Lessons From the Design and Rollout of an Electronic Medical Record System for Cervical Cancer Screening in Rwanda.

BACKGROUND: In its commitment to delivering comprehensive women's cancer early detection services, the Rwanda Ministry of Health rolled out a new cervical cancer screening program. The paper-based medical record system that tracked clients at different points in the continuum of cervical cancer care had challenges with storing data, accessing client information for follow-up visits, and fragmenting information on individual clients. To support the rollout of the new cervical cancer screening program, a new electronic medical record system was designed and implemented to ensure clients were followed along the complete continuum of care. We document the development and implementation of the electronic medical record system and highlight challenges and lessons learned during implementation. METHODS: Implementation took a participatory approach to ensure that the electronic medical record system was efficient in tracking clients along the continuum of care. At every stage, a wide range of stakeholders were engaged, including clinicians, program managers, and software developers. Health facility visits and conversations were conducted with health care providers and data managers to review the existing system and ensure that the design and development of the electronic record system were suitable for the context in which it would be used. RESULTS: Cervical cancer screening sites are currently using the electronic medical record system to document client information and track women along the continuum of care to reduce loss to follow-up. The system has been rolled out to all newly activated screening sites as part of national scale-up. CONCLUSION: Planning, collaboration, and adaptability were the key factors in this system's successful rollout and should be the foundation of future data systems development.

Effect and cost-effectiveness of human-centred design-based approaches to increase adolescent uptake of modern contraceptives in Nigeria, Ethiopia and Tanzania: Population-based, quasi-experimental studies.

Around half of adolescent pregnancies in low- and middle-income countries are unintended, contributing to millions of unsafe abortions per year. Adolescents 360 (A360), a girl-centred initiative, aimed to increase voluntary uptake of modern contraceptives among adolescents in Nigeria, Ethiopia and Tanzania. We evaluated the effectiveness and cost-effectiveness of A360 in increasing modern contraceptive use in selected geographies. We used before-and-after cross-sectional studies of adolescent girls in four settings. Two Nigerian settings had purposefully selected comparison areas. Baseline and endline household surveys were conducted. The primary study outcome was modern contraceptive prevalence rate (mCPR). Secondary outcomes mapped onto the A360 Theory of Change. Interpretation was aided by a process evaluation along with secular mCPR trends and self-reported A360 exposure data. Incremental design and implementation costs were calculated from implementer systems, site visits, surveys, and interviews. mCPR change was modelled into maternal disability-adjusted life years (DALY) averted to calculate incremental cost-effectiveness ratios. In Oromia, Ethiopia, mCPR increased by 5% points (95% CI 1-10; n = 1,697). In Nigeria, there was no evidence of an effect of A360 on mCPR in Nasarawa (risk ratio: 0·96, 95% CI: 0·76-1·21; n = 5,414) or in Ogun (risk ratio: 1·08, 95% CI: 0·92-1·26; n = 3,230). In Mwanza, Tanzania, mCPR decreased by 9% points (-17 to -0.3; n = 1,973). Incremental cost per DALY averted were $30,855 in Oromia, $111,416 in Nasarawa, $30,114 in Ogun, and $25,579 in Mwanza. Costs per DALY averted were 14-53 times gross domestic product per capita. A360 did not lead to increased adolescent use of modern contraceptives at a population level, except in Oromia, and was not cost-effective. This novel adolescent-centred design approach showed some promise in addressing the reproductive health needs of adolescents, but must be accompanied by efforts to address the contextual drivers of low modern contraceptive use.

FLASH-TB: an Application of Next-Generation CRISPR to Detect Drug Resistant Tuberculosis from Direct Sputum.

