Risk Factors For Severe Disease Research Articles

Associations between COVID-19 and Glucose-6-Phosphate Dehydrogenase Activity in Brazil.

Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase (G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription-polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.

Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis Infected with the SARS-CoV-2 Omicron Variant: A Retrospective Study

Background: Maintenance hemodialysis (MHD) patients constitute a distinctive population characterized by unique traits, such as hemodialysis-related immune disturbances, and increased vulnerability to infections, heart failure, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite considerable research on MHD patients with coronavirus disease 2019 (COVID-19), there is limited information available on the clinical characteristics and outcomes of unvaccinated adult MHD patients infected with the SARS-CoV-2 Omicron variant. Methods: A retrospective investigation was conducted in a cohort of 427 unvaccinated MHD patients diagnosed with SARS-CoV-2 Omicron infection. The clinical symptoms, laboratory results, and treatment regimens were comprehensively examined. Multivariate regression identified independent risk factors for disease severity, and two-month follow-up assessments were conducted. Results: The cohort exhibited a spectrum of disease severity, with 37.5% classified as mild, 35.3% as common, 22.5% as severe, and 4.7% as critical. Serum C-reactive protein level, procalcitonin level, and bicarbonate concentration are related to the severity of the disease. Tailored treatment strategies—including nutritional support, hemodialysis management, anti-bacterial interventions, and more—were implemented. There was a 5.6% mortality rate, with a higher prevalence of deaths in the critical subtype. Independent risk factors for disease severity included fever, age, cycle threshold values (Ct values) of ORF1ab gene, and arterial oxygen partial pressure. Follow-up assessments revealed a median duration of 11 days for the negative nucleic acid of SARS-CoV-2. Twelve patients presented a second positive ORF1ab gene during follow-up but remained asymptomatic. Conclusion: These findings suggest the intricate clinical characteristics and outcomes of MHD patients with the SARS-CoV-2 Omicron infection. Tailored treatment strategies, continuous surveillance, and understanding prognostic factors are imperative for managing this high-risk population. Further research is warranted to validate these findings.

Clinical characteristics of liver transplant recipients with COVID-19 and analysis of risk factors for the severe disease.

Liver transplant (LT) recipients were at a high risk of infection during the coronavirus disease 2019 (COVID-19) pandemic. Our purpose was to compare the clinical characteristics of severe and non-severe groups of LT recipients with COVID-19, and to analyze their risk factors for severe disease. 79 LT recipients with COVID-19 were divided into a non-severe group (n = 60) and a severe group (n = 19), and differences in clinical characteristics, laboratory tests, and chest computed tomography (CT) performance were analyzed. Logistic regression was used to identify risk factors with severe COVID-19. Receiver operating characteristic (ROC) curves were plotted and the area under curve (AUC) values were calculated to assess the predictive value for severe COVID-19. Age was statistically different (p < 0.001) between the two groups. The difference in neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), D-dimer, urea, C-reactive protein (CRP), lactate dehydrogenase (LDH), and the number of lung segments involved in inflammation between the two groups were statistically significant (p < 0.05). The results revealed that age (OR = 1.255, 95% CI 1.079-1.460), NLR (OR = 1.172, 95% CI 1.019-1.348), and Scr (OR = 1.041, 95% CI 1.016-1.066) were independent risk factors for severe COVID-19. The ROC results showed that high values for age, NLR and Scr predicted severe COVID-19, with AUC values of 0.775, 0.841 and 0.820, respectively, and 0.925 for the three factors combined. Advanced age, and elevated NLR and Scr are independent risk factors for severe COVID-19 in LT recipients.

Clinical and Laboratory Profile, Management and Outcome of Pediatric SARS-CoV-2 Infection Admitted at the Philippine General Hospital.

