Characteristics and outcomes of multisystem inflammatory syndrome in children: A multicenter, retrospective, observational cohort study in Mexico.

Introduction: Multisystem inflammatory syndrome in children associated with coronavirus disease 2019 (MIS-C), a novel hyperinflammatory condition secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is associated with severe outcomes such as coronary artery aneurysm and death. Methods: This multicenter, retrospective, observational cohort study including eight centers in Mexico, aimed to describe the clinical characteristics and outcomes of patients with MIS-C. Patient data were evaluated using latent class analysis (LCA) to categorize patients into three phenotypes: toxic shock syndrome-like (TSSL)-MIS-C, Kawasaki disease-like (KDL)-MIS-C, and nonspecific MIS-C (NS-MIS-C). Risk factors for adverse outcomes were estimated using multilevel mixed-effects logistic regression. Results: The study included 239 patients with MIS-C, including 61 (26%), 70 (29%), and 108 (45%) patients in the TSSL-MIS-C, KDL-MIS-C, and NS-MIS-C groups, respectively. Fifty-four percent of the patients were admitted to the intensive care unit, and 42%, 78%, and 41% received intravenous immunoglobulin, systemic glucocorticoids, and anticoagulants, respectively. Coronary artery dilatation and aneurysms were found in 5.7% and 13.2% of the patients in whom coronary artery diameter was measured, respectively. Any cause in-hospital mortality was 5.4%. Hospitalization after ten days of symptoms was associated with coronary artery abnormalities (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.2-2.0). Age ≥10 years (OR: 5.6, 95% CI: 1.4-2.04), severe underlying condition (OR: 9.3, 95% CI: 2.8-31.0), platelet count <150,000 /mm3 (OR: 4.2, 95% CI: 1.2-14.7), international normalized ratio >1.2 (OR: 3.8, 95% CI: 1.05-13.9), and serum ferritin concentration >1,500 mg/dl at admission (OR: 52, 95% CI: 5.9-463) were risk factors for death. Discussion: Mortality in patients with MIS-C was higher than reported in other series, probably because of a high rate of cases with serious underlying diseases.

Leukocyte surface expression of the endoplasmic reticulum chaperone GRP78 is increased in severe COVID-19.

Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum-resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.

Long COVID in children and adolescents: COVID-19 follow-up results in third-level pediatric hospital.

Introduction: In children, the manifestations of coronavirus disease 2019 (COVID-19) in the acute phase are considered mild compared with those in adults; however, some children experience a severe disease that requires hospitalization. This study was designed to present the operation and follow-up results of the Post-COVID-19 Detection and Monitoring Sequels Clinic of Hospital Infantil de Mexico Federico Gómez in managing children with a history of SARS-CoV-2 infection. Methods: This was a prospective study conducted from July 2020 to December 2021, which included 215 children aged 0-18 years who tested positive for SARS-CoV-2 on polymerase chain reaction and/or immunoglobulin G test. The follow-up was conducted in the pulmonology medical consultation; ambulatory and hospitalized patients were assessed at 2, 4, 6, and 12 months. Results: The median age of the patients was 9.02 years, and neurological, endocrinological, pulmonary, oncological, and cardiological comorbidities were the most commonly observed among the patients. Moreover, 32.6% of the children had persistent symptoms at 2 months, 9.3% at 4 months, and 2.3% at 6 months, including dyspnea, dry cough, fatigue, and runny nose; the main acute complications were severe pneumonia, coagulopathy, nosocomial infections, acute renal injury, cardiac dysfunction, and pulmonary fibrosis. The more representative sequelae were alopecia, radiculopathy, perniosis, psoriasis, anxiety, and depression. Conclusions: This study showed that children experience persistent symptoms, such as dyspnea, dry cough, fatigue, and runny nose, although to a lesser extent than adults, with significant clinical improvement 6 months after the acute infection. These results indicate the importance of monitoring children with COVID-19 through face-to-face consultations or telemedicine, with the objective of offering multidisciplinary and individualized care to preserve the health and quality of life of these children.

