7th August - the COVID-19 coronavirus compendium

Complement and coagulation disorders, a drop in cancer diagnoses, and racial disparities in Louisiana

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This week we learnt that the virus activates the complement system and that a history of complement or coagulation disorders is a risk factor for severe COVID-19. We also learnt that new cancer diagnoses in the US fell by almost half during the pandemic, and that Black residents of Louisiana were twice as likely to test positive for SARS-CoV-2 as White residents.

Social distancing

Enhanced testing and contact tracing can control the outbreak, in the absence of total lockdown or herd immunity, according to a model based on mobile phone and census data for Boston. The model takes into account those without symptoms and the varying degrees of severity.

A model of the outbreak in Shenzhen, again based on mobile phone data, showed the effects that non-pharmaceutical interventions have on transmission.

Transmission

36% of COVID-19 patients in a community treatment centre in South Korea were asymptomatic at the time of virus isolation, with viral titres similar between those with and without symptoms.

Virology

A viral pore from nsp3 forms in double membraned replication vesicles in coronavirus infected cells, which allows export of RNA to the cytosol. This discovery, which was made using a mouse coronavirus, may allow targeting of this pore by anti-viral drugs, as a treatment for COVID-19.

SARS-CoV-2 causes plaque-like cytopathic effects in human airway epithelial cells, when grown in vitro, unlike human coronavirus NL-63, which replicates to lower titres.

SARS-CoV-2 failed to grow efficiently in any of 13 bat cell lines tested, in contrast to SARS-1, which grew in kidney cells from the Rhinolophus sinicus bat. This may suggest a different evolutionary origin, or path to humans, between these two coronaviruses.

Vaccines

The rapid design of mRNA-1273, an mRNA based vaccine expressing the SARS-CoV-2 spike protein, was described. The vaccine induced a good antibody and CD8 T cell response in mice and is already in phase 3 clinical trials.

Structural biology

A stable pre-fusion spike protein was engineered and expressed, which may be useful for vaccine design and serology testing.

Treatments

The effects of the IL-6 inhibitor, tocilizumab, on COVID-19 infections is described in a single-cell immune cell analysis. The drug reduced inflammation in these two patients, but did not affect T and B cell responses. Further large clinical trials are needed to show its effectiveness.

A rapid pipeline for the discovery of antiviral monoclonal antibodies was developed and used to generate antibodies against Zika virus. The same technology could be used for coronaviruses.

An engineered soluble ACE-2 receptor that binds with high affinity to the coronavirus spike protein was developed, which could be used as an anti-viral, by acting as a decoy.

Risk factors

A history of macular degeneration, which is a complement-activation disorder, and a history of coagulation disorders are both risk factors for severe COVID-19, according to a study of more than 6000 patients. Infection induced the complement cascade, and genes involved in the complement and coagulation response may affect susceptibility, as some mutations were associated with severe disease, although the effects were modest.

Healthcare

Diagnoses for new cancers dropped by almost half during the COVID-19 pandemic period in the US, suggesting that treatment will be delayed, with likely worse outcomes for those patients.

The COVID-19 pandemic is disrupting treatment strategies for other infectious diseases, especially in low and middle income countries. A modelling study looked at the impact on malaria transmission, specifically from the use of long lasting insecticidal nets, and found that the malaria burden in 2020 could be double that in 2019, with 81,000 malaria deaths in Nigeria alone. Minimising this disruption is achievable and should be prioritised.

Home healthcare workers, who provide essential support to patients with chronic illnesses, feel inadequately supported and generally invisible during the outbreak, despite their increased risk for COVID-19, according to a qualitative study of 33 such workers.

Viral RNA was found in an examining room for ophthalmologists, suggesting there may be a risk of transmission during eye examinations.

Diagnostics

4% of Danish healthcare workers tested positive for SARS-CoV-2 by serology testing. Seroprevalence was higher in men and in front line workers, especially those on COVID-19 wards, where 7% tested positive, suggesting hospital transmission. The prevalence of antibodies against the virus in New York health care workers was assessed in another study.

7% of residents of a Louisiana suburb were positive for SARS-CoV-2 by serology testing, 1.6% of whom died. Almost half of the positive tests were from Black participants, with 10% testing positive, compared to 4.5% of White participants. The fatality rate was similar amongst ethnicities, apart from Asian people, who had a lower risk of death. The virus was less common in the Faroe Islands, where less than 1% tested positive by serology.

Immunology

T cell epitopes in uninfected individuals that have reactivity against SARS-CoV-2 were mapped, showing that they were generated from infections with human common cold coronaviruses OC43, 229E, NL63, or HKU1. This suggests that prior exposure to common cold coronaviruses may offer some protection against COVID-19, although further research is needed.

37 COVID-19 patients were tracked during the course of disease, revealing that an IFN-gamma – eosinophil axis was activated before lung hyperinflammation. This mapping of the immune response prior to severe disease may be useful in the clinic. A second study found that infection impairs dendritic cell and T cell function.

Two studies found that infection induced profound changes in the myeloid compartment, with specific changes associated with severe disease, as well as a loss of non-classical monocytes.

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.

1 Comments

Go to the profile of Alexander E. Gorbalenya
Alexander E. Gorbalenya about 2 months ago

SARS-1 -> SARS-CoV