Liver abnormalities following SARS-CoV-2 infection in children under 10 years of age (preprint)

ObjectiveBeginning in October 2021 in the US and elsewhere, cases of severe pediatric hepatitis of unknown etiology were identified in young children. While the adenovirus and adenovirus-associated virus have emerged as leading etiologic suspects, we attempted to investigate a potential role for SARS-CoV-2 in the development of subsequent liver abnormalities. DesignWe conducted a study utilizing retrospective cohorts of de-identified, aggregated data from the electronic health records of over 100 million patients contributed by US health care organizations. ResultsCompared to propensity-score-matched children with other respiratory infections, children aged 1-10 years with COVID-19 had a higher risk of elevated transaminases (Hazard ratio (HR) (95% Confidence interval (CI)) 2.16 (1.74-2.69)) or total bilirubin (HR (CI) 3.02 (1.91-4.78)), or new diagnoses of liver diseases (HR (CI) 1.67 (1.21-2.30)) from one to six months after infection. Patients with pre-existing liver abnormalities, liver abnormalities surrounding acute infection, younger age (1-4 years), or illness requiring hospitalization all had similarly elevated risk. Children who developed liver abnormalities following COVID-19 had more pre-existing conditions than those who developed abnormalities following other infections. ConclusionThese results indicate that SARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. While rare ([~]1 in 1,000), SARS-CoV-2 is a risk for subsequent abnormalities in liver function or the diagnosis of diseases of the liver. What is already known on this topicClusters of severe hepatitis in children in 2022 coincident with the increase in COVID-19 infections in children raised the question of the contribution of SARS-CoV-2 to the hepatitis outbreak, though it was soon determined that SARS-CoV-2 was not the primary etiologic agent. What this study addsSARS-CoV-2 may prime the patient for subsequent development of liver infections or non-infectious liver diseases. How this study might affect research, practice or policyDespite the mild initial disease in children, there may be longer term consequences of COVID-19, such as liver abnormalities, that warrants further investigation.

Post-COVID-19 long term impact on lung function and quality of life: who should be concerned? (preprint)

Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 to 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

Pathological Effects of SARS-CoV-19 Associated With Hematological Abnormalities (preprint)

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has executed 6.9 million people and infected over 765 million. It’s become a major worldwide health alarm and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower res-piratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse out-comes. Prophylactic anticoagulation is essential to prevent complication and death rate associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation exhibits some similarities to DIC induced by sepsis. LDH, D-dimer, ferritin, and CRP biomarker are often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

Abnormal echocardiographic findings after COVID-19 infection: a multicenter registry.

The Coronavirus Disease 2019 (COVID-19) pandemic has transformed health systems worldwide. There is conflicting data regarding the degree of cardiovascular involvement following infection. A registry was designed to evaluate the prevalence of echocardiographic abnormalities in adults recovered from COVID-19. We prospectively evaluated 595 participants (mean age 45.5 ± 14.9 years; 50.8% female) from 10 institutions in Argentina and Brazil. Median time between infection and evaluation was two months, and 82.5% of participants were not hospitalized for their infection. Echocardiographic studies were conducted with General Electric equipment; 2DE imaging and global longitudinal strain (GLS) of both ventricles were performed. A total of 61.7% of the participants denied relevant cardiovascular history and 41.8% had prolonged symptoms after resolution of COVID-19 infection. Mean left ventricular ejection fraction (LVEF) was 61.0 ± 5.5% overall. In patients without prior comorbidities, 8.2% had some echocardiographic abnormality: 5.7% had reduced GLS, 3.0% had a LVEF below normal range, and 1.1% had wall motion abnormalities. The right ventricle (RV) was dilated in 1.6% of participants, 3.1% had a reduced GLS, and 0.27% had reduced RV function. Mild pericardial effusion was observed in 0.82% of participants. Male patients were more likely to have new echocardiographic abnormalities (OR 2.82, p = 0.002). Time elapsed since infection resolution (p = 0.245), presence of symptoms (p = 0.927), or history of hospitalization during infection (p = 0.671) did not have any correlation with echocardiographic abnormalities. Cardiovascular abnormalities after COVID-19 infection are rare and usually mild, especially following mild infection, being a low GLS of left and right ventricle, the most common ones in our registry. Post COVID cardiac abnormalities may be more frequent among males.

