Congenital cytomegalovirus (cCMV) infection is the most common congenital infection. Cleveland Clinic (CC) recognized a substantial underdiagnosis of cCMV compared to the expected incidence. A multidisciplinary team at CC developed and implemented an active cCMV screening program for infants beginning Jan 2022 with a goal of improving detection and follow-up. This report highlights cohort outcomes and key challenges encountered during program execution.cCMV Screening algorithmHybrid screening algorithm for congenital CMV (cCMV) at Cleveland Clinic: universal screening in NICU infants and targeted screening in newborn nurseries based on clinical signs or abnormal newborn hearing screen. Guides audiology follow-up and identifies candidates for antiviral therapy.cCMV Screenings and Detections by YearAnnual cCMV (congenital cytomegalovirus) screening volumes and corresponding detections are shown for the years 2020 through March 31, 2025. Both the number of screenings and the number of confirmed detections increased substantially over time. This analysis highlights the benefits of active newborn screening. With input from caregivers in Laboratory Medicine, Infectious Disease, Otolaryngology, Audiology, Newborn Nursery and Intensive Care, a standardized saliva screening program was developed and implemented. This protocol involves universal screening of newborns admitted to NICU and targeted screening in healthy newborn nurseries (clinical suspicion or abnormal newborn hearing screen (NHS)). Positive saliva screens were confirmed with urine PCR testing. Over 12,000 deliveries occur annually across Ohio and Florida. From 1/1/2022 through 3/31/2025, there was a 1223% increase in screening compared to 2020-21. Of 5513 saliva screens that occurred across 16 newborn wards (9 NICU, 7 nursery) at 8 hospitals in 2 states, 918 were targeted and 4595 were universal. In total, 33 infants were identified by saliva screening and confirmed with urine testing (10 symptomatic with 2 deaths, 23 asymptomatic) nearly tripling the relative rate of identification. Of asymptomatic infants, 15 (65%) passed their NHS. Incidence of cCMV was 0.58% (1.42% targeted, 0.41% universal). The newborn nursery and ICU quickly adapted to using the program without a disruption in workflows. Substantial false-positive saliva results early in the program catalyzed changes in sample testing workflows and ultimately the testing platform. Infectious Disease and Audiology were instrumental in accommodating capacity for longitudinal follow-up and 1-3-6 benchmark auditory screening. Early multidisciplinary involvement and coordination are essential for successful implementation of cCMV screening. This program significantly increased the detection of cCMV in newborns despite many being asymptomatic with normal NHS, highlighting the importance of active screening programs. Samantha Anne, MD, Cochlear: Grant/Research Support|Eli Lilly: Advisor/Consultant|Plural publishing: royalties Daniel D. Rhoads, MD, Abbott: Grant/Research Support|Altona: Grant/Research Support|BD: Grant/Research Support|bioMerieux: Grant/Research Support|Cepheid: Grant/Research Support|Cleveland Diagnostics: Grant/Research Support|HelixBind: Grant/Research Support|Hologic: Grant/Research Support|Luminex/Diasorin: Grant/Research Support|Meridian: Grant/Research Support|Next Gen Diagnostics: Board Member|Next Gen Diagnostics: Ownership Interest|Pattern Bio: Grant/Research Support|Qiagen: Grant/Research Support|Q-Linea: Grant/Research Support|Rapid Diagnostics: Grant/Research Support|Renascent Diagnostics: Advisor/Consultant|Renascent Diagnostics: Financial payments|Renascent Diagnostics: Ownership Interest|Roche: Grant/Research Support|Selux Diagnostics: Grant/Research Support|Thermo Fisher: Grant/Research Support|Vela Diagnostics: Grant/Research Support Hannah Wang, MD, Cepheid: Grant/Research Support|Hologic: Advisor/Consultant|Hologic: Grant/Research Support|Moderna: Honoraria