Long COVID in children and adolescents: COVID-19 follow-up results in third-level pediatric hospital

Introduction In children, the manifestations of coronavirus disease 2019 (COVID-19) in the acute phase are considered mild compared with those in adults;however, some children experience a severe disease that requires hospitalization. This study was designed to present the operation and follow-up results of the Post-COVID-19 Detection and Monitoring Sequels Clinic of Hospital Infantil de Mexico Federico Gómez in managing children with a history of SARS-CoV-2 infection. Methods This was a prospective study conducted from July 2020 to December 2021, which included 215 children aged 0–18 years who tested positive for SARS-CoV-2 on polymerase chain reaction and/or immunoglobulin G test. The follow-up was conducted in the pulmonology medical consultation;ambulatory and hospitalized patients were assessed at 2, 4, 6, and 12 months. Results The median age of the patients was 9.02 years, and neurological, endocrinological, pulmonary, oncological, and cardiological comorbidities were the most commonly observed among the patients. Moreover, 32.6% of the children had persistent symptoms at 2 months, 9.3% at 4 months, and 2.3% at 6 months, including dyspnea, dry cough, fatigue, and runny nose;the main acute complications were severe pneumonia, coagulopathy, nosocomial infections, acute renal injury, cardiac dysfunction, and pulmonary fibrosis. The more representative sequelae were alopecia, radiculopathy, perniosis, psoriasis, anxiety, and depression. Conclusions This study showed that children experience persistent symptoms, such as dyspnea, dry cough, fatigue, and runny nose, although to a lesser extent than adults, with significant clinical improvement 6 months after the acute infection. These results indicate the importance of monitoring children with COVID-19 through face-to-face consultations or telemedicine, with the objective of offering multidisciplinary and individualized care to preserve the health and quality of life of these children.

Characteristics and Outcomes of Cases of Children and Adolescents With Pediatric Inflammatory Multisystem Syndrome in a Tertiary Care Center in Mexico City.

Background: Pediatric inflammatory multisystem syndrome (PIMS) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children that resembles Kawasaki syndrome and places them at high risk of cardiorespiratory instability and/or cardiac damage. This study aims to describe the clinical presentation and outcomes of patients with PIMS in Mexico City. Methods: This was an observational study of children hospitalized for PIMS based on the Centers for Disease Control and Prevention case definition criteria, in a single tertiary care pediatric center in Mexico City between May 1, 2020, and September 30, 2021. Demographic characteristics, epidemiological data, medical history, laboratory tests, cardiologic evaluations, treatment, and clinical outcomes were analyzed. Results: Seventy-five cases fulfilled the case definition criteria for PIMS [median age: 10.9 years, Interquartile range (IQR): 5.6-15.6]. Fifteen (20%) patients had a severe underlying disease, 48 (64%) were admitted to the intensive care unit, 33 (44%) required invasive mechanical ventilation and 39 (52%) received vasopressor support. The patients were clustered through latent class analysis based on identified symptoms: Cluster 1 had rash or gastrointestinal symptoms (n = 60) and cluster 2 were those with predominantly respiratory manifestations (n = 15). Two patients (2.7%) died, and both had severe underlying conditions. Five patients (6.7%), all from cluster 1, developed coronary aneurysms. Conclusion: There were a high proportion of patients with severe respiratory involvement and positive RT-PCR SARS-CoV-2 and very few cases of coronary aneurysms in our study which suggests that a high proportion of the children had severe acute COVID-19. The clinical manifestations and outcomes are comparable to previously reported international studies.

Analysis of the Behaviour of Immunoglobulin G Antibodies in Children and Adults Convalescing From Severe Acute Respiratory Syndrome-Coronavirus-2 Infection.

The pandemic caused by SARS CoV-2 (COVID-19) has affected millions of people since 2020. There are clinical differences and in mortality between the adult and paediatric population. Recently, the immune response through the development of antibodies has gained relevance due to the risk of reinfection and vaccines' development. Objective: Was to compare the association of clinical history and the clinical presentation of the disease with the development of IgG antibodies against SARS-CoV-2 in paediatric and adult patients with a history of positive reverse transcriptase-polymerase chain reaction (RT-PCR) results. Methods: Cross-sectional observational study carried out in a Paediatric Hospital in Mexico City included patients under 18 years of age and health personnel with positive RT-PCR for COVID-19 comparing antibody expression. The development of specific IgG antibodies was measured, the presence of comorbidities, duration, and severity of symptoms was determined. Results: Sixty-one subjects (20 < 18 years and 41 > 18 years) were analysed. The median sample collection was 3 weeks. There were no differences in the expression of specific antibodies; no differences were shown according to the symptoms' severity. A positive correlation (r = 0.77) was demonstrated between the duration of symptoms and antibody levels. Conclusions: In conclusion, there is a clear association between the duration of the symptoms associated with SARS-CoV-2 infection and the IgG units generated in paediatric and adult patients convalescing from COVID-19.

