1st May - the coronavirus COVID-19 compendium

Last week's research on coronaviruses and COVID-19

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This week researchers found that the virus can be found in hospital toilets and in the air of crowded areas, that many nursing home staff and care workers in the US lack health insurance themselves, and that poverty correlates with a higher death rate in New York City boroughs.  

Diagnostics

A new diagnostic platform that can test for all 169 human viruses, including SARS-CoV-2, influenza, and HIV, was published in Nature. This CRISPR-based technology also allows reduced costs, as miniaturisation reduces the amounts of reagents needed.

Excess deaths in Portugal are 3-5 times higher than the official COVID-19 estimates, suggesting gaps in testing.

Transmission

Mobile phone data

The effects of lockdown on the population of Wuhan and the rest of China was measured using data from mobile phones. Travel from Wuhan to neighbouring provinces dropped by 94% from the 23rd to the 24th January, when quarantine was announced. The number of cases of COVID-19 in other provinces correlated with population flow, showing the usefulness of aggregated and anonymised phone data.

Hospital transmission

SARS-CoV-2 could be detected in the toilet areas of hospitals and was found in the air in some crowded areas, suggesting that aerosol transmission may be possible. Room ventilation, disinfection, and other measures were effective at reducing levels of the virus in this hospital setting.

Urine

Infectious virus was isolated from the urine of a patient, suggesting that the kidneys, or other organs may become infected, and idenfiying a potential new route of spread. Viral shedding, as measured by RT-PCR, was detected for 60 days, a new world record. Live virus was not measured.

Death rates and incubation times

Comparisons between the death rates in countries are premature and incomplete, in my humble opinion, but perceived sociability and a late response to COVID-19 seemed to predict higher mortality, based on the death rates estimated so far and data from the European Social Survey.

The average incubation period for SARS-CoV-2 in China outside of Hubei province was 5 days, with traffic restrictions shown to be effective at stopping transmission. Doubling times varied betweeen Chinese provinces, and online graphs can help to track the outbreak.

Even modest reductions in social contact help flatten the curve, according to a modelling study. A new compartmental mathematical model for the spread of the COVID-19 disease was described, as was another based on a Gaussian spreading hypothesis, and another developed for the US.

Vertical transmission

A study showed that transmission of the virus from mother to baby is uncommon, and another found that only 1 out of 7 babies caught the virus from an infected mother. None of 21 healthcare workers who had contact with an infected patient caught the virus, despite the lack of any personal protective equipment.

Influenza

Influenza cases in Singapore, Taiwan, and mainland China, all decreased due to social distancing measures for COVID-19. 

Risk of severe disease

Poverty

In New York City, rates of hospitalisations and deaths were highest in the poorest borough, the Bronx. This borough also has the highest proportion of racial and ethnic minorities, and the lowest levels of educational attainment, again showing a correlation between COVID-19 deaths and poverty. Manhattan had the lowest rate of hospitalisations and deaths, despite the highest population density.

Co-morbidities

Men with comorbidities are at higher risk of severe COVID-19 than women with comorbidities. Some sex-specific laboratory markers of infection were also described. Cardiovascular disease, hypertension, diabetes, respiratory disease, cancers, and being male were all associated with an increased risk of death from COVID-19, in a study of more than 44,000 patients in China.

Some cancer patients had a higher frequency of severe COVID-19, although those with non-metastatic cancer had a similar frequency of severe events as the general population.

Metabolic associated fatty liver disease (MAFLD) in younger patients was associated with severe COVID-19 disease in a retrospective study from China. Levels of heart-fatty acid binding protein correlated with severe disease in another study.

Immunosuppression

Patients with immune-mediated inflammatory disease, such as rheumatoid arthritis, who were receiving immunosuppressive drugs, did not have more severe disease than the general population, according to 86 COVID-19 patients in New York, suggesting that immunosuppression may not increase risk. No increased risk of infection was found in atopic dermatitis patients treated with dupilumab. A description of patients with lupus and COVID-19, who were being treated with hydroxychloroquine, showed the clinical course of disease.