Offering patients with tuberculosis (TB) an optimal and timely treatment regimen depends on the rapid detection of Mycobacterium tuberculosis (Mtb) drug resistance from clinical samples. Finding Low Abundance Sequences by Hybridization (FLASH) is a technique that harnesses the efficiency, specificity, and flexibility of the Cas9 enzyme to enrich targeted sequences. Here, we used FLASH to amplify 52 candidate genes probably associated with resistance to first- and second-line drugs in the Mtb reference strain (H37Rv), then detect drug resistance mutations in cultured Mtb isolates, and in sputum samples. 92% of H37Rv reads mapped to Mtb targets, with 97.8% of target regions covered at a depth ≥ 10X. Among cultured isolates, FLASH-TB detected the same 17 drug resistance mutations as whole genome sequencing (WGS) did, but with much greater depth. Among the 16 sputum samples, FLASH-TB increased recovery of Mtb DNA compared with WGS (from 1.4% [IQR 0.5-7.5] to 33% [IQR 4.6-66.3]) and average depth reads of targets (from 6.3 [IQR 3.8-10.5] to 1991 [IQR 254.4-3623.7]). FLASH-TB identified Mtb complex in all 16 samples based on IS1081 and IS6110 copies. Drug resistance predictions for 15/16 (93.7%) clinical samples were highly concordant with phenotypic DST for isoniazid, rifampicin, amikacin, and kanamycin [15/15 (100%)], ethambutol [12/15 (80%)] and moxifloxacin [14/15 (93.3%)]. These results highlighted the potential of FLASH-TB for detecting Mtb drug resistance from sputum samples.

Epidemiology and psychosocial assessment of COVID-19 among workers of the Nigeria Centre for Disease Control infected with COVID-19.

Background: COVID-19 is a global health crisis. By 2021, Nigeria had 230,000 cases. As the national public health institute, NCDC leads the COVID-19 response. Due to constant contact with infected patients, agency employees are a t high-risk. Here, we describe the transmission and psychosocial effects of COVID- 19 among infected NCDC workers as a learning curve for minimizing occupational transmission among frontline public health workers in future outbreaks. Methods: We approved and enrolled all NCDC COVID-19- infected personnel from November to December 2020. We collected data using SurveyMonkey. STATA 14 analyzed the data. Results: 172 of 300 afflicted NCDC staff participated in this study. One-third were between 30 and 39; most were male (104, 60.5%). Most participants worked in the lab (30%) or surveillance (24%). Only 19% (33/172) of participants confirmed pandemic deployment. Most reported interaction with a confirmed case (112/65.1%). Most people (78, 45.3%) felt unhappy when diagnosed. Anger, worry, and low motivation also ranked high (19). The majority reported adequate financial, moral, or psychosocial assistance (26, 70.6%). Conclusions: NCDC staff had a high SARS-CoV-2 infection rate and emotional damage. We urge stricter infection control methods when sending staff for outbreaks response to prevent additional transmission, as well as ongoing psychosocial and economic assistance for afflicted workers.

Treatment Success Following Standard Antibiotic Treatment for Bacterial Vaginosis Is Not Associated With Pretreatment Genital Immune or Microbial Parameters.

Background: Bacterial vaginosis (BV) is a proinflammatory genital condition associated with adverse reproductive health outcomes, including increased HIV incidence. However, BV recurrence rates are high after standard antibiotic treatment. While the composition of the vaginal microbiota before BV treatment may be linked to BV recurrence, it is unclear whether the preceding genital immune milieu is predictive of treatment success. Methods: Here we assessed whether baseline vaginal soluble immune factors or the composition of the vaginal microbiota predicted treatment success 1 month after metronidazole treatment in 2 separate cohorts of women with BV, 1 in the United States and 1 in Kenya; samples within 48 hours of BV treatment were also available for the US cohort. Results: Neither soluble immune factors nor the composition of the vaginal microbiota before BV treatment was associated with treatment response in either cohort. In the US cohort, although the absolute abundances of key vaginal bacterial taxa pretreatment were not associated with treatment response, participants with sustained BV clearance had a more pronounced reduction in the absolute abundance of Gardnerella vaginalis immediately after treatment. Conclusions: Pretreatment immune and microbial parameters were not predictive of BV treatment success in these clinical cohorts.

Ephrin-B2-expressing natural killer cells induce angiogenesis.

Background: Therapeutic angiogenesis aims to induce new blood vessel growth in ischemic tissues; however, previous clinical trials have had limited success. Studies of uterine angiogenesis revealed a specialized subset of natural killer (NK) cells, called uterine NK (uNK) cells, which have unique proangiogenic abilities. Methods: We show that uNK cells in mice express ephrin-B2, a regulator of angiogenesis, to induce tubule formation in an ex vivo coculture tubule formation assay. We next induced the expression of ephrin-B2 by splenic NK (sNK) cells harvested from male mice. Results: We showed that induced NK (iNK) cells can also instruct endothelial cells to form tubules using ephrin-B2. Conclusions: We concluded that Ephrin-B2 is a marker of proangiogenic uNK cells and that a proangiogenic phenotype characterized by ephrin-B2 can be induced in sNK cells to induce therapeutic angiogenesis.