Influenza vs. COVID-19: Comparison of Clinical Characteristics and Outcomes in Pediatric Patients in Mexico City.

Introduction: Respiratory viruses are among the leading causes of disease and death among children. Co-circulation of influenza and SARS-CoV2 can lead to diagnostic and management difficulties given the similarities in the clinical picture. Methods: This is a cohort of all children hospitalized with SARS-CoV2 infection from March to September 3rd 2020, and all children admitted with influenza throughout five flu-seasons (2013-2018) at a pediatric referral hospital. Patients with influenza were identified from the clinical laboratory database. All hospitalized patients with confirmed SARS-CoV2 infection were followed-up prospectively. Results: A total of 295 patients with influenza and 133 with SARS-CoV2 infection were included. The median age was 3.7 years for influenza and 5.3 years for SARS-CoV2. Comorbidities were frequent in both groups, but they were more common in patients with influenza (96.6 vs. 82.7%, p < 0.001). Fever and cough were the most common clinical manifestations in both groups. Rhinorrhea was present in more than half of children with influenza but was infrequent in those with COVID-19 (53.6 vs. 5.8%, p < 0.001). Overall, 6.4% percent of patients with influenza and 7.5% percent of patients with SARS-CoV2 infection died. In-hospital mortality and the need for mechanical ventilation among symptomatic patients were similar between groups in the multivariate analysis. Conclusions: Influenza and COVID-19 have a similar picture in pediatric patients, which makes diagnostic testing necessary for adequate diagnosis and management. Even though most cases of COVID-19 in children are asymptomatic or mild, the risk of death among hospitalized patients with comorbidities may be substantial, especially among infants.

Restructuring of a pediatric hospital in the face of the COVID-19 pandemic.

Overview of the pandemic In December 2019, a new virus named SARS-CoV-2 was reported in Wuhan province, China. The first case of COVID-19 in Mexico was confirmed on February 28, 2020, and the World Health Organization declared the pandemic on March 11.

Saliva as a promising biofluid for SARS-CoV-2 detection during the early stages of infection.

Background: Diagnostic testing for coronavirus disease (COVID)-19 is performed using nasopharyngeal swabs. This type of sampling is uncomfortable for the patient, dangerous for health workers, and its high demand has led to a global shortage of swabs. One of the alternative specimens is saliva. However, the optimal conditions for the test have not been established. Methods: Reverse transcription-polymerase chain reaction was used to detect the viral genome in saliva samples kept at room temperature, in the fridge or frozen for 2 days. In addition, the influence of brushing teeth and feeding on the detection of the virus in saliva was addressed. Finally, the efficiency of saliva in revealing the presence of the virus during the hospitalization period was determined in children. Results: The viral genome was consistently detected regardless of the storage conditions of saliva samples. Brushing teeth and feeding did not influence the sensitivity of the test. In hospitalized children, positive results were obtained only during the early days. Conclusions: These results support the idea of the use of saliva as an alternative specimen for diagnostic testing for COVID-19. The viral genome is stable and endures perturbations in the oral cavity. However, clearance of the virus from the mouth during the infection may limit the use of the test only to the early stages of the disease.

Introducción: El diagnóstico de COVID-19 (enfermedad por coronavirus 2019) se realiza con un hisopado nasofaríngeo. El procedimiento de toma de muestra es molesto para el paciente y peligroso para el personal de salud, y la alta demanda de análisis ha conducido a la escasez de hisopos. Una alternativa es el uso de saliva, pero las condiciones óptimas para realizar el estudio no han sido establecidas. Métodos: Se usó la reacción en cadena de la polimerasa con transcriptasa reversa para detectar el genoma viral en muestras de saliva mantenidas a temperatura ambiente, en refrigeración o congeladas. Además, se evaluó la influencia del aseo bucal y de la ingesta de alimento en la detección del virus. Finalmente, se determinó el desempeño de la saliva para reportar la presencia del virus durante el periodo de hospitalización en niños. Resultados: El genoma viral fue estable durante 2 días a las diferentes temperaturas ensayadas. El aseo bucal y la ingesta de alimento no influyeron en la detección del virus. En los niños hospitalizados solo se obtuvieron resultados positivos durante los primeros días. Conclusiones: Los resultados coinciden con la idea del uso de la saliva como biofluido alternativo para el diagnóstico de COVID-19. El genoma viral es estable y no se ve afectado por perturbaciones en la cavidad oral; sin embargo, la dinámica de la infección puede provocar que el ensayo solo sea útil durante las primeras etapas de la enfermedad.

