Risk of SARS-CoV-2 reinfection is time- and variant-dependant, France, January 2021 to August 2022

Since the emergence of Omicron, reinfections with SARS-CoV-2 have been rising. We estimated the risk of SARS-CoV-2 reinfection in the widely vaccinated French population, from January to August 2022. At nine weeks post-infection, the relative risk of reinfection, primary infection with pre-Delta variants being the reference group, was estimated at 0.43 [95%CI 0.40-0.47] if the primary infection was attributed to Delta, 0.21 [95%CI 0.19-0.24] with BA.1 and 0.17 [95% CI 0.15-0.18] with BA.2, and rapidly waned overtime. After a BA.1 primary infection the protection was similar against BA.2 or BA.4/5 reinfection.

Serious hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants: an exposed-unexposed cohort study in December 2021 from the COVID-19 surveillance databases in France

BackgroundA rapid increase in incidence of the SARS-CoV-2 Omicron variant occurred in France in December 2021, while the Delta variant was prevailing since July 2021. We aimed to determine whether the risk of a severe hospital event following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. MethodsWe conducted a retrospective cohort study to compare severe hospital events (admission to intensive care unit or death) between Omicron and Delta symptomatic cases matched according to week of virological diagnosis and age. The analysis was adjusted for age, sex, vaccination status, presence of comorbidities and region of residence, using Cox proportional hazards model. FindingsBetween 06/12/2021-28/01/2022, 184 364 cases were included, of which 931 had a severe hospital event (822 Delta, 109 Omicron). The risk of severe event was lower among Omicron versus Delta cases; the difference in severity between the two variants decreased with age (aHR=0{middle dot}11 95%CI: 0{middle dot}07-0{middle dot}17 among 40-64 years, aHR=0{middle dot}51 95%CI: 0{middle dot}26-1{middle dot}01 among 80+ years). The risk of severe event increased with the presence of comorbidities (for very-high-risk comorbidity, aHR=4{middle dot}18 95%CI: 2{middle dot}88-6{middle dot}06 among 40-64 years) and in males (aHR=2{middle dot}29 95%CI: 1{middle dot}83-2{middle dot}86 among 40-64 years) and was higher in unvaccinated compared to primo-vaccinated (aHR=6{middle dot}90 95%CI: 5{middle dot}26-9{middle dot}05 among 40-64 years). A booster dose reduced the risk of severe hospital event in 80+ years infected with Omicron (aHR=0{middle dot}27; 95%CI: 0{middle dot}11-0{middle dot}65). InterpretationThis study confirms the lower severity of Omicron compared to Delta. However, the difference in disease severity is less marked in the elderly.

Head-to-head comparison of direct-input RT-PCR and RT-LAMP against RTqPCR on extracted RNA for rapid SARS-CoV-2 diagnostics

Viral pandemics, such as Covid-19, pose serious threats to human societies. To control the spread of highly contagious viruses such as SARS-CoV-2, effective test-trace-isolate strategies require population-wide, systematic testing. Currently, RT-qPCR on extracted RNA is the only broadly accepted test for SARS-CoV-2 diagnostics, which bears the risk of supply chain bottlenecks, often exaggerated by dependencies on proprietary reagents. Here, we directly compare the performance of gold standard diagnostic RT-qPCR on extracted RNA to direct input RT-PCR, RT-LAMP and bead-LAMP on 384 primary patient samples collected from individuals with suspected Covid-19 infection. With a simple five minute crude sample inactivation step and one hour of total reaction time, we achieve assay sensitivities of 98% (direct RT-PCR), 93% (bead-LAMP) and 82% (RT-LAMP) for clinically relevant samples (diagnostic RT-qPCR Ct <35) and a specificity of >98%. For direct RT-PCR, our data further demonstrate a perfect agreement between real-time and end-point measurements, which allow a simple binary classification similar to the powerful visual readout of colorimetric LAMP assays. Our study provides highly sensitive and specific, easy to implement, rapid and cost-effective alternatives to diagnostic RT-qPCR tests.

SARSeq, a robust and highly multiplexed NGS assay for parallel detection of SARS-CoV2 and other respiratory infections

During a pandemic, mitigation as well as protection of system-critical or vulnerable institutions requires massively parallel, yet cost-effective testing to monitor the spread of agents such as the current SARS-CoV2 virus. Here we present SARSeq, saliva analysis by RNA sequencing, as an approach to monitor presence of SARS-CoV2 and other respiratory viruses performed on tens of thousands of samples in parallel. SARSeq is based on next generation sequencing of multiple amplicons generated in parallel in a multiplexed RT-PCR reaction. It relies on a two-dimensional unique dual indexing strategy using four indices in total, for unambiguous and scalable assignment of reads to individual samples. We calibrated this method using dilutions of synthetic RNA and virions to show sensitivity down to a few molecules, and applied it to hundreds of patient samples validating robust performance across various sample types. Double blinded benchmarking to gold-standard quantitative RT-PCR performed in a clinical setting and a human diagnostics laboratory showed robust performance up to a Ct of 36. The false positive rate, likely due to cross contamination during sample pipetting, was estimated at 0.04-0.1%. In addition to SARS-CoV2, SARSeq detects Influenza A and B viruses as well as human rhinovirus and can be easily expanded to include detection of other pathogens. In sum, SARSeq is an ideal platform for differential diagnostic of respiratory diseases at a scale, as is required during a pandemic.