RSV-associated Hospitalizations in Adults Aged >=18 Years and the Impact of the COVID-19 Pandemic in the United States, October 2018 - February 2022

Background. Respiratory syncytial virus (RSV) is a significant cause of hospitalizations in older adults and typically circulates during the fall and winter in the United States. The COVID-19 pandemic and implementation of nonpharmaceutical interventions (NPIs) including masking, improved handwashing, and social distancing likely impacted RSV circulation. To explore the pandemic's impact on RSV seasonality and hospitalizations in adults aged >=18 years, we analyzed laboratory-confirmed RSV-associated hospitalizations through the RSV Hospitalization Surveillance Network (RSV-NET) across four seasons. Methods. RSV-NET is a population-based surveillance system that collects data on RSV-associated hospitalizations across 75 counties in 12 states. An RSV-NET case is a resident of a defined catchment area who tests positive for RSV through a clinician-ordered test within 14 days prior to or during hospitalization. Surveillance was conducted October-April for the 2018-19 and 2019-20 pre-pandemic seasons and October 2020-September 2021 (2020-21 season). Available data October 2021-February 2022 (ongoing 2021-22 season) are presented. Results. 2,536, 3,195, 618, and 1,758 laboratory-confirmed hospitalizations were identified in adults >=18 years in 2018-19, 2019-20, 2020-21, and 2021-22, respectively;case counts were 4.1 and 5.2 times higher in 2018-19 and 2019-20, respectively, than in 2020-2021. Hospitalizations peaked in January for pre-pandemic and 2021-22 seasons and in September for 2020-21 (Figure). For all years combined, 16.2%, 23.4%, 33.3%, and 27.1% of all RSV-associated hospitalizations were among those aged 18-49, 50-64, 65-79 and >=80 years, respectively. Laboratory-confirmed RSV-associated hospitalizations in adults >=18 years, October 2018 - February 2022 Conclusion. Laboratory-confirmed RSV-associated hospitalizations in adults were lower during the 2020-21 and 2021-22 seasons compared with pre-pandemic seasons, with a marked change in seasonal patterns in 2020-21, likely because of NPIs implemented during the pandemic. Continued monitoring of RSV-associated hospitalizations will be critical to understand ongoing changes in RSV circulation that resulted from the COVID-19 pandemic and associated NPIs. (Figure Presented).

Association between Receipt of COVID-19, Influenza, and Pneumococcal Vaccination

Background. Whether receipt of COVID-19 vaccine associates with receipt of other routinely-recommended adult vaccines such as, influenza and pneumococcal vaccines is not well described. We evaluated this relationship in a population of adults who were hospitalized for acute respiratory infection (ARI). *Odds ratio describing odds of receiving at least one COVID-19 vaccine (vs not) by influenza vaccination status adjusted for race, employment status, chronic cardiac diseases, cancer, solid organ transplant, and chronic kidney disease. **Odds ratio describing odds of receiving at least one COVID-19 vaccine (vs not) by pneumococcal vaccination status adjusted for race and chronic kidney disease. Methods. We enrolled adults (>= 18 years of age) who were hospitalized at Emory University Hospital and Emory University Hospital Midtown with symptoms consistent with ARI. Participants were interviewed and medical records ed to gather demographic information, including social behaviors during the pandemic, medical history, and prior vaccination history (i.e., COVID-19, influenza, and pneumococcal). Using two separate logistic regression analyses, we determined the association between i) receipt of influenza vaccine in the prior year among adults >= 18 years and ii) receipt of any pneumococcal vaccine in the prior 5 years among adults >= 65 years on the receipt of at least one COVID-19 vaccine>= 14 days prior to admission. Adjusted models included demographic information (e.g., age, sex, race/ethnicity, employment status), social behaviors, and history of chronic medical conditions. Results. Overall, 1056 participants were enrolled and had vaccination records available. Of whom, 509/1056 (48.2%) had received at least one dose of COVID-19 vaccine. Adults >= 18 years who received influenza vaccine were more likely to have received >=1 dose of COVID-19 vaccine compared to those who did not (267/373 [71.6%] vs 242/683 [35.4%] P=< .0001;adjusted odds ratio [OR]: 3.3 [95%CI: 2.4, 4.4]). Similarly, adults >=65 years who received pneumococcal vaccine were more likely to have received >= 1 dose of COVID-19 vaccine compared to those who did not (195/257 [75.9%] vs 41/84 [48.8%] P=< .0001;adjusted odds ratio [OR]: 3.0 [95% CI: 1.8, 5.1]). Conclusion. In this study of adults hospitalized for ARI, receipt of influenza and pneumococcal vaccination strongly correlated with receipt of COVID-19 vaccination. Continued efforts are needed to reach adults who remain hesitant to not only receive COVID-19 vaccines, but also other vaccines that lessen the burden of respiratory illness.

