Comparison of SARS-CoV-2 anti-spike IgG and anti-nucleoprotein IgG seroprevalence amongst a pre-vaccine cohort of healthcare workers at an academic medical center in Boston, Massachusetts

Background: Accurate measurement of antibodies is a necessary tool for assessing exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and facilitating an understanding of the role antibodies play in overall immunity. Most available assays are qualitative in nature and employ a threshold to determine the presence of antibodies, however some-quantitative assays are now available. Using cross-sectional data collected as part of an ongoing longitudinal cohort study, we aim to assess the seroprevalence of SARSCoV-2 antibodies using the Abbott AdviseDX SARS-CoV-2 IgG II (anti-S) assay and compare these results to previously measured seroprevalence of anti-nucleoprotein (anti-N) IgG in this cohort of health care workers (HCWs) at an academic medical center in Boston. Method(s): A total of 1,743 HCWs at Boston Medical Center (BMC) provided serum samples that were analyzed for SARS-CoV-2 anti-S IgG and IgM using the Abbott AdviseDx SARS-CoV-2 IgG II and Abbott AdviseDx SARS-CoV-2 IgM assay, respectively. These results were compared to previously assessed anti-N IgG seroprevalence. Precision, linearity, and positive and negative concordance with prior reverse transcription-polymerase chain reaction (RT-PCR) test were evaluated for the anti-S IgG II assay. Seroprevalence and its association with demographic variables was also assessed. Result(s): Linearity and precision results were clinically acceptable. The anti-S IgG positive and negative concordance with RT-PCR results were 88.2% (95% CI: 79.4-94.2%) and 97.4% (95% CI: 95.2-98.8%), respectively. Overall, 126 (7.2%) of 1,743 participants were positive for anti-S IgG. The original agreement in this population with the qualitative, anti-N IgG assay was 70.6%. Upon optimizing the threshold from 1.4 to 0.49 signal to cut-off ratio (S/CO) of the anti-N IgG assay, the positive agreement of the assay increased to 84.7%. Conclusion(s): The anti-S IgG II assay demonstrated reproducible and reliable measurements. Higher anti-S IgG to anti-N IgG seroprevalence highlights the present differences between serum antibodies to different epitopes of the SARS-CoV-2 virus. Further, the greater seroprevalence of anti-S IgG compared to positive RT-PCR results points to a potential for asymptomatic infection among this group of HCWs. Our results also highlight the potential utility in optimizing thresholds of the qualitative SARS-CoV-2 anti-N IgG assay for better agreement with the anti-S IgG II assay by the same vendor.Copyright © 2022 by the Author(s).

Born into an isolating world: family-centred care for babies born to mothers with COVID-19.

Background: The benefits of facilitating breastmilk feeding and close contact between mother and neonate (family-centred care; FCC) in the perinatal period are well-established. The aim of this study was to determine how the delivery of FCC practices were impacted for neonates born to mothers with perinatal SARS-CoV-2 infection during the COVID-19 pandemic. Methods: Neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy were identified from the 'EsPnIC Covid paEdiatric NeonaTal REgistry' (EPICENTRE) multinational cohort between 10 March 2020 and 20 October 2021. The EPICENTRE cohort collected prospective data on FCC practices. Rooming-in and breastmilk feeding practice were the main outcomes, and factors influencing each were determined. Other outcomes included mother-baby physical contact prior to separation and the pattern of FCC components relative to time and local site guidelines. Findings: 692 mother-baby dyads (13 sites, 10 countries) were analysed. 27 (5%) neonates were positive for SARS-CoV-2 (14 (52%) asymptomatic). Most sites had policies that encouraged FCC during perinatal SARS-CoV-2 infection for most of the reporting period. 311 (46%) neonates roomed-in with their mother during the admission. Rooming-in increased over time from 23% in March-June 2020 to 74% in January-March 2021 (boreal season). 330 (93%) of the 369 separated neonates had no FCC physical contact with their mother prior, and 319 (86%) were asymptomatic. Maternal breastmilk was used for feeding in 354 (53%) neonates, increasing from 23% to 70% between March-June 2020 and January-March 2021. FCC was most impacted when mothers had symptomatic COVID-19 at birth. Interpretation: This is the largest report of global FCC practice during the COVID-19 pandemic to date. The COVID-19 pandemic may have impacted FCC despite low perinatal transmission rates. Fortunately, clinicians appear to have adapted to allow more FCC delivery as the COVID-19 pandemic progressed. Funding: The National Health and Medical Research Council (Australia): Grant ID 2008212 (DGT), Royal Children's Hospital Foundation: Grant ID 2019-1155 (EJP), Victorian Government Operational Infrastructure Support Program.

