ABSTRACT
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).
ABSTRACT
Background. Omicron rapidly replaced delta as the predominant strain causing COVID-19 related illness in the United States (US) in December 2021, the same month the US CDC reduced the recommended isolation period from 10 to 5 days for asymptomatic individuals or those with resolving symptoms. New evidence suggests some asymptomatic individuals with omicron remain culture positive beyond 5 days from diagnosis. We sought to evaluate the performance of a SARS-CoV-2 antigen rapid diagnostic test (RDT) in predicting persistent potential for transmission at the end of a five-day isolation period among young, fully vaccinated individuals in a university community setting. Methods. A subgroup of participants enrolled in a longitudinal COVID-19 cohort were asked to self-perform RDTs on days 4 to 6 from diagnostic test date in addition to a separate self-collected anterior nasal swab used for culture and RT-PCR, and a daily symptom screen (15 COVID-19 symptom questions on a 4-point scale). We calculated the daily and overall sensitivity and specificity of the RDTs in comparison to SARS-CoV-2 culture result. We also compared the N1 cycle threshold (CT) values and symptom score on each day of the study by RDT results. Results. Of 23 participants, the mean age was 20 years, all had completed their primary COVID-19 vaccine series, and 13 (65.0%) had received a booster vaccine (Table 1). Compared to culture, sensitivity and specificity of the RDTs were 100% and 62% respectively (Table 2). Compared to participants with negative RDTs, median CT values were lower in those with positive RDTs on each day of the study (Figure 1). Participants who had positive RDTs on all three days had higher symptom scores (Figure 2) than those without. Conclusion. RDTs have a high sensitivity in detecting culture positive SARS-CoV-2 on Days 4 to 6 from initial diagnostic test. However, the high false positive rate of 38% means that over a third of culture negative individuals will stay in isolation longer than necessary if RDTs are used in test to release from isolation protocols. Viral loads (CT values) and symptom scores were higher for participants with persistently positive RDT result. An approach that uses a combination of RDTs, CT values and symptom score may prove useful in guiding isolation duration.
ABSTRACT
Background. Vaccination is a fundamental element of pandemic control;however, insufficient data exists on vaccine's impact on SARS-CoV-2 viral dynamics. We aimed to evaluate the relationship between time to negative viral culture conversion after diagnosis and time since most recent COVID-19 vaccination. Scatterplot illustrating relationship between time since completion of initial COVID-19 vaccine series and time to culture conversion among un-boosted participants. The vaccine type received has also been designated by plot labels. The black solid line shows the best fit for the Spearman correlation model;gray shading denotes 95% confidence interval around this estimate. Spearman correlation coefficient, R, and p-value were estimates for the model. Methods. CoViD Post-vax is longitudinal cohort study collecting baseline clinical questionnaires, and daily anterior nasal swabs and symptom screens on enrolled Boston University SARS-CoV-2 PCR-positive cases detected through a serial screening testing program or symptomatic testing. Data was collected from November 2021 to March 2022. Participants were excluded from analysis if they lacked at least one positive culture or did not culture convert during their study involvement. Scatter plots comparing time to culture conversion to time from initial vaccine series were created.We calculated spearman correlation coefficients to determine the relationship between time to culture conversion and time from last vaccination for all participants, those who completed the initial vaccine series (unboosted), and those who were boosted. Scatterplot illustrating relationship between time since receiving a booster COVID-19 vaccine dose and time to culture conversion among boosted participants. The vaccine type received has also been designated by plot labels. The black solid line shows the best fit for the Spearman correlation model;Gray shading denotes 95% confidence interval around this estimate. Spearman correlation coefficient, R, and p-value were estimates for the model. Results. Of 54 CoViD Post-Vax participants included in this analysis, the mean age was 21 years (SD=2) and culture conversion occurred after a median of 4 days (IQR=3-5.75). There was no association between time to culture conversion and time since last dose of a COVID-19 vaccination (R= -0.13, p= .34). When stratified by vaccination status, there was no association between time to culture conversion and time since initial COVID-19 vaccine series (R= -0.25, p= .21, n=26) or time since COVID-19 booster vaccination (R= -0.24, p= .22, n=28). Conclusion. Our results show no significant relationship between time to culture conversion and time since most recent dose of COVID-19 vaccination in an initially culture positive, young, University-based cohort. More work needs to be done to understand the impact of symptom severity, disease burden, SARS-CoV-2 variants, and COVID-19 vaccine status on duration of transmissible SARS-CoV-2 infection. (Figure Presented).
