27th November - the COVID-19 coronavirus compendium

Secondary infections, fatality rates, and cholesterol

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In the past two weeks, researchers have shown that the majority of secondary infections come from a minority of cases, that the fatality rate in a small town in Germany was 0.36%, and that the virus binds cholesterol.

Transmission

A large serosurvey found that in the majority of states fewer than 10% of the US population have been infected with SARS-CoV-2. Five states - Louisiana, Maryland, Pennsylvania, New Jersey, and New York had higher rates of seropositivity, with up to 23% of New Yorkers testing positive.

In contrast, just 4% of children tested positive for the virus in a screen of more than 135,000, with 8 children (0.2%) having a fatal infection.

A contract tracing study estimated that 80% of secondary infections were from 15% of primary cases. Risk factors were the duration of exposure and closeness of social interactions; infectiousness was predicted to peak just before symptoms appeared.

16% of a small town in Germany became infected during a carnival, based on serology and PCR testing, 0.36% of whom died. 22% of infections were asymptomatic.

Social distancing

A combination of non-pharmaceutical interventions can be as effective as a national lockdown, according to an analysis of more than 6000 interventions across 79 territories. Cancelling small gatherings, closing educational institutions, and border restrictions were rated as the most effective interventions.

Diagnostics

Almost 10 million residents of Wuhan were tested for SARS-CoV-2, with 300 asymptomatic cases (and no symptomatic cases) identified. 0.31% of previously recovered patients tested positive again, which may indicate re-infection.

Alterations in heart rate, number of daily steps, or time asleep, as measured by smartwatch data, could be used to diagnose COVID-19 before symptoms developed. It is not clear how specific these signs of disease are, or whether they are a general response to infection.

A Cas13 based diagnostics test that requires no RNA extraction was developed, as was a metagenomics approach to diagnostics.

At risk groups

Insulin treatment was associated with an increased mortality in type 2 diabetes patients with COVID-19. Out-of-hospital cardiac arrest outcomes were worse during the early pandemic.

Treatments

Convalescent plasma treatment had no effect on clinical status or mortality in a COVID-19 clinical trial.

Vaccines

mRNA vaccines were shown to elicit potent germinal centre B cell responses, which were associated with robust neutralising antibodies. Two of the most promising vaccines use this mRNA approach.

ChAdOx1 nCoV-1 was tested in older age groups in a phase 2/3 trial, and shown to be immunogenic. An inactivated vaccine, CoronaVac, was tested in a phase 1/2  trial and shown to be safe and immunogenic.

A self-assembling nanoparticle comprising the receptor binding domain of the spike protein was shown to be immunogenic in mice.

Immunology

The IL-1 and NLRP3 inflammasome pathways are suppressed during COVID-19 infection, compared to other respiratory infections, which may explain the propensity for pre-symptomatic transmission. Another study found immunosuppression during early infection.

TNF-alpha and IFN-gamma were induced upon infection and perpetuated the cytokine storm often seen. Neutralising these cytokines protected mice against COVID-19 sepsis. Long pentraxin 3 was stimulated during COVID-19, with levels associated with mortality.

The majority of convalescent COVID-19 patients develop neutralising antibodies, some of which also neutralised SARS-CoV and MERS. Another study identified long lasting antibodies for 3 months, even in those with mild disease.

Mental health

Serious psychological distress was reported by 13.6% of US adults in April 2020, and by 13% in July 2020, compared to 4% in 2018. There was no evidence of an increase in suicides during the pandemic in Queensland, Australia, despite a suspected role for COVID-19 in some individual suicides.

Genomics

Another two studies examined the effect of the D614G mutation, finding that it increased infectivity in pseudoviruses and was associated with higher viral loads and a younger patient age, although it was not associated with more severe disease. A third study found that none of the mutations in the virus increase transmission.

Receptors

High-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) helps SARS-CoV-2 enter cells in an ACE-2 dependent manner. The virus itself binds cholesterol and entry is partially inhibited by SR-B1 antagonists, showing a link between lipid metabolism and infection.

Model systems

Human distal lung organoids were created and infected with SARS-CoV-2, showing that club cells become infected, and providing a model system for infection.

African green monkeys develop respiratory disease upon SARS-CoV-2, as well as inflammation and coagulopathy, closely resembling human severe disease. Animals were protected from re-infection. The Roborovski dwarf hamster was also developed as a model system for SARS-CoV-2 infection.

Clinical findings

Chilblain-like lesions during COVID-19 represent a viral-induced type I interferonopathy, according to a study of 40 patients. 28% of older COVID-19 patients presented with delirium, suggesting that it should be included in symptoms.

COVID-19 during pregnancy was not associated with adverse outcomes in a study of more than 3000 women.

Ben Johnson

Magazine Editor, Nature Medicine, Springer Nature

I trained as a virologist, starting with an undergraduate degree in virology from the University of Warwick, UK. My PhD, in influenza virus genetics and immunoevasion, was from Public Health England and the University of Reading, UK, with Maria Zambon and Wendy Barclay. My research interests then moved to smallpox vaccines, viral ion channels and cell adhesion, while a postdoc at Imperial College London with Geoffrey Smith, FRS. I then joined open-access publisher BioMed Central in 2011 as an editor and then associate publisher and was Head of Communities & Engagement at Springer Nature from 2016, running the Nature Research Communities and other online engagement activities for researchers. I joined Nature Medicine in 2021, with responsibility for news and opinion content, and am based in the London office.