4th September - the COVID-19 coronavirus compendium

Hydrocortisone treatment, aerosol transmission, and virus-associated diabetes

Like Comment
Read the paper

This week we learnt that hydrocortisone treatment reduces mortality in COVID-19 patients, saw strong evidence of aerosol transmission on a bus with a single infected passenger, and a case of new type 1 diabetes following an asymptomatic infection with SARS-CoV-2.

Treatments

Three studies looked at the effects of the cheap steroid hydrocortisone on survival of severely ill COVID-19 patients. A prospective meta-analysis combining the results from 7 randomised trials including more than 1700 patients found that 28-day-all-cause mortality was lower in those who were given corticosteroids, compared to usual care or placebo (dexamethasone treatment was also confirmed to reduce mortality).

Two other trials on hydrocortisone were less conclusive, in part because of the small samples of just a few hundred participants each. A multi-centre trial of 384 patients mainly from the US and UK found that hydrocortisone treated patients had more support-free days, compared to those given standard care. Another small trial found no difference in survival in patients taking hydrocortisone, although the authors acknowledge that their study may have been underpowered, with just 149 patients.

A small trial of 299 patients in Brazil found that dexamethasone treatment increased the number of ventilator-free days in COVID-19 patients with acute respiratory distress syndrome, although there was no reduction in all-cause mortality. The study was considerably smaller than the UK RECOVERY trial, or the meta-analysis described above, both of which showed a reduction in mortality, and again highlighting the importance of large, multi-centre, randomised, controlled clinical trials.

Transmission

35% of passengers on a bus in China became infected with SARS-CoV-2 from a single index case. The bus air conditioning was on internal circulation and being closer to the index case did not increase the risk of testing positive, which suggests airborne aerosol transmission. None of the passengers on another bus travelling to the same religious service, which was cleverly used as a control, became infected. Aerosol transmission remains controversial but it does seem to happen in some circumstances.

Reductions in mobile phone activity were associated with lower incidence of COVID-19 cases in the following days, suggesting that this can be used as a proxy measure for non-pharmaceutical interventions, and showing that these interventions are effective at reducing transmission.

76 distinct clusters of virus were identified in a large screening programme in Victoria, Australia. Large clusters were associated with social venues, healthcare, and cruise ships, and interventions were associated with a drop in the reproductive number from 1.6 to 0.5.

Children represent 22% of the US population, but only 1.7% of COVID-19 cases confirmed by testing. A serology study at Seattle Children’s Hospital found that 8 out of 1076 children tested were seropositive in March and April, despite only 2 having any symptoms, representing a seropositivity rate of less than 1%. All seropositive children had neutralising activity against the virus.

Infection of rhesus macaques through the conjunctiva resulted in a productive infection with pneumonia, showing that the eye can act as a route of transmission, at least in this animal model.

Mental health

The prevalence of depression symptoms was 3-fold higher during the COVID-19 pandemic than in the period before, according to a survey of more than 6000 participants. Lower income, low savings, and more exposure to stressors were all associated with depression symptoms.

Vaccines

A high dose of SARS-CoV-2 caused severe disease in hamsters, showing the usefulness of this model for studying the infection. Vaccination with an adenovirus type 26 expressing the coronavirus spike protein protected hamsters from weight loss, pneumonia, and mortality. The Ad26 vaccine is one of several being tested in humans.

The NVX-CoV2373 vaccine, which comprises a purified coronavirus spike protein, was safe and immunogenic in a small phase 1-2 clinical trial of 131 participants. A phase 3 clinical trial to test for efficacy is ongoing.

Immunology

T cell responses were robustly induced by SARS-CoV-2 infection, regardless of severity. T cells were detectable against the membrane, nucleoprotein, and spike proteins, with the M protein triggering a strong CD4 response.

Testing

A large serology study from Iceland found that more than 90% of people infected with SARS-CoV-2 developed antibodies. They estimate that 0.9% of people in Iceland were infected so far, and that the infection was fatal in 0.3%, lower than previous estimates, although it was 4.4% in those over 70 years. Half of the cases were not previously identified during RT-PCR testing, despite 15% of the Icelandic population being tested. Importantly, levels of antibodies did not decline during the 4 month study period.

The vast majority of children who test positive for COVID-19 had either no symptoms, or unrecognised symptoms, and so would be missed by symptomatic screening.

Clinical findings

A case of type 1B diabetes mellitus following an asymptomatic case of COVID-19 was described. The patient had an HLA type that only provides a moderate risk of type 1 diabetes mellitus and no evidence of autoantibodies were observed. Although this does not prove that the virus caused the diabetes, the authors speculate that the virus may damage pancreatic-beta cells, which it can enter via the ACE-2 receptor.

68 autopsies from fatal COVID-19 cases in Italy and the US were described. Diffuse alveolar damage and thrombosis were commonly seen.

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.

No comments yet.