Epidemiology, diagnostics and factors associated with mortality during a cholera epidemic in Nigeria, October 2020-October 2021: a retrospective analysis of national surveillance data.

OBJECTIVES: Nigeria reported an upsurge in cholera cases in October 2020, which then transitioned into a large, disseminated epidemic for most of 2021. This study aimed to describe the epidemiology, diagnostic performance of rapid diagnostic test (RDT) kits and the factors associated with mortality during the epidemic. DESIGN: A retrospective analysis of national surveillance data. SETTING: 33 of 37 states (including the Federal Capital Territory) in Nigeria. PARTICIPANTS: Persons who met cholera case definition (a person of any age with acute watery diarrhoea, with or without vomiting) between October 2020 and October 2021 within the Nigeria Centre for Disease Control surveillance data. OUTCOME MEASURES: Attack rate (AR; per 100 000 persons), case fatality rate (CFR; %) and accuracy of RDT performance compared with culture using area under the receiver operating characteristic curve (AUROC). Additionally, individual factors associated with cholera deaths and hospitalisation were presented as adjusted OR with 95% CIs. RESULTS: Overall, 93 598 cholera cases and 3298 deaths (CFR: 3.5%) were reported across 33 of 37 states in Nigeria within the study period. The proportions of cholera cases were higher in men aged 5-14 years and women aged 25-44 years. The overall AR was 46.5 per 100 000 persons. The North-West region recorded the highest AR with 102 per 100 000. Older age, male gender, residency in the North-Central region and severe dehydration significantly increased the odds of cholera deaths. The cholera RDT had excellent diagnostic accuracy (AUROC=0.91; 95% CI 0.87 to 0.96). CONCLUSIONS: Cholera remains a serious public health threat in Nigeria with a high mortality rate. Thus, we recommend making RDT kits more widely accessible for improved surveillance and prompt case management across the country.

Metagenomic prediction of antimicrobial resistance in critically ill patients with lower respiratory tract infections.

BACKGROUND: Antimicrobial resistance (AMR) is rising at an alarming rate and complicating the management of infectious diseases including lower respiratory tract infections (LRTI). Metagenomic next-generation sequencing (mNGS) is a recently established method for culture-independent LRTI diagnosis, but its utility for predicting AMR has remained unclear. We aimed to assess the performance of mNGS for AMR prediction in bacterial LRTI and demonstrate proof of concept for epidemiological AMR surveillance and rapid AMR gene detection using Cas9 enrichment and nanopore sequencing. METHODS: We studied 88 patients with acute respiratory failure between 07/2013 and 9/2018, enrolled through a previous observational study of LRTI. Inclusion criteria were age ≥ 18, need for mechanical ventilation, and respiratory specimen collection within 72 h of intubation. Exclusion criteria were decline of study participation, unclear LRTI status, or no matched RNA and DNA mNGS data from a respiratory specimen. Patients with LRTI were identified by clinical adjudication. mNGS was performed on lower respiratory tract specimens. The primary outcome was mNGS performance for predicting phenotypic antimicrobial susceptibility and was assessed in patients with LRTI from culture-confirmed bacterial pathogens with clinical antimicrobial susceptibility testing (n = 27 patients, n = 32 pathogens). Secondary outcomes included the association between hospital exposure and AMR gene burden in the respiratory microbiome (n = 88 patients), and AMR gene detection using Cas9 targeted enrichment and nanopore sequencing (n = 10 patients). RESULTS: Compared to clinical antimicrobial susceptibility testing, the performance of respiratory mNGS for predicting AMR varied by pathogen, antimicrobial, and nucleic acid type sequenced. For gram-positive bacteria, a combination of RNA + DNA mNGS achieved a sensitivity of 70% (95% confidence interval (CI) 47-87%) and specificity of 95% (CI 85-99%). For gram-negative bacteria, sensitivity was 100% (CI 87-100%) and specificity 64% (CI 48-78%). Patients with hospital-onset LRTI had a greater AMR gene burden in their respiratory microbiome versus those with community-onset LRTI (p = 0.00030), or those without LRTI (p = 0.0024). We found that Cas9 targeted sequencing could enrich for low abundance AMR genes by > 2500-fold and enabled their rapid detection using a nanopore platform. CONCLUSIONS: mNGS has utility for the detection and surveillance of resistant bacterial LRTI pathogens.

