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Background Rhinovirus (RV) is a common cause of respiratory illness in all people, including those experiencing homelessness. RV epidemiology in homeless shelters is unknown. Methods We analyzed data from a cross-sectional homeless shelter study in King County, Washington, October 2019–May 2021. Shelter residents or guardians aged ≥3 months reporting acute respiratory illness completed questionnaires and submitted nasal swabs. After 1 April 2020, enrollment expanded to residents and staff regardless of symptoms. Samples were tested by multiplex RT-PCR for respiratory viruses. A subset of RV-positive samples was sequenced. Results There were 1066 RV-positive samples with RV present every month of the study period. RV was the most common virus before and during the coronavirus disease 2019 (COVID-19) pandemic (43% and 77% of virus-positive samples, respectively). Participants from family shelters had the highest prevalence of RV. Among 131 sequenced samples, 33 RV serotypes were identified with each serotype detected for ≤4 months. Conclusions RV infections persisted through community mitigation measures and were most prevalent in shelters housing families. Sequencing showed a diversity of circulating RV serotypes, each detected over short periods of time. Community-based surveillance in congregate settings is important to characterize respiratory viral infections during and after the COVID-19 pandemic. Clinical Trials Registration NCT04141917.

We used daily real-time reverse-transcription polymerase chain reaction (RT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study, conducted April 2020–May 2021, to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration. Ct values varied across RT-PCR platforms and by participant age. Specimens collected from children and adolescents had higher Ct values and adults aged ≥50 years showed lower Ct values than adults aged 18–49 years. Ct values were lower on days when participants reported experiencing symptoms, with the lowest Ct value occurring 2–6 days after symptom onset.

