The role and limitations of electronic medical records versus patient interviews for determining symptoms, underlying comorbidities, and medication usage for patients with COVID-19.

Electronic medical records (EMR) are important for rapidly compiling information to determine disease characteristics (e.g., symptoms) and risk factors (e.g., underlying comorbidities, medications) for disease-related outcomes. To assess EMR data accuracy, agreement between EMR abstractions and patient interviews was evaluated. Symptoms, medical history, and medication usage among COVID-19 patients collected from EMR and patient interviews were compared using overall agreement (same answer in EMR and interview), reported agreement (yes answer in both EMR and interview among those who reported yes in either), and Kappa statistics. Overall, patients reported more symptoms in interviews than in EMR abstractions. Overall agreement was high (≥50% for 20/23 symptoms), but only subjective fever and dyspnea had reported agreement of ≥50%. Kappa statistics for symptoms were generally low. Reported medical conditions had greater agreement with all condition categories (10/10) having ≥50% overall agreement and half (5/10) having ≥50% reported agreement. More non-prescription medications were reported in interviews than in EMR abstractions leading to low reported agreement (28%). Discordance was observed for symptoms, medical history, and medication usage between EMR abstractions and patient interviews. Investigations utilizing EMR to describe clinical characteristics and identify risk factors should consider the potential for incomplete data, particularly for symptoms and medications.

Enhancing Eastern Equine Encephalitis Virus Surveillance in New Jersey: Optimized Collection of Culiseta Melanura.

Eastern equine encephalitis virus (EEEV) causes the most clinically severe neuroinvasive arboviral disease in the United States. The virus is endemic in eastern and Gulf Coast states and the Great Lakes region, causing cases annually. To detect EEEV circulation in its enzootic cycle before the virus infects humans and other mammals, mosquito control agencies in New Jersey have conducted mosquito surveillance using a series of permanent wooden resting box sites since 1975. We conducted 2 field studies, 1 evaluating resting traps and 1 evaluating efficacy of CO2 lures, to optimize collection of Culiseta melanura, the primary enzootic vector of EEEV. Resulting mosquito samples were subjected to molecular analysis to determine EEEV infection rates. Corrugated plastic boxes trapped more bloodfed Cs. melanura than other resting trap types (resting boxes, Centers for Disease Control and Prevention [CDC] resting traps, or fiber pots) and were similar to resting boxes in total number of female Cs. melanura caught. Further, non-baited CDC light traps were more successful in trapping host-seeking Cs. melanura than those baited with dry ice, a CO2 lure. The EEEV RNA was identified in Cs. melanura, Aedes vexans, Anopheles quadrimaculatus, and Uranotaenia sapphirina. Our findings indicate that corrugated plastic boxes and non-CO2 baited traps could improve detection of Cs. melanura. Mosquito control agencies are encouraged to periodically assess their surveillance strategy for EEEV.

Effectiveness of Self-Collected, Ambient Temperature-Preserved Nasal Swabs Compared to Samples Collected by Trained Staff for Genotyping of Respiratory Viruses by Shotgun RNA Sequencing: Comparative Study.

BACKGROUND: The SARS-CoV-2 pandemic has underscored the need for field specimen collection and transport to diagnostic and public health laboratories. Self-collected nasal swabs transported without dependency on a cold chain have the potential to remove critical barriers to testing, expand testing capacity, and reduce opportunities for exposure of health professionals in the context of a pandemic. OBJECTIVE: We compared nasal swab collection by study participants from themselves and their children at home to collection by trained research staff. METHODS: Each adult participant collected 1 nasal swab, sampling both nares with the single swab, after which they collected 1 nasal swab from 1 child. After all the participant samples were collected for the household, the research staff member collected a separate single duplicate sample from each individual. Immediately after the sample collection, the adult participants completed a questionnaire about the acceptability of the sampling procedures. Swabs were placed in temperature-stable preservative and respiratory viruses were detected by shotgun RNA sequencing, enabling viral genome analysis. RESULTS: In total, 21 households participated in the study, each with 1 adult and 1 child, yielding 42 individuals with paired samples. Study participants reported that self-collection was acceptable. Agreement between identified respiratory viruses in both swabs by RNA sequencing demonstrated that adequate collection technique was achieved by brief instructions. CONCLUSIONS: Our results support the feasibility of a scalable and convenient means for the identification of respiratory viruses and implementation in pandemic preparedness for novel respiratory pathogens.

Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: report of an investigation.

BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases.

Increase in Colorado Tick Fever Virus Disease Cases and Effect of COVID-19 Pandemic on Behaviors and Testing Practices, Montana, 2020.

In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case-control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers' CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities.

Household characteristics associated with surface contamination of SARS-CoV-2 and frequency of RT-PCR and viral culture positivity-California and Colorado, 2021.

