SARS-CoV-2 N-antigenemia: A new alternative to nucleic acid amplification techniques

Background. Molecular assays on nasopharyngeal swabs remain the cornerstone of COVID-19 diagnostic. Despite massive worldwide efforts, the high technicalities of nasopharyngeal sampling and molecular assays, as well as scarce resources of reagents, limit our testing capabilities. Several strategies failed, to date, to fully alleviate this testing process (e.g. saliva sampling or antigen testing on nasopharyngeal samples). We assessed the performances of a new ELISA microplate assay quantifying SARS-CoV-2 nucleocapsid antigen (N-antigen) in serum or plasma. Methods. The specificity of the assay, determined on 63 non-COVID patients, was 98.4% (95% confidence interval [CI], 85.3 to 100). Performances were determined on 227 serum samples from 165 patients with RT-PCR confirmed SARS-CoV-2 infection included in the French COVID and CoV-CONTACT cohorts. Findings. Sensitivity was 132/142, 93.0% (95% CI, 84.7 to 100), within the first two weeks after symptoms onset. A subset of 73 COVID-19 patients had a serum collected within 24 hours following or preceding a positive nasopharyngeal swab. Among patients with high nasopharyngeal viral loads, Ct value below 30 and 33, only 1/50 and 4/67 tested negative for N-antigenemia, respectively. Among patients with a negative nasopharyngeal RT-PCR, 8/12 presented positive N-antigenemia. The lower respiratory tract was explored for 6/8 patients, showing positive PCR in 5 cases. Interpretation. This is the first demonstration of the N-antigen antigenemia during COVID-19. Its detection presented a robust sensitivity, especially within the first 14 days after symptoms onset and high nasopharyngeal viral loads. These findings have to be confirmed with higher representation of outpatients. This approach could provide a valuable new option for COVID-19 diagnosis, only requiring a blood draw and easily scalable in all clinical laboratories.

Covid-19 and dysregulated cerebral perfusion: observations with multimodal MRI

The pathogenesis of encephalopathy-associated Covid-19 is still unclear. Multimodal brain MRI in 25 Covid-19 patients with neurological symptoms revealed angiographic and brain perfusion changes suggesting an under-recognized dysregulated brain perfusion not identified by morphological neuroimaging alone. Endothelial dysfunction, a key pathomechanism of dysregulated brain perfusion, may contribute to central-nervous-system disturbances in Covid-19.

Observer agreement and clinical significance of chest CT reporting in patients suspected of COVID-19

ObjectivesTo assess inter-observer agreement and clinical significance of chest CT reporting in patients suspected of COVID-19. MethodsFrom 16th to 24th March 2020, 241 consecutive patients addressed to hospital for COVID-19 suspicion had both chest CT and SARS-CoV-2 RT-PCR. Eight observers (2 thoracic and 2 general senior radiologists, 2 junior radiologists and 2 emergency physicians) retrospectively categorized each CT into one out of 3 categories (evocative, compatible for COVID-19 pneumonia, and not evocative or normal). Observer agreement for categorization between all readers and pairs of readers with similar experience was evaluated with the Kappa coefficient. The results of a consensus categorization were correlated to RT-PCR. ResultsObserver agreement across the 3 categories was good between all readers ({kappa} value 0.68 95%CI 0.67-0.70) and good to very good between pairs of readers (0.64-0.85). It was very good ({kappa} 0.81 95%CI 0.79-0.83), fair ({kappa} 0.32 95%CI 0.29-0.34) and good ({kappa} 0.74 95%CI 0.71-0.76) for the categories evocative, compatible and not evocative or normal, respectively. RT-PCR was positive in 97%, 50% and 27% of cases classified in the respective categories. Observer agreement was lower (p=0.045) and RT-PCR positive cases were less frequently categorized evocative in presence of an underlying pulmonary disease (p<0.001). ConclusionInter-observer agreement for chest CT reporting using categorization of findings is good in patients suspected of COVID-19. Among patients considered for hospitalization in an epidemic context, CT categorized evocative is highly predictive of COVID-19, whereas the predictive value of CT decreases between the categories compatible and not evocative. Key resultsO_LIInter-observer agreement for chest CT reporting into categories is good in patients suspected of COVID-19 C_LIO_LIChest CT can participate in estimating the likelihood of COVID-19 in patients presenting to hospital during the outbreak, CT categorized <> being highly predictive of the disease whereas up to a quarter of patients with CT <> had a positive RT-PCR in our study. C_LIO_LIObserver agreement is lower and CTs of positive RT-PCR cases less frequently "evocative" in presence of an underlying pulmonary disease C_LI