Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Evaluation of the Performance and Clinical Impact of a Rapid Phenotypic Susceptibility Testing Method Directly from Positive Blood Culture at a Pediatric Hospital.

Bloodstream infection poses a significant medical emergency that necessitates timely administration of appropriate antibiotics. Standard laboratory workup for antimicrobial susceptibility testing (AST) involves subculture of organisms from positive blood bottles followed by testing using broth microdilution; however, this process can take several days. The Accelerate Pheno Blood Culture panel (Pheno) provides rapid phenotypic testing of selected Gram-negative organisms directly from positive blood cultures. This has the potential to shorten the AST process to several hours and impact time to antimicrobial optimization and subsequent clinical outcomes; however, these metrics have not been assessed in pediatric populations. We retrospectively compared two patient cohorts with blood cultures positive for on-panel Gram-negative organisms: 82 cases tested by conventional AST methods, and 80 cases postintervention at our pediatric hospital. Susceptibility testing from the Pheno yielded 91.5% categorical agreement with a broth microdilution-based reference method with 7.4% minor error, 1.1% major error, and 0.1% very major error rates. The median time from blood culture positivity to AST decreased from 20.0 h to 9.7 h (P < 0.001), leading to an overall decrease in time from blood culture positivity to change in therapy from 36.0 h to 25.0 h (P < 0.001). There was no observed change in length of stay or 30-day mortality. Median duration on meropenem decreased from 64.8 h to 31.6 h (P = 0.04). We conclude the Pheno had accurate performance and that implementation allowed for faster AST reporting, improved time to optimal therapy, and decreased duration on meropenem in children.

Enhancing Green Product Generation of Photocatalytic NO Oxidation: A Case of WO3 Nanoplate/g-C3N4 S-Scheme Heterojunction.

Nitric oxide (NO) removal by photocatalytic oxidation over g-C3N4 has achieved more efficient results. However, there is a concern about the high NO-to-NO2 conversion yield of products, which is not suitable for the photocatalytic NO reaction. In this study, we modify g-C3N4 by WO3 nanoplates for the first time for photocatalytic NO oxidation over a WO3/g-C3N4 composite to enhance the green product selectivity under atmospheric conditions. The results indicate that the photocatalytic efficiency for NO removal by the WO3/g-C3N4 composite is drastically improved and achieves 52.5%, which is approximately 2.1 times higher than that of pure g-C3N4. Significantly, the green product (NO3-) selectivity of the WO3/g-C3N4 composite is 8.7 times higher than that of pure g-C3N4, and the selectivity remained high even after five cycles of photocatalytic tests. We also conclude that the enhanced green product selectivity of photocatalytic NO oxidation by the WO3/g-C3N4 composite is due to the separation and acceleration of the photogenerated charges of the WO3/g-C3N4 S-scheme heterojunction.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

The responses of river discharge and sediment load to historical land-use/land-cover change in the Mekong River Basin.

The large river basins throughout the world have undergone land-use/land-cover (LULC)-induced changes in river discharge and sediment load. Evaluating these changes is consequently important for efficient management of soil and water resources. In addition, these changes in the transboundary Mekong River Basin (Mekong RB) are not well-known. The present study aimed to investigate the impacts of LULC changes on river discharge and sediment load in the Mekong RB during the period 1980-2015 using Soil and Water Assessment Tool (SWAT). The SWAT model was calibrated and validated using measured data of daily river discharge and monthly sediment load. Analysis of LULC change showed a 2.35% decrease in forest land and a 2.29% increase in agricultural land during the period of 1997-2010. LULC changes in 1997 and 2010 caused increases in river discharge and sediment load by 0.24 to 0.32% and 1.78 to 2.86%, respectively in the study region. Moreover, the river discharge and sediment load of the Mekong River have significantly positive correlation with agricultural land and negative correlation with forest land. The findings give beneficial insights to implement appropriate strategies of water and soil conservation measures to adapt and mitigate the adverse impacts of LULC in the Mekong RB. Further study will consider the impact of future LULC changes and uncertainties associated with the LULC projections for future management of soil and water conservation in the study region.

Cell division is antagonized by the activity of peptidoglycan endopeptidases that promote cell elongation.

