15th May - the COVID-19 coronavirus compendium

Cancelled operations, at risk groups, and the therapeutic effect of Angela Merkel

Like Comment
Read the paper

This week we learnt that an estimated 28 million operations will be cancelled due to COVID-19, that 20% of the UK population is at risk from severe COVID-19, and that a speech by Chancellor Angela Merkel reduced anxiety and depression in the German population.

Virology

Rhesus macaques infected with SARS-CoV-2 experience respiratory disease for 8-16 days and shed the virus from the nose and throat, mimicking human disease and providing an invaluable animal model.

The secondary structure of the RNA genome of SARS-CoV-2 was predicted, as were high free energy sites in the coronavirus spike protein, both of which could be targets for antiviral drugs. Similarly, the nsp16/nsp10 heterodimer was modelled and potential drugs that bound to it identified.

Air quality

The lockdown in the north of Italy led to a drop in the levels of several pollutants in the city of Milan, although levels of ozone were increased, probably due to decreased nitrogen oxide.

Social media and apps

A speech by Angela Merkel reduced feelings of anxiety and depression in the German population, according to a large survey of more than 12,000 people which ran over two weeks in March. Anxiety increased prior to the speech, whilst trust in government was shown to increase during the outbreak.

A second study from the COVID-19 symptom tracker app from Kings College London and Massachusetts General Hospital was published, this time showing that 65% of those with a positive test result experienced self-reported loss of taste or smell, compared to 23% who tested negative. Indeed, loss of taste or smell was the symptom with the best predictive value, although a combination of loss of smell and taste, fatigue, persistent cough and loss of appetite was the strongest predictor of a positive test result.

A survey of more than 10,000 Chinese people on WeChat found that they had very high levels of knowledge about the outbreak, with 98% wearing face masks in public and 96% avoiding large crowds. Most got their information from WeChat. Another survey of Nigerians found that most had taken precautions to avoid catching SARS-CoV-2.

The Ministry of Health in Singapore, the Centres for Disease Control in the US, and Public Health England in the UK all used social media to inform the public about COVID-19. A telehealth survey was used to assess the wellbeing of older people with mild cognitive impairment or dementia in Spain. Watching TV was the most popular leisure activity during isolation.

Internet searches on Google or Baidu can be used to track the outbreak worldwide, and some search terms correlated with real world cases and deaths, although others seemed to be in response to media coverage. Older patients in Wuhan used Weibo, another social media platform, to ask for advice about their symptoms, the most common of which was fever. A dataset of almost 9 million COVID-19 related tweets was published. Reddit was also a lively platform for COVID-19 discussion, as was YouTube

Transmission

Two studies from different UK hospitals detected SARS-CoV-2 in healthcare workers with no symptoms, albeit at low numbers. The first found that 3% of healthcare workers in an asymptomatic group had the virus, although further investigation found that only half of these were truly asymptomatic. The second study found that 7% of those with the virus had no symptoms. These studies highlight the importance of testing healthcare workers, regardless of symptoms. Infection control in a Singapore hospital was also described.

27% of countries do not guarantee paid sick leave from the first day of illness, a huge challenge when those with symptoms, however mild, should isolate at home.

Outbreaks across the world

The first cases of COVID-19 in Brazil were described, together with sequence data showing that there were multiple independent importations from Italy. The outbreak in Lima, Peru, was also described, with the reproductive number estimated at 2.3, although social distancing and closures have since slowed the outbreak. 

Epidemic growth of COVID-19 was not associated with latitude or temperature, but there was a weak association with humidity, and a strong association with public health interventions. Cases of COVID-19 in India seem to have been been imported from the Middle East, and not from China, despite frequent air traffic between the two countries, according to an analysis of an airline database, FLIRT. 

Taiwan has been very successful in controlling COVID-19, with only 321 imported cases  identified from 21 January to 6 April 2020. A model of the outbreak in France predicts that there are 8 times more people infected than the official figures report, and that the infection fatatity ratio is 0.8%.