While risk of fomite transmission of SARS-CoV-2 is considered low, there is limited environmental data within households. This January-April 2021 investigation describes frequency and types of surfaces positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) among residences with ≥1 SARS-CoV-2 infection, and associations of household characteristics with surface RT-PCR and viable virus positivity. Of 1232 samples from 124 households, 27.8% (n = 342) were RT-PCR positive with nightstands (44.1%) and pillows (40.9%) most frequently positive. SARS-CoV-2 lineage, documented household transmission, greater number of infected persons, shorter interval between illness onset and sampling, total household symptoms, proportion of infected persons ≤12 years old, and persons exhibiting upper respiratory symptoms or diarrhea were associated with more positive surfaces. Viable virus was isolated from 0.2% (n = 3 samples from one household) of all samples. This investigation suggests that while SARS-CoV-2 on surfaces is common, fomite transmission risk in households is low.

SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge - Denver, Colorado, and San Diego, California, January-April 2021.

BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons.

West Nile Virus and Other Domestic Nationally Notifiable Arboviral Diseases - United States, 2020.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bite of infected mosquitoes and ticks. West Nile virus (WNV), mainly transmitted by Culex species mosquitos, is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses cause sporadic cases of disease and occasional outbreaks. This report summarizes passive data for nationally notifiable domestic arboviruses in the United States reported to CDC for 2020. Forty-four states reported 884 cases of domestic arboviral disease, including those caused by West Nile (731), La Crosse (88), Powassan (21), St. Louis encephalitis (16), eastern equine encephalitis (13), Jamestown Canyon (13), and unspecified California serogroup (2) viruses. A total of 559 cases of neuroinvasive WNV disease were reported, for a national incidence of 0.17 cases per 100,000 population. Because arboviral diseases continue to cause serious illness and the locations of outbreaks vary annually, health care providers should consider arboviral infections in patients with aseptic meningitis or encephalitis that occur during periods when ticks and mosquitoes are active, perform recommended diagnostic testing, and promptly report cases to public health authorities to guide prevention strategies and messaging.

Household Transmission and Symptomology of Severe Acute Respiratory Syndrome Coronavirus 2 Alpha Variant among Children-California and Colorado, 2021.

OBJECTIVE: To assess the household secondary infection risk (SIR) of B.1.1.7 (Alpha) and non-Alpha lineages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children. STUDY DESIGN: During January to April 2021, we prospectively followed households with a SARS-CoV-2 infection. We collected questionnaires, serial nasopharyngeal swabs for reverse transcription polymerase chain reaction testing and whole genome sequencing, and serial blood samples for serology testing. We calculated SIRs by primary case age (pediatric vs adult), household contact age, and viral lineage. We evaluated risk factors associated with transmission and described symptom profiles among children. RESULTS: Among 36 households with pediatric primary cases, 21 (58%) had secondary infections. Among 91 households with adult primary cases, 51 (56%) had secondary infections. SIRs among pediatric and adult primary cases were 45% and 54%, respectively (OR, 0.79; 95% CI, 0.41-1.54). SIRs among pediatric primary cases with Alpha and non-Alpha lineage were 55% and 46%, respectively (OR, 1.52; 95% CI, 0.51-4.53). SIRs among pediatric and adult household contacts were 55% and 49%, respectively (OR, 1.01; 95% CI, 0.68-1.50). Among pediatric contacts, no significant differences in the odds of acquiring infection by demographic or household characteristics were observed. CONCLUSIONS: Household transmission of SARS-CoV-2 from children and adult primary cases to household members was frequent. The risk of secondary infection was similar among child and adult household contacts. Among children, household transmission of SARS-CoV-2 and the risk of secondary infection was not influenced by lineage. Continued mitigation strategies (eg, masking, physical distancing, vaccination) are needed to protect at-risk groups regardless of virus lineage circulating in communities.

Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection.

Importance: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. Objective: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. Design, Setting, and Participants: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. Results: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. Conclusions and Relevance: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing.

Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha Variant-United States, 2021.

BACKGROUND: In Spring 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) became the predominant variant in the United States. Research suggests that Alpha has increased transmissibility compared with non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for 2 weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, reverse transcription-polymerase chain reaction (RT-PCR), and whole-genome sequencing. We stratified SIR and symptoms by lineage and identified characteristics associated with transmission using generalized estimating equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval, 52.4-69.0%]) than non-Alpha (55.6% [44.7-65.9%], P = .49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = .01 and .03, respectively). Close contact (eg, kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs 76.8%, P = .05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households due to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members.

Behaviors Associated With Household Transmission of SARS-CoV-2 in California and Colorado, January 2021-April 2021.

