79. Children with COVID-19 Demonstrate Distinct Serum Cytokines Profiles According to Clinical Presentations

Abstract Background Almost 4 million children have tested positive for Coronavirus Disease 2019 (COVID-19) as of June 3 2021, representing 14% of all cases in USA. Children present with diverse clinical findings including the multisystem inflammatory syndrome in children (MIS-C). In this study, we measured serum cytokine concentrations in children with COVID-19 to identify differences in immune profiles according to clinical presentations. Methods A total of 133 children 0-21 years of age with COVID-19 were enrolled at Nationwide Children’s Hospital, in Columbus, Ohio. Nasopharyngeal swab RT-PCR testing was used for SARS-CoV-2 detection and quantification. Clinical and laboratory information were obtained, and blood samples were collected for measurement of cytokines with a 92-plex inflammation assay (Olink). Normalized cytokine expression levels in patients were compared with serum samples from 66 pre-pandemic age-matched healthy controls. Results COVID-19 children included: 1) those identified by universal screening (n=47); 2) moderate disease (ward; n=48); 3) severe disease (PICU; n=20); 4) MIS-C (n=18). Children identified by universal screening were hospitalized for trauma, appendicitis or new onset diabetes among others. Children with symptomatic COVID-19 had significantly higher SARS-CoV-2 viral loads than children with MIS-C or those identified via universal screening. Concentrations of interferon (IFN) related cytokines (IFNg, CXCL9, CXCL10, CXCL11), interleukins (IL6, IL8, IL10, IL17A, IL18, IL24) and other inflammatory cytokines (TGF, TNF, VEGF, MCP, CD40) were significantly increased in children with acute COVID-19 and MIS-C compared with children identified by universal screening and healthy controls. These cytokines were positively correlated with C-reactive protein, D-dimer and disease severity in COVID-19, but negatively correlated with viral loads (Fig 1). MIS-C showed stronger inflammatory response than acute COVID-19 (Fig 2). Correlation of Age-adjusted cytokine expression values with viral load, disease severity, CRP and D-dimer. Pearson correlation coefficient is shown for each pair. Red: positive correlation; blue: negative correlation Cytokines that differentiate MIS-C from acute COVID-19 Heatmap shows the differential expressed cytokines between MIS-C and acute severe COVID-19 (padj<0.05, FC>2). The age-adjusted expression values are normalized the median of healthy controls. Red: up-regulation, blue: down-regulation. Conclusion We identified three cytokine clusters in children with COVID-19 according to clinical presentations. Correlations of serum cytokines with clinical/laboratory parameters could be used to identify potential biomarkers associated with disease severity in COVID-19 Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)

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1465. Age-Dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children with Respiratory Syncytial Virus Infection (RSV) Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1646 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S734-S735

Author(s):

Helena Brenes-Chacon ◽

Cristina Garcia-Maurino ◽

Melissa Moore-Clingenpeel ◽

Sara Mertz ◽

Fang Ye ◽

...

Keyword(s):

Young Children ◽

Disease Severity ◽

Age Groups ◽

Panel Member ◽

Signs And Symptoms ◽

Research Support ◽

Review Panel ◽

Viral Loads ◽

Age Dependent ◽

Rsv Infection

Abstract Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children < 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) < 3 months, (B) between 3 and 6 months, and (C) > 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children < 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-< 3, 3-6, and >6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (>3 months) than in inpatients (p< 0.01), while fever was more common in inpatients that outpatients (p< 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants >3 months, and higher RSV loads in children >6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

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131. The Protective Role of Mucosal Interferons in Infants with Respiratory Syncytial Virus (RSV) Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.441 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S195-S196

Author(s):

Jeanette Taveras ◽

Cristina Garcia-Maurino ◽

Melissa Moore-Clingenpeel ◽

Sara Mertz ◽

Mark E Peeples ◽

...