The Philippines has recorded over 470,000 COVID-19 cases in children, with over 1,500 deaths during the same period. Although a Philippine online pediatric COVID-19 registry exists, this only relies on passive surveillance. This study determined the clinical and laboratory profile, risk factors for severe COVID-19, and mortality, management, and outcome of pediatric SARS-CoV-2 patients admitted at the Philippine General Hospital (PGH) from April 2020 to June 2022 to fill in knowledge gaps on the epidemiology of COVID-19 infection in children. This was a retrospective cohort study of pediatric COVID-19 cases admitted at the PGH, a designated COVID referral center during the study period. Demographic and clinical profile, risk factors, comorbidities, laboratory and radiologic findings, management, and outcomes across different disease severity states were gathered by chart review and the data were analyzed using STATA 17. There were 448 pediatric patients admitted and diagnosed with COVID-19 during the study period. Most patients belonged to the 1-5-year age group (25.9%), had no known exposure to a COVID-19 case (65.4%), were mild cases (37.3%%), and did not receive any dose of the COVID-19 vaccine (96.7%). The most common presenting symptoms across all disease categories were fever (44.4%), cough (28.6%), and shortness of breath (26.6%). Multisystem inflammatory syndrome in children (MIS-C) presented with fever (100%) and rash (53.9%). The risk factors for severe disease were the presence of a congenital anomaly lung disease, and elevated procalcitonin. Most patients with MIS-C were previously well with no comorbidities. Laboratory findings which were markedly elevated among severe and critical cases were ESR, CRP, D-dimer, LDH, and IL-6. Ferritin, procalcitonin (PCT) and IL-6 were elevated only in severe to critical COVID-19 cases and remained within normal for the other disease categories. As to treatment, asymptomatic, mild, and moderate cases were given supportive medications (zinc, vitamin D, and vitamin C), while investigational drugs particularly corticosteroids, IVIG, and remdesivir, were used in severe cases.Antibiotics were given to 71.7% of patients at the outset. As to the outcomes, 89% recovered, while 8.9% died. The case fatality rate from COVID-19 infection was at 2.2%. Admitted pediatric COVID-19 cases are generally mild but admission is due to underlying illness or comorbidities. Those with severe to critical cases have underlying comorbidities and had either progression or complications due to COVID disease. D-dimer, LDH, IL-6, ferritin and procalcitonin were elevated among severe and critical cases which can be utilized as inflammatory markers.

Outdoor air pollution as a risk factor for testing positive for SARS-CoV-2: A nationwide test-negative case-control study in the Netherlands

Air pollution is a known risk factor for several diseases, but the extent to which it influences COVID-19 compared to other respiratory diseases remains unclear. We performed a test-negative case-control study among people with COVID-19-compatible symptoms who were tested for SARS-CoV-2 infection, to assess whether their long- and short-term exposure to ambient air pollution (AAP) was associated with testing positive (vs. negative) for SARS-CoV-2. We used individual-level data for all adult residents in the Netherlands who were tested for SARS-CoV-2 between June and November 2020, when only symptomatic people were tested, and modeled ambient concentrations of PM10, PM2.5, NO2 and O3 at geocoded residential addresses. In long-term exposure analysis, we selected individuals who did not change residential address in 2017–2019 (1.7 million tests) and considered the average concentrations of PM10, PM2.5 and NO2 in that period, and different sources of PM (industry, livestock, other agricultural activities, road traffic, other Dutch sources, foreign sources). In short-term exposure analysis, individuals not changing residential address in the two weeks before testing day (2.7 million tests) were included in the analyses, thus considering 1- and 2-week average concentrations of PM10, PM2.5, NO2 and O3 before testing day as exposure. Mixed-effects logistic regression analysis with adjustment for several confounders, including municipality and testing week to account for spatiotemporal variation in viral circulation, was used. Overall, there was no statistically significant effect of long-term exposure to the studied pollutants on the odds of testing positive vs. negative for SARS-CoV-2. However, significant positive associations of long-term exposure to PM10 and PM2.5 from specifically foreign and livestock sources, and to PM10 from other agricultural sources, were observed. Short-term exposure to PM10 (adjusting for NO2) and PM2.5 were also positively associated with increased odds of testing positive for SARS-CoV-2. While these exposures seemed to increase COVID-19 risk relative to other respiratory diseases, the underlying biological mechanisms remain unclear. This study reinforces the need to continue to strive for better air quality to support public health.

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients

PurposeAuto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs.MethodsWe evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs.ResultsThree of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor.ConclusionAuto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.

