# Subgenomic RNA and Limited Cross-Reactive Neutralising Antibodies Point to Potential Improvements in SARS-CoV-2 Clinical Handling

## TL;DR

This study shows that current SARS-CoV-2 testing and antibody detection methods may not be optimal due to changes in virus variants.

## Contribution

The study provides new insights into viral shedding and limited cross-reactivity of antibodies in pre-Omicron variants.

## Key findings

- Subgenomic RNA detection shows shorter viral shedding (2.2 weeks) compared to genomic RNA (5.2 weeks).
- Commercial assays are poor at predicting neutralizing antibody capacity against different variants.
- Anti-Alpha and anti-Delta antibodies show low cross-reactivity between SARS-CoV-2 variants.

## Abstract

The current clinical management of SARS-CoV-2 disease control and immunity may be not optimal anymore. Reverse transcription polymerase chain reaction (RT-PCR) of genomic viral RNA is broadly used for diagnosis, even though the virus may still be detectable when it is already non-infectious. Regarding serology, commercial assays mostly still rely on ancestral spike detection despite significant changes in the genetic sequence of the current circulating variants. We followed a group of 105 non-vaccinated individuals, measuring their viral shedding until negativity and antibody response up to six months. The mean viral detection period until a negative RT-PCR result was 2.2 weeks when using subgenomic RNA-E as a detection target, and 5.2 weeks when using genomic RNA as a detection target. Our neutralising antibody results suggest that, when challenged against a variant different from the variant of first exposure, commercial immunoassays are suboptimal at predicting the neutralising capacity of sera. Additionally, anti-Alpha and anti-Delta antibodies showed very low cross-reactivity between variants. This study provides insights into viral shedding and immune response in pre-Omicron variants like Alpha and Delta, which have been understudied in the published literature. These conclusions point to potential improvements in the clinical management of SARS-CoV-2 cases in order to organise vaccination campaigns and select monoclonal antibody treatments.