Diagnosis of congenital cytomegalovirus (cCMV) is challenging. Screening is typically conducted on saliva followed by confirmatory testing on urine. Challenges in saliva screening include many false-positive (FP) results and relatively low throughput of currently FDA-approved platforms. Our institution validated CMV screening using quantitative PCR on the cobas 8800 (Roche) for infant saliva and urine. Following validation, we reviewed viral loads (VL) from a 2 year cohort to determine whether adjustment of reporting thresholds could improve the specificity of saliva screening.Figure 1 illustrates the distribution of log-transformed CMV DNA values in saliva stratified by disease status. Compared to the False Positive group, the True Positive group demonstrates a higher median CMV DNA level. From April 2023-March 2025, quantitative saliva and urine VL for infants < 21 days were tabulated. Saliva PCR sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated at predefined VL thresholds and by Youden’s index. Urine PCR results were used to classify a saliva PCR result as a true vs. false positive (TP, FP). Specimens measuring above or below the limits of quantitation were assigned the maximal or minimal values of 7.01 log IU/mL or 1.53 log IU/mL respectively. CMV PCR was positive in 37/3995 (0.93%) of saliva specimens obtained through targeted screening. Among saliva-positive, 24 (64.9%) had CMV detectable in urine (TP). Higher saliva VL significantly correlated with higher urine VL (Spearman correlation coefficient 0.88, 95% CI: 0.77-0.94). Saliva VL measured a median of 6.63 log IU/mL (IQR 4.69-6.90) for TPs, vs. 1.53 log IU/mL (IQR 1.53-1.53) for FPs (Figure 1). A total of 22 saliva negative infants also had subsequent urine testing; all were negative (TN). Among 59 specimens with both saliva and urine PCR results, saliva PCR sensitivity was 100% (95% CI 85.8-100%), specificity was 62.9% (44.9-78.5%), observed PPV and NPV were 64.8% (54.5-74.0%) and 100% (84.6-100%). If saliva PCR positivity reporting threshold were adjusted such that those with CMV VL < 1.54 log IU/mL were reported as negative, specificity improved to 91.4% (76.9-98.2%) and observed PPV to 88.9% (73.1-95.9%), with no decrement in sensitivity or NPV. The quantitative CMV PCR performed in our lab is highly sensitive with excellent NPV in saliva swabs for cCMV screening. Assay specificity and PPV could be improved by adjusting the threshold of positivity to 1.54 log IU/mL. All Authors: No reported disclosures

Abstract Background The COVID-19 pandemic and resulting worldwide countermeasures immediately impacted the circulation of endemic respiratory viruses. Yet the dynamics of recovery have varied between species. We hypothesize the level of disruption in virus circulation and the time to return to pre-pandemic norms is dependent on circulation overlap with the pandemic strain. Methods Interrupted time series (ITS) analysis and continuous wavelet analysis of univariate times series (Morlet) was conducted on Cleveland Clinic respiratory virus results from 2015 through 2023. Data was analyzed on individual virus species grouped in 3 seasonality patterns: wintertime (FLUA, FLUB, RSV), springtime (HMPV, PIV3) and year-round (ADENO, RHINO/ENTERO). Pre and post pandemic trends in positivity, peak shift analysis and periodic cycle were assessed. Results FLUA positivity dropped by 11% (95% CI 7.4-14%) in first effective quarter post-pandemic and gradually increased (+1.9% per year, p=.046) afterwards. The dominant cycle shifted from annual pre-pandemic to semiannual, with virus incidence peaks (median week) at 21-W50, 22-W17, and 22-W51, respectively, departing from the pre-pandemic baseline (W7, p < 0.001). RSV positivity decreased by 2.6% per year after the pandemic (95% CI 1.2-4.0%). The annual cycle remained dominant, but peak incidence of RSV shifted earlier then gradually normalized (baseline-W1 vs. 21-W39 vs. 23-W45, p< .0001). FLUB positivity significantly decreased postpandemic (0.18% vs 6.1%, p< .0001). No significant impact on PIV3 and HMPV positivity occurred. Both viruses showed an annual cycle dominance throughout, with a semiannual cycle only observed post-pandemic. ADENO showed decreasing trends before the pandemic and increasing trends after the pandemic (-0.63% vs +0.94%, p=.001). Both ADENO and RHINO/ENTERO did not show changes in circulation with no distinct peaks observed. Conclusion Pandemic circulation disproportionately affects co-circulating viruses. Wintertime dominant viruses experienced prolonged displacement and have yet to return to pre-pandemic norms. Conversely, spring and year-round viruses were only modestly displaced and are now near pre-pandemic baseline. This study holds important implications for public health preparedness for future pandemics. Disclosures All Authors: No reported disclosures

BACKGROUND:Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post-transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post-exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness. METHODS:A cross-sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity. RESULTS:Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively. CONCLUSIONS:Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity.