Assessing antiviral treatment efficacy and risk factors for severe COVID-19 in kidney transplant recipients during the Omicron subvariant-dominant period: a retrospective study

BackgroundKidney transplant recipients (KTRs) are at risk of severe coronavirus disease 2019 (COVID-19), and even now that Omicron subvariants have become dominant, cases of severe disease are certain to occur. The aims of this retrospective study were to evaluate the efficacy of antiviral treatment for COVID-19 and to identify risk factors for severe disease in KTRs during Omicron subvariant-dominant periods.MethodsA total of 65 KTRs diagnosed with COVID-19 who received antiviral treatment between July 2022 and September 2023 were analyzed. Mild cases received oral molnupiravir (MP) as outpatient therapy, while moderate or worse cases received intravenous remdesivir (RDV) as inpatient therapy. In principle, mycophenolate mofetil was withdrawn and switched to everolimus. We investigated the efficacy of antiviral treatment and compared the clinical parameters of mild/moderate and severe/critical cases to identify risk factors for severe COVID-19.ResultsAmong 65 cases, 49 were mild, 6 were moderate, 9 were severe, and 1 was of critical severity. MP was administered to 57 cases; 49 (86%) improved and 8 (14%) progressed. RDV was administered to 16 cases; 14 (87%) improved and 2 (13%) progressed. Seventeen (26%) cases required hospitalization, and none died. Comparisons of the severe/critical group (n = 10) with the mild/moderate group (n = 55) demonstrated that the severe/critical group had a significantly higher median age (64 vs. 53 years, respectively; p = 0.0252), prevalence of diabetes (70% vs. 22%, respectively; p = 0.0047) and overweight/obesity (40% vs. 11%, respectively; p = 0.0393), as well as a significantly longer median time from symptom onset to initial antiviral therapy (3 days vs. 1 day, respectively; p = 0.0026). Multivariate analysis showed that a longer time from symptom onset to initial antiviral treatment was an independent risk factor for severe COVID-19 (p = 0.0196, odds ratio 1.625, 95% confidence interval 1.081–2.441).ConclusionThese findings suggest that a longer time from symptom onset to initial antiviral treatment is associated with a higher risk of severe COVID-19 in KTRs. Initiating antiviral treatment as early as possible is crucial for preventing severe outcomes; this represents a valuable insight into COVID-19 management in KTRs.

Predictors of prolonged length of stay in adult patients with respiratory syncytial virus infections - a multi-center historical cohort study.

Several studies have reported risk factors for severe disease and mortality in hospitalized adults with RSV infections. There is limited information available regarding the factors that affect the duration of a patient's hospital length of stay (LOS). This was a multicenter historical cohort study of adult patients hospitalized for laboratory-confirmed RSV in Southeast Michigan between January 2017 and December 2021. Hospitalized patients were identified using the International Classification of Diseases, Tenth Revision 10 codes for RSV infection. Mean LOS was computed; prolonged LOS was defined as greater than the mean. We included 360 patients with a mean age (SD) of 69.9 ± 14.7 years, 63.6% (229) were female and 63.3% (228) of white race. The mean hospital LOS was 7.1 ± 5.4 days. Factors associated with prolonged LOS in univariable analysis were old age, body mass index (BMI), smoking status, Charlson Weighted Index of Comorbidity (CWIC), home oxygen, abnormal chest x-ray (CXR), presence of sepsis, use of oxygen, and antibiotics at the time of presentation. Predictors for prolonged LOS on admission in multivariable analysis were age on admission (p < 0.001), smoking status (p = 0.001), CWIC (p = 0.038) and abnormal CXR (p = 0.043). Our study found that age on admission, smoking history, higher CWIC and abnormal CXR on admission were significantly associated with prolonged LOS among adult patients hospitalized with RSV infection. These findings highlight the significance of promptly recognizing and implementing early interventions to mitigate the duration of hospitalization for adult patients suffering from RSV infection.

Respiratory syncytial virus under 2 years of age: hospitalization trends and risk factors for severe disease Ó? preliminary data from the Portuguese sentinel network

Respiratory syncytial virus under 2 years of age: hospitalization trends and risk factors for severe disease Ó? preliminary data from the Portuguese sentinel network

Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

543 The link between preexisting hypertension and COVID-19 severity in a hamster model

OBJECTIVES/GOALS: Hypertension is a major risk factor for coronavirus disease 2019 (COVID-19) severity. Our goal was to determine if hypertension worsens lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters. METHODS/STUDY POPULATION: Male hamsters (7-8 weeks old) were infused with angiotensin II (AII; 200 ng/kg/min via osmotic minipump) for 4 weeks to induce hypertension. During the last week of the infusion, the hamsters were inoculated intranasally with vehicle (V) or SARS-CoV-2 (S; 1 x 105 plaque forming units/ml). Half of the hamsters were sacrificed 1 day post-inoculation (dpi-1) and the other half on dpi-6. Two scoring systems were applied to lung tissue sections stained with hematoxylin and eosin to determine the degree and severity of lung pathology: the first system assessed all pertinent alterations in the lungs, while the second system only assessed the pathology related to the pulmonary vasculature. Lung histopathology scores were calculated as the sum of the airway and lung alveolar scores in arbitrary units (AU). RESULTS/ANTICIPATED RESULTS: Studies revealed that the SARS-CoV-2-infected hamsters exhibited a 76-fold higher total airway score compared to vehicle controls [(AU): V, 0.25 ± 0.1; S, 19.00 ±1.35; p&lt;0.05; n=4]. Total lung alveolar scores (27-fold) [(AU): V, 0.30 ± 0.11; S, 8.0 ± 4.1; p&lt;0.05; n=4] and total vascular scores (17-fold) [(AU): V, 0.35 ± 0.2; S, 6.0 ±1.4; p&lt;0.05; n=4] were also markedly higher compared to controls on dpi-1. AII increased blood pressure, which was sustained through the 4-week infusion period. Under these conditions, body weight slightly dropped by 4.5%. Ongoing studies are assessing the effect of hypertension on the % of airway, alveoli and vessels affected, airway and alveolar severity, and bronchiolar epithelial and type II pneumocyte hyperplasia. DISCUSSION/SIGNIFICANCE: Establishing the hypertensive hamster as a small animal model of COVID-19 will facilitate investigations into why preexisting hypertension is a risk factor for disease severity. These studies could lead to the development of novel therapeuticsfor treating COVID-19 patients with hypertension.

Predictors of Disease Severity in Patients Hospitalized with COVID-19 during the Omicron Surge of January 2022

Background: The surge of COVID-19 hospitalizations in January 2022, at the onset of the Omicron period and before widespread population immunity, was a window in which to study the impact of vaccination status and other factors on disease severity in Omicron infections. Methods: This was a case-control study of adults hospitalized with COVID-19 during January 2022 that evaluated risk factors for severe disease. Cases were patients with severe COVID-19, defined in three ways: (1) requiring supplemental oxygen &gt; 24 hours if not on home oxygen, (2) requiring high-level oxygen: either high flow of &gt; 15 L/min, noninvasive ventilation, or mechanical ventilation (MV), and (3) the composite of MV or hospital death. Controls were patients hospitalized with COVID-19 who did not meet the respective case definition. Results: Among the 379 patients not on home oxygen before admission, 133 required supplemental oxygen. Among all 393 patients meeting the study criteria, 58 required high-level oxygen, 22 required MV, and 28 died. Factors associated with all case definitions were (1) absence of full vaccination compared to booster vaccination: requiring oxygen, odds ratio [OR], 7.86 [95% CI, 3.78-16.4]; high-level oxygen, OR, 5.17 [95% CI, 2.01-13.3]; MV or hospital death, OR, 5.21 [ 95% CI, 1.63-16.6]; (2) immunocompromised status: requiring oxygen, OR, 2.79 [95% CI, 1.38-5.63]; high-level oxygen, OR, 3.79 [95% CI 1.66-8.67]; MV or hospital death, OR 4.63 [95% CI 1.72-12.5], and (3) age ≥ 75 years compared to 50 to 64 years: requiring oxygen, OR 2.85, [95% CI 1.43-6.07]; high-level oxygen, OR 4.02 [95% CI 1.47-11.0]; MV or hospital death, OR 5.68 [95% CI 1.49-21.7]. Other factors associated with requiring oxygen were obesity: body mass index (BMI) 35.0-39.9 kg/m2, OR, 2.4 [95% CI 1.09-5.26]; BMI ≥ 40.0 kg/m2, OR, 3.29 [95% CI 1.34-8.10] compared to BMI ≤ 24.9 kg/m2; and age 65-74 years compared to 50-64 years, OR, 2.13 [ 95% CI 1.03-4.38]. Factors associated with requiring high-level oxygen were cardiomyopathy, OR, 2.11 [95% CI 1.04-4.32], and male gender, OR 1.93 [95% CI 1.01-3.7]. Factors associated with MV or hospital death were cardiomyopathy, OR, 2.67 [ 95% CI 1.11-6.42], and chronic kidney disease, OR, 3.17 [95% CI 1.27-7.96]. Factors not associated with any case definitions were full vaccination without compared to with a booster: requiring oxygen, OR, 1.07 [95% CI 0.522-2.21], high-level oxygen, OR, 1.08 [0.415-2.81], MV or hospital death, OR 0.992 [0.328-3.0]; age 18-49 years compared to 50-64 years: requiring oxygen, OR, 1.04 [95% CI 0.495-2.2]; high-level oxygen, OR, 1.2 [95% CI 0.418-3.43]; MV or hospital death, OR, 0.355 [95% CI 0.034-3.75]; and other medical conditions. Conclusions: In patients hospitalized with COVID-19 during the Omicron surge of January 2022, factors associated with requiring oxygen were the absence of full vaccination, immunosuppression, age ≥ 65 years, and body mass index ≥ 35 kg/m2, but not the absence of a booster if fully vaccinated. This is further evidence that immune memory mitigates disease severity in Omicron infections.