Social Risk Factors for COVID-19-Related Hospitalizations in Adults

Background. During the COVID-19 pandemic, social interventions such as social distancing and mask wearing have been encouraged. Social risk factors for SARS-CoV-2 infection and subsequent hospitalization remain uncertain. Methods. Adult patients were eligible if admitted to Emory University Hospital or Emory University Hospital Midtown with acute respiratory infection (ARI) symptoms (<= 14 days) or an admitting ARI diagnosis from May 2021 - Feb 2022. After enrollment, an in-depth interview identified demographic and social factors (e.g., employment status, smoking history, alcohol use), household characteristics, and pandemic social behaviors. All patients were tested for SARS-CoV-2 using PCR. We evaluated whether these demographic and social factors were related to a positive SARS-CoV-2 test upon admission to hospital with ARI using a logistic regression model. Results. 1141 subjects were enrolled and had SARS-CoV-2 PCR results available (700 positive and 441 negative). The median age was greater in the SARS-CoV-2 negative cohort than in the positive cohort (60 and 53 years, respectively;P< .0001). Those who tested positive were more likely to have had at least some college education compared to those who tested negative (64.3% vs 52.3%, P< .0001;adjusted odds ratio [aOR]: 1.4 [95%CI: 1.1, 2.0]). Compared to those who tested negative, those who were SARS-CoV-2 positive were also more likely to be employed (48.9% vs 26.5%, P< .0001;aOR: 1.7 [95%CI: 1.1, 2.3]), have children 5-17 yo at home (27.6% vs 17.9%, P=.0002;aOR: 1.5 [95%CI: 1.1, 2.1]). Those with COVID-19 were less likely to receive home healthcare (6.2% vs 13.3%, P< .0001;aOR: 0.5 [95%CI: 0.4, 0.9]) and to be a current or previous smoker (7.6% vs 17.7%, P< .0001;aOR: 0.3 [95%CI: 0.2, 0.5]). Conclusion. Among adults admitted to the hospital for ARI, those who tested positive for SARS-CoV-2 were typically younger, more likely to care for school-aged children, more likely to work outside the home, but were less likely to receive home healthcare or smoke. Personal and public health strategies to mitigate COVID-19 should take into consideration modifiable social risk factors.

Prior SARS-CoV-2 infection and risk of subsequent COVID-19-related hospitalization: a test negative design

Background. Studies show that past SARS-CoV-2 infection provides a protective immune response against subsequent COVID-19, but the degree of protection from prior infection has not been determined. History of previous SARS-COV-2 Infection and Current SARS-COV-2 Infection Status at Admission. *Adjusted for chronic respiratory disease and prior COVID-19 vaccination Methods. From May 2021 through Feb 2022, adults (>= 18 years of age) hospitalized at Emory University Hospital and Emory University Hospital Midtown with acute respiratory infection (ARI) symptoms, who were PCR tested for SARS-CoV-2 were enrolled. A prior history of SARS-CoV-2 infection was obtained from patient interview and medical record review. Previous infection was defined as a self-reported prior SARS-CoV-2 infection or previous evidence of a positive SARS-CoV-2 PCR test >= 90 days before ARI hospital admission. We performed a test negative design to evaluate the protection provided by prior SARS-CoV-2 infection against subsequent COVID-19-related hospitalization. Effectiveness was determined using logistic regression analysis adjusted for patient sociodemographic and clinical characteristics and COVID-19 vaccination status. Results. Of 1152 adults hospitalized for ARI, 704/1152 (61%) were SARS-CoV-2 positive. 96/1152 (8%) had a prior SARS-CoV-2 infection before hospital admission. Patients with a previous history of SARS-CoV-2 infection were less likely to test positive for SARS-CoV-2 upon admission for ARI compared to those who did not have evidence of prior infection (31/96 [32%] vs 673/1056 [64%];adjustedOR: 0.25 [0.15, 0.41] (Table). Conclusion. Reinfections represented a small proportion (< 10%) of COVID-19-related hospitalizations. Prior SARS-CoV-2 infection provided meaningful protection against subsequent COVID-19-related hospitalization. The durability of this infection-induced immunity, variant-specific estimates, and the additive impact of vaccination are needed to further elucidate these findings.

