A SARS-CoV-2 and influenza rapid antigen test-based hospital isolation policy awaiting RT-PCR, a prospective observational study.

OBJECTIVES: This study aimed to evaluate the clinical performance of a combined SARS-CoV-2/influenza rapid antigen test (SIRAT) and to evaluate a SIRAT-based hospital isolation policy awaiting RT-PCR results for patients presenting at the emergency department (ED). METHODS: We performed a prospective observational study including all adult patients presenting with influenza-like symptoms at the ED of two hospitals from 31 October 2022 to 31 March 2023. A SIRAT and SARS-CoV-2 and influenza RT-PCR were performed on upper respiratory samples. SIRAT results were compared with RT-PCR. Droplet and contact isolation measures (DCIM) were imposed based on SIRAT results awaiting RT-PCR. We monitored symptomatic nosocomial SARS-CoV-2 and influenza infections potentially caused by delayed isolation of patients with false negative SIRAT and the hours of unnecessary DCIM saved. RESULTS: We included 1740 patients of whom 1296 were hospitalized. SARS-CoV-2 and influenza A/B prevalence were 12.7% (221/1740) and 9.9% (171/1740). Sensitivity and specificity of the SIRAT were 67.7% (95% CI 61.1-73.9%) (149/220) and 99.4% (95% CI 99.0-99.8%) (1510/1518) for SARS-CoV-2 and 52.7% (95% CI 44.9-60.4%) (89/169) and 99.1% (95% CI 98.5-99.5%) (1530/1544) for influenza A/B. We found a 0% nosocomial transmission risk for SARS-CoV-2 (95% CI 0-8.8%) and influenza (95% CI 0-10%). In all, 8712 hours in total or a median up to 6 hours 59 minutes (IQR (interquartile range) 11h03) per patient of unnecessary DCIM were saved. DISCUSSION: A SIRAT-guided hospital isolation policy awaiting RT-PCR results for patients who present at the ED can save unnecessary isolation hours without having to lead to significant symptomatic nosocomial transmission of SARS-CoV-2 or influenza viruses.

Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab.

BACKGROUND: Prolonged shedding of SARS-CoV-2 in immunocompromised patients has been described. Furthermore, an accumulation of mutations of the SARS-CoV-2 genome in these patients has been observed. METHODS: We describe the viral evolution, immunologic response and clinical course of a patient with a lymphoma in complete remission who had received therapy with rituximab and remained SARS-CoV-2 RT-qPCR positive for 161 days. RESULTS: The patient remained hospitalised for 10 days, after which he fully recovered and remained asymptomatic. A progressive increase in Ct-value, coinciding with a progressive rise in lymphocyte count, was seen from day 137 onward. Culture of a nasopharyngeal swab on day 67 showed growth of SARS-CoV-2. Whole genome sequencing (WGS) demonstrated that the virus belonged to the wildtype SARS-CoV-2 clade 20B/GR, but rapidly accumulated a high number of mutations as well as deletions in the N-terminal domain of its spike protein. CONCLUSION: SARS-CoV-2 persistence in immunocompromised individuals has important clinical implications, but halting immunosuppressive therapy might result in a favourable clinical course. The long-term shedding of viable virus necessitates customized infection prevention measures in these individuals. The observed accelerated accumulation of mutations of the SARS-CoV-2 genome in these patients might facilitate the origin of new VOCs that might subsequently spread in the general community.

SARS-CoV-2 Alpha-Variant Outbreak Amongst a Partially Vaccinated Long-Term Care Facility Population in The Netherlands-Phylogenetic Analysis and Infection Control Observations.

Despite extensive vaccination and booster programs, SARS-CoV-2 outbreaks in long-term care facilities (LTCF) continue to occur. We retrospectively describe a SARS-CoV-2 outbreak amongst a partially vaccinated LTCF population in The Netherlands which occurred in March 2021. The facility comprised three floors functioning as separate wards. Nasopharyngeal swabs for SARS-CoV-2 qRT-PCR were obtained from residents and staff presenting with COVID-19-like symptoms and from all residents and staff during two point prevalence screenings (PPS). Samples meeting technical criteria were included for phylogenetic analysis. Positive SARS-CoV-2 qRT-PCR were obtained from 11 (18%) of 61 residents and 8 (7%) of 110 staff members between March 8 and March 25. Seven (37%) cases and five (63%) vaccinated cases were diagnosed through PPS. Cases were found on all wards. Phylogenetic analysis (n = 11) showed a maximum difference of four nucleotides between sequences on the outer branches of the tree, but identified two identical sequences on the root differing maximum two nucleotides from all other sequences, suggesting all did belong to the same cluster. Our results imply that PPS is useful in containing SARS-CoV-2 outbreaks amongst (vaccinated) LTCF populations, as an entire LTCF might behave as a single epidemiological unit and it is preferable to maximize the number of samples included for phylogenetic analysis.

