28th August - the COVID-19 coronavirus compendium

Point of care testing, violence towards women, and COVID-19 in children

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This past week we learnt that a point-of-care test based on Cas13 was effective at diagnosing SARS-CoV-2 in a low resource setting in Thailand with 100% specificity and 100% sensitivity; that half of Bangladeshi women have reported an increase in emotional or physical violence during lockdown; and that severe complications from COVID-19 in children are rare.

Diagnostics

A Cas13-based point-of-care assay to detect SARS-CoV-2 RNA (termed specific high-sensitivity enzymatic reporter unlocking, or SHERLOCK) was tested on 154 samples in Thailand, where it was 100% sensitive and 100% specific. The assay does not require RT-PCR instruments and the readout can be easily measured without specialist equipment, showing its potential use in low resource settings.

10 point of care serology tests, along with two ELISAs, used to detect antibodies against SARS-CoV-2 were tested and compared. Four tests achieved more than 80% positivity at later time points, but the authors advised that training is needed to correctly interpret these point of care tests, which could be used in airports, schools, or hospitals.

Mental health

Half of Bangladeshi women reported an increase in emotional or physical violence during lockdown, according to a study of more than 2000 mothers. Many reported that paid work was reduced, family income was down, and food insecurity increased, showing the severe impact that lockdown has in low and middle income countries.

Risk factors

627 children in the UK have been hospitalised with COVID-19, of whom 11% met the criteria for multisystem inflammatory syndrome in children (MIS-C). Six (1%) of the hospitalised children died, all of whom had profound comorbidities. This shows that complications associated with COVID-19 in children are uncommon, and deaths are rare. A systemic mucocutaneous-enteric symptom cluster was identified in a small subset of patients, which shares some features with MIS-C.

Less than 2% of asymptomatic children in US hospitals tested positive for SARS-CoV-2, in a study of more than 30,000. Paediatric prevalence correlated with community levels of the virus, although the prevalence was much less in children than in the wider community.

People with leukaemia and COVID-19, especially those who had recent chemotherapy, had a higher case-fatality rate than other cancer patients with the virus, according to a study of more than 1000 patients in the UK. Overall, one third of cancer patients with COVID-19 died during the study period.

Treatments

Remdesivir treatment for 5 days, but not 10 days, improved clinical status in those with moderate COVID-19 infection, according to a randomised phase 3 clinical trial. 1% of patients in the 5-day treatment group died, compared to 2% in the 10-day and no treatment group, although these differences were of unclear clinical importance. This data again suggests possible, but uncertain, benefits from remdesivir.

An anti-viral drug developed against feline infectious peritonitis, a coronavirus of cats, also binds to the protease of both SARS-CoV and SARS-CoV-2, suggesting it may work against COVID-19 in humans.

A monoclonal IgA antibody was isolated and shown to bind and neutralise both SARS-CoV and SARS-CoV-2. A phage display library was used to construct a panel of monoclonal antibodies against SARS-CoV-2, which target different parts of the coronavirus spike protein, and so could be used in combination as a therapeutic.

A defensin-like peptide, P9R, inhibited a range of viruses in tissue culture, including influenza H1N1, SARS-CoV, SARS-CoV-2 and rhinovirus. The peptide also protected mice from lethal challenge with influenza virus and likely works by preventing endosomal acidification, an essential part of the virus life cycle.

Hydroxychloroquine use has no benefit for COVID-19 patients, and may increase the risk of a heart attack. A new study found that long term, but not short term, hydroxychloroquine treatment for rheumatoid arthritis was associated with an increased risk of cardiovascular mortality, especially when taken with azithromycin. Another treatment, sulfasalazine, did not show these side effects.

Vaccines

Another adenovirus-based coronavirus vaccine, based on serotype 5, was developed and protected mice and macaques from disease following infection with SARS-CoV-2.

Immunology

Hyperinflammation is a hallmark of severe COVID-19 disease. To understand this further, levels of IL-6, IL-8, and TNF-alpha were measured in more than 1400 COVID-19 patients in New York and compared to healthy controls. Levels of these cytokines were higher in COVID-19 patients who were male, and older, as well as those with chronic kidney disease. Patients with high levels of one or more cytokine were more likely to have a fatal outcome. Finally, dexamethasone, remdesivir , and tocilizumab (an IL-6 inhibitor) reduced the level of some or all of these cytokine, supporting their effectiveness as therapeutics.

A study from two UK hospitals found that one third of hospitalised COVID-19 patients met the criteria for COVID-related hyperinflammation. Patients with this symptom had a worse outcome than those without.

Host immune defence against Ebola virus and coronaviruses is mediated by the MHC class II transactivator and CD74, which block endosomal entry of coronaviruses into the host cell. This pathway could be further studied to understand host defence.

Transmission

The How We Feel app in the US was used to collect self-reported COVID-19 data on more than 500,000 users. They found that African-American users, Hispanic/Latinx users, healthcare workers, and essential workers are at a higher risk of infection. A majority of users regularly left their homes during lockdown, and many did not engage in social distancing or face protection.

The prevalence of COVID-19 in Massachusetts prisons was 3 times higher than in the general population, with more than 1000 confirmed cases amongst prisoners and staff.

A second outbreak of COVID-19 in Beijing began on 11th June, with 335 confirmed cases and a further 33 asymptomatic infections. 74% of these cases had links to Xinfadi Agricultural Wholesale Market; almost half were market workers. There were no cases after 5th July, showing the effectiveness of containment policies. It is interesting to note that this outbreak, like the index cases in Wuhan, started in a seafood market.

Model systems

Transgenic mice expressing the ACE-2 receptor driven by the cytokeratin-1 gene promoter were generated and shown to have COVID-19 disease similar to humans when infected with SARS-CoV-2. This will provide a useful mouse model for anti-virals and understanding pathogenesis.

Healthcare

Cases of notifiable infectious diseases, such as scarlet fever, acute haemorrhagic conjunctivitis, and influenza (and not including COVID-19) in children in Beijing were down from 165 a day in 2019 to 28 a day in 2020. This could mean that public health interventions to combat COVID-19 are reducing the incidence of other infections, which seems likely for influenza; or it could mean that children are ill but are not visiting hospital, due to concerns about COVID-19.

Clinical findings

Thrombosis, diffuse alveolar damage, haemophagocytosis, and immune cell depletion were seen in 10 fatal COVID-19 patients examined post mortem in an analysis from Imperial College Healthcare Trust in the UK. Several unexpected findings were seen in some, including acute pancreatitis, adrenal micro-infarction, and pericarditis. Viral genome was regularly detected outside the respiratory tract, indicating potential systemic spread in fatal cases.

23% of children hospitalised with COVID-19 in Wuhan had ocular symptoms, including conjunctival discharge and eye rubbing.

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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