Transcriptomic profiling of blood from autoimmune hepatitis patients reveals potential mechanisms with implications for management.

Autoimmune hepatitis (AIH) is a poorly understood, chronic disease, for which corticosteroids are still the mainstay of therapy and most patients undergo liver biopsy to obtain a diagnosis. We aimed to determine if there was a transcriptomic signature of AIH in the peripheral blood and investigate underlying biologic pathways revealed by gene expression analysis. Whole blood RNA from 75 AIH patients and 25 healthy volunteers was extracted and sequenced. Differential gene expression analysis revealed 249 genes that were significantly differentially expressed in AIH patients compared to controls. Using a random forest algorithm, we determined that less than 10 genes were sufficient to differentiate the two groups in our cohort. Interferon signaling was more active in AIH samples compared to controls, regardless of treatment status. Pegivirus sequences were detected in five AIH samples and 1 healthy sample. The gene expression data and clinical metadata were used to determine 12 genes that were significantly associated with advanced fibrosis in AIH. AIH patients with a partial response to therapy demonstrated decreased evidence of a CD8+ T cell gene expression signal. These findings represent progress in understanding a disease in need of better tests, therapies, and biomarkers.

Metronidazole treatment rapidly reduces genital inflammation through effects on bacterial vaginosis-associated bacteria rather than lactobacilli.

BackgroundBacterial vaginosis (BV) causes genital inflammation and increases HIV risk, whereas a vaginal microbiota dominated by Lactobacillus species is associated with immune quiescence and relative HIV protection. BV treatment reduces genital inflammation, but it is unclear whether this reduction is driven by a decrease in BV-associated bacteria or an increase in Lactobacillus species.METHODSTo evaluate the short-term effect of standard BV treatment on genital immunology and the vaginal microbiota, vaginal swabs were collected immediately before and after metronidazole treatment for BV and analyzed with multiplex ELISA, metagenomic sequencing, and quantitative PCR.RESULTSTopical metronidazole treatment rapidly reduced vaginal levels of proinflammatory cytokines, chemokines, and soluble immune markers of epithelial barrier disruption. Although the vaginal microbiota shifted to dominance by L. iners or L. jensenii, this proportional shift was primarily driven by a 2 to 4 log10-fold reduction in BV-associated bacteria absolute abundance. BV treatment induced no change in the absolute abundance of L. crispatus or L. iners and only minor (<1 log10-fold) increases in L. gasseri and L. jensenii that were not independently associated with reduced inflammation in multivariable models.CONCLUSIONThe genital immune benefits that are associated with Lactobacillus dominance after BV treatment were not directly attributable to an absolute increase in lactobacilli, but rather to the loss of BV-associated bacteria.Trial REGISTRATIONParticipants were recruited as part of a randomized controlled trial (ClinicalTrials.gov NCT02766023) from 2016 to 2019.FUNDINGCanadian Institutes of Health Research (PJT-156123) and the National Institute of Allergy and Infectious Diseases (HHSN2722013000141 and HHSN27200007).

Sensitive, Highly Multiplexed Sequencing of Microhaplotypes From the Plasmodium falciparum Heterozygome.

