Association of COVID-19 with risks of hospitalization and mortality from other disorders post-infection: A study of the UK Biobank (preprint)

ObjectiveTo study whether COVID-19 infection may be associated with increased hospitalization and mortality from other diseases. DesignCohort study. SettingThe UK Biobank. ParticipantsAll subjects in the UK Biobank with available hospitalization records and alive as of 31-Jan-2020 (N= 412,096; age 50-87). Main outcome measuresWe investigated associations of COVID-19 with hospitalization and mortality due to different diseases post-infection. We conducted a comprehensive survey on disorders from all systems (up to 135 disease categories). Multivariable Cox and Poisson regression was conducted controlling for main confounders. For sensitivity analysis, we also conducted separate analysis for new-onset and recurrent cases, and other analysis such as the prior event rate adjustment(PERR) approach to minimize effects of unmeasured confounders. We also performed association analyses stratified by vaccination status. Time-dependent effects on subsequent hospitalization and mortality were also tested. ResultsCompared to individuals with no known history of COVID-19, those with severe COVID-19 (requiring hospitalization) exhibited higher hazards of hospitalization and/or mortality due to multiple disorders (median follow-up=608 days), including disorders of respiratory, cardiovascular, neurological, gastrointestinal, genitourinary and musculoskeletal systems. Increased hazards of hospitalizations and/or mortality were also observed for injuries due to fractures, various infections and other non-specific symptoms. These results remained largely consistent after sensitivity analyses. Severe COVID-19 was also associated with increased all-cause mortality (HR=14.700, 95% CI: 13.835-15.619). Mild (non-hospitalized) COVID-19 was associated with modestly increased risk of all-cause mortality (HR=1.237, 95% CI 1.037-1.476) and mortality from neurocognitive disorders, as well as hospital admission from a few disorders such as aspiration pneumonitis, musculoskeletal pain and other general signs/symptoms. All-cause mortalities and hospitalizations from other disorders post-infection were generally higher in the pre-vaccination era. The deleterious effect of COVID-19 was observed to wane over time, with maximum HR in the initial phase. ConclusionsIn conclusion, this study revealed increased risk of hospitalization and mortality from a wide variety of pulmonary and extra-pulmonary diseases after COVID-19, especially for severe infections. Mild disease was also associated with increased all-cause mortality. Causality however cannot be established due to observational nature of the study. Further studies are required to replicate our findings.

Follicular keratosis of the face in pediatric patients of color.

BACKGROUND/OBJECTIVES: Follicular keratosis (FK) is a poorly understood disorder presenting with multiple, grouped hyperkeratotic follicular papules typically affecting the chin or jawline. This study describes the clinical presentation, histopathology, management, and outcomes of a series of pediatric patients of color with FK of the face, thought to be related to rubbing or friction on the skin. METHODS: Retrospective review of 20 pediatric patients with FK of the face who presented to our pediatric dermatology practice between April 2019 and October 2021. RESULTS: Twenty patients (mean age 12.1 years, 13 females), all self-identified as Black/African American, were included. All presented with an initially asymptomatic, hyperpigmented patch containing multiple hyperkeratotic follicular papules, located on the cheek, chin, upper lip, and/or jawline. Five patients endorsed a history of rubbing the site. Nine patients had onset of the lesions during the COVID-19 pandemic. Treatments included topical vitamin D analogs, corticosteroids, and/or retinoids. Topical vitamin D analogs and retinoids improved the texture and hyperpigmentation of the follicular lesions in only four patients, while topical corticosteroids had no effect. Histopathological examination of two patients revealed multiple dilated follicles containing keratinized material and associated with a sparse dermal inflammatory infiltrate in one patient and granulomatous inflammation within the dermis in the other. CONCLUSIONS: In our cohort of pediatric patients with FK, patients of color were preferentially affected, and all cases were associated with hyperpigmentation. Some patients presented during the COVID-19 pandemic suggesting that friction from facial mask wearing may have induced or exacerbated this uncommon condition.

