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Life-threatening "breakthrough" cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

BackgroundPreventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2_ infections in healthcare workers (HCWs) is critical for healthcare delivery. We aimed to estimate and characterize the prevalence and incidence of coronavirus disease 2019 (COVID-19) in a US HCW cohort and to identify risk factors associated with infection.MethodsWe conducted a longitudinal cohort study of HCWs at 3 Bay Area medical centers using serial surveys and SARS-CoV-2 viral and orthogonal serological testing, including measurement of neutralizing antibodies. We estimated baseline prevalence and cumulative incidence of COVID-19. We performed multivariable Cox proportional hazards models to estimate associations of baseline factors with incident infections and evaluated the impact of time-varying exposures on time to COVID-19 using marginal structural models.ResultsA total of 2435 HCWs contributed 768 person-years of follow-up time. We identified 21 of 2435 individuals with prevalent infection, resulting in a baseline prevalence of 0.86% (95% confidence interval [CI], .53%-1.32%). We identified 70 of 2414 incident infections (2.9%), yielding a cumulative incidence rate of 9.11 cases per 100 person-years (95% CI, 7.11-11.52). Community contact with a known COVID-19 case was most strongly correlated with increased hazard for infection (hazard ratio, 8.1 [95% CI, 3.8-17.5]). High-risk work-related exposures (ie, breach in protective measures) drove an association between work exposure and infection (hazard ratio, 2.5 [95% CI, 1.3-4.8). More cases were identified in HCWs when community case rates were high.ConclusionsWe observed modest COVID-19 incidence despite consistent exposure at work. Community contact was strongly associated with infections, but contact at work was not unless accompanied by high-risk exposure.

While SARS-CoV-2 vaccines prevent severe disease effectively, postvaccination "breakthrough" COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type 1 interferon in the presumptive index case.

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.

BackgroundSequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.

Among 3302 persons tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by BinaxNOWTM and reverse transcription polymerase chain reaction (RT-PCR) in a community setting, rapid assay sensitivity was 100%/98.5%/89% using RT-PCR cycle thresholds of 30, 35, and no threshold. The specificity was 99.9%. Performance was high across ages and those with and without symptoms. Rapid resulting permitted immediate public health action.

Of 4133 persons surveyed at a low-barrier coronavirus disease 2019 (COVID-19) test site with high positivity in an urban Latinx community in January 2021, 86% indicated that they would accept a COVID-19 vaccination. The top reasons for vaccine hesitancy included concerns around side effects and safety and distrust of health care systems.

Of 4133 persons surveyed at a low-barrier coronavirus disease 2019 (COVID-19) test site with high positivity in an urban Latinx community in January 2021, 86% indicated that they would accept a COVID-19 vaccination. The top reasons for vaccine hesitancy included concerns around side effects and safety and distrust of health care systems.

Borrelia miyamotoi is a relapsing fever spirochete; infection is recognized in Europe, Japan, and the northeastern United States as an emerging human infectious disease (1,2). First identified in Japan in [...]

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct

BackgroundSequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 1, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12,124 tests were performed yielding 1,099 positives. From these, 928 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants.

BackgroundRapid coronavirus disease 2019 (COVID-19) diagnosis and isolation of infectious persons are critical to stopping forward transmission, and the care cascade framework can identify gaps in the COVID-19 response.MethodsWe described a COVID-19 symptom to isolation cascade and barriers among symptomatic persons who tested polymerase chain reaction positive for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) at a low-barrier testing site serving a low-income Latinx community in San Francisco. Steps in the cascade are defined as days from symptom onset to test, test to result, and result to counseling on self-isolation. We examined SARS-CoV-2 cycle threshold (Ct) values to assess the likelihood of infectiousness on the day of testing and during missed isolation days.ResultsAmong 145 persons, 97% were Latinx and 81% had an income of

Purpose: To understand vaccine attitudes of Latinx parents highly impacted by COVID-19. Methods: In April 2021, we surveyed parents about their attitudes for COVID-19 vaccination of their children at a community-based outdoor testing/vaccination site serving predominantly low-income Latinx persons in San Francisco. Results: Among 1033 parents (75% Latinx), 92% would "definitely" or "probably" vaccinate their children. Vaccine concerns were higher for younger children and included side effects and impacts on fertility. Doctors and community organizations were noted as trusted sources of information, including among vaccine-concerned parents. Conclusion: Latinx parents accessing neighborhood-based COVID-19 testing/vaccination services are highly motivated to vaccinate their children for COVID-19.