Effect of different types of smoking on oral health and on cellular changes in oral mucosa

ObjectivesSmoking is known to be a major risk factor for several diseases. Recently, electronic cigarettes have been introduced to the market; however, their effect on oral health has not been well studied yet. We aim to compare the effect of different types of smoking on oral health and to evaluate cytomorphological changes in oral mucosa among different types of smokers. Study designA total of 112 participants were recruited, conventional cigarette smokers (n = 28), electronic cigarettes smokers (n = 26), hookah smokers (n = 29) and non-smokers (n = 29). Oral examination, brush cytology and salivary flow test were performed. Cytological smears were stained and examined for cytomorphological changes. Oral symptoms, type, and frequency of smoking were obtained through questionnaires. SPSS program was used for statistical analysis. ResultsMost of the oral symptoms reported in this study were among conventional and electronic cigarettes smokers. While hookah smokers reported the least oral symptoms. Increase in DMFT and gingival index were observed among all smokers, mainly among conventional cigarettes smokers. Conventional cigarette and hookah smokers were found to have the most significant cellular changes. Electronic cigarette smokers had certain cellular changes as well. ConclusionAll types of smoking adversely affect oral health and can induce cellular changes in the oral mucosa.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

Characteristics and outcomes of a hospitalized cohort with reduced mortality from COVID-19, White Mountain apache tribal lands, April 1 – July 31, 2020

BackgroundWidespread transmission of COVID-19 continues to threaten public health, particularly of rural, American Indian communities. Although COVID-19 risk factors for severe disease and clinical characteristics are well described in the general population, there has been little shared on hospitalized American Indian populations.MethodsIn this observational study, we performed chart extractions on all persons hospitalized with COVID-19 from April 1 through July 31, 2020 among an exclusively American Indian population living on or near Tribal lands in eastern Arizona. We provide descriptive statistics for the cohort stratified by presentation, comparing those who self-presented or were referred by an outreach program. Exploratory analyses were performed to identify risk factors for morbidity and mortality.ResultsDuring the observation period, 2262 persons were diagnosed with COVID-19 and 490 (22%) were hospitalized. Hospitalized persons had a median age of 54 years; 92% had at least one comorbidity, 72% had greater than one comorbidity, and 60% had a BMI of > 30. Most persons required supplemental oxygen (83%), but the majority (62%) only required nasal cannula and only 11% were intubated. The case fatality rates were 1.7% for the population, 7.1% among hospitalizations, and 9.3% among hospitalized patients 50 years and older. All rates that are significantly lower than those reported nationally during the same period.ConclusionsWe observed a cohort of American Indian patients hospitalized secondary to COVID-19 with greater number of comorbidities compared to the general population but with lower mortality rates. We posit that the primary driver of mortality reduction for this population and the hospitalized cohort was a community-based referral program that led to disproportionately lower fatality rates among the oldest persons.

Clinical characteristics and prognosis of SARS-CoV-2 infection in children with hematological malignancies: A multicenter, retrospective study in China