Oral manifestations of multisystemic inflammatory syndrome in children (MIS-C) and Kawasaki disease associated to COVID-19: A systematic review.

AIMS: Multisystemic inflammatory syndrome in children (MIS-C) is a condition noted in some children asymptomatic but positive to Sars-cov-2 antibody and it presents clinical and laboratory changes similar to Kawasaki disease (KD). Oral changes have also been observed. This systematic review evaluated oral manifestations detected in children with MIS-C and KD associated to COVID-19. METHODS AND RESULTS: This work was registered at PROSPERO (#CRD42020225909), following PRISMA guidelines. A comprehensive research was conducted in MEDLINE, Web of Science, EMBASE, LILACS, Scopus, and Grey Literature through August 2021, based on original research evaluating children diagnosed with MIS-C or KD related to COVID-19. Two authors independently screened all retrieved references. Twenty five selected studies evaluated 624 children, mean age 8.78 years. The assessment of the risk of bias (ROB) showed that most of them presented low ROB. Oral manifestations were erythematous mucous membrane, oral ulcers lesions, dry, swollen and cracked lips, and strawberry tongue. CONCLUSION: MIS-C and KD share the same oral manifestations and their identification may lead to an early diagnosis.

Is it all MIS-C? Unusual findings in a series of nine German patients with multi-system inflammatory syndrome in children after SARS-CoV-2 infection.

OBJECTIVES: Multi-system inflammatory syndrome in children (MIS-C) is a post-viral inflammatory vasculopathy of children and adolescents following Covid-19 infection. Since the incidence of SARS-CoV-infections has been increasing in Germany since October 2020, we observe an increasing number of children presenting with MIS-C. DESIGN: We present detailed clinical characteristics of a cohort of nine children with MIS-C admitted to a tertiary PICU at the University Hospital of Cologne between March 2020 and February 2021. RESULTS: The clinical sings and symptoms are largely in line with recent reports. All but one patient had positive SARS-CoV-2 antibodies. Latency form infection to MIS-C was 4-6 weeks. Two children presented with unusual findings: A girl had encephalomyelitis and a boy developed MIS-C side to side with acute leukemia. CONCLUSION: MIS-C has been increasing in Germany paralell to SARS-CoV-2 infections. Rarely, unuasual findings may be associated with MIS-C.

Toddler With New Onset Diabetes and Atypical Hemolytic-Uremic Syndrome in the Setting of COVID-19.

This is a novel case of a 16-month-old boy with a history of prematurity with intrauterine growth restriction, severe failure to thrive, microcephaly, pachygyria, agenesis of the corpus callosum, and postnatal embolic stroke, who presented with new-onset diabetes mellitus with diabetic ketoacidosis in the setting of severe acute respiratory syndrome coronavirus 2 infection, with a course complicated by atypical hemolytic syndrome (aHUS). This patient demonstrated remarkable insulin resistance in the period before aHUS diagnosis, which resolved with the first dose of eculizumab therapy. There is increasing evidence that COVID-19 is associated with thrombotic disorders and that microangiopathic processes and complement-mediated inflammation may be implicated. In this case report, we describe a pediatric patient with COVID-19 and a new complement-mediated microangiopathic thrombotic disease. Because whole-exome sequencing and extensive workup returned without a clear etiology for aHUS, this is likely a COVID-19 triggered case of aHUS versus an idiopathic case that was unmasked by the infection.

Bell's palsy in a pediatric patient with hyper IgM syndrome and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Bell's palsy is an acute facial paralysis with known association to viral infections. We describe a medically complex 6-year-old male with hyper IgM syndrome who presented with unilateral facial droop and positive SARS-CoV-2 RT-PCR. This is the first reported pediatric case of Bell's palsy in the setting of SARS-CoV-2 infection.

Pediatric Crohn Disease and Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 Treated With Infliximab.