11 cases of COVID-19 in Munich in Febuary came from an advisory board meeting of dermatologists where one participant had asymptomatic infection. The index case likely contracted the disease from a patient he treated in Milan, Italy. At the time, there were less than 20 cases in Germany.

Dialysis patients

2% of dialysis patients in Wuhan tested positive for SARS-CoV-2, 21% of whom had no symptoms.

Pregnancy

There were no cases of vertical transmission, or neonatal death, in 64 pregnant women with COVID-19 in a US study, although another study found that some placental or membrane swabs tested positive for the virus.

New models

A new model predicts that mortality rates will be highest in the United States, Spain, and Italy followed by France, Germany, and the United Kingdom. Another new model, the Epidemic Risk Time Series Model, uses newly diagnosed COVID-19 cases together with immigration data within China to show how well different cities controlled the outbreak. Shanghai and Zhejiang controlled the outbreak well, Heilongjiang less so. A hybrid AI model was also developed, as was a model based on deep learning, which was used to analyse the outbreak in Canada. 

Immune response

Immune dysregulation in COVID-19 patients was further described, showing that severe patients had high levels of proinflammatory macrophages, whereas moderate cases has high levels of clonally expanded CD8+ T cells. Severe patients has high levels of proinflammatory cytokines, suggesting that the cytokine storm seen in avian influenza is also seen in COVID-19.

Treatments

Triple therapy combining interferon beta-1b, lopinavir-ritonavir, and ribavirin was more effective than lopinavir-ritonavir alone in shortening the time taken to clear the virus. None of the 127 patients died, in this phase II clinical trial from Hong Kong.

More than 2500 cases of alcohol poisoning have occured in Iran, due to a false belief that drinking or gargling alcohol will kill the coronavirus. Most hopsitals are ill equipped to deal with alcohol poisoning due to religious prohibition of alcoholic drinks.

COVID-19 patients with acute coronary syndrome should be treated with thrombolysis, according to a clinical study from several Italian hospitals. Use of an IL-6 inhibitor, Tocilizumab, did not reduce risk of death from COVID-19, according to a small Italian study. Another small study treated COVID-19 patients with intravenous allogeneic cardiosphere-derived cells (CAP-1002). 

Existing intravenous immunglobulin products contain antibodies that react against SARS-CoV-2, presumably due to cross reactivity against other human coronaviruses, although further testing is needed.

Hydroxychloroquine and azithromycin treatment did not reduce mortality from COVID-19, and indeed increased the risk of cardiac arrest in a study of 1400 patients in New York. The kinetics of hydroxychloroquine in COVID-19 patients was measured in another study. Fake chloroquine is circulating in Cameroon and the Democratic Republic of Congo, according to thin layer chromatography analysis. 

At risk groups

20% of the UK population is at risk of severe COVID-19 disease, either because of older age or an underlying health condition, according to an analysis of electronic health records from more than 3 million people. Many of these people are not currently on the vulnerable patient list (also known as shielded groups), as shielding does not take into account those with multiple health conditions. The authors also built an online risk calculator to allow anyone to model the excess deaths due to the outbreak.

The incidence of COVID-19 in the UK was analysed and modelled, and showed that the one third of GP practices will likely handle 45% of cases, and require 68% of healthcare resources. These GP practices are urban, have more older people, and a higher proportion who work. 

A risk score and online tool that predicts severe COVID-19 in patients who arrive at hospital was developed using data from patients in China. 10 variables independently predicted risk of severe disease, including chest radiography abnormality, age, number of comorbidities, cancer history, and neutrophil-to-lymphocyte ratio.

Diabetes greatly increased the risk of severe COVID-19, especially those with uncontrolled hyperglycemia, in a study of 88 US hospitals.

25% of heart transplant patients hosptialised with COVID-19 in New York died from the disease. Many had cardiovascular comorbidies and many stopped taking immunosuppressive drugs. A study in Zheijang, China, found that hypertension, diabetes, and chronic liver disease were the most common comorbidities.