ABSTRACT
BACKGROUND: Neonatal gonococcal conjunctivitis is usually transmitted perinatally;however, in adults, gonococcal conjunctivitis occurs primarily via autoinoculation from a preexisting gonorrhea infection at another mucosal site. As the incidence of gonorrhea in California (CA) continues to increase, gonococcal conjunctivitis morbidity may also rise. There are limited data describing the incidence of this extragenital manifestation of gonorrhea. We sought to describe gonococcal conjunctivitis in CA. METHOD(S): All gonorrhea cases reported to the CA Department of Public Health (CDPH) from January 2018 through December 2021 were flagged if the specimen source reported for gonorrhea was suspicious of gonococcal conjunctivitis. A clinician reviewed these cases to determine likelihood of gonococcal conjunctivitis;confirmed cases were summarized and a bivariate negative binomial model was used to evaluate temporal trends. RESULT(S): During the study period, there were 71 gonococcal conjunctivitis cases reported in CA, representing a cumulative incidence of 0.05 cases per 100,000 people. There were 22 (31.0%) cases in 2018, 18 (25.3%) in 2019, 9 (12.7%) in 2020, and 22 (31.0%) in 2021;there was no significant trend in the number of cases reported from 2018- 2021 (p>0.05), but the number of gonococcal conjunctivitis cases reported in 2020 was significantly fewer than other years (p<0.05). There were 12 (16.9%) infants (<1 year old), including 7 (9.8%) neonates (<28 days old). There were 4 (5.6%) cases who were <18 years old and 55 (77.4%) at least 18 years old. The majority (42, 60%) of cases were males. CONCLUSION(S): Though gonorrhea rates continue to increase in CA, gonococcal conjunctivitis rates remained steady, other than both decreasing in 2020 (likely due to COVID-19-related decreases in STI testing and diagnosis). We hypothesize this may be an underestimation of the true incidence of gonococcal conjunctivitis in CA due to the nature of passive surveillance for this infection.
ABSTRACT
Background. SARS-CoV-2 continues to spread globally, including in limited resource settings. It is therefore important to derive general case definitions that can be useful and accurate in the absence of timely test results. We aim to validate the World Health Organization (WHO) case definition, a symptom-screening tool currently used to identify SARS-CoV-2 cases in a cohort of symptomatic health care providers (HCP) who completed a symptom survey interview and received a PCR test at Boston Medical Center (BMC) between March 13, 2020 and May 5, 2020. Methods. We classified each HCP as a probable or not probable case of SARSCoV-2 based on the WHO case definition. Using PCR test as gold standard, we computed the sensitivity and specificity of the WHO case definition. We used a stepwise logistic regression model on all PCR-tested HCP to identify symptoms predictive of PCR positivity. Results. Of 328 included HCP, 109 (33.2%) were PCR positive, 213 (64.9%) negative, and 6 (1.8%) had indeterminate test result. The sensitivity and specificity of the WHO case definition were 65.1% and 74.6%, respectively. The positive predictive value was 56.8% and the negative predictive value was 80.7%. Symptoms found to be predictive of PCR positivity were fever, headache, loss of smell and/or loss of taste, and muscle ache/joint pain. Sore throat was found to be predictive of PCR negativity. The area under the curve using the final model was 0.8412. All statistically significant symptoms included in the final model, were also included in the WHO case definition. Conclusion. In our largely symptomatic HCP cohort, our model yielded similar symptoms to those identified in the WHO probable case definition. As seen in similar studies, it is unlikely that further adjustment will improve the performance of a SARSCoV-2 case definition. However, it is concerning that 35% (38/109) of PCR positive SARS-CoV-2 HCP would have been classified as not probable cases by the WHO definition, given that this definition does not even include asymptomatic cases. This is further evidence for global building of laboratory capacity and development of affordable diagnostics to improve global pandemic control.
