Incidence rate and distinctive characteristics of first episode psychosis during the COVID-19 pandemic: a multicenter observational study.

The COVID-19 pandemic has affected the mental health of people around the world. However, its impact on first-episode psychosis (FEP) remains unclear. The aim of this study was to determine the incidence rate (IR) and the clinical and sociodemographic characteristics of patients who developed FEP during the nine-month period following the COVID-19 outbreak in Spain and to compare these data to the corresponding period in the previous year. We included all patients (n = 220) treated for the first time during these two time periods at three FEP programs in Spain. The IR was 0.42/100,000 person-years during the pandemic vs. 0.54/100,000 in the prior year (p = 0.057). Compared to prior year, women accounted for a significantly higher proportion of FEP patients (46.3% vs. 28%; p = 0.005) during the COVID-19 period. This association was significant on the logistic regression analysis (odds ratio, female: 2.12 [confidence interval 1.17-3.82]; p = 0.014). These data reveal a non-significant trend towards a lower incidence of FEP during the pandemic period. Female sex was associated with a greater risk of developing FEP during the pandemic period, perhaps due to differences between males and females in the susceptibility and expression of psychosis. The findings of this study contribute to a better understanding of stress-related disorders.

Differences and similarities in endothelial and angiogenic profiles of preeclampsia and COVID-19 in pregnancy.

BACKGROUND: COVID-19 presents a spectrum of signs and symptoms in pregnant women that might resemble preeclampsia. Differentiation between severe COVID-19 and preeclampsia is difficult in some cases. OBJECTIVE: To study biomarkers of endothelial damage, coagulation, innate immune response, and angiogenesis in preeclampsia and COVID-19 in pregnancy in addition to in vitro alterations in endothelial cells exposed to sera from pregnant women with preeclampsia and COVID-19. STUDY DESIGN: Plasma and sera samples were obtained from pregnant women with COVID-19 infection classified into mild (n=10) or severe (n=9) and from women with normotensive pregnancies as controls (n=10) and patients with preeclampsia (n=13). A panel of plasmatic biomarkers was assessed, including vascular cell adhesion molecule-1, soluble tumor necrosis factor-receptor I, heparan sulfate, von Willebrand factor antigen (activity and multimeric pattern), α2-antiplasmin, C5b9, neutrophil extracellular traps, placental growth factor, soluble fms-like tyrosine kinase-1, and angiopoietin 2. In addition, microvascular endothelial cells were exposed to patients' sera, and changes in the cell expression of intercellular adhesion molecule 1 on cell membranes and von Willebrand factor release to the extracellular matrix were evaluated through immunofluorescence. Changes in inflammation cell signaling pathways were also assessed by of p38 mitogen-activated protein kinase phosphorylation. Statistical analysis included univariate and multivariate methods. RESULTS: Biomarker profiles of patients with mild COVID-19 were similar to those of controls. Both preeclampsia and severe COVID-19 showed significant alterations in most circulating biomarkers with distinctive profiles. Whereas severe COVID-19 exhibited higher concentrations of vascular cell adhesion molecule-1, soluble tumor necrosis factor-α receptor I, heparan sulfate, von Willebrand factor antigen, and neutrophil extracellular traps, with a significant reduction of placental growth factor compared with controls, preeclampsia presented a marked increase in vascular cell adhesion molecule-1 and soluble tumor necrosis factor-α receptor I (significantly increased compared with controls and patients with severe COVID-19), with a striking reduction in von Willebrand factor antigen, von Willebrand factor activity, and α2-antiplasmin. As expected, reduced placental growth factor, increased soluble fms-like tyrosine kinase-1 and angiopoietin 2, and a very high soluble fms-like tyrosine kinase-1 to placental growth factor ratio were also observed in preeclampsia. In addition, a significant increase in C5b9 and neutrophil extracellular traps was also detected in preeclampsia compared with controls. Principal component analysis demonstrated a clear separation between patients with preeclampsia and the other groups (first and second components explained 42.2% and 13.5% of the variance), mainly differentiated by variables related to von Willebrand factor, soluble tumor necrosis factor-receptor I, heparan sulfate, and soluble fms-like tyrosine kinase-1. Von Willebrand factor multimeric analysis revealed the absence of von Willebrand factor high-molecular-weight multimers in preeclampsia (similar profile to von Willebrand disease type 2A), whereas in healthy pregnancies and COVID-19 patients, von Willebrand factor multimeric pattern was normal. Sera from both preeclampsia and severe COVID-19 patients induced an overexpression of intercellular adhesion molecule 1 and von Willebrand factor in endothelial cells in culture compared with controls. However, the effect of preeclampsia was less pronounced than the that of severe COVID-19. Immunoblots of lysates from endothelial cells exposed to mild and severe COVID-19 and preeclampsia sera showed an increase in p38 mitogen-activated protein kinase phosphorylation. Patients with severe COVID-19 and preeclampsia were statistically different from controls, suggesting that both severe COVID-19 and preeclampsia sera can activate inflammatory signaling pathways. CONCLUSION: Although similar in in vitro endothelial dysfunction, preeclampsia and severe COVID-19 exhibit distinctive profiles of circulating biomarkers related to endothelial damage, coagulopathy, and angiogenic imbalance that could aid in the differential diagnosis of these entities.