Evaluation of the SARS-CoV-2 positivity ratio and upper respiratory tract viral load among asymptomatic individuals screened before hospitalization or surgery in Flanders, Belgium.

INTRODUCTION: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in the Belgian community is mainly estimated based on test results of patients with coronavirus disease (COVID-19)-like symptoms. The aim of this study was to investigate the evolution of the SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) positivity ratio and distribution of viral loads within a cohort of asymptomatic patients screened prior hospitalization or surgery, stratified by age category. MATERIALS/METHODS: We retrospectively studied data on SARS-CoV-2 real-time RT-PCR detection in respiratory tract samples of asymptomatic patients screened pre-hospitalization or pre-surgery in nine Belgian hospitals located in Flanders over a 12-month period (1 April 2020-31 March 2021). RESULTS: In total, 255925 SARS-CoV-2 RT-PCR test results and 2421 positive results for which a viral load was reported, were included in this study. An unweighted overall SARS-CoV-2 real-time RT-PCR positivity ratio of 1.27% was observed with strong spatiotemporal differences. SARS-CoV-2 circulated predominantly in 80+ year old individuals across all time periods except between the first and second COVID-19 wave and in 20-30 year old individuals before the second COVID-19 wave. In contrast to the first wave, a significantly higher positivity ratio was observed for the 20-40 age group in addition to the 80+ age group compared to the other age groups during the second wave. The median viral load follows a similar temporal evolution as the positivity rate with an increase ahead of the second wave and highest viral loads observed for 80+ year old individuals. CONCLUSION: There was a high SARS-CoV-2 circulation among asymptomatic patients with a predominance and highest viral loads observed in the elderly. Moreover, ahead of the second COVID-19 wave an increase in median viral load was noted with the highest overall positivity ratio observed in 20-30 year old individuals, indicating they could have been the hidden drivers of this wave.

Evaluation of the test accuracy of a SARS-CoV-2 rapid antigen test in symptomatic community dwelling individuals in the Netherlands.

BACKGROUND: SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (qRT-PCR) is well suited for the diagnosis of clinically ill patients requiring treatment. Application for community testing of symptomatic individuals for disease control purposes however raises challenges. SARS-CoV-2 rapid antigen tests might offer an alternative, but quality evidence on their performance is limited. METHODS: We conducted an evaluation of the test accuracy of the 'BD Veritor System for Rapid Detection of SARS-CoV-2' (VRD) compared to qRT-PCR on combined nose/throat swabs obtained from symptomatic individuals at Municipal Health Service (MHS) COVID-19 test centers in the Netherlands. In part one of the study, with the primary objective to evaluate test sensitivity and specificity, all adults presenting at one MHS test center were eligible for inclusion. In part two, with the objective to evaluate test sensitivity stratified by Ct (cycle threshold)-value and time since symptom onset, adults who had a positive qRT-PCR obtained at a MHS test center were eligible. FINDINGS: In part one (n = 352) SARS-CoV-2 prevalence was 4.8%, overall specificity 100% (95%CI: 98·9%-100%) and sensitivity 94·1% (95%CI: 71·1%-100%). In part two (n = 123) the sensitivity was 78·9% (95%CI: 70·6%-85·7%) overall, 89·4% (95% CI: 79·4%-95·6%) for specimen obtained within seven days after symptom onset and 93% (95% CI: 86%-97.1%) for specimen with a Ct-value below 30. INTERPRETATION: The VRD is a promising diagnostic for COVID-19 testing of symptomatic community-dwelling individuals within seven days after symptom onset in context of disease control. Further research on practical applicability and the optimal position within the testing landscape is needed.