15th January - the COVID-19 coronavirus compendium

Long lasting immunity, convalescent plasma, and long COVID

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In the past couple of weeks we have learnt that immunity to the vaccine, and following natural infection, seems to be long lived, that convalescent plasma is effective at high titres, and more detail on the prevalence and symptoms of long COVID.

Vaccines

Participants who received the mRNA-1273 vaccine from Moderna still had robust antibodies 3 months after vaccination, suggesting that the vaccine induces durable immunity. Further studies will continue to measure this over the following months and years.

An adenovirus vaccine based on Ad26, Ad26.COV2.S, was shown to be immunogenic in a phase 1 / 2 clinical trial in 805 participants.

A global model of target population sizes for vaccines was developed, based on the proportion of key workers and people with underlying conditions. Both populations were most prevalent in Europe, with 9% of the population essential workers and 37% with underlying conditions. Taking into account vaccine hesitancy, the adult population willing to be vaccinated was estimated to be 3.7 billion.

Nanoparticles that display the receptor-binding domain of 4-8 different animal betacoronaviruses were immunogenic in mice, providing a potential tool for pandemic preparedness. Capsid-like particle (CLP) vaccines displaying the receptor binding domain of the SARS-CoV-2 spike protein were also found to be immunogenic in mice.

Treatments

Two studies showed the benefits of convalescent plasma for COVID-19. Mildly ill older patients who received high titre convalescent plasma were less likely to progress to severe disease than those who received placebo. A second study found that patients who received convalescent plasma with high levels of antibodies were less likely to have a fatal infection than those who received plasma with low level of antibodies, although the effect was only seen in those who did not receive mechanical ventilation.

Nanobodies were engineered with 100-fold improved neutralising activity. An antibody which mimics ACE-2 binding to the spike protein was isolated from a recovered patient and shown to block virus entry. A two-monoclonal antibody cocktail was developed and shown to neutralise the virus in vitro. A soluble ACE-2 receptor was developed as a potential anti-viral.

The action of remdesivir on the viral polymerase was mapped using structural biology.

Transmission

Those without symptoms were estimated to be responsible for half of all transmission, in a model of the virus from CDC in the US. The median duration of viral shedding in hospitalised patients was 8 days after the onset of symptoms, according to a study of 129 patients.

Non-pharmaceutical interventions in the Brazilian state of Bahia have reduced transmission by 36%, but not enough to stop the outbreak, in a mathematical model that can be used for other low-resource settings in low and middle income countries.

The spread of COVID-19 from China to African countries was modelled, showing that 90% of imported cases arrived between January and February, before the first case detections.

Severe disease

A comparison of COVID-19 with other pneumonias found that SARS-CoV-2 infects alveolar macrophages, triggering an influx of T cells, interferon-gamma release, and further pro-inflammatory cytokines, leading to the hallmarks of severe disease.

Virology

Heparan sulfate was shown to be an attachment factor for SARS-CoV-2 infection in human lung cells and ex vivo lung tissue.

Receptor

The pre-fusion conformation of the coronavirus spike protein was studied using cryo-EM.

Genomics

An analysis of more than 26,000 viral genomes from the outbreak in the UK found that there were more than 1000 lineages circulating. The N501Y variant of SARS-CoV-2, a mutation seen in the UK, has now been identified in Italy, and genomics data suggests the mutation has been there since August.

A new, short isoform of ACE-2 was identified and shown to be upregulated in response to interferons and virus infection. This form lacks the binding site for SARS-CoV-2 and so will not contribute to susceptibility to infection.

Immunology

Immunity in 188 COVID-19 cases was shown to be long lasting, with more abundant spike-specific memory B cells at 6 months than at 1 month, and remaining robust up to 8 months after infection.

An analysis of immunological and epidemiological data on COVID-19 suggests that as population immunity increases and primary exposure shifts to childhood, the disease will resemble a common cold. The authors caution that this would not be true of an emergent disease that is severe in children.

SARS-CoV-2 infection is detected by MDA5 and LGP2, activating the interferon response – although this response is delayed compared to other viruses.

Healthcare

There was an increase in out of hospital cardiac arrests in the Detroit area of Michigan during the early pandemic, with higher fatality rates, particularly in older individuals, Black people, and residents of nursing homes.

There was a dramatic drop in referrals for suspected colorectal cancer and colonoscopies in England in April 2020, which had recovered by October. However, over 3500 fewer people had been diagnosed with cancer than would be expected.

Similarly, there was a large drop in incidence of depression, anxiety, antidepressant prescribing, and self-harm in England in April 2020, with levels back to normal later in the year, which may lead to a spike in presentations in 2021.

Clinical findings

At 6 months after infection, many COVID-19 survivors continued to have symptoms, mainly fatigue, muscle weakness, sleep difficulties, and anxiety or depression, known as “long COVID”. Delirium or acute brain dysfunction was common and prolonged in critically ill COVID-19 patients who received mechanical ventilation.

Compared with influenza, COVID-19 patients had a higher risk of organ dysfunction and death, especially in those over 75 years of age, those of black race, and people with obesity, diabetes, or chronic kidney disease.

 

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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