BACKGROUND: Targeted next-generation sequencing offers the potential for consistent, deep coverage of information-rich genomic regions to characterize polyclonal Plasmodium falciparum infections. However, methods to identify and sequence these genomic regions are currently limited. METHODS: A bioinformatic pipeline and multiplex methods were developed to identify and simultaneously sequence 100 targets and applied to dried blood spot (DBS) controls and field isolates from Mozambique. For comparison, whole-genome sequencing data were generated for the same controls. RESULTS: Using publicly available genomes, 4465 high-diversity genomic regions suited for targeted sequencing were identified, representing the P. falciparum heterozygome. For this study, 93 microhaplotypes with high diversity (median expected heterozygosity = 0.7) were selected along with 7 drug resistance loci. The sequencing method achieved very high coverage (median 99%), specificity (99.8%), and sensitivity (90% for haplotypes with 5% within sample frequency in dried blood spots with 100 parasites/µL). In silico analyses revealed that microhaplotypes provided much higher resolution to discriminate related from unrelated polyclonal infections than biallelic single-nucleotide polymorphism barcodes. CONCLUSIONS: The bioinformatic and laboratory methods outlined here provide a flexible tool for efficient, low-cost, high-throughput interrogation of the P. falciparum genome, and can be tailored to simultaneously address multiple questions of interest in various epidemiological settings.

Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh.

We conducted a cluster-randomized trial to measure the effect of community-level mask distribution and promotion on symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in rural Bangladesh from November 2020 to April 2021 (N = 600 villages, N = 342,183 adults). We cross-randomized mask type (cloth versus surgical) and promotion strategies at the village and household level. Proper mask-wearing increased from 13.3% in the control group to 42.3% in the intervention arm (adjusted percentage point difference = 0.29; 95% confidence interval = [0.26, 0.31]). The intervention reduced symptomatic seroprevalence (adjusted prevalence ratio = 0.91 [0.82, 1.00]), especially among adults ≥60 years old in villages where surgical masks were distributed (adjusted prevalence ratio = 0.65 [0.45, 0.85]). Mask distribution with promotion was a scalable and effective method to reduce symptomatic SARS-CoV-2 infections.

COVID-19 mortality rate and its associated factors during the first and second waves in Nigeria.

COVID-19 mortality rate has not been formally assessed in Nigeria. Thus, we aimed to address this gap and identify associated mortality risk factors during the first and second waves in Nigeria. This was a retrospective analysis of national surveillance data from all 37 States in Nigeria between February 27, 2020, and April 3, 2021. The outcome variable was mortality amongst persons who tested positive for SARS-CoV-2 by Reverse-Transcriptase Polymerase Chain Reaction. Incidence rates of COVID-19 mortality was calculated by dividing the number of deaths by total person-time (in days) contributed by the entire study population and presented per 100,000 person-days with 95% Confidence Intervals (95% CI). Adjusted negative binomial regression was used to identify factors associated with COVID-19 mortality. Findings are presented as adjusted Incidence Rate Ratios (aIRR) with 95% CI. The first wave included 65,790 COVID-19 patients, of whom 994 (1∙51%) died; the second wave included 91,089 patients, of whom 513 (0∙56%) died. The incidence rate of COVID-19 mortality was higher in the first wave [54∙25 (95% CI: 50∙98-57∙73)] than in the second wave [19∙19 (17∙60-20∙93)]. Factors independently associated with increased risk of COVID-19 mortality in both waves were: age ≥45 years, male gender [first wave aIRR 1∙65 (1∙35-2∙02) and second wave 1∙52 (1∙11-2∙06)], being symptomatic [aIRR 3∙17 (2∙59-3∙89) and 3∙04 (2∙20-4∙21)], and being hospitalised [aIRR 4∙19 (3∙26-5∙39) and 7∙84 (4∙90-12∙54)]. Relative to South-West, residency in the South-South and North-West was associated with an increased risk of COVID-19 mortality in both waves. In conclusion, the rate of COVID-19 mortality in Nigeria was higher in the first wave than in the second wave, suggesting an improvement in public health response and clinical care in the second wave. However, this needs to be interpreted with caution given the inherent limitations of the country's surveillance system during the study.

Nasopharyngeal SARS-CoV-2 viral loads in young children do not differ significantly from those in older children and adults.

The role of children in the spread of the SARS-CoV-2 coronavirus has become a matter of urgent debate as societies in the US and abroad consider how to safely reopen schools. Small studies have suggested higher viral loads in young children. Here we present a multicenter investigation on over five thousand SARS-CoV-2 cases confirmed by real-time reverse transcription (RT) PCR assay. Notably, we found no discernable difference in amount of viral nucleic acid among young children and adults.

The COVID-19 Symptom to Isolation Cascade in a Latinx Community: A Call to Action.