COVID-19 or seasonal influenza? How to distinguish in people younger than 65 years old: A retrospective observational cohort study comparing the 2009 pandemic influenza A H1N1 with 2022 SARS-CoV-2 Omicron BA.2 outbreaks in China. (preprint)

Objective: This study attempted to explore the difference of clinical characteristics in H1N1 influenza infection and SARS-CoV-2 Omicron infection in people younger than 65 years old, in order to better identify the two diseases. Methods: A total of 127 H1N1 influenza patients diagnosed from May 2009 to July 2009 and 3265 patients diagnosed and identified as SARS-CoV-2 Omicron BA.2 variant from March 2022 to May 2022 were admitted in this study. Through the 1 : 2 match based on age (The difference is less than 2 years), gender and underlying diseases115 patients with H1N1 infection and 230 patients with SARS-CoV-2 Omicron BA.2 infection (referred to as H1N1 group and Omicron group) were included in the statistics. The clinical manifestations of H1N1 group were compared with those of Omicron group. Logistic regression was performed to analyze the possible independent risk factors of H1N1 group and Omicron group. And multiple linear regression was used to analyze the factors for time for nucleic acid negativization (NAN) . Results: The median age of the two groups was 21 [11,26] years. Compared with the H1N1 group, the Omicron group had lower white blood cell count and CRP levels, less fever, nasal congestion, sore throat, cough, sputum and headache, while more olfactory loss, muscle soreness and LDH abnormalities. The Omicron group used less antibiotics and antiviral drugs, and the NAN time was longer (17 [ 14,20] VS 4 [ 3,5], P < 0.001). After logistic regression, it was found that fever, cough, headache, and increased white blood cell count were more correlated with the H1N1 group, while muscle soreness and LDH abnormalities were more correlated with the Omicron group. After analyzing the factors of NAN time, it was found that fever (B 1.529, 95 % CI [0.149,2.909], P = 0.030) significantly predicted longer NAN time in Omicron patients. Conclusion: This study comprehensively evaluated the similarities and differences in clinical characteristics between SARS-CoV-2 Omicron infection and 2009 H1N1 influenza infection, which is of great significance for a better understanding for these diseases.

Glycemia and New-onset Diabetes among COVID-19 Patients with Prediabetes: A Follow-up Study in India (preprint)

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China:a retrospective analysis (preprint)

Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

Renal Biopsy Diagnosis of Acute Tubular Injury After Pfizer-BioNTech COVID-19 Vaccination: A Case Report (preprint)

Recently, there have been reports of new cases of acute kidney injury (AKI) after coronavirus disease 2019 (COVID-19) vaccination. Podocytic damage, IgA nephropathy, vasculitis, tubulointerstitial damage, and thrombotic microangiopathy have been reported as the causes. However, there are no reports of acute tubular injury (ATI) as the sole cause of AKI. In this case, a 54-year-old man with type 2 diabetes visited a local physician. He was highly obese with a body mass index of 36 kg/m2. He was treated with metformin and insulin. Diabetic retinopathy, urinary protein, and occult blood were absent. He had received four COVID-19 vaccines; three were from Pfizer and one from Moderna. He was referred to our hospital 5 days after receiving the fourth dose of the Pfizer-BioNTech COVID-19 vaccine. He had stage 3 AKI. Urinary findings revealed the presence of new proteinuria and glomerular occult blood. Steroids were introduced on the day of admission for rapidly progressive glomerulonephritis. A renal biopsy was performed on the second day, with results obtained on the fifth day revealing no findings other than ATI. The patient was therefore deemed unamenable to steroids. After steroid discontinuation, renal function recovered spontaneously, and urinalysis abnormalities disappeared. In this case, ATI was the sole pathogenesis of COVID-19 vaccine-induced AKI, and treatment with immunosuppressive drugs was not necessary.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron Variant in Shanghai, China (preprint)