Keyword(s):

Disease Severity ◽

Severe Disease ◽

Panel Member ◽

Type I ◽

Research Support ◽

Review Panel ◽

Duration Of Symptoms ◽

Lower Odds ◽

Rsv Infection ◽

Ifn Γ

Abstract Background Despite the high burden associated with RSV infection in young children the factors that determine disease severity are not well understood. The objective of this study was to assess the association of mucosal cytokine profiles, RSV loads (VL) and RSV disease severity. Methods Single-center, prospective study in previously healthy infants with mild (outpatients; OP), moderate (inpatient-IP; ward) or severe (IP-PICU) RSV infection. Mid-turbinate swabs were obtained to measure VL by PCR, and cytokine concentrations (conc.) using a 13-plex panel that included type I (IFN-α2), II (IFN-γ), and III (IFN-λ2/λ3) interferons (IFN), and inflammatory cytokines. Multivariable analyses were performed to identify factors predictive of disease severity. Results From 2014 to 2019 we enrolled 219 infants: 78 with mild RSV infection (OP; median [IQR] age, 6 [3.4–10.5] mo.), 101 with moderate disease (3.5 [1.3–8.3] mo.), and 40 with severe disease (2.3 [1.5–5.7] mo.). Duration of symptoms at enrollment was 4 (3–5) days and comparable between OP and IP, yet RSV VL in OP were significantly higher than in IP (8.1 [7.4–8.6] vs 7.4 [6.4–8.1] log10 copies/mL; p< 0.01) with no differences between ward and PICU infants. Median conc. of IFN-α2, IFN-γ, and IFN-λ2/λ3 were significantly higher in OP vs IP irrespective of hospitalization unit (Table 1). IP-10 conc. were also higher in OP and in ward patients vs PICU patients (p< 0.0001) and were independently associated with lower odds of supplemental O2 needs (OR, 95% CI: 0.4 [0.22–0.69]; p< 0.01) and PICU admission (0.4 [0.23–0.67]; p=0.001). In addition, higher IFN-λ2/λ3 conc. were nearly associated with lower odds of prolonged O2 use (OR: 0.35 [0.11–1.07]; p=0.07), and prolonged hospitalization (OR: 0.42 [0.16–1.03]; p=0.06). Conclusion Infants with mild RSV infection had higher RSV VL and higher conc. of IP-10 and type-I, III IFN than those hospitalized with severe disease. These findings suggest that IP-10 and mucosal IFNs are associated with protection against severe RSV disease and could be used as biomarkers for patient stratification in the clinical setting. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

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1340. The Burden of Influenza and Rhinovirus Among Hospitalized Adults Post the COVID-19 Pandemic

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1532 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S757-S758

Author(s):

Olivia D Reese ◽

Ashley Tippett ◽

Laila Hussaini ◽

Luis Salazar ◽

Megan Taylor ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Healthy Controls ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Tract Infections ◽

The Impact ◽

Research Grant

Abstract Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

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1193. Mucosal Antibody Responses to Respiratory Syncytial Virus (RSV) in Infants and Young Children

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1385 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S688-S688

Author(s):

Cristina Tomatis Souverbielle ◽

Fang Ye ◽

Sara Mertz ◽

Mark E Peeples ◽

Octavio Ramilo ◽

...

Keyword(s):

Disease Severity ◽

Panel Member ◽

Healthy Children ◽

Upper Respiratory Tract ◽

Limited Information ◽

Research Support ◽

Review Panel ◽

Rsv Infection ◽

Syncytial Virus ◽

Research Grant

Abstract Background The burden associated with RSV infection is substantial. Although RSV initially infects the upper respiratory tract, there is limited information of the mucosal concentrations of antibodies (Abs) directed to RSV specific proteins and whether patient’s age and disease severity influence production of mucosal Abs. Methods From 2017 to2019 we enrolled previously healthy children < 2 years of age hospitalized with RSV infection and obtained acute and convalescent (day; D30) nasopharyngeal (NP) samples to measure preF and postF specific IgG and IgA Abs by ELISA. Demographic and clinical data were collected and analyzed according to Abs responses. Results We enrolled 77 children (median [IQR] age: 2.8 [1.5-5.2] months; 49 % females) within the first 24 hours of hospitalization. Of those 25 (33%) patients required PICU care. A significant increase in convalescent IgG preF Abs titers was detected in 62 (81%) children, while IgA preF titers significantly increased in all but one child on D30. The magnitude of the increase was 56-fold higher for preF IgA versus preF IgG (p< 0.0001). PostF IgG and IgA titers were also increased on D30 but at significant lower levels. Infants < 3 months of age compared with those >3-24 months had significantly higher baseline preF and postF IgG Abs titers (p < 0.001) but not IgA antibodies. D30 preF and post F IgG titers were higher in children > 6 months of age (p < 0.0001) but only preF titers fold change significantly correlated with age (r=0.4, p< 0.0001). These correlations were not identified with IgA preF antibodies. There were no statistical differences in antibody titers at baseline and on D30 according to breastfeeding, and disease severity as defined by the need for PICU care. Conclusion Children hospitalized with RSV infection demonstrated significantly increased titers of mucosal preF and post F IgG and IgA specific Abs in convalescent samples. Baseline IgG Abs where higher in younger infants, which likely reflects maternally acquired antibodies. Age significantly correlated with Abs production, suggesting a more robust immune response in older children. Disclosures Mark E. Peeples, PhD, Janssen (Research Grant or Support)Pfizer (Research Grant or Support) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)

