A new study conducted by researchers at University College London reports the potential of a biomarker test that measures the levels of IFI127 in blood, which could help presymptomatic detection of COVID-19. It has been established that viral infectivity is maximal during the first week following infection. This period should therefore be the focus of case detection efforts to effectively isolate infected individuals, along with contact tracing and quarantine.
The study included 96 participants, who gave 169 blood samples for RNA analysis. The study showed that Interferon Alpha Inducible Protein 27 (IFI27) was the most specific discriminatory parameter for SARS-CoV-2 infection, as confirmed by PCR. The sensitivity as determined by a value two standard deviations above the value in healthy controls was 84%, and the specificity 95%. This compared favorably with three other transcriptional signatures, of which IFI27 was lacking in only one.
The scores for the highest performing signatures were negatively associated with PCR cycle thresholds (Ct), suggesting that as viral loads increased, these signature scores also went up. The maximum scores were in the first week following the initial PCR positivity result and were normal in convalescent serum. Scores in the week before the first positive PCR were also higher than in either controls or convalescent serum.
The discriminatory values for scores at this time were also statistically valid but lower than for scores at the time when PCR was positive. By way of example, one week preceding the first positive score, the IFI27 was able to predict infection with 79% accuracy, with 40% sensitivity and 95% specificity. The researchers say this is the first time host transcription profiles have been assessed for their use in the detection of presymptomatic SARS-CoV-2 infection. It capitalizes on the accuracy of the IFI27 gene that is the best-performing marker in a set of signatures found to have a high predictive value for this infection relative to controls.
The connection of these signatures with type I interferon responses is significant since the latter is a specific feature of antiviral responses in the host. Severe COVID-19 is more common when this pathway is affected by genetic or immune system dysregulation factors. IFI27 has been studied for its role in type I IFN-dependent apoptosis, as part of interferon effects on tumor growth.
More work may show how such IFN-inducible genes are regulated during this infection. The study applies at present only to presymptomatic infection and may not be useful in severe or critical COVID-19. They are found in multiple viral infections and could thus be best viewed as a potential tool for screening contacts to allow infection control and identify those who might most probably be PCR positive.
Reference: Gupta, R. K. et al. (2021). Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection. medRxiv preprint. doi: https://doi.org/10.1101/2021.01.18.21250044. https://www.medrxiv.org/content/10.1101/2021.01.18.21250044v1