Prospective Observational Cohort Study of Serological Responses to COVID-19 Vaccines in Pediatric Kidney Transplant Recipients at a Single Institution

Background. Pediatric kidney transplant recipients (PKTR) are at risk of poor outcomes from COVID-19. Data on serologic responses to COVID-19 vaccines in PKTR remain sparse. We characterized the magnitude, breadth, and longevity of SARS-CoV-2 spike protein binding antibody responses in PKTR. Methods. This single institution, prospective observational study enrolled PKTR presenting to a transplant clinic for routine care who had received or were eligible to receive a COVID-19 vaccine. Demographic data, history of prior COVID-19, and vaccination details were collected. Plasma samples obtained from standard-of-care residual specimens were analyzed for SARS-CoV-2 spike variant IgG using the MesoScale Discovery V-PLEX platform, which quantitatively measures antibodies to SARS-CoV-2 full-length spike wild-type (Wuhan-hu-1), Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529;BA.1) variants. Vaccine time points with > 5 samples available were analyzed. Geometric mean titers (GMTs) were calculated and log-transformed titers were compared using one-way ANOVA with Tukey's post-hoc comparisons test. Results. 61 PKTR enrolled (Table1);47 (77%) received at least 1 dose of COVID-19 vaccine in transplant clinic. 47 (77%) PKTR had at least one sample available for analysis, but serial specimens were lacking for many. By 6 months post-dose 2 of COVID-19 mRNA vaccination, spike (Wuhan-hu-1) IgG titers had waned to prevaccination levels (GMT 24 vs 47 binding antibody units (BAU)/mL, P=0.988). Administration of a 3rd dose of mRNA vaccine significantly boosted IgG antibodies (GMT 492 BAU/mL, P=0.007), and titers were maintained at 3 months (GMT 656 BAU/mL, P=0.001) but gradually waned by 6 months (GMT 223 BAU/mL, P=0.070). Administration of a 4th dose elicited a non-significant increase in titers (GMT 905 BAU/mL, P=0.870). Binding IgG antibodies to SARS-CoV-2 variant spike proteins post-vaccination were not significantly different from Wuhan spike. Conclusion. In this cohort of PKTR, a 3rd dose of COVID-19 mRNA vaccine significantly boosted broadly cross-reactive binding IgG antibodies to SARS-CoV-2 spike variants, including Omicron. Decreasing titers at 6 months post-dose 3 raise concern for waning protective immunity and support 4th dose vaccination.

Viral and bacterial infections among adults hospitalized with COVID-19, Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, 14 states, March 2020-February 2022

Background. Coinfections, both bacterial and viral, occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but prevalence, risk factors, and associated clinical outcomes are not fully understood. Methods. We used the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance platform to investigate the occurrence of viral and bacterial coinfections among hospitalized adults with laboratory-confirmed SARS-CoV-2 infection during March 2020 and February 2022. Patients receiving additional standard of care (SOC) molecular testing for viral pathogens (14 days prior to admission or 7 days after), including respiratory syncytial virus, rhinovirus/enterovirus (RV/EV), influenza, adenovirus, human metapneumovirus, parainfluenza viruses, and endemic coronaviruses, were included. SOC testing for clinically relevant bacterial pathogens (7 days before admission or 7 days after) from sputum, deep respiratory, and sterile sites were included. The demographic and clinical features of those with and without bacterial infections were compared. Results. Among 2,654 adults hospitalized with COVID-19 and tested for all 7 virus groups, another virus was identified in 3.1% of patients. RV/EV (1.2%) and influenza (0.4%) were the most commonly detected viruses. Half (17,842/35,528, 50.2%) of hospitalized adults with COVID-19 had bacterial cultures taken within 7 days of admission, and 1,092 (6.1%) of these had a clinically relevant bacterial pathogen. A higher percentage of those with a positive culture died compared to those with negative cultures (32.3% vs 13.3%, p< 0.001). Staphylococcus aureus was the most common isolate overall;Pseudomonas aeruginosa was the second most common respiratory isolate This figure includes 1,408 bacterial cultures from 1,066 individuals. Deep respiratory sites include endotracheal aspirate, bronchoalveolar lavage fluid, bronchial washings, pleural fluid, and lung tissue. Commensal organisms were excluded. Conclusion. Consistent with previous studies, a relatively low proportion of adults hospitalized with COVID-19 had concomitantly identified viral or bacterial infections. Identification of a bacterial infection within 7 days of admission is associated with increasedmortality among adults hospitalized with COVID-19. Conclusions about the clinical relevance of bacterial infections is limited by the retrospective nature of this study.