Respiratory syncytial virus (RSV) is a threat to infants globally causing bronchiolitis and pneumonia. Despite decades of research, RSV outbreaks occur with only modest advancements in prevention or treatment. Vaccine development faced challenges because past attempts caused enhanced disease and treatment options demonstrated limited efficacy. Recent advancements, including maternal vaccines focusing on the prefusion form of the F glycoprotein are now showing significant benefits in preventing severe RSV-related illness in infants. Additionally, monoclonal antibodies offer prevention directly to newborns within 1 week of birth. These innovations have the potential to substantially change the impact of RSV.

SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14 . Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5–20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8–96.4], 40.7 (95%CI 38.9–42.6) and 34.7 (95%CI 33.0–36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.

Abstract Background Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited. Method Viral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio. Major variants were correlated with disease severity and patient outcomes. Results In total 2779 patients identified with either Alpha (n = 1153), Gamma (n = 122), Delta (n = 808), or Omicron variants (n = 696) were selected for analysis. No difference in frequency of hospitalization, intensive care unit (ICU) admission, and death were found among Alpha, Gamma, and Delta variants. However, patients with Omicron infection were significantly less likely to be admitted to the hospital, require oxygen, or admission to the ICU (χ2 = 12.8, P < .001; χ2 = 21.6, P < .002; χ2 = 9.6, P = .01, respectively). In patients whose vaccination status was known, a substantial number had breakthrough infections with Delta or Omicron variants (218/808 [26.9%] and 513/696 [73.7%], respectively). In breakthrough infections, hospitalization rate was similar regardless of variant by multivariate analysis. No difference in disease severity was identified between Omicron subvariants BA.1 and BA.2. Conclusions Disease severity associated with Alpha, Gamma, and Delta variants is comparable while Omicron infections are significantly less severe. Breakthrough disease is significantly more common in patients with Omicron infection.

Background: Congenital cytomegalovirus (CMV) infection is a significant cause of childhood hearing loss and developmental delay. Congenital CMV screening was implemented at two large hospital-affiliated laboratories using the FDA-approved Alethia CMV Assay Test System. In July 2022, an increase in suspected false-positive results was noted, leading to implementation of prospective quality management strategies.Methods: The Alethia assay was performed per manufacturer-provided instructions on saliva swab specimens. After discovery of possible elevated false-positive rates, all positive results were confirmed by repeat Alethia testing on the same specimen, orthogonal polymerase chain reaction (PCR) on the same specimen, and/or clinical adjudication. Additionally, root cause analyses were conducted to pinpoint the source of false-positive results.Results: At Cleveland Clinic (CCF), 696 saliva specimens were tested after initiation of the prospective quality management strategy, of which 36 (5.2%) were positive for CMV. Five of 36 (13.9%) were confirmed CMV positive by repeat Alethia testing and orthogonal PCR. Vanderbilt Medical Center (VUMC) tested 145 specimens, of which 11 (7.6%) were positive. Two of 11 (18.2%) confirmed as positive by orthogonal PCR or clinical adjudication. The remaining specimens (31 from CCF and 9 from VUMC) were negative for CMV by repeat Alethia and/or orthogonal PCR testing.Discussion: These findings suggest a false positive rate of 4.5-6.2%, higher than the 0.2% reported for this assay in FDA claims. Laboratories using Alethia CMV may consider prospective quality management to evaluate all positive results. False-positive results can lead to unnecessary follow-up care and testing, and decreased confi-dence in laboratory testing.