From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals

Background Families with children may be at higher risk for influenza infection. Community transmission can suffer from underreporting as testing is often not performed. We studied the epidemiology of influenza in households with school-aged children using home-based sample collection. Methods We conducted a remote household study surveilling respiratory viruses from November 2019-June 2021, in King County, Washington (WA), USA. Households with school-aged children were enrolled, mailed home specimen collection kits, and asked to self-assess for weekly acute respiratory illness (ARI) using remote survey platforms. Participants with ARI symptoms were prompted to complete serial illness surveys and self-collect/parent collect mid-turbinate nasal swabs. Samples were sent to a University of Washington study laboratory for RT-PCR influenza testing. Influenza rates were compared to WA Department of Health (DOH) reporting. Results A total of 1861 ARI events were reported among 992 adults and 869 children in 470 households; 75 influenza cases were detected (36 influenza A and 39 influenza B). The study participant median age was 32 years (0-84), 10 years (1-49) for influenza A, and 11 years (3-49) for influenza B cases. Overall 13% of households had an influenza case, of which 13 (22%) reported >1 case. A total of 81% of participants reported receipt of one dose of the 2019-2020 influenza vaccine, including 91% of influenza A and 90% of influenza B cases, and 84% received the 2020-2021 influenza vaccine. Like WA DOH, we observed a wave of influenza B cases followed by influenza A in 2019-2020. During influenza season 2020-2021, WA DOH reported 9 positive influenza tests and none observed in our study. Commonly, influenza case-patients reported were fever, cough, rhinorrhea, and fatigue. GI symptoms were more common in children than adults. Of the cases, 92% of influenza A and 78% of influenza B occurred in children. Figure 1.Influenza A and B cases from 2019-2021Figure 2A.Reported Symptoms of Influenza A D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 30 participants responded and of respondents, 13% D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 28 participants responded and of respondents, 4% Conclusion Influenza illness in 2019-2020 was initially influenza B, and subsequently replaced by influenza A. Most cases were in children and adolescents, despite at least one dose of influenza vaccine. Symptoms were widely distributed and similar between influenza A and B. Influenza incidence in our cohort declined to zero with the rise of SARS-CoV-2 cases and widespread mitigation efforts. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background COVID-19 vaccines are important to mitigate severe disease in congregate settings, yet uptake remains lower among people experiencing homelessness (PEH) than in the general population. This study aimed to explain changes in COVID-19 vaccination intent over time and identify modifiable factors to improve vaccine acceptance among PEH. Methods We utilized the Health Belief Model and 3Cs Model of Vaccine Hesitancy to develop a conceptual framework to explore factors that may influence COVID-19 vaccination intent among PEH. Between July 27 - October 15, 2021, we conducted semi-structured interviews (SSIs) and focus group discussions (FGDs) across six homeless shelters in Seattle-King County, Washington. Residents and staff aged 18 years and older were recruited through purposive sampling for SSIs and convenience sampling for FGDs. We captured retrospective information about perceptions of and intent to receive COVID-19 vaccines between March 2020 - August 2021. Thematic analysis was conducted using Dedoose. Results We conducted 31 SSIs (25 residents and six staff) and eight FGDs with 43 residents. Participants reported that too much contradictory and changing information about COVID-19 vaccines led to confusion. Information deemed trustworthy (i.e., objective, honest, professional, and recommended by others) contributed to individual’s knowledge and in some cases changed their vaccination intent. Despite intention to vaccinate, participants reported barriers to COVID-19 vaccine access including availability, eligibility, appointments, and timeliness. While many intended to get vaccinated on their own, others were motivated by incentives and requirements. Participants presented recommendations to improve COVID-19 information content and dissemination, access, and incentives in shelter settings (Table 1). Table 1.Recommendations for Interventions to Increase COVID-19 Vaccine Uptake in Shelter Settings Conclusion COVID-19 vaccination strategies that are rooted in the voices and experiences of PEH are presented and can inform improved vaccine implementation among key stakeholders. Future research should test recommended strategies to determine feasibility and effectiveness in shelter settings. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Non-pharmaceutical interventions (NPIs), such as masking and social distancing, can reduce SARS-CoV-2 transmission. Longitudinal behavioral data in individuals with acute respiratory illness (ARI) during the COVID-19 pandemic are limited. We describe changes in adherence to NPIs and the impact of ARIs on work or school in families before and during the COVID-19 pandemic. Methods From November 2019 to June 2021, households with school-aged children in King County, WA, were remotely monitored on a weekly basis for symptoms of respiratory illness. Participants with ARI (cough or ≥2 qualifying symptoms) were asked about illness-related behavior changes (e.g. masking, isolation, hand hygiene, surface cleaning, public transit use) and impacts on school/work 7 days after initial symptom report. Using generalized estimating equations for household clusters, we compared the frequency of behavior changes and school/work impact during 3 time periods: the pre-/early COVID-19 pandemic period (11/14/19-3/22/20), pre-vaccine period (3/23/20-12/10/20), and post-COVID-19 vaccine period (12/11/20-6/19/21). Results Of 1861 participants in 470 households, 695 (37%, from 70% of households) reported 1157 ARIs. Over the 3 time periods, the percent of ill participants who reported staying home (34 vs 34 vs 54%, respectively, P< .001), avoiding contact with others (25 vs 28 vs 45%, P< .001), and masking (3 vs 23 vs 38%, P< .001) increased (Fig 1A). Other illness-related behaviors, including washing hands and disinfecting surfaces, were unchanged over time. The percent of ill participants who worked from home (7 vs 9 vs 3%, P= .02) and missed work due to ARI (13 vs 8 vs 8%, P= .03) decreased over time (Fig 1B). Figure 1A.Participant reported illness-related health behaviors in the past week — Seattle, WA, 2019–2021.Figure 1B.Participant reported illness-related school or work impact in the past week due to illness — Seattle, WA, 2019–2021 Time periods were defined as: Period 1: 11/14/19 – 3/22/20 (pre-/early COVID-19 pandemic), Period 2: 3/23/20 – 12/10/20 (post-Washington State Stay at Home order), and Period 3: 12/11/20 – 6/19/21 (United States Food and Drug Administration Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine for those 16 years and older). Illness was defined per Acute Respiratory Illness (ARI) case definition: cough or two qualifying symptoms (fever, sore throat, runny nose, muscle or body aches, headache, difficulty breathing, fatigue, nausea or vomiting; for participants < 18 years of age, ear pain or drainage, rash, and diarrhea were also qualifying symptoms). Conclusion As the COVID-19 pandemic progressed, households with school-aged children engaged in isolation, social distancing, and masking more frequently in response to ARI. The impact of ARIs on work decreased during the pandemic. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Human parainfluenza viruses (HPIV) cause respiratory illness in individuals of all ages. However, HPIV epidemiology data in people experiencing homelessness (PEH) are limited. Methods We analyzed cross-sectional data from a clinical trial and SARS-CoV-2 surveillance study in 23 homeless shelters in King County, Washington from October 2019-May 2021. Questionnaires and nasal swab specimens were obtained from eligible participants at enrollment. Between October 2019-March 31, 2020, participants included those aged > 3 months with acute respiratory illness. Monthly shelter surveillance was also conducted where participants were recruited regardless of symptoms. With the community spread of SARS-CoV-2, the study design transitioned from a clinical trial to a SARS-CoV-2 surveillance study which expanded enrollment eligibility to include participants with or without symptoms from April 1, 2020, onward. Participants were not followed longitudinally but were permitted to enroll multiple times during the study period. Specimens were tested for HPIV 1-4 and other respiratory viruses using RT-PCR. Results Among 14,464 specimens, 32 were HPIV-positive from 29 participants (median age 9 years, range 0.3-64 years; 45% female; 28% Black; 10% with chronic conditions) of which 59% were children. Family shelters had the highest percentage of HPIV infections (Table). HPIV was detected every month before the community spread of SARS-CoV-2. All HPIV-positive samples in May 2021 came from a single family shelter (Figure). Only 67% of HPIV-positive participants had symptoms with runny nose, cough and sore throat the most commonly reported. HPIV co-detection with other respiratory viruses occurred in 19% of HPIV-positive specimens; Rhinovirus co-detection (16%) was the most common. Human Parainfluenza Encounters by Shelter Type Before and After April 1, 2020 Human Parainfluenza Positive Samples by Shelter Type Among Unique Participants Conclusion HPIV affected PEH of all ages with most cases in shelters with children. Coinciding with community-wide SARS-CoV-2 mitigation efforts, the number of HPIV infections were reduced. However, a cluster of HPIV infections still occurred within one family shelter. Shelter-specific public health measures including non-pharmaceutical interventions used during the COVID-19 pandemic may reduce HPIV infections among residents. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Coronavirus disease 2019 (COVID-19) causes a range of illness severity. Mild illness has been reported, but whether illness severity correlates with infectivity is unknown. We describe the public health investigation of a mildly ill, nonhospitalized COVID-19 case who traveled to China. Methods The case was a Maricopa County resident with multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive specimens collected on 22 January 2020. Contacts were persons exposed to the case on or after the day before case diagnostic specimen collection. Contacts were monitored for 14 days after last known exposure. High-risk contacts had close, prolonged case contact (≥ 10 minutes within 2 m). Medium-risk contacts wore all US Centers for Disease Control and Prevention–recommended personal protective equipment during interactions. Nasopharyngeal and oropharyngeal (NP/OP) specimens were collected from the case and high-risk contacts and tested for SARS-CoV-2. Results Paired case NP/OP specimens were collected for SARS-CoV-2 testing at 11 time points. In 8 pairs (73%), ≥ 1 specimen tested positive or indeterminate, and in 3 pairs (27%) both tested negative. Specimens collected 18 days after diagnosis tested positive. Sixteen contacts were identified; 11 (69%) had high-risk exposure, including 1 intimate contact, and 5 (31%) had medium-risk exposure. In total, 35 high-risk contact NP/OP specimens were collected for SARS-CoV-2 testing; all 35 pairs (100%) tested negative. Conclusions This report demonstrates that SARS-CoV-2 infection can cause mild illness and result in positive tests for up to 18 days after diagnosis, without evidence of transmission to close contacts. These data might inform public health strategies to manage individuals with asymptomatic infection or mild illness.

Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

Despite recommendations, few children aged 6–35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012–2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged

Background Vaccination is the best way to prevent influenza; however, greater benefits could be achieved. To help guide research and policy agendas, we aimed to quantify the magnitude of influenza disease that would be prevented through targeted increases in vaccine effectiveness (VE) or vaccine coverage (VC). Methods For 3 influenza seasons (2011–12, 2015–16, and 2017–18), we used a mathematical model to estimate the number of prevented influenza-associated illnesses, medically attended illnesses, and hospitalizations across 5 age groups. Compared with estimates of prevented illness during each season, given observed VE and VC, we explored the number of additional outcomes that would have been prevented from a 5% absolute increase in VE or VC or from achieving 60% VE or 70% VC. Results During the 2017–18 season, compared with the burden already prevented by influenza vaccination, a 5% absolute VE increase would have prevented an additional 1 050 000 illnesses and 25 000 hospitalizations (76% among those aged ≥65 years), while achieving 60% VE would have prevented an additional 190 000 hospitalizations. A 5% VC increase would have resulted in 785 000 fewer illnesses (56% among those aged 18–64 years) and 11 000 fewer hospitalizations; reaching 70% would have prevented an additional 39 000 hospitalizations. Conclusions Small, attainable improvements in effectiveness or VC of the influenza vaccine could lead to substantial additional reductions in the influenza burden in the United States. Improvements in VE would have the greatest impact in reducing hospitalizations in adults aged ≥65 years, and VC improvements would have the largest benefit in reducing illnesses in adults aged 18–49 years.

Background The severity of the 2017–2018 influenza season in the United States was high, with influenza A(H3N2) viruses predominating. Here, we report influenza vaccine effectiveness (VE) and estimate the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the 2017–2018 influenza season. Methods We used national age-specific estimates of 2017–2018 influenza vaccine coverage and disease burden. We estimated VE against medically attended reverse-transcription polymerase chain reaction–confirmed influenza virus infection in the ambulatory setting using a test-negative design. We used a compartmental model to estimate numbers of influenza-associated outcomes prevented by vaccination. Results The VE against outpatient, medically attended, laboratory-confirmed influenza was 38% (95% confidence interval [CI], 31%–43%), including 22% (95% CI, 12%–31%) against influenza A(H3N2), 62% (95% CI, 50%–71%) against influenza A(H1N1)pdm09, and 50% (95% CI, 41%–57%) against influenza B. We estimated that influenza vaccination prevented 7.1 million (95% CrI, 5.4 million–9.3 million) illnesses, 3.7 million (95% CrI, 2.8 million–4.9 million) medical visits, 109 000 (95% CrI, 39 000–231 000) hospitalizations, and 8000 (95% credible interval [CrI], 1100–21 000) deaths. Vaccination prevented 10% of expected hospitalizations overall and 41% among young children (6 months–4 years). Conclusions Despite 38% VE, influenza vaccination reduced a substantial burden of influenza-associated illness, medical visits, hospitalizations, and deaths in the United States during the 2017–2018 season. Our results demonstrate the benefit of current influenza vaccination and the need for improved vaccines.

Background In recent influenza seasons, the effectiveness of inactivated influenza vaccines against circulating A(H3N2) virus has been lower than against A(H1N1)pdm09 and B viruses, even when circulating viruses remained antigenically similar to vaccine components. Methods During the 2016-2017 influenza season, vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Results Among 7083 enrollees, 1342 (19%) tested positive for influenza A(H3N2), 648 (9%) were positive for influenza B (including B/Yamagata, n = 577), and 5040 (71%) were influenza negative. Vaccine effectiveness was 40% (95% confidence interval [CI], 32% to 46%) against any influenza virus, 33% (95% CI, 23% to 41%) against influenza A(H3N2) viruses, and 53% (95% CI, 43% to 61%) against influenza B viruses. Conclusions The 2016-2017 influenza vaccines provided moderate protection against any influenza among outpatients but were less protective against influenza A(H3N2) viruses than B viruses. Approaches to improving effectiveness against A(H3N2) viruses are needed.