A comprehensive, multidisciplinary approach to breast cancer treatment during the COVID-19 pandemic improves time to treatment

A recently published study from the National COVID Cohort Collaborative (N3C) revealed that COVID-19 (CoV) positive status in cancer patients (pts) was associated with an increased risk of all-cause mortality at 1 year when compared to CoV negative status. In addition, age ≥65 years, Southern or Western US residence, an adjusted Charlson Comorbidity Index score ≥4, multi-tumor sites, and recent cytotoxic therapy were associated with increased risk of all-cause mortality. The CoV pandemic significantly impacted our hospital's operations in 03/2020. Regardless, the hospital remained operational for cancer pts through the entire pandemic. The objective of this study is to investigate the impact of CoV pandemic on breast cancer (BC) treatment and outcomes in our academic medical center in East Tennessee. A retrospective cohort group was identified from a prospectively monitored Cancer Registry database of 706 pts comparing those diagnosed with BC from 3/1/2019-12/31/2019 (G1=406 pts) to those diagnosed from 3/1/2020-12/31/2020 (G2=300 pts). The impact of CoV pandemic was studied utilizing SPSS statistical software. During the pandemic, 26% fewer pts were treated for BC in our hospital, likely resulting from decreased screening rates. Pts in G2 were significantly younger than in G1 (mean age 61.4 vs 63.5), but no difference was observed in racial and insurance status or diagnosis with invasive BC vs DCIS (Table 1). CoV test results for 20 pts from G1 and all 300 pts in G2 (Table 2) were analyzed. Only 8 pts (2.6%) tested positive for CoV (all in G2). For 5 of these 8 pts, CoV positivity had no impact on their care or survival, since CoV infection happened either before or after their BC diagnosis and therapy. CoV caused delay of the first course of treatment in 9/300 (3%) G2 pts: 3/9 delays were due to CoV infection and 6/9 delays were due to implementation of nation-wide CoV pandemic guidelines for care of BC pts. Of the 6/9 pts who experienced delayed treatment, 5 were diagnosed with BC in 03/2020 and 1 in 06/2020, all in the time period of the national "lock-down". Delayed surgical treatment had no impact on patient outcomes. During the pandemic, the number of days from diagnosis to chemotherapy or hormonal treatment was significantly shorter (p<0.05) in the G2 cohort than in the pre-pandemic G1 cohort. The number of days to surgery or radiation treatment although non-significant was also lower in the G2 cohort. CoV did not impact readmission to our hospital within 30 days of surgery. None of the BC pts died from CoV. One-year overall survival of our BC pts was not negatively impacted by the CoV pandemic. Our results show that during the CoV pandemic, BC pts were receiving chemotherapy and hormonal treatment sooner than in the pre-pandemic time, likely due to effective teamwork while implementing national guidelines for triaging and administering neoadjuvant treatment during the pandemic. In contrast to N3C data, CoV pandemic did not negatively impact outcomes or 1-year overall survival in our patients. Future studies will determine if these findings remain at the 5 and 10-year follow-up period.

Impact of School Opening Model on Cases of SARS-CoV-2 in Surrounding Communities: A Nationwide, Retrospective Cohort Study

