COVID-19 - The elephant in the room

We are not talking about it anymore – almost like it has just disappeared – but the dreaded COVID-19 infections are still out there. COVID-19 infections have been rumbling along in the UK throughout 2023 and are expected to increase significantly as we move into autumn and winter. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Which is a single stranded RNA virus, first isolated in Wuhan, Hubei, China in 2019. The virus is related to the SARS-CoV-1 which caused outbreaks in over 30 countries in the early 2000s. As the journal Nature suggests, Coronaviruses are here and they are not going away any time soon.¹ There is a need to learn to live with the virus as we do effectively with other respiratory viruses that circulate every year. The need to have effective diagnostics and epidemiology for these respiratory pathogens is imperative.

As extensively reported in the press there is a long list of genomically different SARS-CoV-2 variances, and these have been classified into a number of different groups. These being variances under monitoring (VUM), variances of interest (VOI) and variances of concern (VOC).² These sequences are reported to the Global Initiative on Sharing Avian Influenza Data (GISAID), which expanded its database to include SARS-CoV-2, and this data enables quick and effective global epidemiological mapping of circulating strains to be made available.³

The UKHSA recently reported a new SARS-CoV-2 variance of concern, BA.2.86, is circulating, with 34 cases reported as of 4 September 2023 in the UK.⁴ The BA.2.86 is an Omicron subvariant of SARS-CoV-2 and appears to have a high number of mutations from the BA2 and XBB strains currently circulating. Genomic sequences confirm that the BA.2.86 variant is seen across the  globe and suggest recent emergence and rapid growth. Although more sequences are required to confirm and it is too early to predict the effect of this variant, the number of mutations do suggest significant antigenic change.⁴

SARS-CoV-2 is circulating in the UK and between 19-26 August 2023, UKHSA reported 6,963 confirmed cases from a total of 32,151 assays performed in England.4 However, the data collected from King’s College London, ZOE Health Study 2023, suggest the number infected is likely to be north of 1 million.⁵ The COVID-19 vaccination booster campaign is being brought forward,⁶ and there are suggestions to re-commence diagnostic screening.⁴ Zoonotic spread has also been identified, and the recent paper in trending cell and molecular biology that suggests over 50 different species including dogs and cats can be infected with SARS-CoV-2.⁷ Of particular interest in the spread in white-tailed deer in Ohio, US, where viral variants are evolving three times faster than in humans.⁷

Winter is coming

As Jon Snow would say, ‘winter is coming,’ and we need to prepare for an increase in infections of the winter respiratory viruses. SARS-CoV-2 has firmly established itself as a respiratory virus and as previous years suggest, the numbers will go up as we head into autumn and winter. We cannot just focus on COVID-19 infections though, we need to consider the other respiratory viruses which include Influenza A (Flu A), Influenza B (Flu B) and Respiratory Syncytial Virus (RSV). Each of these cause infections each year and diagnostic monitoring is required.

RSV is a common and very contagious virus that causes infections in the respiratory tract and is thought to have infected over 80% of children in the UK by their second birthday. It usually causes a mild respiratory infection in most people causing rhinitis, cough, and sneezing. High-risk groups are those under a year old and can cause bronchiolitis and pneumonia. Infections start to rise in October and last for four to five months, with a peak of infections in December.⁸

As you would expect, monitoring of these infections is important for us to understand their epidemiology and the health and economic impact. Diagnostic screening is not free but does enable us to confidently identify individual infections, which in turn allows assessment of the epidemiology and disease impact. These viruses are prone to mutate, we see this with the antigenic shift and drift in Influenza A, and the emergence of variances in SARS-CoV-2. We detect these variances by whole and next genome sequencing which provides a genetic signature for each virus. 

Molecular RT-PCR diagnostic assays are very specific and only amplify the target we are looking for. It is imperative to assess the assay against any new variance to make sure it covers the change in molecular code and can successfully pick up these mutations and variances. To enable this the virus must be available for assay development at each of the manufacturers. However, with new and emerging infections the virus is not always available, and in-silico computer analysis using the genetic signature is  undertaken. This in-silico analysis enables manufacturers to predict if their assay would identify the new variance or mutation. For SARS-CoV-2 the MHRA require manufacturers to supply in-silico analysis every other month.9 Companies providing SARS-CoV-2 diagnostic assays in the UK will have previously had to satisfy the Coronavirus Test Device Approval (CTDA) that the assay is fit for use in the UK.10 Only CTDA approved assays are available in the UK and each manufacturer must submit monthly Post Market Surveillance Reports to confirm that their assays are suitable to detect all variants and mutations. In the UK ProLab Diagnostics is the distributer for the Viasure range of molecular and lateral flow assays from Certest Biotech. All the Viasure assays have been analysed and the efficacy of the assay is not compromised, and the assays can successfully identify all forms of SARS-CoV-2.

Dr (hc) Neil Bentley OBE BMS

References
1 Philips, N. The coronavirus is here to stay – here’s what that means. Nature 2021 (https://www.nature.com/articles/d41586- 021-00396-2)
2 European Centre for Disease Prevention and Control. SARS-CoV-2 variants of concern. ECDC 2023 (https://www.ecdc.europa.eu/en/covid-19/variants-concern)
3 Global Initiative on Sharing Avian Influenza Data (GISAID) (https://gisaid.org/)
4 UK Health Security Agency. Investigation of SARS-CoV-2 variants of concern: variant risk assessments. GOV.UK 2023 (https:// www.gov.uk/government/publications/ investigation-of-sars-cov-2-variants-ofconcern-variant-risk-assessments)
5 ZOE Health Study. 2023 (https://healthstudy.zoe.com/the-health-study)
6 Joint Committee on Vaccination and Immunisation (JCVI). JCVI advises on eligible groups for 2023 autumn booster. UK Health Security Agency 2023 (https://www.gov.uk/government/news/ jcvi-advises-on-eligible-groups-for-2023- autumn-booster)
7 Leitch, C. SARS-CoV-2 is evolving rapidly in white-tailed deer. Labroots 2023 (https:// www.labroots.com/trending/cell-andmolecular-biology/25831/sars-cov-2- evolving-rapidly-white-tailed-deer)
8 UK Health Security Agency. Guidance: Respiratory syncytial virus (RSV): symptoms, transmission, prevention, treatment. Gov.co.uk 2023 (https:// www.gov.uk/government/publications/ respiratory-syncytial-virus-rsv-symptoms-transmission-prevention-treatment/ respiratory-syncytial-virus-rsv-symptoms-transmission-prevention-treatment
9 Medicines and Healthcare products Regulatory Agency. MHRA guidance on coronavirus (COVID-19). Gov.co.uk 2020 (https://www.gov.uk/government/ collections/mhra-guidance-on-coronavirus-covid-19)
10 Medicines and Healthcare products Regulatory Agency. Guidance for manufacturers: diagnostic assurance with SARS-CoV-2 variants in circulation. Gov.co.uk 2023 (https://www.gov.uk/ government/publications/how-tests-and-testing-kits-for-coronavirus-covid-19-work/ guidance-for-manufacturers-diagnostic-assurance-with-sars-cov-2-variants-in-circulation