Treatments

Protease inhibitor

A new crystal structure of the coronavirus protease allowed rational design of an alpha-ketoamide inhibitor, which could be developed into an inhaled anti-viral drug. Small molecules that target SARS-CoV-2 proteins were designed using computational methods, although they also now need testing against the virus.

Caution over hydroxychloroquine

A high dose of hydroxychloroquine was associated with more toxic effects, electrocardiogram abnormalities (a longer QT interval), and death than those given a lower dose, in a randomised clinical trial from Manaus in the Brazilian Amazon. It's use was not recommended. Another study showed that these drugs increase the QT interval, causing electrocardiogram abnormalities, but a study of 201 hydroxychloroquine-treated patients found that none had a cardiac arrest. Another study showed that hydroxychloroquine and azithromycin act against the virus in cell culture, but more human studies are still needed.

Google searches for purchasing chloroquine and hydroxychloroquine increased by more than 1000% following premature claims from celebrities and politicians that they were effective against COVID-19, with 216,000 total searches for both drugs over 14 days. Online searches remained high even after the first fatal poisoning using the drug. Poison centres in the US received an increase in calls relating to potential poisoning with cleaners and disinfectants from January to March, compared to previous years.

Convalescent plasma

Convalescent plasma needs to be given early during infection, according to a trial of 6 patients who were treated, 5 of whom died. Despite their deaths, they all cleared the virus within 3 days of treatment.

Hypertension drugs

Patients with hypertension who continue to use angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors do not fare worse from COVID-19, backing up previous data that their use is safe, despite their effects on ACE-2, the coronavirus receptor.

Use of existing drugs

A small trial of the immunosupressive drug, methylprednisolone, seemed to improve severe disease. Umifenovir, used to treat influenza in Russia and China, did not improve the prognosis of COVID-19 patients in a small clinical trial. A patient treated with the IL-6 inhibitor, tocilizumab developed viral myocarditis, cautioning against this drug's use.

Health care

Healthcare workers

Many nursing home staff or care workers in the US, who care for COVID-19 patients, lack health insurance themselves. This detailed survey also described the rates of poverty in these front line workers, who put themselves at risk of infection. Another study estimated that 10% of US workers come into weekly contact with disease or infection.

Cardiac arrest

There was a 58% increase in out-of-hospital cardiac arrests in the Lombardy region of Italy during the first 40 days of the COVID-19 outbreak. Most of the increased cases tested positive for the virus. Ambulances also took 3 minutes longer, which may have contributed to excess deaths.

Face masks

Self-cleaning, graphene-coated surgical masks were created. The masks are superhydrophobic, causing water droplets to bounce off, and can be sterilised using sunlight, with the temperature increasing to 80°C. The effectiveness of different readily available fabrics for facemasks was also evaluated, showing that mixed fabrics and high thread count cotton were most effective.

A 3D printed adaptor was designed and tested that allows respirators to fit with anaesthesia circuit filters, creating a reusable mask to replace N95 respirators. Half of the eight test users experienced discomfort. Another styudy tested 4 different designs of 3D printed face shields.

Nosocomial infections

64% of residents in a skilled nursing facility in King County, Washington, tested positive for SARS-CoV-2, many of whom were presymptomatic or asymptomatic. Almost half of patients admitted to hospital with COVID-19 in northern California were under 60 years old, showing that not just older people are at risk. Italian hospices had all changed policies to prepare for COVID-19, and several had had cases of the infection, according to a survey. 

A new system of hospital triage of suspected COVID-19 patients in Hong Kong was described. Hong Kong has so far controlled the spread of infection, with less than 1000 cases so far and only 4 deaths at the time the study was written. An outbreak in a pediatric dialysis unit of the University Hospital of Münster was caused by transmission between patients and healthcare workers.