A peptidoglycan (PG) cell wall composed of glycans crosslinked by short peptides surrounds most bacteria and protects them against osmotic rupture. In Escherichia coli, cell elongation requires crosslink cleavage by PG endopeptidases to make space for the incorporation of new PG material throughout the cell cylinder. Cell division, on the contrary, requires the localized synthesis and remodeling of new PG at midcell by the divisome. Little is known about the factors that modulate transitions between these two modes of PG biogenesis. In a transposon-insertion sequencing screen to identify mutants synthetically lethal with a defect in the division protein FtsP, we discovered that mutants impaired for cell division are sensitive to elevated activity of the endopeptidases. Increased endopeptidase activity in these cells was shown to interfere with the assembly of mature divisomes, and conversely, inactivation of MepS was found to suppress the lethality of mutations in essential division genes. Overall, our results are consistent with a model in which the cell elongation and division systems are in competition with one another and that control of PG endopeptidase activity represents an important point of regulation influencing the transition from elongation to the division mode of PG biogenesis.

Saliva Is a Promising Alternative Specimen for the Detection of SARS-CoV-2 in Children and Adults.

Testing efforts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been burdened by the scarcity of testing materials and personal protective equipment for health care workers. The simple and painless process of saliva collection allows for widespread testing, but enthusiasm is hampered by variable performance compared to that of nasopharyngeal swab (NPS) samples. We prospectively collected paired NPS and saliva samples from a total of 300 unique adult and pediatric patients. SARS-CoV-2 RNA was detected in 32.2% (97/300) of the individuals using the TaqPath COVID-19 Combo kit (Thermo Fisher). Performance of saliva and NPS was compared against the total number of positives regardless of specimen type. The overall concordances for saliva and NPS were 91.0% (273/300) and 94.7% (284/300), respectively. The values for positive percent agreement (PPA) for saliva and NPS were 81.4% (79/97) and 89.7% (87/97), respectively. Saliva yielded detection of 10 positive cases that were negative by NPS. For symptomatic and asymptomatic pediatric patients not previously diagnosed with COVID-19, the performances of saliva and NPS were comparable (PPA, 82.4% versus 85.3%). The overall values for PPA for adults were 83.3% and 90.7% for saliva and NPS, respectively, with saliva yielding detection of 4 fewer cases than NPS. However, saliva performance for symptomatic adults was identical to NPS performance (PPA of 93.8%). With lower cost and self-collection capabilities, saliva can be an appropriate sample choice alternative to NPS for detection of SARS-CoV-2 in children and adults.

Blocking Allergic Reaction through Targeting Surface-Bound IgE with Low-Affinity Anti-IgE Antibodies.

Allergic disorders have now become a major worldwide public health issue, but the effective treatment options remain limited. We report a novel approach to block allergic reactivity by targeting the surface-bound IgE of the allergic effector cells via low-affinity anti-human IgE Abs with dissociation constants in the 10-6 to 10-8 M range. We demonstrated that these low-affinity anti-IgE mAbs bind to the cell surface-bound IgE without triggering anaphylactic degranulation even at high concentration, albeit they would weakly upregulate CD203c expression on basophils. This is in contrast to the high-affinity anti-IgE mAbs that trigger anaphylactic degranulation at low concentration. Instead, the low-affinity anti-IgE mAbs profoundly block human peanut- and cat-allergic IgE-mediated basophil CD63 induction indicative of anaphylactic degranulation; suppress peanut-, cat-, and dansyl-specific IgE-mediated passive cutaneous anaphylaxis; and attenuate dansyl IgE-mediated systemic anaphylaxis in human FcεRIα transgenic mouse model. Mechanistic studies reveal that the ability of allergic reaction blockade by the low-affinity anti-IgE mAbs was correlated with their capacity to downregulate the surface IgE and FcεRI level on human basophils and the human FcεRIα transgenic mouse bone marrow-derived mast cells via driving internalization of the IgE/FcεRI complex. Our studies demonstrate that targeting surface-bound IgE with low-affinity anti-IgE Abs is capable of suppressing allergic reactivity while displaying an excellent safety profile, indicating that use of low-affinity anti-IgE mAbs holds promise as a novel therapeutic approach for IgE-mediated allergic diseases.

A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone.