Clinical risk profile associated with SARS-CoV-2 infection and complications in the emergency area of a pediatric COVID-19 center.

Background: In February 2020, the disease caused by the novel coronavirus (SARS-CoV-2), was classified as a pandemic. In the pediatric population, coronavirus disease (COVID)-19 has a reported mortality of less than 6% in complicated cases; however, the clinical characteristics and severity are not the same as those presented in the adult population. This study aimed to describe the clinical manifestations of patients younger than 18 years old and their association with the confirmation of the test and outcomes. Methods: We conducted an analytical cross-sectional study of symptoms suggestive for SARS-CoV-2 infection. All subjects with a confirmatory test for SARS-CoV-2 were included. Initial symptoms, history of influenza vaccination, and previous contact were documented, and mortality and the requirement for assisted mechanical ventilation were identified. The proportions of the variables were compared with the χ2 test. The odds ratio for a positive test and the requirement of intubation was calculated. Results: Of a total of 510 subjects, 76 (15%) were positive for SARS-CoV-2. The associated symptoms were chest pain, sudden onset of symptoms, and general malaise. The variable most associated with contagion was the exposure to a relative with a confirmed diagnosis of COVID-19. Infants and subjects without the influenza vaccine showed an increased risk for respiratory complications. Conclusions: The frequency of positivity in the test was 15% (infants and adolescents represented 64% of the confirmed cases), and the associated factors identified were contact with a confirmed case, sudden onset of symptoms, and chest pain.

Introducción: En 2019 se reportaron los primeros casos de SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave), causante de la COVID-19, que alcanzó el grado de pandemia en febrero de 2020. La presentación en la etapa pediátrica reporta una mortalidad menor del 6% en los casos complicados; sin embargo, las características clínicas y su gravedad no son iguales que en la población adulta. El objetivo de este estudio fue describir las manifestaciones clínicas de los pacientes menores de 18 años y su asociación con la confirmación de la prueba, la intubación endotraqueal y la muerte. Métodos: Estudio transversal analítico por cuadro sugestivo de infección por SARS-CoV-2. Se incluyeron sujetos positivos para SARS-CoV-2. Se documentaron los síntomas iniciales, los antecedentes de vacunación contra la influenza y los contactos previos, y se identificaron los desenlaces de mortalidad y requerimiento de ventilación mecánica asistida. Se compararon las proporciones de las variables con la prueba χ2 y se calculó la razón de momios para la presencia de una prueba positiva y requerir intubación. Resultados: De un total de 510 sujetos, 76 (15%) fueron positivos para SARS-CoV-2. Los síntomas asociados fueron dolor precordial, inicio súbito y malestar general. La variable asociada con mayor frecuencia el contagio fue la exposición a un familiar con COVID-19 confirmada. Los sujetos sin vacuna de la influenza presentaron un riesgo mayor de complicaciones respiratorias. Conclusiones: La frecuencia de positividad en la prueba fue del 15%. Se identificaron como factores asociados a prueba positiva el contacto con un caso confirmado de COVID-19, el inicio súbito de los síntomas y el dolor precordial.

Clinical risk profile associated with SARS-CoV-2 infection and complications in the emergency area of a pediatric COVID-19 center

