Potential recurrence of COVID-19 in a healthcare professional: SARS-CoV-2 genome sequencing confirms contagiousness after re-positivity.
ABSTRACT: Re-positivity of SARS-CoV-2 tests is widely reported, raising discussion about guidance for patient discharge and ending isolation. The unsuccessful recovery of replication-competent virus and/or absence of secondary cases has suggested that re-positive patients are not contagious. This study reports SARS-CoV-2 re-positivity in a healthcare professional 16 days after three negative tests, with viral genome sequencing supporting contagiousness leading to secondary cases.
Project description:<h4>Background</h4> The most sensitive method to detect SARS-CoV-2 relies on rRT-PCR; however, viral RNA can be detected weeks/months after clinical resolution. Since rRT-PCR cannot discern between non- and infectious virus, it is unclear whether the presence of viral RNA after recovery reflects infectious SARS-CoV-2. However, recent studies suggest a positive correlation between antigen rapid tests (Ag-RDT) and virus isolation that is more suited to assess contagiousness. <h4>Objectives</h4> To assess the utility of SARS-CoV-2 diagnostic tests in different settings we evaluated the performance of Ag-RDT-based and a cell culture-based SARS-CoV-2 assay in comparison to rRT-PCR. <h4>Study design</h4> A total of 61 Nasopharyngeal-Swabs tested positive by cobasⓇ SARS-CoV-2 rRT-PCR were in parallel evaluated with the Roche Ag-RDT and a cell culture-based assay to detect SARS-CoV-2. <h4>Results</h4> SARS-CoV-2 was successfully isolated in 51/61 samples corresponding to 83.6%, which was 97.3% or 96.2% when considering samples with E-gene Ct-value <25 and <28, respectively. In comparison, the Ag-RDT showed an overall sensitivity of 85.2%, that increased to 100% and 96.2% using an E-gene Ct-value cut-off of <25 and <28, respectively. There was an overall good agreement between the commercial Ag-RDT and our in-house cell culture-based SARS-CoV-2 detection assay. However, SARS-CoV-2 could be isolated from two samples that tested negative by Ag-RDT. <h4>Conclusions</h4> Our results support the use of the Roche Ag-RDT to detect SARS-CoV-2 exposure in large scale populations. However, it is recommended to use rRT-PCR, potentially in conjunction with cell culture-based SARS-CoV-2 assay, to support clinicians in making decisions regarding fragile patient groups.
Project description:Until treatment and vaccine for coronavirus disease-2019 (COVID-19) becomes widely available, other methods of reducing infection rates should be explored. This study used a retrospective, observational analysis of deidentified tests performed at a national clinical laboratory to determine if circulating 25-hydroxyvitamin D (25(OH)D) levels are associated with severe acute respiratory disease coronavirus 2 (SARS-CoV-2) positivity rates. Over 190,000 patients from all 50 states with SARS-CoV-2 results performed mid-March through mid-June, 2020 and matching 25(OH)D results from the preceding 12 months were included. Residential zip code data was required to match with US Census data and perform analyses of race/ethnicity proportions and latitude. A total of 191,779 patients were included (median age, 54 years [interquartile range 40.4-64.7]; 68% female. The SARS-CoV-2 positivity rate was 9.3% (95% C.I. 9.2-9.5%) and the mean seasonally adjusted 25(OH)D was 31.7 (SD 11.7). The SARS-CoV-2 positivity rate was higher in the 39,190 patients with "deficient" 25(OH)D values (<20 ng/mL) (12.5%, 95% C.I. 12.2-12.8%) than in the 27,870 patients with "adequate" values (30-34 ng/mL) (8.1%, 95% C.I. 7.8-8.4%) and the 12,321 patients with values ?55 ng/mL (5.9%, 95% C.I. 5.5-6.4%). The association between 25(OH)D levels and SARS-CoV-2 positivity was best fitted by the weighted second-order polynomial regression, which indicated strong correlation in the total population (R2 = 0.96) and in analyses stratified by all studied demographic factors. The association between lower SARS-CoV-2 positivity rates and higher circulating 25(OH)D levels remained significant in a multivariable logistic model adjusting for all included demographic factors (adjusted odds ratio 0.984 per ng/mL increment, 95% C.I. 0.983-0.986; p<0.001). SARS-CoV-2 positivity is strongly and inversely associated with circulating 25(OH)D levels, a relationship that persists across latitudes, races/ethnicities, both sexes, and age ranges. Our findings provide impetus to explore the role of vitamin D supplementation in reducing the risk for SARS-CoV-2 infection and COVID-19 disease.
Project description:<h4>Background</h4>Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures.<h4>Methods</h4>Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality.<h4>Results</h4>We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity.<h4>Conclusions</h4>This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.
Project description:We evaluated the clinical protection of BNT162b2 mRNA vaccine in healthcare workers (HCWs) and how COVID-19 manifestations and contagiousness change as the time since first dose increases. A matched (1:2 ratio) parallel cohort study was performed. During the first three months of vaccination campaign, HCWs of the entire health district ASL Città di Torino (Turin, Italy) were classified according to SARS-CoV-2-positivity in respect of the vaccination schedule: post-first-dose (fHCWs, <12 days), partially (PHCWs, ≥12 from first dose to ≤7 days after the second), and totally vaccinated (THCWs, ≥8 days after the second dose). Age-/sex-matched unvaccinated controls were randomly selected from all the SARS-CoV-2-positivity detected in the same district and period. Previous infections were excluded. Clinical and virologic data (ORF1ab gene cycle threshold values, Ct) were recorded. In total, 6800 HCWs received at least one dose, and 55 tested positive subsequently: 20 fHCWs, 25 PHCWs, 10 THCWs. Furthermore, 21.8% of breakthrough infections were in male, with a median age of 49 years (32-56), and 51.4% occurred while SARS-CoV-2 B.1.1.7 variant was predominant. The incident relative risk was 0.13 (0.12-0.15) for PHCWs and 0.06 (0.05-0.07