Influenza-Associated Hospitalization Rates and Proportion of Hospitalizations with Influenza and SARS-CoV-2 Coinfection, FluSurv-NET, October 1, 2021-April 23, 2022

Background. Influenza-associated hospitalization rates were low during the 2020-21 season. We describe influenza-associated hospitalization rates and prevalence of influenza and SARS-CoV-2 coinfection among patients hospitalized with influenza during 2021-22. Methods. We used data from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratoryconfirmed influenza-associated hospitalizations active from October-April of each year. We calculated cumulative and weekly hospitalization rates per 100,000 population and compared preliminary rates during 2021-22 with prior season rates (2010-11 through 2020-21). We determined the proportion of influenza-associated hospitalizations with SARS-CoV-2 coinfection during 2021-22. Results. During October 1, 2021-April 23, 2022, 3,262 influenza-associated hospitalizations were reported to FluSurv-NET;the cumulative hospitalization rate of 11.1 was higher than 2011-12 and 2020-21 season rates, but lower than rates observed during all other seasons since 2010-11 (Figure 1A). After peaking in the week ending January 1, 2022 (MMWR week 52), weekly hospitalization rates declined until the week ending February 19, 2022 (MMWR week 7) when they began to rise modestly, similar to patterns observed during several prior seasons (Figure 1B). Among the 3,262 hospitalizations, 87 (2.7%) had SARS-CoV-2 coinfection;the prevalence by age group was as follows: 0-17 years 3.4%, 18-49 years 2.8%, 50-64 years 3.5%, 65-74 years 2.5%, >= 75 years 1.6%. Among the 3,262 influenza-associated hospitalizations, the prevalence of SARS-CoV-2 coinfection by month (October 2021- April 2022), respectively, was 11.4%, 2.5%, 2.6%, 8.9%, 3.4%, 0.8%, and 0.5%. Conclusion. SARS-CoV-2 coinfection was uncommon among patients hospitalized with influenza during 2021-22. Likely due to ongoing COVID-19 mitigation measures, the influenza-associated hospitalization rate during 2021-22 was lower than rates observed in most seasons in the decade preceding the COVID-19 pandemic. A late rise in weekly influenza hospitalization rates in 2021-22 might have been a result of relaxation of COVID-19 mitigation measures and/or a late season peak in influenza activity. (Figure Presented).

Burden of Respiratory Syncytial Virus (RSV) Infection among Hospitalized Older Adults and Those with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)

Background. The burden of Respiratory Syncytial Virus (RSV)-associated hospitalization in adults is incompletely understood. The COVID-19 pandemic has resulted in multiple public health measures (e.g., social distancing, handwashing, masking) to decrease SARS-CoV-2 transmission, which could impact RSV-associated hospitalizations. We sought to compare RSV-associated hospitalizations from 2 pre- and one mid-COVID-19 winter viral respiratory seasons. Methods. We conducted an IRB-approved prospective surveillance at two Atlanta-area hospitals during the winter respiratory viral seasons from Oct 2018-Apr 2021 for adults ≥ 50 years of age admitted with acute respiratory infections (ARI) and adults of any age with COPD or CHF-related admissions. Adults were eligible if they were residents of an 8 county region surrounding Atlanta, Georgia. Those with symptoms > 14 days were excluded. Standard of care test results were included. Asymptomatic adults ≥ 50 years of age were enrolled as controls in Seasons 1 and 2. Nasopharyngeal swabs from cases and controls were tested for RSV using BioFireR FilmArrayR Respiratory Viral Panel (RVP). We compared the demographic features and outcomes of RSV+ cases and controls. Results. RSV was detected in 71/2,728 (2.6%) hospitalized adults with ARI, CHF, or COPD and 4/466 (0.9%) controls. In Season 1, RSV occurred in 5.9% (35/596 patients), in Season 2 3.6% (35/970 patients), but in only 0.09% (1/1,162 patients) in Season 3 (P < 0.001 for both seasons). RSV detection in Season 3 was similar to RSV detection among controls during Seasons 1 and 2 (P=0.6). Median age of cases and controls was 67 years (Table 1). Of cases with RSV 11% were admitted to the ICU and two required mechanical ventilation. The majority of hospitalized patients were discharged home (95.8%) with a median length of hospitalization of three days (IQR 2-7). Conclusion. Over 3 seasons, RSV was detected in 2.6% of adults admitted to the hospital with ARI, CHF or COPD. The rate of RSV dramatically declined during the 2020-21 winter respiratory viral season, likely due to public health measures implemented in response to COVID-19.

Outcomes among Influenza and SARS-CoV-2 Infection in Hospitalized Adults Age ≥ 50 Years and with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)

Background. A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses. Methods. Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses. Results. Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization. Conclusion. COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden.

The Burden of Influenza and Rhinovirus among Hospitalized Adults Post the COVID-19 Pandemic

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 eightcounty 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. 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.

Clinical features and management of pediatric patients presenting with new onset acute leukemia and concomitant COVID-19

Background: Infections represent a significant cause of morbidity and mortality in pediatric patients undergoing treatment for hematologic malignancies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a worldwide pandemic of coronavirus disease 2019 (COVID-19) and pediatric patients with cancer appear to be at higher risk of severe disease than reported in the general pediatric population. Data are limited on the optimal management of children infected with SARS-CoV-2 and a new diagnosis of leukemia. The objective of this study was to describe our experience of six children who presented with a new diagnosis of acute leukemia and concurrent COVID-19.

Clinical features and antibody responseof two pediatric patients presenting with new-onset acutemyeloid leukemia and concomitant severe COVID-19

Objective: SARS-CoV-2 infection has led to a worldwide pandemic of COVID-19 (coronavirus disease 2019), placing individuals with pre-existing medical conditions at a higher risk for morbidity and mortality. Limited data inpediatric patients with malignancies suggest that severe COVID-19 illness is rare. The objective of this study was todescribe our experience of two adolescents who presented with new diagnoses of acute myeloid leukemia (AML)and concurrent COVID-19. Methods: The clinical presentation, treatment, and serology of two patients who presented with AML andconcurrent SARS-CoV-2 infection were abstracted. Residual blood was tested for serial quantitative IgG by ELISA tothe SARS-CoV-2 spike protein receptor binding domain, which has high sensitivity and specificity to SARS-CoV-2.The study was approved by Children's Healthcare of Atlanta and Emory University IRBs. Results: Patient 1 was a 16-year-old Caucasian male with previously treated classical Hodgkin's lymphoma whopresented with fever, cough, hyperleukocytosis, and pulmonary infiltrates and was diagnosed with therapy-relatedAML (TR-AML). SARS-CoV-2 was detected by nasopharyngeal (NP) RT-PCR testing on admission. He receivedremdesivir for treatment of COVID-19 and modified induction therapy with cytarabine alone starting on hospital day(HD) 3. He demonstrated high SARS-CoV-2 IgG titer (1:1327.3) on HD 4 and cleared SARS-CoV-2 with a negativeNP RT-PCR on HD 14. He went on to receive additional myelosuppressive AML therapy on HD 26 with azacitidineand gemtuzamab ozogamicin. On HD 34, his IgG titer remains elevated (1:5621.4) and he is currently awaitingcount recovery. Patient 2 was a 19-year-old Hispanic, previously healthy male who presented with fever, cough, dyspnea, and hyperleukocytosis and was diagnosed with de novo AML (D-AML). He also tested positive for SARS-CoV-2 via NP RT-PCR on admission. He began standard induction therapy with cytarabine, etoposide, anddaunorubicin on HD 2. He developed hypoxemic respiratory failure on HD 4 and received COVID-19 directedtherapies of convalescent plasma, remdesivir, and tocilizumab. His serologic testing showed low SARS-CoV-2 IgGtiter (1:619.3) on HD 4 despite administration of convalescent plasma. His titers waned over the subsequent twoweeks and he continued to test positive for SARS-CoV-2 via NP RT-PCR on HD 21. He remains critically ill inmultiorgan failure with signs of neutrophil recovery on HD 25. Conclusion: COVID-19 can be severe in children with AML and make treatment decisions challenging. Clinicalpresentation, curative modalities (hematopoietic stem cell transplantation for TR-AML versus potentiallychemotherapy alone for D-AML), and concurrent COVID-19 were considered in determining induction therapy. Whiledifficult to draw definite conclusions from two patients, the differential serologic response in these patients seems tocorrelate with the intensity of therapy they received and may have contributed to the overall severity of their COVID-19.