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1714. Influenza C Virus in U.S. Children with Acute Respiratory Infection 2016-2019

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1892 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S840-S841

Author(s):

Bethany K Sederdahl ◽

Geoffrey A Weinberg ◽

Angela P Campbell ◽

Rangaraj Selvarangan ◽

Jennifer E Schuster ◽

...

Keyword(s):

Acute Respiratory Infection ◽

Vaccine Trial ◽

Panel Member ◽

Population Based ◽

Healthy Controls ◽

Research Support ◽

Review Panel ◽

Influenza C Virus ◽

Support Research ◽

Research Grant

Abstract Background Influenza C virus (ICV) is associated with acute respiratory infection (ARI); however, the burden of ICV is not well-described. We sought to determine the burden and characteristics of ICV in a prospective, population-based cohort. Methods The study was conducted within the New Vaccine Surveillance Network (NVSN), a CDC-led, seven-site network that performs population-based surveillance for ARI in children < 5 years. Nasal/throat swabs were collected from emergency department (ED) or inpatient children with ARI, or healthy controls in clinic, between 12/05/2016-10/31/2019 and tested by real-time RT-PCR for ICV and other respiratory viruses. Preliminary data were extracted and demographic/clinical features of ICV+ cases analyzed. We sequenced the hemagglutinin-esterase (HE) gene from ICV+ Pittsburgh samples. Results Among 19,321 children with ARI or healthy controls enrolled and tested for ICV from 2016-2019, 115/17,668 (0.7%) ARI cases and 8/1653 (0.5%) healthy controls tested positive for ICV. The median age of ICV+ ARI subjects was 19 months (IQR 10,46) and 81(70%) were ≤36 months. 42.6% (49) were white, 33.9% (39) black, and 16.5% (19) Hispanic, with the remainder Asian or unknown; 56.5% (62) attended daycare. Among ICV+ ARI cases, 67.8% (78) had fever, 94.8% (109) cough, and 60.8% (70) wheezing. 45.2% (52) ICV+ cases occurred in 2016-17, 6.5% (8) in 2017-2018, and 47.8% (55) in 2018-19 (Table). 40% (46) of ICV+ cases were seen in the ED, while the remainder were inpatients. Median length of stay was 2d (IQR,1-3) with 15 admitted to ICU. 67.8% (78/115) ARI cases had 1 or 2 co-detected pathogens, with rhinovirus (26), respiratory syncytial virus (26), and adenovirus (14) most frequently co-detected. ARI symptoms including fever, myalgias, chills, and wheezing did not differ significantly between coinfected subjects and those who were only ICV+. HE sequences were in the two currently circulating Kanagawa and Sao Paulo lineages. ICV+ Cases by Site and Year Conclusion ICV was an uncommon cause of ARI symptoms leading to healthcare encounters in young children. The prevalence varied year-to-year and between different geographic regions. Most children infected with ICV were ≤3 years old and had co-detected pathogens. ICV was similarly rarely detected in healthy controls. Disclosures Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) 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) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member)

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77. Risk of Virologic Failure Among Treatment-experienced Suppressed People with HIV (PWH) Treated with Single-Tablet 2-Drug (2DR) vs 3-Drug (3DR) Regimens

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.077 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S50-S51

Author(s):

Paul Sax ◽

Joseph J Eron ◽

Janna Radtchenko ◽

Helena Diaz-Cuervo ◽

Mark Moore ◽

...