Background During the 2014-2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence. Methods NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1-4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B. Results Among the 320 patients, 65% were male, median age was 14.5 years (range, 0-90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, ≥2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses. Conclusions Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.

Altered mental status in cryptococcal meningitis results in poorer survival, but underlying causes of altered mentation are poorly understood. Within two clinical trials, we assessed risk factors for altered mental status (GCS score

Background Shortages of swabs and transport medium for sample collection have made identification of SARS-CoV-2 infections challenging. We examined the agreement in SARS-CoV-2 detection between two types of self-collected samples: nasal swabs (NS) and saliva (SA). Figure 1. Bland-Altman plot of SARS-CoV-2-N1 CT values for SA and NS samples Figure 2. Bland-Altman plot of SARS-CoV-2-N2 CT values for SA and NS samples Methods Paired daily self-collected NS and SA samples were collected in May 2020 in an ongoing case-ascertained study of SARS-CoV-2 household transmission in Nashville, TN. After informed consent was obtained, index cases and household members were remotely trained in the self-collection of daily nasal swabs (from both nares and preserved in transport medium) and saliva samples (participants were asked to spit in a sterile urine cup approximately 6 times during a minute). Samples were refrigerated in closed double bags and delivered to the laboratory within ~72–96 hours of collection. NS and SA samples were tested using qRT-PCR at a research laboratory. We computed the agreement in detections between sample types using the McNemar test and compared median qRT-PCR cycle threshold (CT) values between sample types for 2 targets (SARS-CoV-2-N1 and SARS-CoV-2-N2) using a Wilcoxon signed rank test. Bland-Altman plots were used to visually inspect agreement between NS and SA CT values. Results Among 144 self-collected samples (72 pairs) from 13 unique participants (5 index cases and 8 household members), there were 30 pairs with concordant positive detections in both sample types, 35 with concordant negative detections in both samples, 1 pair with positive NS only, and 6 pairs with positive SA only. The overall agreement between NS and SA was 90.3% (p=0.1). The median SARS-CoV-2-N1 CT value for NS samples was 33.3 (interquartile range: 30.2–35.3) and for SA samples was 30.5 (29.8–33.3, p=0.04); the median CT value for SARS-CoV-2-N2 was 34.4 (31.5–37.5) and 31.5 (30.4–34.9), respectively (p=0.01). Bland-Altman plots indicated that most observations were contained within the limits of agreement but suggested NS tended to have higher CT values than SA samples (Figures). Conclusion Self-collection of saliva samples provides a simple, non-invasive, and practical strategy for identification of SARS-CoV-2 infections. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ (Grant/Research Support)Campbell Alliance (Grant/Research Support)CDC (Grant/Research Support)FDA (Grant/Research Support)Merck (Consultant)NIH (Scientific Research Study Investigator)Pfizer (Consultant)Sanofi (Consultant)Sanofi (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Background Social distancing measures, such as shelter-in-place or stay-at-home orders, are recommended for control of community transmission of SARS-CoV-2. Few studies, however, have characterized the transmission of SARS-CoV-2 infections in households. Methods We conducted a case-ascertained study of household transmission in Nashville, TN starting in April 2020, after recommendations to stay at home were enacted. Index cases were ambulatory patients identified through clinical RT-PCR testing at Vanderbilt walk-in-clinics dispersed across the Nashville metropolitan area. For this study, the index case was the first person presenting with respiratory or compatible symptoms in a household and who lived with at least one other household member. After