BackgroundData on SARSCoV-2 infection in children with hematological malignancies (HM) are limited. Here, we describe the clinical features of children with HM after SARS-CoV-2 infection and investigate the potential risk factors for disease severity. MethodsChildren with HM and SARS-CoV-2 infection from five hospitals in five cities in Henan, China from October 2022 to January 2023 were retrospectively included. Clinical information and Coronavirus disease 2019 (COVID-19) vaccination status were collected for further analyses. ResultsA total of 285 children with HM and SARS-CoV-2 infections were included. COVID-19 was asymptomatic in 3.2% of the patients (n = 9), mild in 89.1% (n = 254), moderate in 5.3% (n = 15), severe in 1.8% (n = 5), and critical in 0.7% (n = 2). Fever (92.4%) and cough (56.9%) were the most common symptoms. Most (249, 88.3%) children were managed at home during their COVID-19 illness. Of the 36 children admitted to the hospital, two required intensive care unit care, 11 required supplementary oxygen, and two non-invasive ventilation. A total of 283 (99.3%) children fully recovered and two (0.7%) died due to COVID-19. Significant risk factors for increased severity of infection in multivariable analyses were the presence of comorbidity (OR, 10.4; 95%CI, 2.8–38.7; p < 0.0001), neutropenia (OR, 10.4; 95%CI, 2.6–41.8; p = 0.001), and lymphopenia (OR, 4.2; 95%CI, 1.2–15.4; p = 0.029). A total of 30.9% (88/285) of the children received at least one dose of the inactivated COVID-19 vaccine at COVID-19 diagnosis. Compared with children who received at least one dose of the COVID-19 vaccine, fever was significantly more common in unvaccinated children (79.3% vs. 93.8%, p < 0.001). ConclusionsChildren with HM are not at an increased risk of severe COVID-19 compared to the general pediatric population. However, comorbidities such as lymphopenia and neutropenia may increase the risk of developing moderate or severe/critical disease. Our data may help in management decisions for this vulnerable population.

Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy

IntroductionVarious risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. MethodsThe study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. ResultsPatients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70–31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. ConclusionsZinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

Respiratory syncytial virus subtypes in children with bronchiolitis: does it correlate with clinical severity?

BackgroundIn this retrospective study, we aimed to evaluate the factors associated with the severity of respiratory syncytial virus (RSV) bronchiolitis in children aged under 2 years who were admitted to the Children’s Hospital of Hebei between June 2018 and January 2019.MethodsSputum samples positive for RSV via multiplex PCR were subtyped using real-time PCR. Data collected included risk factors for disease severity, demographics, microbiology, and outcomes.ResultsOf the 82 children with RSV bronchiolitis, 79 were treated and discharged with improvement, while 3 died. All three patients had underlying medical conditions, including complex congenital heart disease and severe combined immunodeficiency. Further, disease severity was associated with preexisting underlying disease, fever duration, and bacterial co-infection, but not with the RSV subtype.ConclusionsOur findings suggest that an appropriate therapeutic regimen should include the detection of bacterial co-infections and the identification of underlying diseases for the effective management of severe RSV bronchiolitis.

Clinical and immunological outcomes of SARS-CoV-2-infected vaccine responders, vaccine non-responders, and unvaccinated patients evaluated for neutralizing monoclonal antibody treatment at a single German tertiary care center: a retrospective cohort study with prospective follow-up

PurposeThis study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status.MethodsIn this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients’ initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs.ResultsIn total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs.ConclusionVNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.

Age-specific predictors of disease severity in children with respiratory syncytial virus infection beyond infancy and through the first 5 years of age.

Respiratory syncytial virus (RSV) infection is associated with significant morbidity in infants. Risk factors for severe disease beyond the first 2 years of life have not been fully defined. Children <5 years hospitalized with virologically confirmed RSV infection were identified over six respiratory seasons (10/2012-4/2018) and their medical records manually reviewed. Multivariable analyses were performed to define the age-specific (<6, 6-24, and >24-59 months) risk factors associated with oxygen administration, PICU admission, mechanical ventilation, and duration of hospitalization. We identified 5143 children hospitalized with RSV infection: 53.5% (n = 2749) <6 months; 31.7% (n = 1631) 6-24 months; and 14.8% (n = 763) >24-59 months. Rates of ICU admission were high (35%-36%) and comparable across age groups, while children >24-59 and 6-24 versus those <6 months required supplemental oxygen more frequently (73%; 71%; 68%, respectively; p = .003). The presence of comorbidities increased with age (25%, <6 months; 46%, 6-24 months; 70%, >24-59 months; p < .001). Specifically, neuromuscular disorders, chronic lung disease, and reactive airway disease/asthma were predictive of worse clinical outcomes in children aged 6-24 and >24-59 months, while RSV-viral codetections increased the risk of severe outcomes in children aged <6 and 6-24 months of age. Almost half of children hospitalized with RSV infection were >6 months. Underlying comorbidities increased with age and remained associated with severe disease in older children, while RSV-viral codetections were predictive of worse clinical outcomes in the youngest age groups. These data suggest the importance of defining the clinical phenotype associated with severe RSV according to age, and the persistent burden associated with RSV beyond infancy.