Background: In February 2020, the disease caused by the novel coronavirus (SARS-CoV-2), was classified as a pandemic. In the pediatric population, coronavirus disease (COVID)-19 has a reported mortality of less than 6% in complicated cases;however, the clinical characteristics and severity are not the same as those presented in the adult population. This study aimed to describe the clinical manifestations of patients younger than 18 years old and their association with the confirmation of the test and outcomes. Methods: We conducted an analytical cross-sectional study of symptoms suggestive for SARS-CoV-2 infection. All subjects with a confirmatory test for SARS-CoV-2 were included. Initial symptoms, history of influenza vaccination, and previous contact were documented, and mortality and the requirement for assisted mechanical ventilation were identified. The proportions of the variables were compared with the &#967;2 test. The odds ratio for a positive test and the requirement of intubation was calculated. Results: Of a total of 510 subjects, 76 (15%) were positive for SARS-CoV-2. The associated symptoms were chest pain, sudden onset of symptoms, and general malaise. The variable most associated with contagion was the exposure to a relative with a confirmed diagnosis of COVID-19. Infants and subjects without the influenza vaccine showed an increased risk for respiratory complications. Conclusions: The frequency of positivity in the test was 15% (infants and adolescents represented 64% of the confirmed cases), and the associated factors identified were contact with a confirmed case, sudden onset of symptoms, and chest pain. Resumen Introducción: En 2019 se reportaron los primeros casos de SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo grave), causante de la COVID-19, que alcanzó el grado de pandemia en febrero de 2020. La presentación en la etapa pediátrica reporta una mortalidad menor del 6% en los casos complicados;sin embargo, las características clínicas y su gravedad no son iguales que en la población adulta. El objetivo de este estudio fue describir las manifestaciones clínicas de los pacientes menores de 18 años y su asociación con la confirmación de la prueba, la intubación endotraqueal y la muerte. Métodos: Estudio transversal analítico por cuadro sugestivo de infección por SARS-CoV-2. Se incluyeron sujetos positivos para SARS-CoV-2. Se documentaron los síntomas iniciales, los antecedentes de vacunación contra la influenza y los contactos previos, y se identificaron los desenlaces de mortalidad y requerimiento de ventilación mecánica asistida. Se compararon las proporciones de las variables con la prueba &#967;2 y se calculó la razón de momios para la presencia de una prueba positiva y requerir intubación. Resultados: De un total de 510 sujetos, 76 (15%) fueron positivos para SARS-CoV-2. Los síntomas asociados fueron dolor precordial, inicio súbito y malestar general. La variable asociada con mayor frecuencia el contagio fue la exposición a un familiar con COVID-19 confirmada. Los sujetos sin vacuna de la influenza presentaron un riesgo mayor de complicaciones respiratorias. Conclusiones: La frecuencia de positividad en la prueba fue del 15%. Se identificaron como factores asociados a prueba positiva el contacto con un caso confirmado de COVID-19, el inicio súbito de los síntomas y el dolor precordial.

Saliva as a promising biofluid for SARS-CoV-2 detection during the early stages of infection

Background: Diagnostic testing for coronavirus disease (COVID)-19 is performed using nasopharyngeal swabs. This type of sampling is uncomfortable for the patient, dangerous for health workers, and its high demand has led to a global shortage of swabs. One of the alternative specimens is saliva. However, the optimal conditions for the test have not been established. Methods: Reverse transcription-polymerase chain reaction was used to detect the viral genome in saliva samples kept at room temperature, in the fridge or frozen for 2 days. In addition, the influence of brushing teeth and feeding on the detection of the virus in saliva was addressed. Finally, the efficiency of saliva in revealing the presence of the virus during the hospitalization period was determined in children. Results: The viral genome was consistently detected regardless of the storage conditions of saliva samples. Brushing teeth and feeding did not influence the sensitivity of the test. In hospitalized children, positive results were obtained only during the early days. Conclusions: These results support the idea of the use of saliva as an alternative specimen for diagnostic testing for COVID-19. The viral genome is stable and endures perturbations in the oral cavity. However, clearance of the virus from the mouth during the infection may limit the use of the test only to the early stages of the disease. Resumen Introducción: El diagnóstico de COVID-19 (enfermedad por coronavirus 2019) se realiza con un hisopado nasofaríngeo. El procedimiento de toma de muestra es molesto para el paciente y peligroso para el personal de salud, y la alta demanda de análisis ha conducido a la escasez de hisopos. Una alternativa es el uso de saliva, pero las condiciones óptimas para realizar el estudio no han sido establecidas. Métodos: Se usó la reacción en cadena de la polimerasa con transcriptasa reversa para detectar el genoma viral en muestras de saliva mantenidas a temperatura ambiente, en refrigeración o congeladas. Además, se evaluó la influencia del aseo bucal y de la ingesta de alimento en la detección del virus. Finalmente, se determinó el desempeño de la saliva para reportar la presencia del virus durante el periodo de hospitalización en niños. Resultados: El genoma viral fue estable durante 2 días a las diferentes temperaturas ensayadas. El aseo bucal y la ingesta de alimento no influyeron en la detección del virus. En los niños hospitalizados solo se obtuvieron resultados positivos durante los primeros días. Conclusiones: Los resultados coinciden con la idea del uso de la saliva como biofluido alternativo para el diagnóstico de COVID-19. El genoma viral es estable y no se ve afectado por perturbaciones en la cavidad oral;sin embargo, la dinámica de la infección puede provocar que el ensayo solo sea útil durante las primeras etapas de la enfermedad.