informed consent was obtained, household members were remotely trained in the self-collection of nasal swabs and use of REDCap electronic questionnaires. Household members completed daily symptom diaries and collected daily nasal swabs for 14 days. Contact patterns within households before and after disease onset were ascertained. Nasal swab samples were tested using RT-PCR at an academic research laboratory. Results At the time of writing, 18 families were enrolled (including 18 index cases and 34 household members) with at least 1 follow-up nasal swab tested. The median age of index cases and household members was 37 years (IQR: 26–46) and 27 years (15–39), respectively. The median number of days from index patient onset of symptoms to first sample collected in the household was 4 (2–5). Before onset of symptoms, 83% of index cases spent >4 hours in the same room with at least one other household member, whereas after disease onset and diagnosis, 44% did. Among 34 non-index household members, 18 (53%) had a positive test during follow-up; the median number of days from index case’s symptoms onset to first positive detection in a household member was 4.5 (3–5) days. Interestingly, 13 (72%) of 18 secondary infections were detected within the first 3 days of follow-up, whereas 5 (28%) were detected during subsequent days. Conclusion These observations suggest that transmission of SARS-CoV-2 within households is high, with many infections detected during the initial days of study follow-up. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ (Grant/Research Support)Campbell Alliance (Grant/Research Support)CDC (Grant/Research Support)FDA (Grant/Research Support)Merck (Consultant)NIH (Scientific Research Study Investigator)Pfizer (Consultant)Sanofi (Consultant)Sanofi (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Background Few studies have quantified the risk of community-acquired pneumonia (CAP) among adults with co-morbidities. Combining data from the population-based, prospective Etiology of Pneumonia in the Community study (EPIC) and the nationwide health-related Behavioral Risk Factor Surveillance System (BRFSS) telephone-survey, we estimated the annual risk of hospitalization for CAP among adults with co-morbidities. Methods We identified adults hospitalized with radiographic and clinical CAP at hospitals in Chicago, IL and Nashville, TN from July 2010 to June 2012. Using 2011 BRFSS data, we estimated the prevalence of the population with selected co-morbidities (chronic lung disease [CLD], cardiovascular disease [CVD], chronic kidney disease [CKD], or diabetes) in the EPIC study catchment counties, as well as the population without co-morbidities. We estimated the incidence of hospitalized CAP, age-adjusted relative risk (RR) using Poisson regression, and population attributable fraction for each co-morbidity. Results Among 2,061 adult patients enrolled in EPIC, 1,428 (69%) had at least one selected co-morbidity, most commonly CLD (42%) and CVD (35%). Among the adult population in the EPIC catchment area, 17% had ≥1 selected co-morbidity. The overall incidence of hospitalized CAP was 24.8/10,000, 118.7/10,000 among adults with ≥1 co-morbidity, and 11.2/10,000 among adults without a co-morbidity. Compared with patients without co-morbidities, the incidence of hospitalization for CAP was higher among patients with CLD (aRR: 20.7 [95% confidence interval [CI]: 20.0–21.5]), CKD (aRR: 14.5 [CI: 13.8–15.1]), CVD (aRR: 14.0 [CI: 13.5–14.6]), and diabetes (aRR: 6.2 [CI: 5.9–6.4]). While CLD and CVD accounted for high proportions of the incidence of CAP hospitalizations in the study population, the contribution of the selected co-morbidities varied by age groups (figure). Conclusion There is an increased risk of hospitalization for CAP among adults with co-morbidities, particularly chronic lung and cardiovascular disease. As a large portion of CAP is attributable to these co-morbidities, targeted public health interventions, such as vaccination and risk communication, need to be reinforced among these high-risk groups. Disclosures All authors: No reported disclosures.