BackgroundCOVID-19 vaccine coverage in the Latinx community depends on delivery systems that overcome barriers such as institutional distrust, misinformation, and access to care. We hypothesized that a community-centered vaccination strategy that included mobilization, vaccination, and "activation" components could successfully reach an underserved Latinx population, utilizing its social networks to boost vaccination coverage.MethodsOur community-academic-public health partnership, "Unidos en Salud," utilized a theory-informed approach to design our "Motivate, Vaccinate, and Activate" COVID-19 vaccination strategy. Our strategy's design was guided by the PRECEDE Model and sought to address and overcome predisposing, enabling, and reinforcing barriers to COVID-19 vaccination faced by Latinx individuals in San Francisco. We evaluated our prototype outdoor, "neighborhood" vaccination program located in a central commercial and transport hub in the Mission District in San Francisco, using the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework during a 16-week period from February 1, 2021 to May 19, 2021. Programmatic data, city-wide COVID-19 surveillance data, and a survey conducted between May 2, 2021 and May 19, 2021 among 997 vaccinated clients ≥16 years old were used in the evaluation.ResultsThere were 20,792 COVID-19 vaccinations administered at the neighborhood site during the 16-week evaluation period. Vaccine recipients had a median age of 43 (IQR 32-56) years, 53.9% were male and 70.5% were Latinx, 14.1% white, 7.7% Asian, 2.4% Black, and 5.3% other. Latinx vaccinated clients were substantially more likely than non-Latinx clients to have an annual household income of less than $50,000 a year (76.1% vs. 33.5%), be a first-generation immigrant (60.2% vs. 30.1%), not have health insurance (47.3% vs. 16.0%), and not have access to primary care provider (62.4% vs. 36.2%). The most frequently reported reasons for choosing vaccination at the site were its neighborhood location (28.6%), easy and convenient scheduling (26.9%) and recommendation by someone they trusted (18.1%); approximately 99% reported having an overall positive experience, regardless of ethnicity. Notably, 58.3% of clients reported that they were able to get vaccinated earlier because of the neighborhood vaccination site, 98.4% of clients completed both vaccine doses, and 90.7% said that they were more likely to recommend COVID-19 vaccination to family and friends after their experience; these findings did not substantially differ according to ethnicity. There were 40.3% of vaccinated clients who said they still knew at least one unvaccinated person (64.6% knew ≥3). Among clients who received both vaccine doses (n = 729), 91.0% said that after their vaccination experience, they had personally reached out to at least one unvaccinated person they knew (61.6% reached out to ≥3) to recommend getting vaccinated; 83.0% of clients reported that one or more friends, and/or family members got vaccinated as a result of their outreach, including 18.9% who reported 6 or more persons got vaccinated as a result of their influence.ConclusionsA multi-component, "Motivate, Vaccinate, and Activate" community-based strategy addressing barriers to COVID-19 vaccination for the Latinx population reached the intended population, and vaccinated individuals served as ambassadors to recruit other friends and family members to get vaccinated.

Abstract: Background: San Francisco implemented one of the earliest shelter-in-place public health mandates in the U.S., with flattened curves of diagnoses and deaths. We describe demographics, clinical features and outcomes of COVID-19 patients admitted to a public health hospital in a high population-density city with an early containment response. Methods: We analyzed inpatients with COVID-19 admitted to San Francisco General Hospital (SFGH) from 3/5/2020–5/11/2020. SFGH serves a network of >63,000 patients (32% Latinx/24% Asian/19% African American/19% Caucasian). Demographic and clinical data through 5/18/2020 were abstracted from hospital records, along with ICU and ventilator utilization, lengths of stay, and in-hospital deaths. Results: Of 157 admitted patients, 105/157 (67%) were male, median age was 49 (range 19-96y), and 127/157 (81%) of patients with COVID-19 were Latinx. Crowded living conditions were common: 60/157 (38%) lived in multi-family shared housing, 12/1578 (8%) with multigenerational families, and 8/157 (5%) were homeless living in shelters. Of 102 patients with ascertained occupations, most had frontline essential jobs: 23% food service, 14% construction/home maintenance, and 10% cleaning. Overall, 86/157 (55%) of patients lived in neighborhoods home to majority Latinx and African-American populations. Overall, 45/157 (29%) of patients needed ICU care, and 26/157 (17%) required mechanical ventilation; 20/26 (77%) of ventilated patients were successfully extubated, and 137/157 (87%) were discharged home. Median hospitalization duration was 4 days (IQR, 2–10), and only 6/157 (4%) patients died in hospital. Conclusion: In San Francisco, where early COVID-19 mitigation was enacted, we report a stark, disproportionate COVID-19 burden on Latinx patients, who accounted for 81% of hospitalizations despite making up only 32% of the patient base and 15% of San Francisco’s total population. Latinx inpatients frequently lived in high-density settings, increasing household risk, and frequently worked essential jobs, potentially limiting the opportunity to effectively distance from others. We also report here favorable clinical outcomes and low overall mortality. However, an effective COVID-19 response must urgently address racial and ethnic disparities. Disclosures: All Authors: No reported disclosures

Among 3,302 persons tested for SARS-CoV-2 by BinaxNOW TM and RT-PCR in a community setting, rapid assay sensitivity was 100%/98.5%/89% using RT-PCR Ct thresholds of 30, 35 and none. The specificity was 99.9%. Performance was high across ages and those with and without symptoms. Rapid resulting permitted immediate public health action.

