Coronavirus Research Tracking - 17 September - non-vaccine edition

Monoclonal antibodies, a travel risk model, long Covid in young people, transmissibility risks, and weakening immune systems in the elderly

This week non-vaccine related papers include monoclonal antibody therapies, modelling inter-regional travel risks, identifying long Covid in adolescents, very high levels of virus in fine aerosols seen for the Alpha variant, and mutations associated with higher transmissibility in variants.

See today’s separate Tracker for vaccine-related papers.

The tracker is shared with the COVID-19 Vaccine Media Hub.

The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre.

Non-vaccine-related papers

Monoclonal antibody therapies

It has been reported by the NZ government that an application to NZ’s medicine regulator Medsafe has been made for approving the use of the monoclonal antibody treatment Ronapreve (also called REGEN-COV). This was approved by the UK medicines regulator in August for use on at-risk people who have been exposed to the virus or infected but have not yet produced antibodies to it. 

A paper published in The New England Journal of Medicine in August describes the results of a clinical trial of the therapy. REGEN-COV (which uses 2 monoclonals) was effective in preventing infections and reducing symptoms. The study was covered in the 6 August Tracker.

Another monoclonal antibody treatment, Sotrovimab, has been approved for emergency use in the US  (and Australia) for people at higher risk. A clinical trial reported its efficacy and safety in people who had not been hospitalised with Covid-19. A paper on that trial has not yet been peer reviewed.

A recent paper in PLOS Pathogens reviewed the current status of monoclonal antibody trials for SARS-CoV-2. Eight have been given emergency use authorisation by the US Food and Drug Administration to treat non-hospitalised Covid-19 patients who are at high risk of severe illness.

A randomised trial with the monoclonal antibody bamlanivimab found that viral resistance to it developed in 7% of those treated with a lower dose. Older patients and patients with higher viral loads before treatment were more likely to develop resistance. The spike protein mutation E484K/Q was associated with resistance to the antibody.

The authors note that monoclonal antibody therapies now often use combinations of two antibodies, which reduces the risk of resistance developing. The paper has not yet been peer reviewed.

New Zealand’s drug funding agency, Pharmac, funds the monoclonal antibody tocilizumab for Covid-19 treatment. It is also funding a new treatment for arthritis, because the global demand for tocilizumab (an arthritis treatment) for Covid-19 has reduced supplies.

The Science Media Centre published an Expert Reaction to the funding of tocilizumab for Covid-19.

Risks of infections from moving between regions in New Zealand

Te Punaha Matatini has examined inter-regional movements during the recent outbreak. It used this data to identify boundaries that would have the greatest impact on reducing inter-regional spread of the virus, while permitting strong connections within regions. The paper has not yet been peer reviewed.

Alpha variant infections associated with more viral particles in aerosols

People infected with the Alpha variant produced 43 times more fine aerosol viral RNA than those with earlier variants. When correcting for the higher levels of viral particles seen in Alpha variant infections, there was still an 18-fold increase in viral RNA in fine aerosols produced by people with the Alpha variant. 

The confidence intervals associated with viral levels in aerosols were, however, very broad, indicating substantial variation between individuals. Tests were done several days after symptoms appeared and the authors note that this may be after peak infectivity, with virus-laden fine aerosols more prevalent earlier. 

Loose fitting face masks reduced viral RNA by 48% in fine aerosols, so these masks reduce but do not eliminate infection risks. Participants with infections only had mild symptoms, so the results may differ in cases of more severe Covid-19. The paper has not yet been peer reviewed.

Mutations associated with greater transmissibility

An analysis of over 2 million SARS-CoV-2 genomes identified mutations in several genes that increase transmissibility. These include sites in the spike and nucleocapsid proteins, as well as in Open Reading Frame 1. The paper highlights that attention shouldn’t just be focussed on the spike protein. The paper has not yet been peer reviewed.

Long Covid in adolescents

An analysis of 7,000 young people in the UK found that their post-covid symptoms are different from those in adults. This is based on a survey that is part of the CLoCk study. Symptoms associated with Covid-19 were more common three months after a positive PCR test than at the time of testing. Symptoms frequently reported were tiredness, headache, shortness of breath, dizziness and anosmia (loss of sense of smell &/or taste). 

In young people having multiple symptoms at 3 months, rather than just one or two, was a more reliable indicator of prolonged Covid. So the number of symptoms should be a part of the diagnosis. 

Long lasting symptoms were more likely to occur in females, older age groups, and in those who had poorer physical and mental health before Covid-19. The paper has not yet been peer reviewed

The UK Science Media Centre produced an Expert Reaction to the study.

Declines in immune responses in older people

A review in Nature Aging discusses immune responses in older people and the implications for those infected by SARS-CoV-2. It suggests a productive line of new research would be developing therapies that target aging-associated pathways.

Other SMC resources