UNLABELLED: Burkholderia thailandensis has three acyl-homoserine lactone (AHL) LuxR-LuxI quorum-sensing circuits and two orphan LuxR homologs. Orphans are LuxR-type transcription factors that do not have cognate LuxI-type AHL synthases. One of the orphans, MalR, is genetically linked to the mal gene cluster, which encodes enzymes required for production of the cytotoxic polyketide malleilactone. Under normal laboratory conditions the mal gene cluster is silent; however, antibiotics like trimethoprim induce mal transcription. We show that trimethoprim-dependent induction of the mal genes requires MalR. MalR has all of the conserved amino acid residues characteristic of AHL-responsive LuxR homologs, but in B. thailandensis, MalR activation of malleilactone synthesis genes is not responsive to AHLs. MalR can activate transcription from the mal promoter in E. coli without addition of AHLs or trimethoprim. Expression of malR in B. thailandensis is induced by trimethoprim. Our data indicate that MalR binds to a lux box-like element in the mal promoter and activates transcription of the mal genes in an AHL-independent manner. Antibiotics like trimethoprim appear to activate mal gene expression indirectly by somehow activating malR expression. MalR activation of the mal genes represents an example of a LuxR homolog that is not a receptor for an AHL quorum-sensing signal. Our evidence is consistent with the idea that mal gene activation depends solely on sufficient transcription of the malR gene. IMPORTANCE: LuxR proteins are transcription factors that are typically activated by acyl-homoserine lactone (AHL) signals. We demonstrate that a conserved LuxR family protein, MalR, activates genes independently of AHLs. MalR is required for transcription of genes coding for synthesis of the cytotoxic polyketide malleilactone. These genes are not expressed when cells are grown under normal laboratory conditions. In laboratory culture, MalR induction of malleilactone requires certain antibiotics, such as trimethoprim, which increase malR expression by an unknown mechanism. At sufficient levels of malR expression, MalR functions independently of any external signal. Our findings show that MalR is an activator of the silent malleilactone biosynthesis genes and that MalR functions independently of AHLs.

Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models.

WNK1 (with-no-lysine[K]-1) is a protein kinase of which mutations cause a familial hypertension and hyperkalemia syndrome known as pseudohypoaldosteronism type 2 (PHA2). Kidney-specific (KS) WNK1 is an alternatively spliced form of WNK1 kinase missing most of the kinase domain. KS-WNK1 downregulates the Na(+)-Cl(-) cotransporter NCC by antagonizing the effect of full-length WNK1 when expressed in Xenopus oocytes. The physiological role of KS-WNK1 in the regulation of NCC and potentially other Na(+) transporters in vivo is unknown. Here, we report that mice overexpressing KS-WNK1 in the kidney exhibited renal Na(+) wasting, elevated plasma levels of angiotensin II and aldosterone yet lower blood pressure relative to wild-type littermates. Immunofluorescent staining revealed reduced surface expression of total and phosphorylated NCC and the Na(+)-K(+)-2Cl(-) cotransporter NKCC2 in the distal convoluted tubule and the thick ascending limb of Henle's loop, respectively. Conversely, mice with targeted deletion of exon 4A (the first exon for KS-WNK1) exhibited Na(+) retention, elevated blood pressure on a high-Na(+) diet and increased surface expression of total and phosphorylated NCC and NKCC2 in respective nephron segments. Thus, KS-WNK1 is a negative regulator of NCC and NKCC2 in vivo and plays an important role in the control of Na(+) homeostasis and blood pressure. These results have important implications to the pathogenesis of PHA2 with WNK1 mutations.

Electrochemical water splitting of 3D binder-free hydrothermally synthesized Co3O4/unidirectional carbon cloth.

The development of hydrogen energy sources based on electrochemical water splitting is of increasing interest due to its advantages in energy and environmental fields. In this study, Co3O4 was decorated on carbon cloth (CC) by a hydrothermal method and was used as an electrode for water splitting. The structural and morphological properties of the materials are assessed using a range of reliable techniques such as X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) with EDX mapping, and diffuse reflectance spectroscopy (DRS). Results indicate that the Co3O4/CC material was synthesized at 140 °C for 9 h and calcined at 350 °C achieving a superior overall water-splitting activity in the direction of hydrogen evolution reaction (HER) reaction than that of the oxygen evolution reaction (OER). In detail, HER characteristics with an overpotential at -0.234 V and a current density at 10 mA cm-2. In addition, the Co3O4/CC material also gives overpotential at 0.54 V for OER process. Furthermore, the electrochemical surface area of Co3O4/CC material is 7.6 times higher than CC electrode. Moreover, the CC fabric is destroyed when the annealing temperature is higher than 350 °C, leading to a significant decrease in the activity of Co3O4/CC. The as-prepared Co3O4 shows good adhesion and stability based on CC substrate without binder substance or further treatment of CC.