Abstract Background Our understanding of SARS-CoV-2 evolution is limited. Most estimates arise from analysis of global databases populated with unrelated sequences and is currently estimated at ∼27.7 substitutions/genome/year. SARS-CoV-2 polymerase contains a proofreading function encoded by NSP-14 limiting change. Additionally, virus evolution may be influenced by patient comorbidity. Intra-host mutational rate (MR) during infection remain poorly studied. Methods To minimize effect of vaccination and/or natural immunity on MR analysis, paired samples from adults originating from the initial pandemic wave (3/17/2020 through 5/27/2020) were retrieved and analyzed at Cleveland Clinic. Viral genome analysis was performed using next generation sequencing, and mutations between paired samples were quantified at allele frequencies (AF) ≥ 0.1, ≥ 0.5 and ≥ 0.75 and compared. MR was calculated employing F81 and JC69 evolution­­­­ models and compared between isolates with (Δ NSP-14) and without (wildtype, wt) non-synonymous mutations in NSP-14 and by comorbidity. Results A total of 40 patients (80 sample pairs) were identified. Median interval between paired tests was 15 days [range 5-32]. The estimated MR by F81 modeling was 317.2 (95%CI 312.0-322.3), 54.6 (95%CI 52.5-56.7) and 45.1 (95%CI 43.1-47.0) substitutions/genome/year at AF of ≥0.1, ≥0.5, ≥0.75 respectively. Rates in ΔNSP-14 (n=13) vs wt (n=27) groups were 557.7 (95%CI 537.0-578.2) vs 193.1 (95%CI 187.1-199.1) p-value 0.001, 50.8 (95%CI 44.3-57.3) vs 56.3 (95%CI 53.1-59.4) p-value 0.144, and 31.0 (95%CI 25.9-36.1) vs 51.3 (95%CI 48.3-54.3) p- value < 0.001 at AF ≥0.1, ≥0.5, ≥0.75 respectively. Patients with immune comorbidities (n=6) had significantly higher MR of 137.6 (95%CI 114.6-160.5) vs 40.5 (95%CI 38.4-42.7) p-value < 0.001, and 113.7 (95%CI 92.8-134.5) vs 33.4 (95%CI 31.5-35.4) p-value < 0.001 at AF ≥0.5 and ≥0.75 respectively. Similar results were obtained when using the JC69 model. Conclusion Intra-host SARS-CoV-2 mutation rates are higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated MR at low AF. Immunosuppressed patients have elevated MR at higher AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling. Disclosures Frank Esper, M.D, Johnson and Johnson: Advisor/Consultant Daniel D. Rhoads, M.D. PhD, Luminex: Advisor/Consultant|Talis Biomedical: Advisor/Consultant|Thermo Fisher: Advisor/Consultant.

Key Points Question Are SARS-CoV-2 variants, virus clades, or clade groups associated with disease severity and patient outcomes? Findings In this cross-sectional study of 302 SARS-CoV-2 isolates, 6 different Global Initiative on Sharing All Influenza Data clades circulated in the community followed by a rapid reduction in clade diversity. Several variants, including 23403A>G (D614G), were significantly associated with lower hospitalization rates and increased patient survival. Meaning These findings suggest that SARS-CoV-2 clade assignment is an important factor that may aid in estimating patient outcomes.

Determining whether and when multiplex nucleic acid amplification tests (NAATs) for respiratory viruses should be repeated is difficult. We analyzed 5 years of results for a multiplex NAAT targeting 14 respiratory viruses, to determine how often repeat tests were ordered and the time period in which results were likely to change. Results for NAATs performed on nasopharyngeal specimens and repeated within 90 days after initial testing were analyzed.

Two infants treated for syphilis born to at risk mothers who screened negative at their first prenatal visit but were not rescreened at delivery are described. The first presented with classic, but unrecognized, features of congenital syphilis. In the second case, possible early maternal syphilis was diagnosed soon after delivery using the treponemal first reverse-screening algorithm. Although the child's physical exam was normal and the maternal rapid plasma reagin (RPR) negative, the child was treated for syphilis because maternal confirmatory treponemal tests suggested recent seroconversion. Given the re-emergence of congenital syphilis, our report aims to demonstrate the importance of rescreening women at increased risk and improve awareness of common manifestations of the syphilis disease in the newborn. For women at increased risk, repeat syphilis testing early in the third trimester and again at delivery in communities and populations with a high prevalence of syphilis is recommended.

E-consults replace "curbside" interactions, facilitate provider-specialist communication, document within the medical record, and track relative value units (RVUs). Pediatric infectious diseases (PID) E-consults commonly relate to vaccines, exposures, diagnoses, and treatments. The documented RVU effort of 197 consecutive PID E-consults was equivalent to 70 level 4 new outpatient consults.

