26th June - the COVID-19 coronavirus compendium

Increased risk of severe COVID-19 in cancer patients, use of statins and colchicine, and lack of exercise during lockdown

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This week we learnt that cancer patients treated with immune check point inhibitors are at an increased risk of severe COVID-19, that statins and colchicine may show some benefit for hospitalised patients, and that Italians are exercising less often during lockdown, with negative effects on their mental health.

At risk groups

20% of cancer patients with COVID-19 had severe disease, and 12% died, according to an analysis from Memorial Sloan Kettering Cancer Center in New York City. Most of the cancer patients with COVID-19 had a comorbidity, such as diabetes, or hypertension. Older age and treatment with immune checkpoint inhibitors were associated with severe illness, but chemotherapy and surgery were not. All seven children with cancer had mild disease.

Obesity and abnormal liver function both increase the length of hospitalisation with COVID-19, according to an analysis of patients at a Wenzhou Medical University hospital in Zhejiang, China.

Another study, this time of almost half a million patients with hypertension, found that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of SARS-CoV-2 infection, confirming previous studies.

Transmission

The Haiyu community in Shenzhen, China, has managed to avoid an outbreak of COVID-19, despite 7 imported cases. Contact tracing and quarantine were effective, and those at higher risk were moved into home isolation.

Age groups tend to mix with people of a similar age, and social activity varies within and between age groups. In such an age-structured population, immunity to SARS-CoV-2 will develop at different rates in different age groups and social groups, according to a new mathematical model, which will delay the development of herd immunity in the general population.

Another model shows that the use of antiviral drugs, in combination with contact tracing, quarantine, and social isolation, can reduce the size of a SARS-CoV-2 outbreak. Anti-virals are still being tested in humans.

Social distancing

Gradual relaxation of lockdown will result in less infections and less deaths than a sudden release of a large population of susceptible people, according to a new modelling study of Spain and Italy. The model also showed that non-pharmaceutical interventions, such as social distancing and face masks, should continue, to avoid a large second wave – with even moderate reductions in transmission having large effects on disease burden.

A dataset of government policies across 195 countries, CoronaNet v1.0, was published in Nature Human Behaviour, which provides a useful resource for tracking these costly policies, and their effects.

Mental health

Physical activity amongst Italians significantly decreased during lockdown, especially amongst men, and was associated with poorer mental health, according to a survey of more than 2000.

Treatments

Patients in Hubei who took statins were almost half as likely to die from COVID-19 as those not on statins, according to a retrospective study of 13,000 people in the province. Statins may act by dampening the inflammatory response, which is suspected to contribute to severe disease.

Patients on colchicine had an improved time to clinical deterioration, compared to a control group, in a small clinical trial of 105 participants in Greece. Colchicine is an anti-inflammatory drug traditionally used to treat gout and rheumatic disease.

The curated Corona Drug Interactions Database, or CORDITE, was created to support clinical studies, meta-analyses, or literature searches.

Immunology

More neutralising antibodies were isolated from convalescent COVID-19 patients. In this study, they were shown to neutralise SARS-CoV-2, SARS, and MERS viruses. The researchers also crystallised a neutralising antibody in complex with the spike protein receptor binding domain, which will assist with the rational design of antibody therapies and vaccines.

Another neutralising antibody, named CR3022, binds to the receptor binding domain of the spike protein, inducing a conformational change to inhibit the fusion activity of the spike. Yet another neutralising antibody unusually binds to the N terminal domain of the spike, away from the receptor binding domain, showing that this region can also be a target for therapeutic antibody treatments.

7 asymptomatic patients from South Korea all had neutralising antibodies against SARS-CoV-2, 8 weeks post-infection, although the serological testing by ELISA was only positive in 5.

Model systems

Human intestinal epithelial cells can be infected with SARS-CoV-2 and produce infectious virus, suggesting they may be important in the disease in vivo. Both type I and type II interferons controlled the infection in this model.

Organoids derived from human pluripotent stem cells were infected with SARS-CoV-2 pseudovirus and live virus to show that the virus can infect various cell types, including human pancreatic cells and liver organoids. These pancreatic cells produced high levels of chemokines when infected, and a transgenic mouse with human pancreatic cells was used to show that the virus can infect pancreatic cells in vivo. This model should be an improvement on the transformed cell lines frequently used by virologists, which contain many mutations and do not well represent normal human tissue.

Healthcare

Deaths in skilled nursing facilities increased during March, April, and May in Detroit and New York City, compared to 2019, but not in Cleveland, corresponding to the size of the COVID-19 outbreaks in each city. Deaths were 10-fold higher in New York City, which had the worst COVID-19 outbreak in the US. Admissions were reduced, perhaps due to a decrease in elective surgeries.

There was a 3-fold increase in out of hospital resuscitations due to cardiac arrests in New York City during the COVID-19 outbreak, compared to the previous year. Those who had a cardiac arrest were more likely to be older, less likely to be white, and more likely to have comorbidities.

Pollution

Lockdown in Delhi, India, caused a 50% drop in pollution, including PM2.5 measured from the US embassy, which in turn increased the amount of sunlight reaching the city.

Disinfection

Far UV light, which unlike germicidal UV light doesn’t harm human tissue, kills human coronaviruses OC43 and 299E, which cause the common cold, with 90% inactivation in 8 minutes. SARS-CoV-2 was not tested, but the effects are likely to be similar.

Diagnostics

A probabilistic model to estimate the risk of false negatives when pooling patient samples for testing was developed and recommended that 13 samples are tested per group.

Structure

The room temperature X-ray structure of the SARS-CoV-2 3CL Mpro (the protease) was solved, which may aid the design of anti-virals.

Clinical findings

Another study found pathological evidence of diffuse alveolar damage in the lungs of COVID-19 patients.

Go to the profile of Ben Johnson

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. I am based in our London office.

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