Timing and necessity of staging imaging in clinical stage II cutaneous melanoma: Cost-effectiveness and clinical decision analysis.

BACKGROUND: Preoperative imaging in clinical stage II melanoma is not indicated per National Comprehensive Cancer Network (NCCN) guidelines but remains common in clinical practice. METHODS: Patients presenting with cutaneous clinical stage II melanoma from 2007 to 2019 were retrospectively reviewed. A clinical decision analysis with cost data was designed to understand ideal practice patterns in managing stage II melanoma, with pre-versus selective post-operative imaging as the initial decision node. RESULTS: There were 277 subjects included, and 143 underwent preoperative imaging (49.5%). This changed management (i.e. no surgery) in one patient (0.4%). Overall, 16 patients had additional findings on imaging (5.8%). Upfront surgery with selective postoperative imaging was a more cost-effective strategy than routine performance of preoperative imaging, with savings of $1677 per patient. CONCLUSION: Preoperative imaging is a low yield, costly approach for patients with clinical stage II melanoma with minimal impact on the decision to proceed with surgical management.

High accurate and explainable multi-pill detection framework with graph neural network-assisted multimodal data fusion.

Due to the significant resemblance in visual appearance, pill misuse is prevalent and has become a critical issue, responsible for one-third of all deaths worldwide. Pill identification, thus, is a crucial concern that needs to be investigated thoroughly. Recently, several attempts have been made to exploit deep learning to tackle the pill identification problem. However, most published works consider only single-pill identification and fail to distinguish hard samples with identical appearances. Also, most existing pill image datasets only feature single pill images captured in carefully controlled environments under ideal lighting conditions and clean backgrounds. In this work, we are the first to tackle the multi-pill detection problem in real-world settings, aiming at localizing and identifying pills captured by users during pill intake. Moreover, we also introduce a multi-pill image dataset taken in unconstrained conditions. To handle hard samples, we propose a novel method for constructing heterogeneous a priori graphs incorporating three forms of inter-pill relationships, including co-occurrence likelihood, relative size, and visual semantic correlation. We then offer a framework for integrating a priori with pills' visual features to enhance detection accuracy. Our experimental results have proved the robustness, reliability, and explainability of the proposed framework. Experimentally, it outperforms all detection benchmarks in terms of all evaluation metrics. Specifically, our proposed framework improves COCO mAP metrics by 9.4% over Faster R-CNN and 12.0% compared to vanilla YOLOv5. Our study opens up new opportunities for protecting patients from medication errors using an AI-based pill identification solution.

Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb.

Kidney-specific WNK1 (KS-WNK1) is a variant of full-length WNK1. Previous studies have reported that KS-WNK1 is predominantly expressed in the distal convoluted tubule (DCT) where it regulates sodium-chloride cotransporter. The role of KS-WNK1 in other nephron segments is less clear. Here, we measured the expression of KS-WNK1 transcript in microdissected renal tubules and found that KS-WNK1 was most abundant in the DCT, followed by cortical thick ascending limb (cTAL), connecting tubule, and cortical collecting duct. A high K(+) diet enhanced the expression of KS-WNK1 in the DCT and cTAL, selectively. It has been reported that a high-K diet suppresses Na(+) reabsorption in TAL. To understand the role of KS-WNK1 in Na(+) transport in cTAL and the regulation by dietary K(+), we examined Na(+) reabsorption using in vitro microperfusion in cTAL isolated from KS-WNK1-knockout mice and wild-type littermates fed either a control-K(+) or high-K(+) diet. Furosemide-sensitive Na(+) reabsorption in cTAL was higher in KS-WNK1-knockout (KO) mice than in wild-type. A high-K(+) diet inhibited Na(+) reabsorption in cTAL from wild-type mice, but the inhibition was eliminated in KS-WNK1-KO mice. We further examined the role of KS-WNK1 using transgenic mice that overexpress KS-WNK1. Na(+) reabsorption in cTAL was lower in transgenic than in wild-type mice. In whole animal clearance studies, a high-K(+) diet increased daily urine volume and urinary Na(+) and K(+) excretion in wild-type mice, which was blunted in KS-WNK1-KO mice. Thus KS-WNK1 inhibits Na(+) reabsorption in cTAL and mediates the inhibition of Na(+) reabsorption in the segment by a high-K diet.

Rapid Antigen Assays for SARS-CoV-2: Promise and Peril.

