Optimized workplace risk mitigation measures for SARS-CoV-2 in 2022.

596 million SARS-CoV-2 cases have been reported and over 12 billion vaccine doses have been administered. As vaccination rates increase, a gap in knowledge exists regarding appropriate thresholds for escalation and de-escalation of workplace COVID-19 preventative measures. We conducted 133,056 simulation experiments, evaluating the spread of SARS-CoV-2 virus in hypothesized working environments subject to COVID-19 infections from the community. We tested the rates of workplace-acquired infections based on applied isolation strategies, community infection rates, methods and scales of testing, non-pharmaceutical interventions, variant predominance, vaccination coverages, and vaccination efficacies. When 75% of a workforce is vaccinated with a 70% efficacious vaccine against infection, then no masking or routine testing + isolation strategies are needed to prevent workplace-acquired omicron variant infections when the community infection rate per 100,000 persons is ≤ 1. A CIR ≤ 30, and ≤ 120 would result in no workplace-acquired infections in this same scenario against the delta and alpha variants, respectively. Workforces with 100% worker vaccination can prevent workplace-acquired infections with higher community infection rates. Identifying and isolating workers with antigen-based SARS-CoV-2 testing methods results in the same or fewer workplace-acquired infections than testing with slower turnaround time polymerase chain reaction methods. Risk migration measures such as mask-wearing, testing, and isolation can be relaxed, or escalated, in commensurate with levels of community infections, workforce immunization, and risk tolerance. The interactive heatmap we provide can be used for immediate, parameter-based case count predictions to inform institutional policy making. The simulation approach we have described can be further used for future evaluation of strategies to mitigate COVID-19 spread.

Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

PURPOSE: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies. METHODS: We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status. RESULTS: Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36]; and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter. CONCLUSION: Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.

Optimized Post-Vaccination Strategies and Preventative Measures for SARS-CoV-2.

Introduction: Since March of 2020, over 210 million SARS-CoV-2 cases have been reported and roughly five billion doses of a SARS-CoV-2 vaccine have been delivered. The rise of the more infectious delta variant has recently indicated the value of reinstating previously relaxed non-pharmacological and test-driven preventative measures. These efforts have been met with resistance, due, in part, to a lack of site-specific quantitative evidence which can justify their value. As vaccination rates continue to increase, a gap in knowledge exists regarding appropriate thresholds for escalation and de-escalation of COVID-19 preventative measures. Methods: We conducted a series of simulation experiments, trialing the spread of SARS-CoV-2 virus in a hypothesized working environment that is subject to COVID-19 infections from the surrounding community. We established cohorts of individuals who would, in simulation, work together for a set period of time. With these cohorts, we tested the rates of workplace and community acquired infections based on applied isolation strategies, community infection rates (CIR), scales of testing, non-pharmaceutical interventions, variant predominance's and testing strategies, vaccination coverages, and vaccination efficacies of the members included. Permuting through each combination of these variables, we estimated expected case counts for 33,462 unique workplace scenarios. Results: When the CIR is 5 new confirmed cases per 100,000 or fewer, and at 50% of the workforce is vaccinated with a 95% efficacious vaccine, then testing daily with an antigen-based or PCR based test in only unvaccinated workers will result in less than one infection through 4,800 person weeks. When the community infection rate per 100,000 persons is less than or equal to 60, and the vaccination coverage of the workforce is 100% with 95% vaccine efficacy then no masking or routine testing + isolation strategies are needed to prevent workplace acquired infections regardless of variant predominance. Identifying and isolating workers with antigen-based SARS-CoV-2 testing methods results in the same or fewer workplace acquired infections than testing with polymerase chain reaction (PCR) methods. Conclusions: Specific scenarios exist in which preventative measures taken to prevent SARS-CoV-2 spread, including masking, and testing plus isolation strategies can safely be relaxed. Further, efficacious testing with quarantine strategies exist for implementation in only unvaccinated cohorts in a workplace. Due to shorter turnaround time, antigen-based testing with lower sensitivity is more effective than PCR testing with higher sensitivities in comparable testing strategies. The general reference interactive heatmap we provide can be used for site specific, immediate, parameter-based case count predictions to inform appropriate institutional policy making.

Reducing COVID-19 quarantine with SARS-CoV-2 testing: a simulation study.

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules. DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies. RESULTS: We found that SARS-CoV-2 testing can effectively reduce the length of a quarantine without compromising safety. A single reverse transcription-PCR (RT-PCR) test performed before the end of quarantine can reduce quarantine duration to 10 days. Two tests can reduce the duration to 8 days, and three highly sensitive RT-PCR tests can justify a 6-day quarantine. More strategic testing schedules and longer quarantines are needed if tests are administered with less-sensitive RT-PCR tests or antigen tests. Shorter quarantines can be used for applications that tolerate a residual postquarantine transmission risk comparable to a 10-day quarantine. CONCLUSIONS: Testing could substantially reduce the length of isolation, reducing the physical and mental stress caused by lengthy quarantines. With increasing capacity and lowered costs of SARS-CoV-2 tests, test-assisted quarantines could be safer and more cost-effective than 14-day quarantines and warrant more widespread use.