Immunology

Several studies delve into the immune dysfunction seen in more studies of COVID-19 patients.

Some details of the antibody response in COVID-19 patients was described, as well as a finding that a stronger antibody response was found in more severely ill patients.

Genomics and phenomics

Genetic variation

Three clades of SARS-CoV-2 are circulating, according to an analysis of 160 complete genomes. Another analysis of SARS-CoV-2 genomes is presented. 

A mutation in the IFITM3 gene was associated with more severe COVID-19 disease in a group of 80 patients in Beijing. The mutation is found in 26% of the Beijing population, but was seen in 35% of severely ill patients, and is involved in the immune response to infection.

Receptor expression

Expression of the coronavirus receptors, ACE-2 and TMPRSS2, did not differ in the sputum cells of asthma patients, but were higher in men, African Americans, and patients with diabetes mellitus, suggesting this may affect their risk of disease. Inhaled corticosteroids lowered ACE-2 and TMPRSS2, and so may be protective, although further research is needed.

Tobacco smoking increases the expression of ACE-2, the SARS-CoV-2 receptor. ACE-2 expression in various stages and types of lung cancer was shown, suggesting these patients can be infected with SARS-CoV-2 infection. TMPRSS2 was suppressed in both lung adenocarcinoma and lung squamous cell carcinoma, with the authors suggesting that it may be a tumour suppressor. ACE-2 expression in various other tissues was measured; the study found no difference between men and women or between asian and non-asian populations.

Diagnostics

Four FDA-approved molecular diagnostics were assessed, as were three sample-to-answer platforms, and a variety of transport media. Another new RT-LAMP for rapid diagnosis was described.

Social media

Almost a quarter of tweets about older people and COVID-19 contained ageist content, according to an analysis of Twitter posts during the outbreak. 

Clinical findings

Coagulopathy

5 cases of large-vessel stroke in patients under 55 years were reported in New York City over two weeks in March and April, more than 6 times the usual incidence. There is growing evidence that coagulopathy and vascular endothelial dysfunction are symptoms of severe infection.

There was a decrease in patients presenting at hospital with acute coronary syndrome in Italy in February and March, suggesting that patients may have avoided seeking medical attention, and contributing to excess deaths during the outbreak.

Coagulopathy is associated with severe COVID-19 disease in Caucasian patients, although progression to diffuse intravascular coagulation (DIC) was rare. Thrombotic risk is generally lower in Chinese populations, higher in Caucasians, and highest in African Americans. Three cases of COVID-19 pulmonary embolism, with elevated d-dimer were described. Treatment with heparin reduced mortality in patients with coagulopathy.

More symptoms

The pathophysiology of COVID-19 respiratory failure in 66 patients was described, with dyspnea the most common finding. Abdominal pain was also found in some COVID-19 patients, as was a case of invasive pulmonary aspergillosis, a disease sometimes seen in those with acute respiratory distress syndrome.

Two studies found skin conditions associated with COVID-19 in Spain, including chilblains and lesions, as did a study from Italy, and a case study of cutaneous eruptions. Loss of smell was  reported in patients early on during infection, and seemed to associate with milder disease.

75% of hospitalised COVID-19 patients had abnormal urine dipstick tests, indicating kidney injury. A case study of acute kidney injury associated with COVID-19 was also described. Conflicting data on COVID-19 in liver transplant patients was discussed - more research is needed. 

Symptoms of COVID-19 patients in China were described, as were descriptions of cases in Santa Clara County, California, more from Zhejiang, China. and Tongji hospital

Contact tracing

And finally, an example of testing and contact tracing was carried out during a COVID-19 outbreak in Remanzacco, a 6000-inhabitant town in Italy, after an agricultural engineering conference. 18 people were infected from the index case, many with no symptoms, but none of them passed on the virus further, showing the success of this approach.

 

 

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, 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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