Coronavirus disease 2019 (COVID-19) may lead to a severe inflammatory response referred to as a cytokine storm. We describe a case of severe COVID-19 infection in a recently diagnosed pediatric Crohn disease patient successfully treated with tumor necrosis factor-alpha (TNF-α) blockade. The patient presented with 5 days of fever, an erythematous maculopapular facial rash, and abdominal pain without respiratory symptoms. SARS-CoV-2 polymerase chain reaction was positive. Despite inpatient treatment for COVID-19 and a perianal abscess, the patient acutely decompensated, with worsening fever, tachycardia, fluid-refractory hypotension, elevation of liver enzymes, and transformation of the rash into purpura extending from the face to the trunk, upper and lower extremities, including the palmar and plantar surfaces of the hands and feet. Cytokine profile revealed rising levels of interleukin (IL)-6, IL-8, and TNF-α, higher than those described in either inflammatory bowel disease or severe COVID-19 alone. The patient was treated with infliximab for TNF-α blockade to address both moderately to severely active Crohn disease and multisystem inflammatory syndrome in children temporally related to COVID-19. Within hours of infliximab treatment, fever, tachycardia, and hypotension resolved. Cytokine profile improved with normalization of TNF-α, a decrease in IL-6, and IL-8 concentrations. This case supports a role for blockade of TNF-α in the treatment of COVID-19 inflammatory cascade. The role of anti-TNF agents in patients with multisystem inflammatory syndrome in children temporally related to COVID-19 requires further investigation.

An Analysis on the Clinical Features of MHD Patients with Coronavirus Disease 2019: A Single Center Study (preprint)

Background: In this study, we aimed to find out the features of the maintenance hemodialysis (MHD) patients infected with Coronavirus Disease 2019 (COVID-19) in the Blood Purification Center of Wuhan No.1 Hospital, Hubei Province, China, and provide evidences for clinical treatment.Methods: We collected the data of all the MHD patients in this hemodialysis center by February 20, 2020, including those infected with COVID-19. These patients were divided into three groups: the control group (537 cases), confirmed group (66 cases) and suspected group (24 cases). We compared the relevant data of the three groups and analyzed the factors that may affect the possibility of catching COVID-19.Results: 1. By February 20, 2020, there were 627 MHD patients in the Hemodialysis Center of Wuhan No.1 Hospital. The prevalence rate of the COVID-19 was 14.35% (90/627, including 66 confirmed cases and 24 suspected cases); the fatality rate 13.33% (12/90, including 12 death cases); the mortality rate 1.91% (12/627).2. The comparison between the three groups revealed the following results: weekly hemodialysis duration (WHD), ultrafiltration volume (UFV) and ultrafiltration rate (UFR) of the confirmed group were obviously lower than those of the control and suspected groups (P＜0.05); the neutrophil ratio (N%), neutrophil (N#), monocyte (M#) and total carbon dioxide (TCO2) were significantly higher than those of the control group while the lymphocyte ratio (L%) was much lower (P＜0.05).3. The lung CT scans found three common features: bilateral abnormalities (81.54%), multiple abnormalities (84.62%) and patchy opacity (61.54%).4. The binary logstic regression analysis showed that diabetes (OR=5.404,95% CI 1.950～14.976, P=0.001) and hypertension (OR=3.099,95% CI 1.380～6.963, P=0.006) are independent risk factors for MHD patients to be infected with COVID-19; WHD (OR=0.846,95% CI 0.737～0.970, P=0.017), UFR (OR=0.012,95% CI 0.002～0.058, P＜0.001) and serum ferritin (SF, OR=0.823,95% CI 0.748～0.906, P＜0.001) are independent protective factors.Conclusion: MHD patients with diabetes or hypertension are more likely to be infected with COVID-19. In clinical treatment, hemodialysis duration, UFR and SF levels should be controlled appropriately to reduce the risk of infection.