Abstract Objectives: This study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during Omicron variant outbreak. Methods: This retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, household vaccination rates were collected through electronic health records and telephone interviews. Results: The total of 603 pediatric cases confirmed with COVID-19 was included in this study. Both Univariate and multivariate analysis were performed to filter independent factors for the duration to viral RNA negative conversion. Data on cases re-detected SARS-CoV-2 after showing negative results on RT-PCR test (intermittent negative status) were also analyzed. The median duration of virus shedding was 12(Interquartile Qange,IQR: 10-14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patient who had abnormal defecation or with more severe condition would delay virological clearance, while patient accepted 2 doses vaccination or with higher household vaccination rates would accelerate virological clearance. Loss of appetite (Odds Ratio (OR) :5.343; 95%CI: 3.307-8.632) and abnormal defecation (OR:2.840; 95%CI: 1.736-4.645) were significantly associated with intermittent negative status. Conclusion: These findings could provide clues for early identification of pediatric patients with prolonged viral shedding, enriching the evidence for development of prevention and control strategies especially the vaccination policies for children and adolescents.

The prognostic value of transthoracic echocardiography findings in hospitalized adult patients with COVID-19: A single-center retrospective analysis (preprint)

Background: Cardiac involvement in coronavirus disease 2019 (COVID-19) is associated with poor outcomes. Transthoracic echocardiography (TTE) can be used to assess cardiac structure and function non-invasively, and has been shown to influence management in COVID-19. Objectives: We aim to investigate the prognostic value of TTE findings in hospitalized adults with confirmed COVID-19. Methods: All consecutive hospitalized adult patients with confirmed COVID-19 who underwent TTE assessment between 3rd April 2020-6th April 2021 were included. Comprehensive clinical data including TTE findings were collected from electronic medical records. Patients with mild-moderate and severe-critical COVID-19 were compared. Within the severe-critical group, patients who survived hospitalization and died were compared. Further analyses were conducted after matching for age >60 years, obesity, and diabetes. Results: A total of 488 COVID-19 patients were included in this study; 202 with mild-moderate and 286 severe-critical disease. All mild-moderate patients and 152 severe-critical patients survived hospitalization. In the matched cohorts, TTE findings associated with severe-critical COVID-19 included left ventricular (LV) hypertrophy (OR: 1.91; CI: 1.21-3.02), LV diastolic dysfunction (OR: 1.55; CI: 1.00-2.38), right ventricular (RV) dysfunction (OR: 3.86; CI: 1.06-14.08), wall motion abnormalities (WMAs) (OR: 2.76; CI: 1.28-5.96), and any TTE abnormalities (OR: 2.99; CI: 1.73-5.17). TTE findings associated with mortality included RV dysfunction (OR: 3.53; CI: 1.12-11.19) and WMAs (OR: 2.63; CI: 1.26-5.49). Conclusion: TTE is a non-invasive modality that can potentially be used for risk-stratification of hospitalized COVID-19 patients. These findings must be confirmed in larger prospective studies.

COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging (preprint)

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of coronavirus disease 2019 (COVID-19), binds via ACE2 receptors, highly expressed in ciliated cells of the nasal epithelium. Micro-optical coherence tomography (OCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-m resolution, enabling real time visualization and quantification of epithelial anatomy, ciliary motion, and mucus transport. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as reduced ciliated cell function and mucociliary abnormalities, features readily visualized by OCT. Symptomatic outpatients with SARS-CoV-2 aged [≥] 18 years were recruited within 14 days of symptom onset. Data was interpreted for subjects with COVID-19 (n=13) in comparison to healthy controls (n=8). Significant reduction in functional cilia, diminished ciliary beat frequency, and abnormal ciliary activity were evident. Other abnormalities included denuded epithelium, presence of mucus rafts, and increased inflammatory cells. Our results indicate that subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa underscoring the importance of mucociliary health in viral illness and disease transmission. Ciliary imaging enables investigation of early pathogenic mechanisms of COVID-19 and may be useful for evaluating disease progression and therapeutic response.