Children

The majority of children hospitalised with COVID-19 in the US and Canada had pre-existing co-morbidities. Paediatric cancer patients are at a low risk of severe coronavirus infection, with only 5% requiring hospitalisation for COVID-19. However, 15% of their asymptomatic carers tested positive, showing the important of testing care givers, whether they have symptoms or not. Of the 20 children who tested positive, only 3 were female, suggesting that previously seen sex differences may be biological, rather than linked to comorbidities. Less than 1% of children who presented at Australian Emergency Departments or Respiratory Infection Clinics tested positive for the virus.

Lung cancer patients are at risk of severe COVID-19 infection, but previous PD-1 blockade did not increase this risk. HIV patients on anti-retroviral therapy are not at increased risk of severe disease, according to a small study of 33 patients. Plasma concentrations of ACE-2, the coronavirus receptor, were higher in men than women with heart failure.

Healthcare

28 million operations worldwide are predicted to be cancelled during the peak 12 weeks of the COVID-19 outbreak, mostly benign surgery. It will take almost a year to clear the backlog.

Fewer stroke patients are presenting at hospitals within the therapeutic time window, according to a study from the Alsace region of France. Increased public awareness is needed.

PPE

Hydrogen peroxide vapour can be used to sterilise N95 respirators. A head isolation unit, made from inexpensive materials for less than $5 was described, as was a protective sleeve for intubation. This was used in Taiwan during SARS and can be worn prior to patient contact. The use of a modified Wake Forest protective shield during intubation was recommended. Aerosol boxes, in contrast, increased intubation times, and damaged conventional PPE, and so need further study. 

Healthcare workers

27% of healthcare professionals showed psychological distress during COVID-19. 11% of frontline healthcare staff in China had poor mental health status due to COVID-19, according to a survey of more than 1000 people from a smartphone app. 28% experienced stress and 17% had poor sleep quality.

30% of healthcare workers in China reported pressure injuries from wearing PPE, accroding to a large survey of more than 4000 people. 5 healthcare workers with pressure ulcers due to N95 masks were identified in a hopsital in Malaysia.

Anxiety about COVID-19 was common both in patients with Parkinson's disease, and their carers, according to a small survey in Iran.

Diabetes

Glycaemic control of diabetes patients improved during lockdown in Italy, although the effect was only seen in those that stopped working, not those that continued to work.

Diagnostics

A consortium of academia, medical, and commercial companies designed and created nasopharagneal swabs by 3D printing, and showed them to be effective, They can be ordered at http://printedswabs.org.

A panel of three RT-PCR tests was developed by CDC and shown to be sensitive and specific against SARS-CoV-2. Two commercial serology assays both showed poor sensitivity during the first 14 days of symptoms.

Clincal findings

A case report of COVID-19 related acute kidney injury occurred at Massachusetts General Hospital. Purpuric acral lesions may represent a convalescent phase cutaneous reaction to COVID-19. Erythema multiforme-like lesions were seen in 4 hospitalized patients with COVID-19 infection. Three patients in Italy developed abdominal viscera infarction.

Respiratory mechanics and recruitability in SARS-CoV-2 acute respiratory distress syndrome was assessed.

Symptoms of COVID-19 in patients in Huanggang, Hubei and Taian, Shandong, were described.

And finally, the lockdown has led to a doubling of cases of severe alcohol withdrawal syndrome, as seen by psychiatric emergency services in Bangalore. Alcohol has been banned during lockdown, leading to an abrupt cessation of drinking in alcohol-dependent people.

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.

2 Comments

Go to the profile of Mark Cannon
Mark Cannon 4 months ago

Hello, new member here: Would it be appropriate for me to present a question here for possible discussion?

Go to the profile of Emma Thompson
Emma Thompson 4 months ago

Hi Mark, welcome to the community.  Yes, please do post any comments or discussion points here.