Keyword(s):

Research Study ◽

Virologic Failure ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Viral Loads ◽

Study Investigator ◽

Baseline Characteristics ◽

Research Grant

Abstract Background The single-tablet regimen (STR) dolutegravir/rilpivirine (DTG/RPV) was approved in 2017 for use in virologically suppressed PWH, followed by approval in 2019 of dolutegravir/lamivudine (DTG/3TC). There is a need to evaluate outcomes of 2DR regimens in stable switch population by measuring risk of virologic failure. Methods This retrospective observational study of the Trio Health HIV Research Network cohort of nearly 60,000 PWH evaluated risk of virologic failure among treatment-experienced virologically suppressed PWH switching to a 2DR or 3DR STR (index = time of switch). Eligible patients (pts) were ≥ 18 yrs, treatment-experienced, suppressed at index, with post-index viral loads, ≥ 6 mo pre-index history, with dispenses for DTG/RPV, DTG/3TC or commonly used 3DR STRs initiated after Nov. 2017. Univariate comparisons were performed using Χ2 for categorical and t-test for continuous variables; Kaplan-Meier analysis was used to evaluate time to virologic failure and Cox Proportional Hazards analysis was used to evaluate risk of virologic failure accounting for age, gender, race, and baseline eGFR. Virologic failure was defined as 2 consecutive viral loads >200 cells/ml. Results Of 1668 pts, 132 (8%) received 2DR. Significant differences in baseline characteristics between groups are shown in Table 1. In unadjusted analysis the difference in proportion of pts with virologic failure did not reach significance: 7% (9 pts) on 2DR experienced virologic failure vs 4% (65 pts) on 3DR (p=0.166). Additionally, unadjusted risk of virologic failure and time to virologic failure were not statistically different [Figure 1, Table 2]. Based on prespecified adjusted analysis accounting for race, gender, age, and baseline eGFR, the risk of virologic failure was higher for 2DR compared to 3DR STRs (HR=2.2 CI 95% 1.1-4.5, p=0.032) [Table 2]. Adjusting for baseline CD4 was not feasible due to high proportion of missing CD4 at index. Table 1 Baseline (index) characteristics Figure 1 Unadjusted time to virologic failure Table 2 Risk of virologic failure Conclusion This early evaluation showed higher risk of virologic failure among virologically suppressed pts who switched to 2DR vs 3DR STRs after adjusting for differences in baseline characteristics. Future analysis is warranted using a larger sample of 2DR pts with additional adjustment for prior regimen failure. Disclosures Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) Janna Radtchenko, MBA, Trio Health (Employee) Helena Diaz-Cuervo, PhD, Gilead Sciences (Employee) Mark Moore, PhD, Gilead Sciences (Employee) Steven Santiago, MD, Gilead Sciences (Advisor or Review Panel member, Speaker's Bureau)Janssen (Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Karam Mounzer, MD, Epividian (Advisor or Review Panel member)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker's Bureau)Merck (Research Grant or Support, Speaker's Bureau)ViiV Healthcare (Consultant, Speaker's Bureau) Richard Elion, MD, Gilead Sciences (Grant/Research Support, Advisor or Review Panel member, Speaker's Bureau)Janssen (Speaker's Bureau)Proteus (Grant/Research Support)Trio Health (Employee)ViiV (Advisor or Review Panel member)

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999. Nasal Mucosal Cytokines: Potential Biomarkers for Pediatric Pneumonia Severity and Etiology

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1193 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S590-S591

Author(s):

Rouba Sayegh ◽

Ki Wook Yun ◽

Zhaohui Xu ◽

Rebecca Wallihan ◽

Sarah Marzec ◽

...

Keyword(s):

Protein Expression ◽

Disease Severity ◽

Panel Member ◽

Community Acquired Pneumonia ◽

Arbitrary Unit ◽

Research Support ◽

Review Panel ◽

Whitney Test ◽

Mild Disease ◽

Mann Whitney Test

Abstract Background Community acquired pneumonia (CAP) is a leading cause of mortality in children < 5 years, but our understanding of disease pathogenesis remains limited. The objective of this study was to define the local host immune response in the respiratory tract by measuring nasal mucosal cytokine (NMC) concentrations (conc.). We hypothesized that NMC represent a potential biomarker to help assessing disease severity and pathogen classification. Methods We leveraged nasopharyngeal (NP) samples and clinical data from an observational multicenter study [Children’s Hospital’s Initiative for Research in Pneumonia (CHIRP)] conducted between 2015 and 2018. We measured conc. of 92 NMC using the Olink immunoassay. NMC conc. were compared by severity-defined by need for hospitalization, mild (outpatient) and severe (inpatient), and by identified pathogen using Mann-Whitney U test. Results This substudy included 182 children with CAP (mild=61; severe=121) and 30 healthy controls (HC). The pathogens identified included: 101 viruses; 32 bacteria (pyogenic=10; atypical=22); 12 with >1 pathogen; and 37 with no pathogen. Children with severe CAP had greater CCL23 and MCP-3 conc. than those with mild disease (p=0.012; p=0.011 respectively). When comparing NMC profiles of children with CAP of viral and bacterial etiology, the viral group had greater conc. of proinflammatory cytokines IL-6 and TNF, (p=0.0002; p=0.0098 respectively). Further subgroup analysis showed that CAP secondary to influenza virus had greater conc. of IL-6, TNF, and antiviral INF-γ and IP-10 compared with CAP caused by pyogenic bacteria. IL-6 and MCP1-4 were significantly increased in the influenza group compared to the atypical bacteria group. Quantification of NMC in children with CAP based on disease severity NMC nasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between mild and severe pneumonia Quantification of NMC in children with CAP based on pathogen classification NMC: nasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between bacterial CAP and viral CAP. Conclusion Children with severe CAP had higher monocyte chemoattractant NMC conc. than children with mild disease. Children with viral CAP, particularly influenza, had a more robust mucosal response including both proinflammatory and antiviral NMC than children with bacterial CAP. These findings show differences in NMC conc. based on etiology and disease severity. Further studies are needed to determine whether NMC are reliable predictive biomarkers of CAP etiology and severity. Disclosures Lilliam Ambroggio, PhD, MPH, Pfizer Inc (Grant/Research Support) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)

