Mucosal plasma cells are required to protect the upper airway and brain from infection.

While blood antibodies mediate protective immunity in most organs, whether they protect nasal surfaces in the upper airway is unclear. Using multiple viral infection models in mice, we found that blood-borne antibodies could not defend the olfactory epithelium. Despite high serum antibody titers, pathogens infected nasal turbinates, and neurotropic microbes invaded the brain. Using passive antibody transfers and parabiosis, we identified a restrictive blood-endothelial barrier that excluded circulating antibodies from the olfactory mucosa. Plasma cell depletions demonstrated that plasma cells must reside within olfactory tissue to achieve sterilizing immunity. Antibody blockade and genetically deficient models revealed that this local immunity required CD4+ T cells and CXCR3. Many vaccine adjuvants failed to generate olfactory plasma cells, but mucosal immunizations established humoral protection of the olfactory surface. Our identification of a blood-olfactory barrier and the requirement for tissue-derived antibody has implications for vaccinology, respiratory and CNS pathogen transmission, and B cell fate decisions.

The COVID-19 Pandemic Response and Its Impact on Post-Pandemic Health Emergency and Disaster Risk Management in the United States

Among the impacts of the Coronavirus Disease 2019 (COVID-19) pandemic on the public health system in the United States has been a reevaluation of emergency response systems and procedures. This study uses publicly available literature from government, private sector, and academic sources to identify changes and lessons learned during the COVID-19 pandemic in specific aspects of emergency response, namely human resources, health service delivery, and logistics, determined based on the World Health Organization Health Emergency and Disaster Risk Management (WHO Health EDRM) Framework. Major themes of changes implemented include those intended to increase mobility and flexibility of workforce and resources, integration of various parts of the health system, and effective communication, and are anticipated to be incorporated into response systems going forward.

Characteristics of SARS-CoV-2 Seropositivity among Emergency Department Healthcare Workers at a Tertiary Care Center in Baltimore.

Early in the COVID-19 pandemic (March-July 2020 in Baltimore), emergency department (ED) healthcare workers (HCWs) were considered to be at greater risk of contracting SARS-CoV-2. Limited data existed, however, on the prevalence of SARS-CoV-2 infection and its impact in this workforce population. We enrolled 191 ED HCWs from a tertiary academic center, administered baseline and weekly surveys, and tested them twice (July and December 2020) for serum antibodies against SARS-CoV-2 spike protein. Approximately 6% (11 of 191, 5.8%) of ED HCWs had spike antibodies in July, a prevalence that doubled by December (21 of 174, 12.1%). A positive PCR test was self-reported by 15 of 21 (71%) seropositive and 6 of 153 (4%) seronegative HCWs (p < 0.001). Of the total 27 HCWs who had antibodies and/or were PCR positive, none required hospitalization, 18 (67%) had a self-perceived COVID-19 illness, and 12 of the 18 reported symptoms. The median number of missed workdays was 8.5 (ranging from 2 to 21). While most seropositive ED HCWs who reported symptoms took work absences, none required hospitalization, indicating that COVID-19's impact on staffing prior to vaccination was not as great as feared.

Characteristics of SARS-CoV-2 testing for rapid diagnosis of COVID-19 during the initial stages of a global pandemic.

Accurate SARS-CoV-2 diagnosis is essential to guide prevention and control of COVID-19. Here we examine SARS-CoV-2 molecular-based test performance characteristics and summarize case-level data related to COVID-19 diagnosis. From January 11 through April 22, 2020, Public Health Ontario conducted SARS-CoV-2 testing of 86,942 specimens collected from 80,354 individuals, primarily using real-time reverse-transcription polymerase chain reaction (rRT-PCR) methods. We analyzed test results across specimen types and for individuals with multiple same-day and multi-day collected specimens. Nasopharyngeal compared to throat swabs had a higher positivity (8.8% vs. 4.8%) and an adjusted estimate 2.9 Ct lower (SE = 0.5, p<0.001). Same-day specimens showed high concordance (98.8%), and the median Ct of multi-day specimens increased over time. Symptomatic cases had rRT-PCR results with an adjusted estimate 3.0 Ct (SE = 0.5, p<0.001) lower than asymptomatic/pre-symptomatic cases. Overall test sensitivity was 84.6%, with a negative predictive value of 95.5%. Molecular testing is the mainstay of SARS-CoV-2 diagnosis and testing protocols will continue to be dynamic and iteratively modified as more is learned about this emerging pathogen.