BackgroundMost data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have been presented as case series without comparison to patients with other acute respiratory illnesses.MethodsWe examined emergency department patients between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared clinical presentation, diagnostics, treatment, and outcomes.FindingsAmong 316 patients, 33 tested positive for SARS-CoV-2; 31 without COVID-19 tested positive for another respiratory virus. Among patients with additional viral testing (27/33), no SARS-CoV-2 co-infections were identified. Compared to those who tested negative, patients with COVID-19 reported longer symptoms duration (median 7d vs. 3d, p

BACKGROUND:Emerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. METHODS:We examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FINDINGS:In a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days), and were more likely to report fever (82% vs. 44%), fatigue (85% vs. 50%), and myalgias (61% vs 27%); p

The maturation and installation of the active site metal cluster (FeMo-co, Fe7S9CMo-R- homocitrate) in Mo-dependent nitrogenase requires the protein product of the nifB gene for production of the FeS cluster precursor (NifB-co, [Fe8S9C]) and the action of the maturase complex composed of the protein products from the nifE and nifN genes. However, some putative diazotrophic bacteria, like Roseiflexus sp. RS-1, lack the NifEN genes, suggesting an alternative pathway for maturation of FeMo-co that does not require NifEN. In this study, the Roseiflexus NifH, NifB, and apo-NifDK proteins produced in Escherichia coli are shown to be sufficient for FeMo-co maturation and insertion into the NifDK protein to achieve active nitrogenase. The E. coli expressed NifDKRS contained P-clusters but was devoid of FeMo-co (referred to as apo-NifDKRS). Apo-NifDKRS could be activated for N2 reduction by addition of preformed FeMo-co. Further, it was found that apo-NifDKRS plus E. coli produced NifBRS and NifHRS were sufficient to yield active NifDKRS when incubated with the necessary substrates (homocitrate, molybdate, and S-adenosylmethionine [SAM]), demonstrating that these proteins can replace the need for NifEN in maturation of Mo-nitrogenase. The E. coli produced NifHRS and NifBRS proteins were independently shown to be functional. The reconstituted NifDKRS demonstrated reduction of N2, protons, and acetylene in ratios observed for Azotobacter vinelandii NifDK. These findings reveal a distinct NifEN-independent pathway for nitrogenase activation involving NifHRS, NifBRS, and apo-NifDKRS. [ABSTRACT FROM AUTHOR]

Individuals with Parkinson's disease (PD) have a higher risk of developing dementia compared to age-matched controls. Rapid eye movement sleep behavior disorder (RBD) and hyposmia can influence symptoms severity. We report associations between polysomnography-assessed sleep architecture, olfactory identification, and cognition. Twenty adults with early-stage PD (mean age 69 ± 7.9; 25% female) completed cognitive assessments, the Brief Smell Identification Test (BSIT), and overnight in-clinic polysomnography. A global cognitive score was derived from principal component analysis. Linear regression models examined associations between sleep variables, BSIT performance, and cognition. Cognitive performance was compared between participants with and without RBD. Deep sleep attainment (β ± SE: 1.18 ± 0.45, p =.02) and olfactory identification (0.37 ± 0.12, p =.01) were associated with better cognition. Light sleep, REM sleep, arousal index, and sleep efficiency were not (all p >.05). Participants with RBD had significantly worse cognition (t -test = −1.06 ± 0.44, p =.03) compared to those without RBD; none entered deep sleep. Deep sleep attainment was associated with better memory (1.20 ± 0.41, p =.01) and executive function (2.94 ± 1.13, p =.02); sleep efficiency was associated with executive function (0.05 ± 0.02, p =.02). These findings suggest interrelationships between lack of deep sleep, hyposmia, and poorer cognition in PD, particularly among individuals with RBD. Assessing these markers together may improve early identification of high-risk individuals and access to interventions. [ABSTRACT FROM AUTHOR]

The public service media Radio Televisión Española (RTVE) conducted a proof-of-concept study to automatically generate reports on the results of the local elections of 28 May 2023 in Spanish communities with fewer than 1000 inhabitants. This study describes the creation, testing and application of the methodological tool used to evaluate the quality of the reports generated using artificial intelligence in order to optimize the algorithm. The application of the proposed datasheet provided a systematic analysis, and the iterative use of the tool made it possible to gradually improve the results produced by the system until a suitable threshold was reached for publication. The study also showed that, despite the ability of AI systems to automatically generate a large volume of information, both human labour and the reliability of the data that feed the system are essential to ensure journalistic quality. [ABSTRACT FROM AUTHOR]

NifB utilizes two equivalents of S-adenosyl methionine (SAM) to insert a carbide atom and fuse two substrate [Fe-S] clusters forming the NifB cofactor (NifB-co), which is then passed to NifEN for further modification to form the iron-molybdenum cofactor (FeMo-co) of nitrogenase. Here, we demonstrate that NifB from the methanogen Methanocaldococcus infernus is a radical SAM enzyme able to reductively cleave SAM to 5'-deoxyadenosine radical and is competent in FeMo-co maturation. Using electron paramagnetic resonance spectroscopy we have characterized three [4Fe-4S] clusters, one SAM binding cluster, and two auxiliary clusters probably acting as substrates for NifB-co formation. Nitrogen coordination to one or more of the auxiliary clusters in NifB was observed, and its mechanistic implications for NifB-co dissociation from the maturase are discussed.