ABSTRACT
OBJECTIVEUsing data from European prospective household studies, we systematically compared the symptom burden of the wild-type and Alpha variant infected individuals versus the Omicron BA.1 and BA.2 infected individuals across paediatric and adult age-groups. In addition, we measured the impact of COVID-19 vaccination on the Omicron symptom burden. METHODSThe household transmission studies were conducted during the wild-type and Alpha period (April 2020 to April 2021) and the early Omicron BA.1 and BA.2 dominant period (January to March 2022). All three studies used similar protocols. Households were prospectively followed from detection of the first SARS-CoV-2 index case until at least day 21 including (repeated) PCR testing, paired serology and daily symptom reporting for all household members. To avoid possible index-case ascertainment bias, we restricted analyses to secondary household cases. Age-stratified SARS-CoV-2 symptom burden was compared for wild-type/Alpha versus Omicron infections and for primary versus primary plus booster series vaccinated adult cases. FINDINGSIn total 216 secondary cases from wild-type/Alpha, and 130 from the Omicron period were included. Unvaccinated children <12 years experienced more symptoms and higher maximum and cumulative severity scores during the Omicron compared to the wild-type/Alpha period (p=0.004, p=0.011 and p=0.075, respectively). In adults, disease duration and maximum and cumulative severity scores were reduced during the Omicron period. Adjusted for age, gender and prior immunity Omicron was associated with lower odds for loss of smell or taste (Odds Ratio [OR]: 0.14; 95%CI 0.03-0.50), and higher, but non-significant odds for upper respiratory symptoms, fever and fatigue (ORs varying between 1.85-2.23). Comparing primary versus primary plus booster vaccinated adult cases during the Omicron period no differences were observed in disease severity or duration (p[≥]0.12). INTERPRETATIONIn children, the Omicron variant causes higher symptom burden compared to the wild-type/Alpha. Adults experienced a lower symptom burden possibly due to prior vaccination. A shift in most frequently reported symptoms occurred with a marked reduction in loss of smell or taste during the Omicron period. An additional effect of booster vaccination on symptom severity in infected adults compared to primary series only, could not be demonstrated.
ABSTRACT
BackgroundDespite high vaccination rates in the Netherlands, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate. Longitudinal sewage monitoring was implemented along with the notification of cases as two parts of the surveillance pyramid to validate the use of sewage surveillance for monitoring SARS-CoV-2, as an early warning tool, and to measure the effect of interventions. MethodsSewage samples were collected from nine neighborhoods from September 2020 to November 2021, and compared with reported cases. Comparative analysis and modeling were performed to understand the correlation between wastewater and case trends. FindingsUsing high resolution sampling, normalization of wastewater SARS-CoV-2 concentrations and normalization of reported positive tests for testing delay and intensity, the incidence of reported positive tests could be modeled based on sewage data, and trends in both surveillance systems coincided. The high collinearity implied that high levels of viral shedding around the onset of disease largely determines SARS-CoV-2 levels in wastewater and the observed relation was independent of SARS-CoV-2 variants and vaccination levels. InterpretationWastewater surveillance can accurately display SARS-CoV-2 dynamics for small and large locations, and is sensitive enough to measure small variations in the number of infected individuals within or between neighborhoods. With the transition to a post-acute phase of the pandemic, continued sewage surveillance can help to keep sight on reemergence, but continued "pyramid" validation studies are needed to assess the predictive value of sewage surveillance with new variants. FundingHorizon H2020, Adessium Foundation, STOWA, TKI, Ministry of Health, Welfare and Sport
ABSTRACT