BACKGROUND:More than 60 years since the discovery of the respiratory syncytial virus (RSV), the effects of prenatal exposure to this virus remain largely unknown. In this investigation, we sought to find evidence of RSV seroconversion in cord blood and explore its clinical implications for the newborn. METHODS:Offspring from 22 pregnant women with a history of viral respiratory infection during the third trimester of pregnancy (respiratory viral illness [RVI] group) and 40 controls were enrolled in this study between 1 September 2016 and 31 March 2019. Cord blood sera were tested for anti-RSV antibodies by indirect fluorescent antibody assay. RSV seropositivity was defined as the presence of anti-RSV immunoglobulin M (IgM) or immunoglobulin A (IgA), in addition to IgG in cord blood serum at ≥1:20 dilution. RESULTS:Anti-RSV IgG was present in all cord blood serum samples from infants born to RVI mothers (95% confidence interval [CI] = 82%-100%), with 16 samples also having elevated titers for either anti-RSV IgA or IgM (73%; 95% CI = 52%-87%). No controls had evidence of anti-RSV antibodies. Eight (50%) seropositive newborns developed at least one respiratory tract finding, including respiratory distress syndrome (N = 8), respiratory failure (N = 3), and pneumonia (N = 1). RSV seropositive newborns also required more days on oxygen, had leukocytosis and elevated C-reactive protein (P = .025, P = .047, and P < .001, respectively). CONCLUSION:This study provides evidence of acute seropositivity against RSV in cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester. Cord blood seropositivity for anti-RSV IgA or IgM was associated with adverse clinical and laboratory outcomes in newborns.

Abstract Background Curbside consultation is a ubiquitous practice within the medical field informally providing advice to community providers. The electronic consult (E-Consult) allows direct provider-to-provider communication between the primary care provider (PCP) and specialists using a secure electronic platform while documenting these interactions within the patient’s medical record (EMR). They offer PCP’s a forum for asking nonurgent questions. For the specialist, it allows review of the EMR, reduces medical liability of the curbside consult and provides a mechanism for generating RVUs. This service was implemented in our healthcare network (of over 300 pediatricians and pediatric specialists who see more than 500,000 pediatric visits each year) in April 2018. Our aim was to review and analyze the E-consults provided by the Pediatric Infectious Diseases (PID) service. Methods Cross-sectional study of E-consults performed by the PID from April 11 -2018-April 22 2019. Clinical queries were categorized by type and tabulated. Consult Billing was as following: Level 1=5 minutes (min); Level 2 =10min; Level 3= 15 minutes; Level 4= 25 minutes. RVU values were institutionally derived and assigned. Results We performed 171 E- consults with an average of 13 per month (range 3–18) generated from 59 providers (52 (88%) physicians and 7 (12%) certified nurse practitioners). Common reasons for the E-consult included: vaccine questions (25.7%), diagnosis questions (21.6%), exposure questions (20.4%) and treatment recommendations (10.5%). Of vaccine questions, 43% related to vaccine schedules /boosters, 13% vaccines for travel and 11.3% vaccines for the immunocompromised host. Consultation in the PID clinic was recommended for 25.7% patients, 9% requiring urgent evaluation. Of the 171 E-consults, 12.2% were evaluated in the PID clinic and 5% by another specialty. Billing was performed for 168 of the E consults= 9 level 1, 35 level 2, 83 level 3 and 41 level 4 generating 161 RVUs (equivalent to 53 level 4 new outpatient visits at our institution). Conclusion E-consults are an alternative to informal curbside consults for nonurgent clinical queries. Encounters are documented in the EMR and professional effort devoted to the task is tracked providing an additional source of RVU generation for the PID physician. Disclosures All authors: No reported disclosures.

Background Respiratory syncytial virus (RSV) is capable of transient viremia and extrapulmonary dissemination. Recently, this virus has been identified in fetal cord blood, suggesting the possibility of in utero acquisition in humans. Here, we assess permissivity and kinetics of RSV replication in primary human placental cells, examine their potential to transfer this infection to neighboring cells, and measure the inflammatory response evoked by the virus. Methods and findings Human placental villus tissue was collected immediately upon delivery and processed for isolation of placental cytotrophoblast, fibroblast, and macrophage (Hofbauer) cells. Isolated cells were infected with a recombinant RSV-A2 strain (rrRSV) expressing red fluorescent protein (RFP) and analyzed by fluorescence microscopy, Western blot, and quantitative PCR (qPCR). Based on RFP expression, rrRSV exhibited differential tropism for the three major placental cell types. Placental fibroblasts and Hofbauer cells were permissive and supported productive rrRSV replication. While infected cytotrophoblast cells expressed viral glycoprotein (G protein), only limited RSV replication was detected. Importantly, qPCR and fluorescence-focused unit assay revealed that the viral progeny remains trapped within infected Hofbauer cells for up to 30 days, with no release into surrounding media. Yet, Hofbauer cells passed the infection onto overlaid naïve 16HBE cells, suggesting contact-dependent trans-infection. Lastly, a significant increase in proinflammatory cytokines, particularly IL-6, TNF-alpha, and IFN-gamma was measured in the supernatant of infected Hofbauer cells by multiplex cytokine assay and conventional ELISA. Conclusions This study demonstrates that RSV can replicate in human placenta, exhibits differential tropism for distinct placental cell types, can be stored and transferred to neighboring cells by Hofbauer cells, and elicits an inflammatory response. It also supports the hypothesis that this respiratory virus can be vertically transferred to the fetus and potentially affect its development and the outcome of pregnancies.

