8 days after diagnosis, and can be isolated from convalescent patients.

Model systems

Pigs and chickens cannot be infected with SARS-CoV-2, whereas fruit bats and ferrets can be infected and transmit the virus to other animals.  Fruit bats had mild symptoms, whereas ferrets had little or no symptoms, despite virus in the upper respiratory tract.

Another group has infected rhesus macaques with SARS-CoV-2 and shown that they develop pneumonia. They also found that infected monkeys were protected from re-infection with the same virus, thereby demonstrating protective immunity in this animal model.

Receptor

The cryo-EM structures of both the SARS-CoV-2 spike protein, and the spike of a related bat coronavirus, showed that the SARS-CoV-2 spike binds 1000-fold more strongly to ACE-2, through a decreased stability compared to the bat virus.

Media

A targeted public health campaigns using a Dutch social media influencer increased hand washing in those who watched the video, according to a study from the Netherlands.

More than half of news headlines about the coronavirus pandemic evoked negative sentiments, compared to 30% that were positive and 18% that were neutral.

Diagnostics

A detailed comparison of serology tests found that the Wantai ELISA performed the best; another study compared RT-PCR primer sets, and found that all but one showed good sensitivity.

Healthcare

44% of healthcare workers in a UK-based screening study showed evidence of SARS-CoV-2 infection either by RT-PCR or serology. All but one of those that tested positive by serology failed to show any later evidence of infection by RT-PCR, suggesting that they were protected from future infection. The high infection rate may be explained by the lack of PPE during the study period in March.

Clinical findings

A detailed study described the clinical findings of children in the UK with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Cases of this type of paediatric inflammatory condition are 11-fold higher than usual. Male patients and children from ethnic minority backgrounds were over-represented, and symptoms included fever, shock, abdominal pain, vomiting and diarrhoea. Coronary artery aneurysms occurred in one third.

Many COVID-19 patients presenting to emergency medical services did not have an obvious febrile respiratory illness, presenting challenges for diagnosis; most had chronic health conditions.

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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