Higher Limbic and Basal Ganglia volumes in surviving COVID-negative patients and the relations to fatigue. (preprint)

BackgroundAmong systemic abnormalities caused by the novel coronavirus, little is known about the critical attack on the central nervous system (CNS). Few studies have shown cerebrovascular pathologies that indicate CNS involvement in acute patients. However, replication studies are necessary to verify if these effects persist in COVID-19 survivors more conclusively. Furthermore, recent studies indicate fatigue is highly prevalent among long-COVID patients. How morphometry in each group relate to work-related fatigue need to be investigated. MethodCOVID survivors were MRI scanned two weeks after hospital discharge. We hypothesized, these survivors will demonstrate altered gray matter volume (GMV) and experience higher fatigue levels when compared to healthy controls, leading to stronger correlation of GMV with fatigue. Voxel-based morphometry was performed on T1-weighted MRI images between 46 survivors and 30 controls. Unpaired two-sample t-test and multiple linear regression were performed to observe group differences and correlation of fatigue with GMV. ResultsThe COVID group experienced significantly higher fatigue levels and GMV of this group was significantly higher within the Limbic System and Basal Ganglia when compared to healthy controls. Moreover, while a significant positive correlation was observed across the whole group between GMV and self-reported fatigue, COVID subjects showed stronger effects within the Posterior Cingulate, Precuneus and Superior Parietal Lobule. ConclusionBrain regions with GMV alterations in our analysis align with both single case acute patient reports and current group level neuroimaging findings. We also newly report a stronger positive correlation of GMV with fatigue among COVID survivors within brain regions associated with fatigue, indicating a link between structural abnormality and brain function in this cohort.

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children.

BACKGROUND: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. OBJECTIVES: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. METHODS: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. RESULTS: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). CONCLUSION: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

Evaluating the Efficacy and Side Effects of Corticosteroid Therapy in Severely ill COVID-19 Patients (preprint)

Background: Cytokine storms are a common complication in severely ill patients with COVID-19, for which corticosteroid therapy (CsT) is used as adjuvant treatment. Therefore, we evaluated the efficacy and safety of CsT in patients with COVID-19. Methods: : A single-center, retrospective cohort study was conducted in 1,392 severely ill patients with COVID-19 from Wuhan Huoshenshan Hospital. Patients received at least one dose (1–2 mg·kg -1 ·day -1 for 3–5 days) of methylprednisolone were divided into CsT group, whereas the rest were assigned into the non-CsT group. Results: : Of 1,392 patients, 116 were assigned to the CsT group and 1,226 to the non-CsT group. Patients in the CsT group showed comparable mortality rate (1.8% vs. 1.2%, P > 0.99) and viral clearance time (44.5 days vs. 46.0 days, P = 0.48), but longer hospitalization time (21 days vs. 12 days, P < 0.001) than those in non-CsT group. During CsT, the proportion of lymphocytes was lower (14.7 % vs. 18.5 %, P = 0.01), while neutrophils was higher (77.1 % vs. 69.8 %, P < 0.001), than before treatment. The C-reactive protein (CRP) level was significantly lower after CsT (3.1 mg/L vs. 9.5 mg/L, P < 0.001). Furthermore, indicators of liver function (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST]) and cardiac function (brain natriuretic peptide [BNP], α-hydroxybutyrate dehydrogenase [α-HBDH], and lactate dehydrogenase [LDH]) increased significantly during CsT but returned to normal after CsT. Patients who developed liver damage showed higher GGT, ALT, AST, LDH, Cre, and CRP; patients who developed heart injury had higher AST, LPH, CRP, lymphocyte (LYM), glucose, BNP, and α-HBDH; and patients who developed kidney failure had higher α-HBDH, LDH, CRP, and LYM values than before CsT. Additionally, patients who received CsT with cardiovascular disease showed a continuous elevation in D-dimer levels. Conclusions: : CsT effectively attenuates the inflammatory response in severely ill patients with COVID-19 at a relatively low dose in a short duration; however, CsT increases the risk of hepatic and cardiac abnormalities.

