Men and those with unhealthy lifestyles are at increased risk of severe COVID-19 - and other news

In this week's COVID-19 coronavirus compendium: an adenovirus vaccine was tested, and men are at higher risk of severe disease.

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An adenovirus-based vaccine was safe and immunogenic in a phase I clinical trial, and more evidence from the UK and the US found that men and those with an unhealthy lifestyle are at a higher risk of hospitalisation and death from COVID-19.

This and more in this week's COVID-19 coronavirus compendium.

Anti-virals

The following study has since been retracted by The Lancet, due to concerns about the underlying database used (edited 5th June 2020)

Hydroxychloroquine with azithromycin doubled the risk of death from COVID-19 in a study of almost 100,000 people from a large multi-national registry of 671 hospitals, mainly in North America. 18% of those who took both drugs died from COVID-19, compared to 9% in the control group, who did not receive the drugs. An increased mortality rate was also seen in those taking chloroquine, and both drugs (with or without azithromycin) increased the frequency of ventricular arrhythmia. The WHO has removed hydroxychloroquine from its list of potential treatments being trialled. A higher risk of death was also associated with age, body mass index, and race; black people and Hispanics were more likely to have a fatal outcome, compared to white people.

A clinical trial for remdesivir gave patients the drug for either 5 days or 10 days, but there were no differences between the groups. A placebo group would have been useful.

None of the potential anti-virals, lopinavir-ritonavir, hydroxychloroquine sulfate, or emtricitabine-tenofovir reduced viral loads or significantly reduced symptoms in SARS-CoV-2 infected ferrets.

Vaccines                                                            

An adenovirus 5 vector containing the spike protein of SARS-CoV-2 was safe and immunogenic in 108 participants in Wuhan, China, who were given low, medium, or high doses. Antibody and T cell responses were induced, and the antibodies from more than half the respondents neutralised live virus in vitro, although a past adenovirus infection reduced the immune response. This is the first trial of an adenovirus-based COVID-19 vaccine in humans, although it is not known if the immune responses seen protect from real world infection.

Virology

SARS-CoV-2 has a unique S1/S2 cleavage site, which mimics the human epithelial sodium channel α-subunit, allowing cleavage by human proteases.

An analysis of the virus in 6 patients in Lazio, Italy, showed 2 distinct clusters of virus and therefore predicted multiple introductions from China. A tool to validate SARS-CoV-2 sequences submitted to the GenBank database was created.

Immunology

Thymosin alpha 1 treatment was used in China during the COVID-19 outbreak and was associated with a reduction in mortality, through reversing T cell exhaustion. Lymphopenia was seen in a study from Guangzhou, and in another from Italy.

Antibodies

Two more neutralising antibodies against SARS-CoV-2 have been isolated from infected patients. One of these protected rhesus monkeys from infection, both as a prophylactic and a treatment. The antibody bound to the spike protein in the same place as ACE-2, suggesting that it blocks the receptor-virus interaction.

Transmission

An après-ski bar in Ischgl, a popular ski town in the Austrian Alps, was responsible for the importation of several cases into Münster in Germany, as well as other cities across Europe. A barkeeper was diagnosed with the disease and may have been the source of these infections. A cluster of cases at a church in Arkansas was described, with more than one third infected and three deaths. The pastor was the index case.

One third of COVID-19 cases in Seattle, Washington State, were in nursing homes, and the majority of patients had three or more comorbidities. Rapid spread in a nursing home was seen in a Seattle nursing home, with 64% of residents testing positive for the virus, many of whom were asymptomatic.

The travel ban in Australia was estimated to have reduced cases by 86%, due to restrictions on Chinese visitors.

Those with and without symptoms seem to be equally responsible for transmission, according to a re-analysis of data from the Chinese city of Ningbo, and another from Chongqing. More cases of presymptomatic transmission in  China were described.

Social distancing

Weekly universal testing, contact tracing and use of facemasks should supplement the lockdown in London, according to a model of the outbreak in the city. Such measures would half the number of deaths, and would allow lockdown to be relaxed more quickly.

Diagnostics

Loss of smell, as recorded in an online survey, can be used to track the spread of COVID-19 in a large population, according to a study of more than 2000 Swedes.

Less than 30% of samples that were positive for SARS-CoV-2 by RT-PCR had any live virus, and infectivity correlated with Ct value. SARS-CoV-2 could be detected in the lungs in post mortem tissue, and caused diffuse alveolar damage, according to this pathology study.

A deep learning system trained on CT scans was used to detect COVID-19. Two more antibody ELISAs were assessed, as was the use of saliva-based tests, a one-step RT-PCR, and a droplet digital PCR for detection of low levels of RNA.