Optimal test-assisted quarantine strategies for COVID-19.

OBJECTIVE: To evaluate the effectiveness of SARS-CoV-2 testing on shortening the duration of quarantines for COVID-19 and to identify the most effective choices of testing schedules. DESIGN: We performed extensive simulations to evaluate the performance of quarantine strategies when one or more SARS-CoV-2 tests were administered during the quarantine. Simulations were based on statistical models for the transmissibility and viral loads of SARS-CoV-2 infections and the sensitivities of available testing methods. Sensitivity analyses were performed to evaluate the impact of perturbations in model assumptions on the outcomes of optimal strategies. RESULTS: We found that SARS-CoV-2 testing can effectively reduce the length of a quarantine without compromising safety. A single RT-PCR test performed before the end of quarantine can reduce quarantine duration to 10 days. Two tests can reduce the duration to 8 days, and three highly sensitive RT-PCR tests can justify a 6-day quarantine. More strategic testing schedules and longer quarantines are needed if tests are administered with less sensitive RT-PCR tests or antigen tests. Shorter quarantines can be utilized for applications that tolerate a residual post-quarantine transmission risk comparable to a 10-day quarantine. CONCLUSIONS: Testing could substantially reduce the length of isolation, reducing the physical and mental stress caused by lengthy quarantines. With increasing capacity and lowered costs of SARS-CoV-2 tests, test-assisted quarantines could be safer and more cost-effective than 14-day quarantines and warrant more widespread use. RESEARCH IN CONTEXT: What is already known on this topic?: Recommendations for quarantining individuals who could have been infected with COVID-19 are based on limited evidence.Despite recent theoretical and case studies of test-assisted quarantines, there has been no substantive investigation to quantify the safety and efficacy of, nor an exhaustive search for, optimal test-assisted quarantine strategies. WHAT THIS STUDY ADDS: Our simulations indicate that the 14-day quarantine approach is overly conservative and can be safely shortened if testing is performed.Our recommendations include testing schedules that could be immediately adopted and implemented as government and industry policies. ROLE OF THE FUNDING SOURCE: A major technology company asked that we perform simulations to understand the optimal strategy for managing personnel quarantining before forming cohorts of individuals who would work closely together. The funding entity did not influence the scope or output of the study but requested that we include antigen testing as a component of the quarantining process. Patrick Yu and Peter Matos are employees of Corporate Medical Advisors, and International S.O.S employs Julie McCashin. Other funding sources are research grants and did not influence the investigation.

Pituitary antibodies in women with Hashimoto's thyroiditis: prevalence in diagnostic and prediagnostic sera.

BACKGROUND: Pituitary antibodies have been reported with greater frequency in patients with Hashimoto's thyroiditis than in healthy controls, although there is significant variability in the strength of the association and the methodologies used. METHODS: We designed a nested case-control study to characterize the prevalence of pituitary antibodies at the time of the clinical diagnosis of Hashimoto's thyroiditis, as well as at 2, 5, and 7 years before diagnosis. Active component female service member cases (n=87) and matched female controls (n=107) were selected using the Defense Medical Surveillance System database (DMSSD) between January 1998 and December 2007. Pituitary antibodies were measured by immunofluorescence using human pituitary glands collected at autopsy as the substrate. RESULTS: At diagnosis, pituitary antibodies were present in 9% of cases with Hashimoto's (8 of 87) and 3% of controls (3 of 107). When the data were analyzed using a conditional logistic regression model, which takes into account the matching on age and work status, pituitary antibodies increased the odds of having Hashimoto's thyroiditis by sevenfold (95% confidence interval from 1.3 to 40.1, p=0.028), after adjusting for components of the DMSSD-category-termed race and for thyroperoxidase antibodies. Before diagnosis, pituitary antibodies were positive in 3 of the 11 subjects (2 cases and 1 control) at the -2-year time point, and negative in all 11 subjects at the -5- and -7-year time points. CONCLUSIONS: In summary, using a nested case-control design, we confirm that pituitary antibodies are more common in Hashimoto's thyroiditis and suggest that they appear late during its natural history.

Histopathologic changes related to fibrotic oviduct occlusion after genital tract infection of mice with Chlamydia muridarum.

OBJECTIVES: We sought to determine if intraluminal occluding fibrosis of the oviduct occurs after urogenital Chlamydia muridarum infection in mice. STUDY: Oviduct occlusion was assessed by infusing dye into the distal uterus and tracking the diffusion of the dye into the oviduct. We also conducted histologic assessment of the affected tissues using hematoxylin and eosin (H&E) and Masson trichrome stains. RESULTS: All previously infected susceptible mice had occluded oviducts compared with 17.5% of previously uninfected mice. Oviduct occlusion correlated with hydrosalpinx formation and infertility. Intraluminal oviduct fibrosis was observed in several sections of tissue displaying hydrosalpinx but not in tissues without hydrosalpinx. Fibrosis was localized to the oviduct isthmus and oviduct proper, proximal to the uterus. CONCLUSION: Intralumenal occluding fibrosis of the oviduct is a sequela of infection with C. muridarum in this model. These observations support the use of the murine model to study pathogenesis of chlamydial upper genital tract infection.