A 42-year-old female patient, who underwent commercial living unrelated kidney transplant of unknown donor status for end stage renal disease two weeks prior to presentation, was admitted for acute renal failure and rejection. Ultrasound of transplanted kidney showed hydronephrosis and absent blood flow. She underwent nephrectomy of the transplanted kidney with intraoperative findings of extensive necrosis of the kidney, subcutaneous tissue and muscle fascia. The donor renal artery was anastomosed to the internal iliac artery which was ligated and the donor renal vein was anastomosed to the external iliac vein. There was gross infection of the native iliac vessels. Kidney pathology showed hyphal elements and culture was positive for Aspergillus (Figure 1). Liposomal amphotericin and voriconazole were started. Unfortunately, she developed right lower extremity ischemia due to septic embolus from the iliac artery requirMohamed Alhosani1*; Woosup Michael Park2; Mohamad Mooty3; Bashir Sankari4; Samar Farha5 1Al Falah Street, Al Mariyah Island, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE 2Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE 3Infectious Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE 4Surgical Subspecialties Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE 5Respiratory and Critical Care Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE

Abstract Background The clinical relevance of respiratory viral co-infections is unclear. Few studies determine epidemiology and impact of specific co-infection pairings. Here we assess the dynamics of respiratory viral co-infections, determine any predisposition for specific pairings to occur and evaluate resulting clinical impact on hospitalization. Methods We reviewed respiratory viral panel results collected at The Cleveland Clinic between November 2013 to Jun 2018. Monthly prevalences, mono-infections and co-infections of 13 viral pathogens were tabulated. Employing a mathematical model which utilized each individual virus’ co-infection rate and prevalence patterns of concurrent circulating respiratory viruses, we calculated an expected number of occurrences for 132 viral pairing permutations. Expected vs observed co-infection occurrences were compared using binomial tests. For viral pairings occurring at significantly higher prevalence than expected, logistic regression models were used to compare hospitalization between patients with co-infection to ones with mono-infection. Results Of 30,535 respiratory samples, 9,843 (32.2%) samples were positive for at least 1 virus and 1,018 (10.82%) were co-infected. Co-infections occurred in 18% of pediatric samples and only 3% of adult samples (P < 0.001). Adenovirus C (ADVC had the highest co-infection rate (68.3%) while influenza B had the lowest (10.07%). Using our model, ADVC – rhinovirus (HRV), RSVA - HRV, and RSVB - HRV pairings occurred at significantly higher prevalence than expected (P < 0.05). In children, HRV-RSVB co-infection were significantly less likely to be hospitalized than patients with HRV mono-infections (ORmono/co = 2.3; 95% CI 1.1 to 4.7; P = 0.028). Additionally, HRV - ADVC co-infected children were less likely to be hospitalized than either HRV (ORmono/co = 3.3; 95% CI 1.6 to 6.8; P < 0.001) or ADVC (ORmono/co = 1.9; 95% CI 1.1 to 3.2; P = 0.024) mono-infected children. Regardless of the infecting virus, children were less likely to be hospitalized than similarly-infected adults. Conclusion Respiratory viral co-infections are largely a pediatric phenomenon. Select viral pairings occur more often than predicted by our model, many of which are associated with altered severity of resultant disease. Disclosures All authors: No reported disclosures.

Current prevention options for upper respiratory infections (URIs) are not optimal. We conducted a randomized, double-blinded, placebo-controlled pilot clinical trial to evaluate the safety and efficacy of ARMS-I™ (currently marketed as Halo™) in the prevention of URIs.