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204. Mucosal Cytokine Profiles in Children with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.000 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S1-S1

Author(s):

Shira H Cohen ◽

Cameron Mertz ◽

Rebecca M Glowinski ◽

Sara Mertz ◽

Fang Ye ◽

...

Keyword(s):

Children And Adolescents ◽

Clinical Presentation ◽

Panel Member ◽

Multiple Comparisons ◽

Research Support ◽

Review Panel ◽

Viral Loads ◽

Non Invasive ◽

Cytokine Profiles ◽

Gates Foundation

Abstract Background The mechanisms associated with COVID-19 in children are not well understood. We sought to define the differences in nasopharyngeal (NP) cytokine profiles according to clinical presentation in children with COVID-19. Methods Single-center, prospective study in 137 children and adolescents < 21 years of age hospitalized with COVID-19, and 35 age, sex and race matched pre-pandemic (2016-2019) healthy controls. Children with COVID-19 were categorized according to their clinical presentation in: COVID-19-symptomatic; COVID-19-screening, and multisystem inflammatory syndrome (MIS-C). NP swabs were obtained within 24 hours of admission to measure SARS-CoV-2 loads by rt-PCR, and a 92-cytokine panel. Unsupervised and supervised analysis adjusted for multiple comparisons were performed. Results From 3/2020 to 1/2021, we enrolled 76 COVID-19-symptomatic children (3.5 [0.2-15.75] years); 45 COVID-19-screening (11.1 [4.2-16.1] years), and 16 MIS-C (11.2 [5.9-14.6] years). Median NP SARS-CoV-2 loads were higher in COVID-19-symptomatic versus screening and MIS-C (6.8 vs 3.5 vs 2.82 log10 copies/mL; p< 0.001). Statistical group comparisons identified 15 cytokines that consistently differed between groups and were clustered in three functional categories: (1) antiviral/regulatory, (2) pro-inflammatory/chemotactic, and (3) a combination of (1) and (2); (Fig 1). All 15 cytokines were higher in COVID-19-symptomatic versus controls (p< 0.05). Similarly, and except for TNF, CCL3, CCL4 and CCL23, which were comparable in COVID-19-symptomatic and screening patients, the remaining cytokines were higher in symptomatic children (p< 0.05). PDL-1 (p=0.01) and CCL3 (p=0.03) were the only cytokines significantly decreased in children with MIS-C versus symptomatic COVID-19 children. The 15 cytokines identified by multiple comparisons were correlated using Person’s in R software. Red reflects a positive correlation and blue a negative correlation with the intensity of the color indicating the strength of the association. Conclusion Children with symptomatic COVID-19 demonstrated higher viral loads and greater mucosal cytokines concentrations than those identified via screening, whereas in MIS-C concentrations of regulatory cytokines were decreased. Simultaneous evaluation of viral loads and mucosal immune responses using non-invasive sampling could aid with the stratification of children and adolescents with COVID-19 in the clinical setting. Disclosures Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member).

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1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1198 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S534-S535

Author(s):

Charlotte-Paige M Rolle ◽

Vu Nguyen ◽

Kiran Patel ◽

Dan Cruz ◽

Federico Hinestrosa ◽

...

Keyword(s):

Older Adults ◽

Drug Interactions ◽

Real World ◽

Research Study ◽

Panel Member ◽

Median Number ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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