Background. Early in the COVID-19 pandemic, elementary and secondary schools were closed. There was variation in school opening mode (traditional, hybrid, remote) in fall 2020.The aim of this national, retrospective cohort study is to evaluate the impact of in-person learning on community incidence of SARS-CoV-2 and COVID-19-related deaths. Methods. Data were extracted from several data sources. School opening mode was collected from the Burbio school tracker, which tracks school openings in a sample of school districts across the US. Incidence of SARS-CoV-2 and COVID-19 related deaths were obtained from the CDC. Data on community-level SARS-CoV-2 mitigation measures were obtained from the Oxford University COVID-19 Government Response Tracker. The effect of school mode on SARS-CoV-2 cases and deaths/100,000 during the 12-weeks following the start of school was estimated using a log-linear model with state, week, and state-week fixed effects. Models were stratified by 9 US Census divisions and adjusted for variables determined a priori to be potentially associated with the outcome. Results. 519 US counties were included (Figure 1);mean cases of COVID-19 were increasing across all regions during the weeks following the start of school, regardless of school mode. Adjusted absolute differences in COVID-19 cases in counties with hybrid and traditional school opening modes relative to fully remote learning models are presented in Figure 2. In the Northeast and Midwest regions of the country, COVID-19 case rates were not statistically different between different school modes. However, in the South and West regions, there was a statistically significant increase in cases per week among counties that opened in an in-person relative to remote learning model, ranging from 17.1 (95% CI: 0.3-33.8) to 24.4 (95% CI: 7.3-41.5) in the South and from 19.0 (95% CI: 8.8-29.3) to 109.2 (95% CI: 50.4-168.0) in the West. There was no impact of school opening mode on COVID-19-related deaths. Conclusion. Impact of school mode on community case-rates of SARS-CoV-2 varied across the US. In some areas of the country, traditional school mode was associated with increases in case rates relative to virtual while there were no differences in other regions.

It's Time to Rethink How We Screen for Communicable Diseases in the Emergency Department: Lessons Learned From COVID-19

Study Objectives: COVID-19 symptom severity varies between patients, and some remain asymptomatic. During early April 2020, 70% of patients admitted to the emergency department (ED) of a major hospital in New England had COVID-19, many of whom required treatment in the intensive care unit. As the volume of COVID-19 cases presenting to the ED increased, it became essential to develop accurate triage protocols to separate COVID-positive from COVID-negative patients. This study assessed which of three different clinical screening tools – a nursing triage screen (NTS), an ED clinician Review of Systems (ROS), and a standardized ED attending physician COVID-19 probability assessment – was best at identifying patients who had COVID-19 (based on subsequent PCR confirmation). Methods: All 748 patients admitted from the ED between April 27, 2020, and May 17, 2020 were included. Sensitivity, specificity, and positive and negative predictive values were calculated for each screening tool. Logistic regression was used to assess each tool’s performance. A principal components analysis (PCA) was performed;the resulting factors were used to model COVID-19 positivity. Results: The emergency physician’s probability assessment yielded higher sensitivity (0.62, 95% confidence interval [CI] 0.53-0.71, Table 1) than the NTS (0.46, 95% CI 0.37-0.56), and had higher specificity (0.76, 95% CI 0.72-0.80) than the NTS (0.71, 95% CI 0.66-0.75) and the emergency clinician ROS (0.62, 95% CI 0.58-0.67). Categorization as moderate or high probability on the emergency physician’s probability assessment was also associated with the highest odds of having COVID-19 in regression analyses (adjusted odds ratio=4.61, 95% CI 3.01-7.06). Moderate agreement (kappa 0.41-0.60) was observed between the NTS and ED clinician ROS for fever, cough, shortness of breath, and diarrhea;fair agreement (kappa 0.21-0.40) for sore throat, headache, abdominal pain, and vomiting;and poor agreement (kappa 0.00-0.20) for myalgias and chills. The 323 patients who had a response recorded for every symptom were included in the PCA. Only Factor 1 (fever, chills, fatigue, sore throat, rhinorrhea, and cough) was associated with increased odds of testing positive for COVID-19. Conclusion: While the emergency physician’s probability assessment had higher sensitivity and specificity than the other two tools, none of the tools evaluated in this study was sufficiently accurate enough to replace a COVID-19 PCR test on a patient entering a clinical setting where transmission control is crucial. These findings suggest that hospitals not rely on symptom or probability assessment in determining infection status but continue to utilize widespread testing. We recommend that providers in other countries experiencing COVID-19 surges consider the relevance of these findings and that as the pandemic develops (with the potential for continued new variant strains), diagnostic testing efforts should supersede the use of clinical screening tools. [Formula presented]