Diagnostics
Navigating a shifting disease landscape
Dr. Andrew Birnie, Dr. Paul Oladimeji and Gemma Stokes highlight the difficulties of adapting diagnostic testing to new clinical threats and ever-changing disease targets, and discuss the modern approaches that are future-proofing the way that we manage respiratory diseases.
Patient management during the COVID-19 pandemic was driven by the development of rapid and accurate diagnostic tests that aided the prompt isolation of infected individuals to curb disease transmission. The associated social distancing measures were also effective at curtailing a range of other respiratory diseases, including influenza A, influenza B and RSV. As these precautions have eased, the resurgence of seasonal illnesses has placed additional strain on healthcare systems, underscoring the pressing need for discriminatory assays capable of identifying a range of pathogens. Fortunately, leading diagnostics companies have responded to this challenge by developing multiplexed testing kits to differentiate between prevalent respiratory illnesses. Only a few years ago, surging cases of
COVID-19 threatened to overwhelm healthcare systems worldwide. Reliable testing procedures, novel vaccines and widespread public biosecurity measures were essential
to restrict the initial rapid spread of the virus, and society has now adapted to a ‘new normal’ in which SARS-CoV-2 is just another condition to be managed, alongside a suite of other common seasonal respiratory illnesses. However, our acclimatisation to a changing disease landscape would not have been possible without collaborative efforts from clinicians, bioinformaticians and diagnostics companies to develop and implement surveillance strategies, detect genomic changes in quickly evolving viral pathogens, and continually adapt their approaches to tackle a range of diseases.
The ongoing viral evolution All viruses undergo a process of continuous natural selection, rapidly adapting as they replicate and spread in a population. However, those with RNA as genetic material – such as SARS-CoV-2 and influenza – mutate much faster than DNA viruses.1
transmission but, sometimes, changes in certain areas of the genome will improve the way that a virus survives and reproduces, resulting in viral lineages with a competitive advantage. These lineages that gain superior transmission abilities and higher severity as a result of mutations are usually referred to by scientists as ‘variants of interest’.1
Additionally, multiple mutations can occasionally occur in the same viral genome, resulting in a particularly virulent strain. A perfect example of this was the Omicron variant of COVID-19, which contained around 50 mutations within its genome.2 Genome sequencing can be used to decipher
Often, these mutations will not alter the major proteins involved in infection and
the order of the nucleotides that spell out a virus’s genetic code and identify any deletions or alterations in the genome, especially in the areas that encode essential viral elements – such as membrane proteins that interact with hosts’ immune systems – that control how virulent the variant is. Scientists can then use these genetic sequences in combination with bioinformatics approaches to characterise, understand and track the prevalence of disease variants in the community, as well as how efficient medical interventions and vaccines are in reducing their spread. The process of collecting and tracking this information is known as genomic surveillance.3
Figure 1: Rigorous testing was carried out during the height of the COVID-19 pandemic, but a resurgence of seasonal respiratory diseases calls for more complex assays that can detect a range of common pathogens.
Surveillance strategies Many people will remember the genomic surveillance reports that were regularly broadcast during the COVID-19 pandemic to inform members of the public about new outbreaks, novel variants and spikes in the number of disease cases in certain areas. In fact, at the start of the pandemic, major diagnostics companies downloaded SARS-CoV-2 sequences every day to aid their development of up-to-date diagnostic tests. Scientists were particularly interested in mutations within a specific region of the genome encoding the
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