Though rapid antigen tests have historically problematic performance characteristics for the diagnosis of respiratory viral infections such as influenza, they have attained an unprecedented level of use in the context of the COVID-19 pandemic. Ease of use and scalability of rapid antigen tests has facilitated a democratization and scale of testing beyond anything reasonably achievable by traditional laboratory-based testing. In this chapter, we discuss the performance characteristics of rapid antigen testing for SARS-CoV-2 detection and their application to non-traditional uses beyond clinical diagnostic testing.

Tin dioxide nanomaterial-based photocatalysts for nitrogen oxide oxidation: a review.

Semiconducting SnO2 photocatalyst nanomaterials are extensively used in energy and environmental research because of their outstanding physical and chemical properties. In recent years, nitrogen oxide (NO x ) pollutants have received particular attention from the scientific community. The photocatalytic NO x oxidation will be an important contribution to mitigate climate change in the future. Existing review papers mainly focus on applying SnO2 materials for photocatalytic oxidation of pollutants in the water, while studies on the decomposition of gas pollutants are still being developed. In addition, previous studies have shown that the photocatalytic activity regarding NO x decomposition of SnO2 and other materials depends on many factors, such as physical structure and band energies, surface and defect states, and morphology. Recent studies have been focused on the modification of properties of SnO2 to increase the photocatalytic efficiency of SnO2, including bandgap engineering, defect regulation, surface engineering, heterojunction construction, and using co-catalysts, which will be thoroughly highlighted in this review.

Insight into the degradation of p-nitrophenol by visible-light-induced activation of peroxymonosulfate over Ag/ZnO heterojunction.

In this report, the peroxymonosulfate activation over Ag/ZnO heterojunction under visible light (Ag/ZnO/PMS/Vis) for p-nitrophenol (p-NP) contaminant degradation was conducted in detail. Herein, the catalyst dosage was decreased, and the results showed that a dosage of 0.5 g L-1 Ag/ZnO and 4 mM PMS almost completely degraded 30 mg L-1 p-NP after 90 min of irradiation. In addition, the PMS activation mechanism of Ag/ZnO/PMS/Vis system was proposed by investigations of the influence of PMS concentration, the FTIR spectra, UV-Vis spectroscopy, and electrochemical analyses. Additionally, the role of SO4•- in the photocatalytic reaction is determined by a combination of a trapping test using isopropanol and tert-butanol as probe compounds and electron spin resonance (ESR) spectroscopy. This report provides a potential alternative to remove persistent organic contaminants in sewage using PMS incorporated with Ag/ZnO under visible light irradiation.

Persistent SARS-CoV-2 infection and increasing viral variants in children and young adults with impaired humoral immunity.

Background: There is increasing concern that persistent infection of SARS-CoV-2 within immunocompromised hosts could serve as a reservoir for mutation accumulation and subsequent emergence of novel strains with the potential to evade immune responses. Methods: We describe three patients with acute lymphoblastic leukemia who were persistently positive for SARS-CoV-2 by real-time polymerase chain reaction. Viral viability from longitudinally-collected specimens was assessed. Whole-genome sequencing and serological studies were performed to measure viral evolution and evidence of immune escape. Findings: We found compelling evidence of ongoing replication and infectivity for up to 162 days from initial positive by subgenomic RNA, single-stranded RNA, and viral culture analysis. Our results reveal a broad spectrum of infectivity, host immune responses, and accumulation of mutations, some with the potential for immune escape. Interpretation: Our results highlight the need to reassess infection control precautions in the management and care of immunocompromised patients. Routine surveillance of mutations and evaluation of their potential impact on viral transmission and immune escape should be considered. Funding: The work was partially funded by The Saban Research Institute at Children's Hospital Los Angeles intramural support for COVID-19 Directed Research (X.G. and J.D.B.), the Johns Hopkins Center of Excellence in Influenza Research and Surveillance HHSN272201400007C (A.P.), NIH/NIAID R01AI127877 (S.D.B.), NIH/NIAID R01AI130398 (S.D.B.), NIH 1U54CA260517 (S.D.B.), an endowment to S.D.B. from the Crown Family Foundation, an Early Postdoc.Mobility Fellowship Stipend to O.F.W. from the Swiss National Science Foundation (SNSF), and a Coulter COVID-19 Rapid Response Award to S.D.B. L.G. is a SHARE Research Fellow in Pediatric Hematology-Oncology.