ABSTRACT
Background. Persistent symptoms after acute COVID-19 are being increasingly reported. To date, little is known about the cause, clinical associations, and trajectory of "Long COVID". Methods. Participants of an outpatient clinical trial of Peginterferon-Lambda as treatment for uncomplicated SARS-CoV-2 infection were invited to long term follow-up visits 4, 7, and 10 months after initial COVID-19 diagnosis. Ongoing symptoms and functional impairment measures (work productivity and activity index (WPAI), NIH toolbox smell test, 6-minute walk test) were assessed and blood samples obtained. "Long COVID" was defined as presence of 2 or more typical symptoms (fatigue, hyposmia/hypogeusia, dyspnea, cough, palpitations, memory problems, joint pain) at follow up. Associations between baseline characteristics, initial COVID-19 clinical course, and presence of "Long COVID" during follow-up were assessed using generalized estimating equations accounting for repeated measurements within individuals. Results. Eighty-seven participants returned for at least one follow-up visit. At four months, 29 (34.1%) had "Long COVID";19 (24.7%) met criteria at 7 months and 18 (23.4%) at 10 months (Figure 1). Presence of "Long COVID" symptoms did not correlate significantly with functional impairment measures. Female gender (OR 3.01, 95% CI 1.37-6.61) and having gastrointestinal symptoms during acute COVID-19 illness (OR 5.37, 95% CI 1.02-28.18) were associated with "Long COVID" during follow-up (Figure 2). No significant associations with baseline immunologic signatures were observed. Conclusion. "Long COVID" was prevalent in this outpatient trial cohort and had low rates of resolution over 10 months of follow up. Female sex and gastrointestinal symptoms during acute illness were associated with "Long COVID". Identifying modifiable risk factors associated with the development of persistent symptoms following SARS-CoV-2 infection remains a critical need.
ABSTRACT
Background Adult data have shown that Infliximab (IFX) impairs the antibody response to a single dose of the mRNA-BNT162b2 SARS-CoV-2 vaccine in patients with inflammatory bowel disease (IBD). The true impact of IFX on SARS-CoV-2 vaccine efficacy in pediatric IBD (PIBD) patients is unknown. Aims To evaluate the humoral immune response to the BNT162b2 SARS-CoV-2 in PIBD patients treated with anti-tumor necrosis factor (TNF) therapy. Methods PIBD patients treated with anti-TNF therapy either alone or in combination with an immunomodulator, who received at least one dose of the BNT162b2 SARS-CoV-2 vaccine, were prospectively enrolled from 1st June 2021 at BC Children’s Hospital. Serum antibody levels for [spike (S) protein and receptor-binding domain (RBD)] were determined at baseline and 28 days after their first and second vaccine doses. Antibody responses were assessed using multiplex serology IgG assay against four SARS-CoV-2 antigens: S-protein, RBD, N-terminal domain (NTD) and N-protein using the SARS-CoV-2 Panel 2 (Meso Scale Diagnostics). Results Forty-two PIBD patients received a single dose of BNT162b2 (median age 14.5yrs (IQR 14–16);43% female;79% crohn’s disease, 21%, ulcerative colitis). Of those on IFX monotherapy (43%), both S-protein and RBD antibody concentrations 28 days post BNT162b2 were comparable to healthy adult controls (n=20, median age: 36yrs (IQR 29–40);65% female) who had received one dose of BNT162b2 (p = 0.07) [Figure 1]. In PIBD patients on IFX in combination with either azathioprine or methotrexate (57%) both S-protein and RBD antibody concentrations were significantly lower than controls after 1 dose of BNT162b2 (p = 0.0003) [Figure 1]. In the PIBD cohort (n=27) who received 2 doses of BNT162b2 vaccine (median age 14yrs (IQR 14–16);41% female;63% crohn’s disease, 37% ulcerative colitis;median interval between doses 56 days (IQR 22–105)), there was no difference in antibody response after 2 doses compared to healthy adult controls (n=14, median age: 44 years (IQR 36–51);29% female) whether they were on IFX monotherapy (41%) or in combination with an immunomodulator (59%) [Figure 1]. Conclusions We provide evidence of an attenuated antibody response in PIBD patients on IFX in combination with an immunomodulator after a single dose of BNT162b2. However, our data show a robust antibody response in PIBD patients, despite their infliximab treatment, after two doses of BNT162b2 vaccine. Our results are consistent with adult IBD data and highlight the importance of administering the second vaccine dose to achieve protection in this vulnerable patient population. Long-term follow-up to assess longevity of vaccine protection is warranted. Figure 1: SARS-CoV-2 IgG RBD and S-protein antibody levels [AU/ml] in PIBD patients and healthy adults before and after receiving the BNT162b2 SARS-CoV-2 vaccine. IFX monotherapy (black triangles), IFX with immunomodulator (white triangles), healthy adults (white circles) at baseline, 28 days post first vaccine dose and 3-months post first vaccine dose (two doses of BNT162b2 vaccine). Data presented as boxes (IQR) and whiskers with p values Funding Agencies None