Background. The Cryptococcus neoformans polysaccharide capsule is a well-characterised virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure(ICP) in cryptococcal meningitis(CM) by mechanical obstruction of cerebrospinal fluid(CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.\ud \ud Methods. 134 HIV-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines. 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.\ud \ud Results. Cryptococcal strains producing larger ex vivo capsules in the baseline(pre-treatment) CSF correlated with higher ICP(P=.02), slower rate of fungal clearance(P=.02), and paucity of CSF inflammation, including decreased CSF white blood cell(WBC) count(P\ud \ud Conclusions. Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.

We examined respiratory viral testing and influenza antiviral prescriptions at a US tertiary care hospital. During the 2010–11 to 2012–13 influenza seasons, antiviral prescriptions among acute respiratory illness (ARI) hospitalizations were associated with viral testing (rate ratio = 15.0), and empiric prescriptions were rare (

Intracranial pressure management with repeat lumbar puncture (LP) was investigated in patients with cryptococcal meningitis in sub-Saharan Africa. Conducting at least 1 additional LP soon after cryptococcal diagnosis was related to decreased risk of acute mortality regardless of initial pressure., Introduction. Cryptococcal meningitis is the most common cause of adult meningitis in sub-Saharan Africa. Raised intracranial pressure (ICP) is common in cryptococcosis. Prior studies suggest elevated ICP is associated with mortality, and guidelines recommend frequent lumbar punctures (LPs) to control ICP. However, the magnitude of the impact of LPs on cryptococcal-related mortality is unknown. Methods. In sum, 248 individuals with human immunodeficiency virus (HIV)-associated cryptococcal meningitis, screened for the Cryptococcal Optimal ART Timing (COAT) trial in Uganda and South Africa, were observed. Individuals received an LP to diagnose meningitis, and subsequent therapeutic LPs were recommended for elevated ICP (>250 mmH2O) or new symptoms. We compared survival, through 11 days, between individuals receiving at least 1 therapeutic LP with individuals not receiving therapeutic LPs. The COAT trial randomized subjects at 7–11 days; thus, follow-up stopped at time of death, randomization, or 11 days. Results. Seventy-five (30%) individuals had at least 1 therapeutic LP. Individuals receiving therapeutic LPs had higher cerebrospinal fluid (CSF) opening pressures, higher CSF fungal burdens, and were more likely to have altered mental status at baseline than those with no therapeutic LPs. Thirty-one deaths (18%) occurred among 173 individuals without a therapeutic LP and 5 deaths (7%) among 75 with at least 1 therapeutic LP. The adjusted relative risk of mortality was 0.31 (95% confidence interval: .12–.82). The association was observed regardless of opening pressure at baseline. Conclusions. Therapeutic LPs were associated with a 69% relative improvement in survival, regardless of initial intracranial pressure. The role of therapeutic LPs should be reevaluated.

Cryptococcal meningitis is the most common cause of adult meningitis in Africa and accounts for 20% of acquired immune deficiency syndrome (AIDS)-associated mortality in sub-Saharan Africa [1–4]. With amphotericin-based combination antifungal therapy, 10-week mortality from human immunodeficiency virus (HIV)-associated cryptococcosis can be as low as 20%–30% [5–7]. However, at the end of amphotericin treatment, 40%–50% of individuals continue to have viable Cryptococcus neoformans in their cerebrospinal fluid (CSF), which has historically been associated with 2- to 3-fold excess risk of detrimental clinical outcomes, including, death, immune reconstitution inflammatory syndrome (IRIS), or relapse [8–12]. After amphotericin induction therapy, consolidation therapy of fluconazole 400 mg/day is recommended to further suppress infection and support long-term recovery [13, 14]. However, 400 mg/day fluconazole is primarily fungistatic, which may allow persistence of the fungus through consolidation therapy [15]. Persistent culture positivity and failure to clear the organism is thought to be detrimental in HIV, setting the stage for paradoxical IRIS upon ART initiation and ultimately increasing the risk of neurologic deterioration and death [16–18]. However low-grade culture positivity might not be detrimental if fungicidal therapy is continued and sterilizes the CSF as the immune responses are restored with ART. Few contemporary studies have investigated the detriments of residual cryptococcal infection after induction therapy. One recent study of 106 South Africans reported that residual fungemia was associated with a 3-fold higher hazard of paradoxical IRIS and an 8-fold higher hazard of culture-positive cryptococcal relapse when using traditionally recommended fluconazole 400 mg/day consolidation therapy [18]. During a recent clinical trial, we evaluated the association between persistent CSF culture positivity and detrimental clinical outcomes among participants treated with fluconazole 800 mg/day “enhanced consolidation” therapy.

Standard electrolyte monitoring and supplementation as compared to sporadic electrolyte monitoring and replacement improves mortality., Background Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (