Vaccine Era Research Articles

2632. Duration of viable SARS-CoV-2 shedding in immunocompromised COVID-19 patients during the widespread vaccination era

Abstract Background Individuals with COVID-19 who are immunocompromised have been reported to experience prolonged shedding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to those who are immunocompetent. However, it remains unclear how long viable SARS-CoV-2 shedding persists in immunocompromised individuals during the era of widespread vaccination against COVID-19. This study aimed to evaluate the association between the duration of viable SARS-CoV-2 detection among immunocompromised individuals and their COVID-19 vaccination status. Methods We retrospectively reviewed patients who admitted to our institute for COVID-19 treatment between November 2022 and March 2023. We defined immunocompromised individuals as those who had received corticosteroids, immunosuppressants, or cytotoxic chemotherapy. We performed daily COVID-19 rapid antigen detection tests (RAD) on immunocompromised patients from 10 days after the onset of COVID-19 until two consecutive negative results were obtained. Results Among 181 patients admitted for COVID-19 treatment, 22 immunocompromised patients participated in this study. Of these, 14 (64%), 6 (27%), and 10 (46%) patients received corticosteroids, immunosuppressants, and cytotoxic chemotherapy, respectively. Twelve (55%) patients were fully vaccinated. Nine (41%) patients required oxygen therapy for respiratory failure. All patients received antiviral therapy, with 5 (23%), 12 (55%), 5 (23%) patients receiving remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir, respectively. Three (14%) patients died from COVID-19. The median duration from COVID-19 onset to confirmation of negative RAD or death was 15.5 (interquartile range: 12 to 17) days. Until 20 days after the onset of COVID-19, 17 (77%) patients had achieved two consecutive negative RAD results. There was no association between vaccination status and the duration of positive RAD results (p = 0.59) or the proportion of patients achieving negative RAD results within 20 days of COVID-19 onset (P > 0.99). Conclusion Most immunocompromised COVID-19 patients in our hospital achieved two consecutive negative RAD results within 20 days of COVID-19 onset. Vaccination status was not associated with the duration of detectable SARS-CoV-2 shedding. Disclosures All Authors: No reported disclosures

Outcomes of COVID-19 in kidney transplant recipients in the vaccination Era: A national multicenter cohort from Thailand

IntroductionThe mortality rate of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTR) has significantly decreased with the implementation of vaccination programs. However, the real-world information on the impact of vaccinations, particularly in resource limited settings in Asia, is still limited. MethodsThe Thai Transplant Society conducted a prospective multicenter cohort registry, including KTR diagnosed with COVID-19. Cox proportional hazards regression was used to examine factors associated with poor COVID-19 outcomes and complications, including death, COVID-19 pneumonia, and superimposed bacterial infection. ResultsA total of 413 patients from 17 transplant centers who developed COVID-19 were analyzed. The COVID-19 mortality rate was 5.6 % and the incidence of pneumonia was 18.8 %. With each 10-year increase in age, the risk of death, pneumonia, and bacterial infection increased by 61 %, 32 %, and 43 %, respectively. A total of 11.4 % of KTR received one dose of COVID vaccination (incomplete vaccination), 25.7 % received two doses (complete primary vaccination), 42.6 % received three doses (first booster dose), and 10.4 % received four doses of vaccination (second booster dose). Even a single dose of vaccination significantly decreased the risk of death, pneumonia, and superimposed bacterial infection among KTR compared to those who remained unvaccinated. Completing the primary vaccination (2-dose) reduced the risk of death by 89 %, pneumonia by 88 %, and bacterial infection by 83 % compared to unvaccinated KTR. Receiving a booster dose (third or fourth dose) further reduced the risk of death by 94 %, pneumonia by 95 %, and bacterial infection by 96 % compared to unvaccinated individuals. ConclusionsThis Asian cohort demonstrated that the mortality and complications of COVID-19 significantly decreased in KTR after the national immunization. Our study suggests that any type of COVID-19 vaccine can be beneficial in preventing adverse outcomes. Administering booster vaccinations is strongly recommended.

Cross-sectional population-based estimates of a rural-urban disparity in prevalence of long COVID among Michigan adults with polymerase chain reaction-confirmed COVID-19, 2020-2022.

To (1) assess whether residential rurality/urbanicity was associated with the prevalence of 30- or 90-day long COVID, and (2) evaluate whether differences in long COVID risk factors might explain this potential disparity. We used data from the Michigan COVID-19 Recovery Surveillance Study, a population-based probability sample of adults with COVID-19 (n = 4,937). We measured residential rurality/urbanicity using dichotomized Rural-Urban Commuting Area codes (metropolitan, nonmetropolitan). We considered outcomes of 30-day long COVID (illness duration ≥30 days) and 90-day long COVID (illness duration ≥90 days). Using Poisson regression, we estimated unadjusted prevalence ratios (PRs) to compare 30- and 90-day long COVID between metropolitan and nonmetropolitan respondents. Then, we adjusted our model to account for differences between groups in long COVID risk factors (age, sex, acute COVID-19 severity, vaccination status, race and ethnicity, socioeconomic status, health care access, SARS-CoV-2 variant, and pre-existing conditions). We estimated associations for the full study period (Jan 1, 2020-May 31, 2022), the pre-vaccine era (before April 5, 2021), and the vaccine era (after April 5, 2021). Compared to metropolitan adults, the prevalence of 30-day long COVID was 15% higher (PR = 1.15 [95% CI: 1.03, 1.29]), and the prevalence of 90-day long COVID was 27% higher (PR = 1.27 [95% CI: 1.09, 1.49]) among nonmetropolitan adults. Adjusting for long COVID risk factors did not reduce disparity estimates in the pre-vaccine era but halved estimates in the vaccine era. Our findings provide evidence of a rural-urban disparity in long COVID and suggest that the factors contributing to this disparity changed over time as the sociopolitical context of the pandemic evolved and COVID-19 vaccines were introduced.

Outcomes of COVID-19 in Thai kidney transplant recipients in the vaccination era

Outcomes of COVID-19 in Thai kidney transplant recipients in the vaccination era

Emergency Department point-of-care antiviral host response testing is accurate during periods of multiple respiratory virus co-circulation

FebriDx is a CE-marked, FDA-approved point-of-care test that detects the antiviral host response protein Myxovirus Resistance Protein A (MxA), in addition to C-reactive protein, using finger-prick blood. FebriDx MxA detection had a high negative predictive value for COVID-19 in symptomatic adults presenting to hospital in the first waves of the pandemic and was used subsequently as a 'rule out' triage tool in Emergency departments. The diagnostic accuracy of FebriDx MxA in the current context of co-circulation of influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), and in the era of COVID-19 vaccination, is unknown. We retrospectively evaluated the diagnostic performance of FebriDx MxA in adults with acute respiratory symptoms presenting to the Emergency Department (ED) of a large UK teaching hospital using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the reference standard (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV). Between March 9th 2022 and March 8th 2023, 5426 patients had both FebriDx and RT-PCR testing with valid results. 999 (18.4%) of patients had influenza detected, 520 (9.6%) SARS-CoV-2, and 190 (3.5%) RSV. Negative Predictive Value (NPV) of MxA detection by FebriDx was 97.5% (96.9-98.0) for influenza, 97.1% (96.4-97.7) for SARS-CoV-2, 98.1% (97.5-98.6) for RSV, and 92.8% (91.8-93.7) for all viruses combined. In symptomatic adults, FebriDx MxA had a high NPV for influenza and RSV, and retained a high NPV for SARS-CoV-2, in the context of virus co-circulation and widespread COVID-19 vaccination. FebriDx continues to be a useful 'rule out' triage tool in the ED and could potentially be scaled to provide a national triage solution for future viral pandemics.

Prevalence of prolonged otitis media with effusion among 2 to 3 years old Cameroonian children in the era of 13-valent pneumococcal conjugate vaccines

ObjectivesThere is data scarcity on the overall effects of pneumococcal conjugate vaccines (PCVs) on otitis media (OM) in low- and middle-income countries. The impact of the 13-valent PCV (PCV13) program on OM was evaluated in Cameroon where infant vaccination was implemented in July 2011 using a 3-dose primary series at 6, 10 and 14 weeks of age. MethodsThrough community-based surveillance, we used a retrospective cohort study design to assess OM prevalence among PCV13-vaccinated children aged 24 to 36 months in 2015. This was compared with a 2013 age-matched cohort of PCV13-unvaccinated children. OM was diagnosed by clinical inspection for chronic suppurative OM (CSOM) and tympanometry for OM with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than 2 weeks and prolonged OME was defined as a flat ‘type B’ tympanogram. PCV13-vaccinated and PCV13-unvaccinated cohorts were compared by calculating prevalence odds ratios for OM and baseline characteristics. ResultsAltogether, 111 OM cases were identified; 42/433 (9.7%) in the PCV13-unvaccinated in 2013 and 69/413 (16.7%) in the PCV13-vaccinated cohort in 2015. In the 2013 baseline survey, 3/433 (0.7%) children were identified with unilateral CSOM compared to 9/413 (2.2%) in the PCV13-vaccinated cohort in 2015. Bilateral prolonged OME was diagnosed in 7/433 (1.6%) PCV13-unvaccinated children and in 12/413 (2.9%) in PCV13-vaccinated children. Proportions of children with unilateral prolonged OME were 31/433 (7.2%) in the PCV13-unvaccinated group compared with 48/413 (11.6%) in the PCV13-vaccinated group. Multivariate logistic regression analysis showed evidence that PCV13-vaccinated children in 2015 had 40% less risk of contracting OM compared to PCV13-unvaccinated children in 2013 (adjusted prevalence odds ratios = 0.60 [95% confidence interval: 0.38 to 0.94], P = 0.025). Additionally, attributable proportion estimates show that, 58% of OM infections among the PCV13-vaccinated group would still have occurred despite PCV13 vaccination. ConclusionOur findings provide significant evidence on the effect of PCV13 in decreasing OM or OME among children in this age group. It also supports justification for government's continuation of PCV13 immunization program in the absence of GAVI's funding. Further research is needed to assess the long-term impact of the PCV13 program on in OM Cameroon.

Clinical and Laboratory Diagnosis of Exanthems Among Japanese Children Younger Than 6 Years Old in the Post-Measles-Rubella Vaccine Era.

Exanthems are a common reason for visits to the pediatric emergency department. However, epidemiological data in the post-measles-rubella vaccine era is limited. We sought to determine the recent causes of exanthems in children younger than 6 years old in the pediatric emergency department. A prospective single-center study was conducted in Japan from August 2019 to March 2020. Children younger than 6 years old with exanthems were enrolled. Exanthems were classified into 7 morphological patterns. Varicella, herpes zoster, impetigo, urticaria and Kawasaki disease were diagnosed clinically. Nasopharyngeal swab specimens were collected from patients with nonspecific exanthems and evaluated by polymerase chain reaction (PCR) assays capable of detecting 24 pathogens. The final diagnosis was made by discussion of 3 physicians based on clinical course and microbiology. There were 9705 pediatric visits, of which 296 (3%) had exanthems and were younger than 6 years old. Clinical diagnosis was possible for 160 (54%), including urticaria in 110 (37%), Kawasaki disease in 29 (10%), impetigo in 10 (3%), varicella or herpes zoster in 7 (2%) and group A Streptococcus in 4 (1%). Among the remaining 136 (46%) children, 75 (25%) underwent testing by PCR. One or more pathogens were detected in 49 (65%), specifically enterovirus in 14 (19%), cytomegalovirus in 13 (17%), human herpesvirus type-6 in 12 (16%), adenovirus in 11 (15%) and human herpesvirus type-7 in 8 (11%). Final infectious disease diagnoses were roseola infantum in 11 (15%), enterovirus in 9 (12%), adenovirus in 6 (8%), mixed virus infection in 5 (7%), group A Streptococcus in 3 (4%), parechovirus-A in 3 (4%) and influenza in 3 (4%). The most common causes of pediatric exanthems were noninfectious diseases and viral exanthema. PCR assay was instrumental for etiological diagnosis of nonspecific exanthems.

Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.

Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

Application of bidirectional LSTM deep learning technique for sentiment analysis of COVID-19 tweets: post-COVID vaccination era

BackgroundSocial media platforms, especially Twitter, have turned out to be a major source of data repositories. They have become a platform that citizens can use to voice their concerns about issues that affect them. Most importantly, during the COVID-19 era, the platform was greatly used by governments and health organizations to sensitize people about the safety guidelines that they must adhere to so as to remain safe during the pandemic. As expected, people also used Twitter and other social media platforms to voice their opinions about how governments are handling the COVID-19 pandemic outbreak. Governments and organizations could, therefore, use these social media as a feedback mechanism that can help them know the view of the citizens about their policies. This could help them in making informed decisions about their policies.AimThe aim of this paper is to explore the use of BiLSTM deep learning technique for sentiment analysis of COVID-19 tweets.MethodologyThe study retrieved 197,327 tweets from the Nigeria Twitter domain using #COVID or #COVID-19 hashtags as keywords. The dataset was retrieved within the 1st month of COVID-19 vaccination in Nigeria, i.e., March 15–June 15, 2021. BiLSTM deep learning technique was trained using 789,306 sentiment annotated tweets obtained from Kaggle Sentiment140 tweet datasets. The preprocessed case study tweets were then used to evaluate the proposed model. Also, a precision of 78.26% and a recall value of 78.27% were also obtained.ResultsWith an accuracy of 78.29%, 98,545 (49.93%) positive sentiments and 98,782 negative sentiments (50.06%) were recorded. Also, a precision of 78.26% and a recall value of 78.27% were also obtained. However, the presence of outliers which are tweets not related to COVID but which used the hashtag was observed.ConclusionThis study has revealed the strength of BiLSTM deep learning technique for sentiment analysis. The results obtained revealed an almost balanced sentiments toward the pandemic with 49.93% positive disposition to the pandemic as compared to 50.06% negative disposition. This showed affirmed the impact of COVID vaccine in dousing citizen’s tension when it was made available for public use. However, the presence of outliers in the classified tweets could be a pointer to the reason why aspect-based sentiment analysis could be preferred to sentence-based sentiment analysis.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance.A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Second-Line Therapy Sequencing in Primary Warm Autoimmune Hemolytic Anemia: Splenectomy-Rituximab Versus Rituximab-Splenectomy

Introduction: Primary warm autoimmune hemolytic anemia (wAIHA) is a hematologic condition that affects approximately 1 in 8000 people and occurs when IgG antibodies directed against self-erythrocytes cause hemolysis and exceed the bone marrow's ability to compensate. First-line treatment with glucocorticoids yields sustained remission in less than 30% of individuals. For patients requiring second-line treatment, splenectomy was the preferred treatment for over 50 years, being recommended over rituximab by leading experts as recently as 2010. In the last decade this practice shifted due to concerns of tripartite risk of splenectomy with rates of infection, thrombosis, and perioperative mortality, juxtaposed against the increased experience with rituximab. These risks are outdated as they predate the modern-day vaccination, thromboprophylaxis, and laparoscopic splenectomy era, respectively. Summarily, the 2017 British guidelines dropped splenectomy from second- to third-line for patients with primary wAIHA, consistent with expert opinion in the United States in 2023. Over these same twenty years, the mortality and morbidity of splenectomy has greatly decreased, owing to updated preoperative vaccination standards, prevention of thrombosis, and widespread use of the laparoscopic (i.e., rather than open) technique. Despite these advancements, splenectomy is now used in fewer than 10% of patients with wAIHA. In the absence of a clinical trial randomizing patients to splenectomy versus rituximab, we conducted the first simulation of second-line therapeutic sequencing for adult patients with primary wAIHA with a focus on short-run and long-run effectiveness results. Methods: We constructed a Markov simulation of adult patients with primary wAIHA and requiring second-line therapy to compare the effectiveness of strategy #1: splenectomy followed by rituximab, if necessary, versus strategy #2: rituximab followed by splenectomy, if necessary. Transition probabilities for initial response and time-variant relapse risk with rituximab and with splenectomy were drawn from retrospective primary-wAIHA-specific literature. For rituximab, we assumed that 1) patients maintained in remission for three years following treatment with a rituximab cycle would remain in remission and 2) all patients who relapse more than a year after receiving rituximab, would be retreated with rituximab. Costs were sourced from the Centers for Medicare & Medicaid Services and the Centers for Disease Control and Prevention. Utility values for patients with wAIHA were specific to the reported patient disease status, whether in relapse, partial remission (defined as hemoglobin >10g/dL) or complete remission (defined as hemoglobin >12g/dL). These were sourced from the Global Burden of Disease Study and weighted for the degree of anemia corresponding with each status. Effectiveness was calculated in quality-adjusted life-years (QALYs). The primary outcomes were lifetime discounted costs, QALYs, and net monetary benefits across accepted willingness-to-pay thresholds over short- and long-runs at 5 years and lifetime, respectively. Probabilistic sensitivity analysis was employed to vary all parameters across their uncertainty intervals simultaneously over 10,000 Monte Carlo iterations. Results: In the short-run, strategies #1 and #2 cost $39,700 and $47,100 and accrued 5.21 and 5.26 QALYs (Table 1). In the long run, costs were $909,000 and $912,000 while accruing 22.0 and 22.1 QALYs. Net monetary benefit point estimates were similar across the accepted range of WTP thresholds in both the short- and long-runs. Conclusion: The balance of costs and quality-adjusted life expectancy appears to be comparatively tightly balanced in the sequencing of second-line therapies in primary wAIHA with splenectomy-rituximab versus rituximab-splenectomy. The absence of a clear rituximab-early advantage on a population level may be driven by advancements in vaccination, thromboprophylaxis, and laparoscopic surgical techniques for splenectomy over the last 20 years. Value-of-information analysis would help identify parameters whose uncertainty reduction with future study in the real world would yield a treatment strategy with a definitive advantage. In the meantime, patients whose values and preferences align with splenectomy should not be dissuaded from pursuing it due to perceived risk.

Decades of Improvement in Cardiovascular Morbidity and Mortality in Leukemia Patients Reversed in 2020: Covid? Novel Agents? Neither?

Introduction: The incidence of many types of leukemia increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Regimens for the treatment of ALL are also often anthracycline-based. Anthracyclines are associated with a significant risk of cardiotoxicity including anthracycline-related left ventricular dysfunction. Comprehensive baseline evaluation of cardiac function and risk may lead to better risk stratification and selection of patients who are best suited to anthracycline-based therapy. With the advent of more effective, yet less chemo-intense regimens for the management of older or unfit adults with leukemia, for example hypomethylator and venetoclax-based combinations, which gained widespread use with their accelerated approval in November 2018, one would hypothesize decreased rates of cardiovascular complications associated with the treatment of adult leukemia. To further investigate this hypothesis, we performed a nationwide analysis for adults age 25 and older with leukemia of all types and their associated cardiovascular disease related mortality. Methods: We utilized the Wide-ranging Online Data for Epidemiologic Research from the CDC. Patients were identified using ICD codes: C91 (Lymphoid leukaemia, C92 (Myeloid leukaemia), C93 (Monocytic leukaemia), C94 (Other leukaemias of specified cell type), and C95 (Leukaemia of unspecified cell type) with an underlying cause of death I00-I99 (Diseases of the circulatory system). Data was reviewed between 1999 to 2020 and included patients who were aged ≥25. We analyzed the age adjusted mortality rate (AAMR) per 100,000 people and stratified the data by sex, race/ethnicity, and geographical location within the USA by census region. Results: There were a total of 19,368 cardiovascular related deaths in leukemia patients between 1999 and 2020. There has been a decreasing trend in overall mortality associated with cardiovascular diseases from 1999 to 2019, falling from 4.6 to 3.9 deaths per 100,000 people, with an annual percent change of -2.89% (Figure 1). Both sexes mirrored this trend, with female mortality rates improving from 3.4 to 2.7 (APC -3.26%) and male rates from 6.5 to 5.6 (APC -3.07%) between 1999 and 2019. In 2020, it was observed that leukemia patients had an increased cardiovascular related mortality: 4.5 AAMR overall, 3.0 AAMR in females, and 6.5 AAMR in males . There was not a statistically significant difference in mortality changes by race (Table 1). Conclusion: Our study reveals a decrease in mortality rates from cardiovascular disease in leukemia patients from 1999 to 2018 followed by a relatively sharp increase noted in 2020. The steady improvements noted from the early 2000s to the 2010s may be attributable to awareness of known toxicities that led to enhanced screening and active monitoring for cardiovascular complications. Electrocardiograms, echocardiograms, and cardiotoxic markers including troponins and natriuretic peptides have served as diagnostic and risk-stratification tools. In 2020 leukemia patients exhibited a sudden increase in mortality across all sub-groups. One may postulate that this is related to COVID-19-related complications/delays in treatment, however, another possible explanation may be incompletely recognized toxicities of novel therapeutics. Interestingly, preclinical data have demonstrated that venetoclax treatment resulted in cardiac damage as evidenced by major changes in histopathology and markedly elevated cardiac enzymes and hypertrophic genes markers. Moreover, a drastic increase in oxidative stress, as well as inflammatory and apoptotic markers, with a remarkable decline in the levels of Bcl-2 has been observed (AlAsmari et al Int J Mol Sci 2022). Clearly, continued monitoring and further exploration is needed to identify the reason or reasons for the noted 2020 phenomenon. Continued data collection in the post-Covid vaccine era is likely to help to further elucidate the reasons for the unexpected uptick in cardiovascular-related morbidity and mortality in our leukemia patients.

Determination of Pneumococcal Serotypes by Sequetyping and Sequential Conventional Multiplex PCR in the Vaccine Era

Pneumococcal serotyping is required for epidemiological surveillance to guide vaccination strategy. DNA-based approaches are more affordable, but the combination of sequetyping and sequential conventional multiplex polymerase chain reaction (cmPCR) may complement one another. A total of 101 isolates were subjected to sequetyping and sequential cmPCR following previously published protocols, and the outputs were compared. The sequetyping method determined up to the serotype level for 99 isolates (98%). On the other hand, the sequential cmPCR technique identified 91 isolates (90.1%), with 63 of them (62.4%) up to the serotype level. Sequetyping generated discrete serotypes for 6A/B, 11A/D, 15A/F, and 15B/C as 6A (n = 11), 6B (n = 10), 11A (n = 5), 15C (n = 1), and 15A (n = 1). In conclusion, the cpsB gene sequetyping method produced a comparable output with sequential cmPCR, further discriminating some sub-serogroups among the isolate collection.

Incidence and Transmission of SARS-CoV-2 in US Child Care Centers After COVID-19 Vaccines

SARS-CoV-2 surveillance studies in US child care centers (CCCs) in the post-COVID-19 vaccine era are needed to provide information on incidence and transmission in this setting. To characterize SARS-CoV-2 incidence and transmission in children attending CCCs (students) and their child care providers (CCPs) and household contacts. This prospective surveillance cohort study was conducted from April 22, 2021, through March 31, 2022, and included 11 CCCs in 2 cities. A subset (surveillance group) of CCPs and students participated in active surveillance (weekly reverse transcription-polymerase chain reaction [RT-PCR] swabs, symptom diaries, and optional baseline and end-of-study SARS-CoV-2 serologic testing), as well as all household contacts of surveillance students. Child care center directors reported weekly deidentified self-reported COVID-19 cases from all CCPs and students (self-report group). SARS-CoV-2 infection in CCC students. SARS-CoV-2 incidence, secondary attack rates, and transmission patterns were determined from diary entries, self-reports to CCC directors, and case logs. Incidence rate ratios were measured using Poisson regression clustering on centers with a random intercept and unstructured matrix. From a total population of 1154 students and 402 CCPs who self-reported cases to center directors, 83 students (7.2%; mean [SD] age, 3.86 [1.64] years; 55 male [66%]), their 134 household contacts (118 adults [mean (SD) age, 38.39 (5.07) years; 62 female (53%)], 16 children [mean (SD) age, 4.73 (3.37) years; 8 female (50%)]), and 21 CCPs (5.2%; mean [SD] age, 38.5 [12.9] years; 18 female [86%]) participated in weekly active surveillance. There were 154 student cases (13%) and 87 CCP cases (22%), as defined by positive SARS-CoV-2 RT-PCR or home antigen results. Surveillance students had a higher incidence rate than self-report students (incidence rate ratio, 1.9; 95% CI, 1.1-3.3; P = .01). Students were more likely than CCPs to have asymptomatic infection (34% vs 8%, P < .001). The CCC secondary attack rate was 2.7% to 3.0%, with the upper range representing possible but not definite secondary cases. Whether the index case was a student or CCP, transmission within the CCC was not significantly different. Household cumulative incidence was 20.5%, with no significant difference in incidence rate ratio between adults and children. Household secondary attack rates were 50% for children and 67% for adults. Of 30 household cases, only 5 (17%) represented secondary infections caused by 3 students who acquired SARS-CoV-2 from their CCC. Pre- and poststudy seroprevalence rates were 3% and 22%, respectively, with 90% concordance with antigen or RT-PCR results. In this study of SARS-CoV-2 incidence and transmission in CCCs and students' households, transmission within CCCs and from children infected at CCCs into households was low. These findings suggest that current testing and exclusion recommendations for SARS-CoV-2 in CCCs should be aligned with those for other respiratory viruses with similar morbidity and greater transmission to households.

Socioeconomic differences in SARS-CoV-2-antigen contacts after one year of the vaccination campaign

Abstract Background Evidence on the SARS-CoV-2 serological status of the German population by socioeconomic position (SEP) is still limited for the vaccine era of the pandemic, but could contribute to the understanding of the unequal risks of severe COVID-19. This study aims to evaluate the socioeconomic patterns of antigen contacts through infection, vaccination or both (‘hybrid immunity’) after one year of vaccination campaign in Germany. Methods We used nationwide serological and self-reported data from the population-based German seroepidemiological Corona Monitoring Nationwide study (RKI-SOEP-2, November 2021-February 2022) to estimate prevalence ratios (PR) of SARS-CoV-2 infection, COVID-19 vaccination (at least one dose of vaccine), basic immunization (at least two SARS-CoV-2 antigen contacts), and three antigen contacts by education and income. Estimates were derived from Poisson regression models adjusted for age, sex, migration status, urban-rural residence, federal state and date of participation. Results Across 10,448 adult participants, low-education groups had a 1.35-fold greater risk of SARS-CoV-2 infection compared to high-education groups (95% CI 1.01-1.82, p = 0.045). COVID-19 vaccination and basic immunization decreased with lower education and income. Low-education and low-income groups were less likely to have had at least three SARS-CoV-2 antigen contacts (PR low vs. high education: 0.74, 95% CI 0.65-0.84, p &amp;lt; 0.001; PR low vs. high income: 0.66, 95% CI 0.57-0.77, p &amp;lt; 0.001) Conclusions The results show socioeconomic inequalities in SARS-CoV-2 infections, COVID-19 vaccinations and antigen contacts, suggesting a lower level of protection against severe COVID-19 for individuals with low and medium SEP. The majority of the German population exhibits further prevention potential, which could be addressed via more targeted interventions. Future research, pandemic response and vaccination campaigns should address the specific needs and barriers of these groups. Key messages • Multiple antigen contacts, especially through vaccination, are less prevalent in groups with low or medium socioeconomic position. • Potential to prevent severe COVID-19 exists in the majority of the German population after one year of vaccination campaign.

Immunosuppressive Medications and COVID-19 Outcomes in Patients with Noninfectious Uveitis in the Era of COVID-19 Vaccinations

To determine the risk of coronavirus disease 2019 (COVID-19) infection, hospitalization, and death in the era of COVID-19 vaccination among patients with noninfectious uveitis (NIU) taking immunosuppressive therapies. Retrospective cohort study from July 1, 2021, to June 30, 2022, using data from the Optum Labs Data Warehouse (OLDW) de-identified claims database. Patients with a diagnosis of NIU from January 1, 2017, and who had ≥ 1year of continuous enrollment in the OLDW. Incidence rates (IRs) were calculated for each COVID-19 outcome. Unadjusted and adjusted hazard ratios (HRs) were estimated for each variable and COVID-19 outcome using Cox proportional hazards models with time-updated dichotomous indicators for outpatient immunosuppressive medication exposure. To assess the dose-dependent effect of systemic corticosteroid (SC) exposure, the average daily dose of prednisone over the exposed interval was included in the adjusted models. Hazard ratios and IRs for COVID-19 infection, hospitalization, and death. This study included 62 209 patients with NIU. A total of 12 895 (20.7%) were exposed to SCs during the risk period. Incidence rates were increased when exposed to SCs versus unexposed for all COVID-19 outcomes. Incidence rates were also increased for all COVID-19 outcomes when exposed to SCs without COVID-19 vaccination versus exposed to SCs with ≥ 1 vaccination. In adjusted models, SCs were associated with increased risk of COVID-19 infection (HR, 3.57; 95% confidence interval [CI], 3.24-3.93; P<0.0001), hospitalization (HR, 2.75; 95% CI, 2.07-3.65; P<0.0001), and death (HR, 2.49; 95% CI 1.29-4.82; P= 0.007). Incremental increases in SC dose were associated with a greater risk for all outcomes. Disease-modifying anti-rheumatic drugs were associated with a decreased risk of infection (HR, 0.84; 95% CI, 0.74-0.96; P= 0.01), and tumor necrosis factor-α inhibitors were associated with an increased risk of infection (HR, 1.18; 95% CI, 1.01-1.39; P= 0.04). Systemic corticosteroid exposure continues to be associated with greater risk of COVID-19 infection, hospitalization, and death among patients with NIU in an era of widespread COVID-19 vaccination. Unvaccinated individuals who are exposed to immunosuppressive treatments have a greater risk of severe outcomes. Coronavirus disease 2019 vaccination should be strongly encouraged in these patients. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Bacteriological and molecular characterization of temperature- and CO2-dependent Streptococcus pneumoniae serotype 24F ST162 isolated from Japanese children.

Streptococcus pneumoniae serotype 24F is one of the most prevalent non-vaccine serotypes that causes invasive pneumococcal disease (IPD) in many countries, including Japan. This study aimed to analyze the bacteriological and molecular characteristics of serotype 24F sequence type (ST) 162, which has been increasingly isolated from pediatric patients with IPD in Japan recently. The examination of growth conditions, sequencing of genes associated with the CO2 dependence, and antimicrobial susceptibility testing at 35°C under 5% CO2 were performed for 10 isolates obtained from Japanese children with IPD caused by serotype 24F ST162. All isolates failed to grow at 35°C in ambient air; however, they showed growth at 30°C in ambient air and at 35°C under 5% CO2. Sequencing of murF involved in cell wall synthesis indicated that all isolates had a single amino acid substitution, MurFA179V. Additionally, all isolates were sensitive to penicillin G and resistant to trimethoprim-sulfamethoxazole. Furthermore, 25 non-capnophilic strains were obtained from all CO2-dependent isolates, and their murF sequences were compared. Thirteen of the 25 non-capnophilic strains displayed a different amino acid substitution, MurFV179A, whereas the other 12 presented the previously described MurFA179V. This suggests that a proportion of the CO2-dependent phenotype of serotype 24F ST162 may have been conferred by MurFA179V; however, the mechanism for the CO2 dependence of these isolates warrants further investigation. The CO2-dependent serotype 24F ST162 pneumococcal isolates shared common characteristics in terms of growth patterns, molecular basis, and antimicrobial susceptibility; therefore, future epidemiological trends of this clone must be closely monitored. IMPORTANCE We characterized Streptococcus pneumoniae serotype 24F sequence type (ST) 162 isolated from Japanese children with invasive pneumococcal disease (IPD). Owing to its highly invasive nature, serotype 24F is expected to be isolated from clinically significant cases. Serotype 24F ST162 isolates tested in the present study did not grow at 35°C in ambient air. Therefore, antimicrobial susceptibility testing using the broth microdilution method, which is usually conducted in ambient air, cannot be performed, posing a clinical challenge. Clinical practitioners and laboratory personnel should be aware of the epidemiological, bacteriological, and molecular characteristics of serotype 24F ST162. We believe that our findings can help diagnose and treat IPD caused by serotype 24F ST162, a serotype expected to become problematic in the post-13 valent pneumococcal conjugate vaccine era.

Addressing the Risks of Respiratory Syncytial Virus for Patients With Inflammatory Bowel Disease in the Era of Novel Vaccines.

Addressing the Risks of Respiratory Syncytial Virus for Patients With Inflammatory Bowel Disease in the Era of Novel Vaccines.

PB0073 A Retrospective Study of Two Anticoagulation Therapies In Critically Ill Covid-19 Patients Prior to Vaccination Era

PB0073 A Retrospective Study of Two Anticoagulation Therapies In Critically Ill Covid-19 Patients Prior to Vaccination Era

Invasive Bacterial Infections in Children With Sickle Cell Disease: 2014-2019.

Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.