Introduction: Mitigation behaviors are key to preventing SARS-CoV-2 transmission. We identified the behaviors associated with secondary transmission from confirmed SARS-CoV-2 primary cases to household contacts and described the characteristics associated with reporting these behaviors. Methods: Households with confirmed SARS-CoV-2 infections were recruited in California and Colorado from January to April 2021. Self-reported behaviors and demographics were collected through interviews. We investigated behaviors associated with transmission and individual and household characteristics associated with behaviors using univariable and multivariable logistic regression with generalized estimating equations to account for household clustering. Results: Among household contacts of primary cases, 43.3% (133 of 307) became infected with SARS-CoV-2. When an adjusted analysis was conducted, household contacts who slept in the same bedroom with the primary case (AOR=2.19; 95% CI=1.25, 3.84) and ate food prepared by the primary case (AOR=1.98; 95% CI=1.02, 3.87) had increased odds of SARS-CoV-2 infection. Household contacts in homes ≤2,000 square feet had increased odds of sleeping in the same bedroom as the primary case compared with those in homes >2,000 square feet (AOR=3.97; 95% CI=1.73, 9.10). Parents, siblings, and other relationships (extended family, friends, or roommates) of the primary case had decreased odds of eating food prepared by the primary case compared with partners. Conclusions: Sleeping in the same bedroom as the primary case and eating food prepared by the primary case were associated with secondary transmission. Household dimension and relationship to the primary case were associated with these behaviors. Our findings encourage innovative means to promote adherence to mitigation measures that reduce household transmission.

West Nile Virus Transmission by Solid Organ Transplantation and Considerations for Organ Donor Screening Practices, United States.

West Nile virus (WNV) is the most common domestic arbovirus in the United States. During 2018, WNV was transmitted through solid organ transplantation to 2 recipients who had neuroinvasive disease develop. Because of increased illness and death in transplant recipients, organ procurement organizations should consider screening during region-specific WNV transmission months.

The microbiota protects from viral-induced neurologic damage through microglia-intrinsic TLR signaling.

Symbiotic microbes impact the function and development of the central nervous system (CNS); however, little is known about the contribution of the microbiota during viral-induced neurologic damage. We identify that commensals aid in host defense following infection with a neurotropic virus through enhancing microglia function. Germfree mice or animals that receive antibiotics are unable to control viral replication within the brain leading to increased paralysis. Microglia derived from germfree or antibiotic-treated animals cannot stimulate viral-specific immunity and microglia depletion leads to worsened demyelination. Oral administration of toll-like receptor (TLR) ligands to virally infected germfree mice limits neurologic damage. Homeostatic activation of microglia is dependent on intrinsic signaling through TLR4, as disruption of TLR4 within microglia, but not the entire CNS (excluding microglia), leads to increased viral-induced clinical disease. This work demonstrates that gut immune-stimulatory products can influence microglia function to prevent CNS damage following viral infection.

T cell-mediated regulation of the microbiota protects against obesity.

The microbiota influences obesity, yet organisms that protect from disease remain unknown. During studies interrogating host-microbiota interactions, we observed the development of age-associated metabolic syndrome (MetS). Expansion of Desulfovibrio and loss of Clostridia were key features associated with obesity in this model and are present in humans with MetS. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. Inappropriate immunoglobulin A targeting of Clostridia and increased Desulfovibrio antagonized the colonization of beneficial Clostridia. Transcriptional and metabolic analysis revealed enhanced lipid absorption in the obese host. Colonization of germ-free mice with Clostridia, but not Desulfovibrio, down-regulated genes that control lipid absorption and reduced adiposity. Thus, immune control of the microbiota maintains beneficial microbial populations that constrain lipid metabolism to prevent MetS.

Commensal regulation of T cell survival through Erdr1.

The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway. Suppression of Erdr1 leads to survival of autoreactive T cells and exacerbated autoimmune disease in the EAE model, and overexpression of Erdr1 results in lessened disease. This novel T cell apoptotic factor has implications for autoimmunity, cancer biology, and invasive pathogens and thus represents a novel therapeutic target in disease.

Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor.

Symbiotic microbes impact the severity of a variety of diseases through regulation of T-cell development. However, little is known regarding the molecular mechanisms by which this is accomplished. Here we report that a secreted factor, Erdr1, is regulated by the microbiota to control T-cell apoptosis. Erdr1 expression was identified by transcriptome analysis to be elevated in splenic T cells from germfree and antibiotic-treated mice. Suppression of Erdr1 depends on detection of circulating microbial products by Toll-like receptors on T cells, and this regulation is conserved in human T cells. Erdr1 was found to function as an autocrine factor to induce apoptosis through caspase 3. Consistent with elevated levels of Erdr1, germfree mice have increased splenic T-cell apoptosis. RNA sequencing of Erdr1-overexpressing cells identified the up-regulation of genes involved in Fas-mediated cell death, and Erdr1 fails to induce apoptosis in Fas-deficient cells. Importantly, forced changes in Erdr1 expression levels dictate the survival of auto-reactive T cells and the clinical outcome of neuro-inflammatory autoimmune disease. Cellular survival is a fundamental feature regulating appropriate immune responses. We have identified a mechanism whereby the host integrates signals from the microbiota to control T-cell apoptosis, making regulation of Erdr1 a potential therapeutic target for autoimmune disease.