BACKGROUND: Rapid 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. METHODS: We 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. RESULTS: Among 145 persons, 97% were Latinx and 81% had an income of <$50 000. The median time from symptom onset to isolation (interquartile range [IQR]) was 7 (5-10) days, leaving a median (IQR) of 3 (0-6) days of isolation. Eighty-three percent had moderate to high levels of virus (Ct <33), but by disclosure 23% were out of their isolation period. The longest intervals were symptom onset to test (median [IQR], 4 [2-9] days) and test to results notification (median [IQR], 3 [2-4] days). Access to a test site was the most common barrier to testing, and food and income loss was the most common barrier to isolation. CONCLUSIONS: Over half of the 10-day isolation period passed by the time of disclosure, and over a fifth of people were likely outside the window of infectiousness by the time they received results. Improvements in test access and turnaround time, plus support for isolation, are needed for epidemic control of SARS-CoV-2 in highly impacted communities.

Modern contraceptive use among unmarried girls aged 15-19 years in South Western Nigeria: results from a cross-sectional baseline survey for the Adolescent 360 (A360) impact evaluation.

PURPOSE: Adolescents 360 (A360) is an initiative being rolled out across Nigeria with the aim of increasing voluntary modern contraception use among women aged 15 to 19 years. Using evaluation study baseline data, we identified sexuality, fertility and contraceptive use characteristics of young unmarried girls in South Western Nigeria. METHODS: A cross-sectional baseline survey of unmarried girls aged 15 to 19 years was conducted in Ogun state, Nigeria in August 2017. A clustered sampling design was used. We identified determinants of modern contraceptive use in this subpopulation using logistic regression. RESULTS: Of 12,024 women interviewed, 15.3% reported sexual intercourse in the past year. The majority of respondents (79.6%, 9525/11,967) had heard of contraception. 45.3% of sexually active respondents were using a modern contraceptive method. Of those using any method of contraception, male condoms (50.3%) were the most widely used modern method followed by the emergency contraceptive pill (16.7%). Following adjustment for socio-demographic characteristics, there was evidence that the use of modern contraception was positively associated with having never given birth, living in an urban area, current enrolment in education, high level of education, high socioeconomic status, exposure to information about contraception, perceived social support for contraception, and self-efficacy for contraception. CONCLUSIONS: In South Western Nigeria, unmarried sexually active adolescent girls have relatively low levels of modern contraceptive use. Programmes should aim to increase access to modern contraception and to increase social support and acceptability of contraceptive use.

Performance Characteristics of a Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Detection Assay at a Public Plaza Testing Site in San Francisco.

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 <30, indicating high viral load; of these, 40% (6 of 15) were asymptomatic. Using this Ct threshold (<30) for Binax-CoV2 evaluation, the sensitivity of Binax-CoV2 was 93.3% (95% confidence interval, 68.1%-99.8%) (14 of 15) and the specificity was 99.9% (99.4%-99.9%) (855 of 856).

Amplification-free detection of SARS-CoV-2 with CRISPR-Cas13a and mobile phone microscopy.

The December 2019 outbreak of a novel respiratory virus, SARS-CoV-2, has become an ongoing global pandemic due in part to the challenge of identifying symptomatic, asymptomatic, and pre-symptomatic carriers of the virus. CRISPR diagnostics can augment gold-standard PCR-based testing if they can be made rapid, portable, and accurate. Here, we report the development of an amplification-free CRISPR-Cas13a assay for direct detection of SARS-CoV-2 from nasal swab RNA that can be read with a mobile phone microscope. The assay achieved ∼100 copies/µL sensitivity in under 30 min of measurement time and accurately detected pre-extracted RNA from a set of positive clinical samples in under 5 min. We combined crRNAs targeting SARS-CoV-2 RNA to improve sensitivity and specificity and directly quantified viral load using enzyme kinetics. Integrated with a reader device based on a mobile phone, this assay has the potential to enable rapid, low-cost, point-of-care screening for SARS-CoV-2.

Community Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Disproportionately Affects the Latinx Population During Shelter-in-Place in San Francisco.

BACKGROUND: There is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates. METHODS: We offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. RESULTS: We tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income <$50 000/year. Five SARS-CoV-2 phylogenetic lineages were detected. CONCLUSIONS: SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco's shelter-in-place ordinance.