Fatality rate

In a large cohort study from a health centre in Louisiana, black people were twice as likely to be hospitalised with COVID-19 as white people. Black people had higher rates of some co-morbidities, although they did not have a higher fatality rate, and the authors speculated that occupation drives racial differences, such as the likelihood of working in service jobs, including food preparation.

The case-fatality rate in Canada was estimated at just under 2%, while that in the US was estimated at just over 2%, although the study assumes that the reporting rate is less than 50%. The mortality rate amongst those admitted to ICU in Vancouver, Canada, was estimated at 15%, lower than previous estimates.

Risk factors

The average age of 20,000 hospitalised patients in the UK was 73 years, 60% of whom were men, and 77% had a major co-morbidity.  Of those hospitalised, 26% had died and 41% were discharged, with the remainder still in hospital at the time of writing. Age, sex and several co-morbidities were predictors of mortality, and only 1.5% of those admitted to hospital were children. Age, sex, obesity and other co-morbidities were also risk factors for severe disease in a study of 5000 patients in New York hospitals, where markers of inflammation predicted mortality.

The risk of ICU admission and case fatality rate amongst hospital patients in California and Washington was also higher for male than female patients. The incidence of COVID-19 hospital admissions was between 14 and 23 cases per 100,000 and highest in Southern California and the average age was 61 years.

Patients with neurological disease, including stroke, have a higher risk of in hospital mortality from COVID-19, according to a multi-centre study from Italy. A higher mortality rate was also seen in cancer patients in Spain

An unhealthy lifestyle, including physical inactivity and obesity, were associated with 4-fold increased risk of hospital admission for COVID-19, according to a study using UK Biobank data. Heavy alcohol consumption was not a risk factor. Obesity was a risk factor for mortality, especially in younger people, in another study from New York City.

Mental health                                       

Anxiety in the UK population was associated with somatic symptoms, including gastrointestinal illness and fatigue, in a survey of more than 2000.

A psychiatric clinic at UC Davis rapidly converted to 100% telehealth services during COVID-19, and remained financially viable.

Healthcare

No infectious virus was found on surfaces in the emergency unit and the sub-intensive care ward in an Italian hospital, although two samples tested positive by RT-PCR. 8% of cancer patients tested in the United Arab Emirates tested positive for COVID-19, despite showing no symptoms at the time of testing, highlighting the importance of routine testing within hospitals. A real-time location system was used to track potential contacts between patients and healthcare workers in a hospital in Singapore, and performed better than using electronic medical records. An anti-viral filter attached to a pleural drain bottle was used to prevent environmental contamination with SARS-CoV-2.

Vaccine coverage in children has declined in Michigan since the COVID-19 outbreak started, apart from Hepatitis B vaccination, which is given in hospital shortly after birth.

Face masks cause itching in 20% of those who wear them, according to a survey of more than 2300. Hand washing caused acute hand dermatitis in 90% of healthcare workers in Munich, Germany, and hand eczema in 15%. The impact of COVID-19 on healthcare workers was assessed from an online survey in Italy.

Markers of severe disease

C-reactive protein (CRP) level is a predictor of severe disease, along with several other biomarkers.

Microbiome

The airway microbiome appears to be disrupted during COVID-19, and various immune responses are altered, in a transcriptomic study from infected patients.

Technology

Google and Apple mobility data sets were used to show that social distancing policies explained almost half the difference in transmission rates between countries, showing their effectiveness.

Knowledge

Searches for “coronavirus” peaked after news items, but fell back to baseline rapidly. Searches for community level responses did not appear to increase, according to the US study.

Health and information support for Latino immigrant communities in New York City was achieved through community-based organisations and multi-disciplinary teams.

Social media

Reports of symptoms on Weibo, a Chinese social media platform, predicted the transmission of disease in Chinese cities, according to an analysis of 250 million accounts.

Public sentiment shifted from fear to anger, according to data from Twitter. Some anger was xenophobic early on, but then shifted towards the stay at home policy. Data from NAVER, a Korean web portal, was also analysed, with discussion of symptoms the most popular topic.

More than a third of YouTube videos about rheumatic disease and COVID-19 were deemed low quality, in an analysis of 360 such videos. An interactive web app in the Czech Republic was described.

Receptor

Expression of ACE-2 was predicted by dynamic inference from existing expression data.

Clinical findings

Measurements of viral load during SARS-CoV-2 infection were tracked. Two cases of erythema multiforme and Kawasaki disease associated with COVID-19 in children were described, along with 6 cases of Multisystem Inflammatory Syndrome. Co-infections of COVID-19 and Clostridioides difficile were found in Detroit.

DPP-4 inhibitors (DPP-4i), a treatment for diabetes, had no effect on COVID-19 disease, according to an Italian study. Neither did RAAS inhibitors, confirming previous findings.

Pregnant women report more distress during COVID-19 than before it, in a perhaps unsurprising study.

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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