Comparing Apples to Apples in Post-COVID-Associated Multisystem Inflammatory Syndrome in Children (MIS-C) (preprint)

Background: The full clinical continuum of post-COVID-associated multisystem inflammatory syndrome of childhood (MIS-C)/Paediatric Inflammatory Multi-system Syndrome (PIMS) is still being defined, with different names and case definitions continuing to be used across jurisdictions. Refinement of criteria and better stratification of affected children will facilitate international collaborations towards improving health outcomes. Our objective is to describe the clinical characteristics and outcomes of children with MIS-C/PIMS stratified by case definition and clinical phenotype.Methods: Prospective study of 137 multi-ethnic hospitalized patients with presumed MIS-C, at a tertiary care pediatric centre in Toronto, Canada from March 2020 to February 2021. Clinical and laboratory features at presentation, organ system complications, therapeutic management, and outcomes were captured. Descriptive statistics were performed to assess differences between case definitions and clinical phenotype.Findings: The most striking differences between the case definitions were reflected in measures of disease severity and outcomes, with the MIS-C classifications capturing the more severe end of the hyperinflammatory spectrum compared to PIMS. Children in the MIS-C group were older and had more cardiac abnormalities and macrophage activation syndrome, which were reflected in more intensive care admission and corticosteroid therapy. Comparisons of clinical phenotypes (shock, Kawasaki Disease, and fever with hyperinflammation) and COVID exposure demonstrate similar clinical features, disease severity and outcomes.Interpretation: Case definition had the greatest impact on measures of disease severity, course, and outcome. Stratification by known disease phenotype led to homogeneous groupings of patients regardless of SARS-CoV-2 exposure status, confirming that recognition of known clinical entities can guide case recognition, classification and management, with our data supporting the notion that KD and MIS-C both fit on the same disease spectrum. The use of a common case definition is needed to ensure comparability in studies among international networks, reliability of public health surveillance data, and proper case ascertainment.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: These studies were approved by the institutional Research Ethics Board, and the requirement for individual consent was waived.

Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children.

Importance: Information on underlying conditions and severe COVID-19 illness among children is limited. Objective: To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity. Design, Setting, and Participants: This cross-sectional study included patients aged 18 years and younger with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 (COVID-19) or B97.29 (other coronavirus) during an emergency department or inpatient encounter from March 2020 through January 2021. Data were collected from the Premier Healthcare Database Special COVID-19 Release, which included data from more than 800 US hospitals. Multivariable generalized linear models, controlling for patient and hospital characteristics, were used to estimate adjusted risk of severe COVID-19 illness associated with underlying medical conditions and medical complexity. Exposures: Underlying medical conditions and medical complexity (ie, presence of complex or noncomplex chronic disease). Main Outcomes and Measures: Hospitalization and severe illness when hospitalized (ie, combined outcome of intensive care unit admission, invasive mechanical ventilation, or death). Results: Among 43 465 patients with COVID-19 aged 18 years or younger, the median (interquartile range) age was 12 (4-16) years, 22 943 (52.8%) were female patients, and 12 491 (28.7%) had underlying medical conditions. The most common diagnosed conditions were asthma (4416 [10.2%]), neurodevelopmental disorders (1690 [3.9%]), anxiety and fear-related disorders (1374 [3.2%]), depressive disorders (1209 [2.8%]), and obesity (1071 [2.5%]). The strongest risk factors for hospitalization were type 1 diabetes (adjusted risk ratio [aRR], 4.60; 95% CI, 3.91-5.42) and obesity (aRR, 3.07; 95% CI, 2.66-3.54), and the strongest risk factors for severe COVID-19 illness were type 1 diabetes (aRR, 2.38; 95% CI, 2.06-2.76) and cardiac and circulatory congenital anomalies (aRR, 1.72; 95% CI, 1.48-1.99). Prematurity was a risk factor for severe COVID-19 illness among children younger than 2 years (aRR, 1.83; 95% CI, 1.47-2.29). Chronic and complex chronic disease were risk factors for hospitalization, with aRRs of 2.91 (95% CI, 2.63-3.23) and 7.86 (95% CI, 6.91-8.95), respectively, as well as for severe COVID-19 illness, with aRRs of 1.95 (95% CI, 1.69-2.26) and 2.86 (95% CI, 2.47-3.32), respectively. Conclusions and Relevance: This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19.

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers.

OBJECTIVES: The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection. BACKGROUND: Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease. METHODS: Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available. RESULTS: A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals. CONCLUSIONS: Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.