BackgroundHousehold transmission studies are useful to obtain granular data on SARS-CoV-2 transmission dynamics and to gain insight into the main determinants. In this interim report we investigated secondary attack rates (SAR) by household and subject characteristics in the Netherlands and Belgium. MethodsHouseholds with a real-time reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 index case were enrolled <48 hours following report of the positive test result. Daily symptom follow-up, standardized nose-throat sampling at enrollment and at new-onset acute respiratory illness (ARI) and paired dried blood spots (DBS) were collected from each participant. Children 0-2 years of age were additionally requested to collect a stool sample 7 days after enrollment and at new-onset of ARI. Swabs and stool samples were tested by RT-PCR for virus detection and DBS by multiplex protein microarray for detection of SARS-CoV-2 antibodies. The SAR was calculated 1) per-household as the proportion of households with [≥]1 secondary SARS-CoV-2 case and 2) per-person as the probability of infection in household members at risk. We explored differences in SARs by household and subject characteristics. ResultsThis analysis includes 117 households that completed follow-up between April-December 2020. Among 382 subjects, 74 secondary infections were detected, of which 13 (17.6%) were asymptomatic and 20 (27.0%) infections were detected by seroconversion only. Of cases detected by RT-PCR, 50 (67.6%) were found at enrollment. The household SAR was 44.4% (95%-CI: 35.4-53.9%) and was higher for index cases meeting the ARI case definition (52.3%; 95%-CI 41.4-62.9%) compared to mildly symptomatic (22.2%; 95%-CI: 9.4-42.7%) and asymptomatic index cases (0.0%; 95%-CI: 0.0-80.2%). The per-person SAR was 27.9% (95%-CI: 22.7-33.8%). Transmission was lowest from child to parent (9.1%; 95%-CI: 2.4-25.5%) and highest from parent to child (28.1%; 95%-CI: 19.7-38.4%) and in children 6-12 years (34.2%; 95%-CI: 20.1-51.4%). Among 141 subjects with RT-PCR confirmed SARS-CoV-2 infections, seroconversion was detected in 111 (78.7%). ConclusionWe found a high household SAR, with the large majority of transmissions detected early after identification of the index case. Our findings confirm differential SAR by symptom status of the index. In almost a quarter of RT-PCR positive cases, no antibodies were detected. Other factors influencing transmission will be further explored as more data accumulate.
ABSTRACT
BackgroundRapid detection of infectious individuals is essential in stopping the further spread of SARS-CoV-2. Although rapid antigen test is not as sensitive as the gold standard RT-PCR, the time to result is decreased by day(s), strengthening the effectiveness of contact tracing. MethodsThe Roche/SD Biosensor lateral flow antigen rapid test was evaluated in a mild symptomatic population at a large drive through testing site. A second nasopharyngeal swab was directly tested with the rapid test on site and results were compared to RT-PCR and virus culture. Date of onset and symptoms were analysed using data from a clinical questionnaire. ResultsWe included 970 persons with complete data. Overall sensitivity and specificity were 84.9% (CI95% 79.1-89.4) and 99.5% (CI95% 98.7-99.8) which translated into a positive predictive value of 97.5% (CI95% 94.0-99.5) under the current regional PCR positivity of 19.2%. Sensitivity for people with high loads of viral RNA (ct <30, 2.17E+05 E gene copy/ml) and who presented within 7 days since symptom onset increased to 95.8% (CI95% 90.5-98.2). Band intensity and time to result correlated strongly with viral load thus strong positive bands could be read before the recommended time. Around 98% of all viable specimen with ct <30 were detected successfully indicating that the large majority of infectious people can be captured with this test. ConclusionAntigen rapid tests can detect mildly symptomatic cases in the early phase of disease thereby identifying the most infectious individuals. Using this assay can have a significant value in the speed and effectiveness of SARS-CoV-2 outbreak management. SummaryO_LIPeople with early onset and high viral load were detected with 98.2% sensitivity. C_LIO_LI97% of individuals in which virus could be cultured were detected by the rapid test. C_LIO_LIThis test is suitable to detect mild symptomatic cases. C_LI
ABSTRACT
We present an in-depth analysis of data from drive through testing stations using rapid antigen detection tests (RDTs), RT-PCR and virus culture, to assess the ability of RDTs to detect infectious cases. We show that the detection limits of five commercially available RDTs differ considerably, impacting the translation into the detection of infectious cases. We recommend careful fit-for-purpose testing before implementation of antigen RDTs in routine testing algorithms as part of the COVID-19 response.