Distinctive Biomarker Features in the Endotheliopathy of COVID-19 and Septic Syndromes.

BACKGROUND: Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood. OBJECTIVE: To characterize circulating biomarkers of endothelial damage in different COVID-19 clinical disease stages compared with sepsis syndrome and normal volunteers. METHODS: Patients with COVID-19 pneumonia (n = 49) were classified into moderate, severe, or critical (life-threatening) disease. Plasma samples were collected within 48 to 72 h of hospitalization to analyze endothelial activation markers, including soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1), von Willebrand Factor (VWF), A disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 (ADAMTS-13) activity, thrombomodulin (TM), and soluble TNF receptor I (sTNFRI); heparan sulfate (HS) for endothelial glycocalyx degradation; C5b9 deposits on endothelial cells in culture and soluble C5b9 for complement activation; circulating dsDNA for neutrophil extracellular traps (NETs) presence, and α2-antiplasmin and PAI-1 as parameters of fibrinolysis. We compared the level of each biomarker in all three COVID-19 groups and healthy donors as controls (n = 45). Results in critically ill COVID-19 patients were compared with other intensive care unit (ICU) patients with septic shock (SS, n = 14), sepsis (S, n = 7), and noninfectious systemic inflammatory response syndrome (NI-SIRS, n = 7). RESULTS: All analyzed biomarkers were increased in COVID-19 patients versus controls (P < 0.001), except for ADAMTS-13 activity that was normal in both groups. The increased expression of sVCAM-1, VWF, sTNFRI, and HS was related to COVID-19 disease severity (P < 0.05). Several differences in these parameters were found between ICU groups: SS patients showed significantly higher levels of VWF, TM, sTNFRI, and NETS compared with critical COVID-19 patients and ADAMTS-13 activity was significantly lover in SS, S, and NI-SIRS versus critical COVID-19 (P < 0.001). Furthermore, α2-antiplasmin activity was higher in critical COVID-19 versus NI-SIRS (P < 0.01) and SS (P < 0.001), whereas PAI-1 levels were significantly lower in COVID-19 patients compared with NI-SIRS, S, and SS patients (P < 0.01). CONCLUSIONS: COVID-19 patients present with increased circulating endothelial stress products, complement activation, and fibrinolytic dysregulation, associated with disease severity. COVID-19 endotheliopathy differs from SS, in which endothelial damage is also a critical feature of pathobiology. These biomarkers could help to stratify the severity of COVID-19 disease and may also provide information to guide specific therapeutic strategies to mitigate endotheliopathy progression.

Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?

Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death. Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (PASC) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating. Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved. The clinical manifestations of the COVID-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition. The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus. Cytokine release syndrome can also drive endothelial damage independently. Consequently, a distinctive feature of SARS-CoV-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage. Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe COVID-19 complications. Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity. In addition, the endothelium could represent a very attractive target to both prevent and treat these complications. To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified. In this review, the clinical features of COVID-19, the central role of the endothelium in COVID-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in COVID-19 patients are addressed.

The Impact of COVID-19 on Acute and Elective Corneal Surgery at Moorfields Eye Hospital London.

PURPOSE: Moorfields Eye Hospital sits as a major tertiary centre for ophthalmic care in the United Kingdom and became a central hub to provide safe and effective ophthalmic care across London and surrounding regions during the COVID-19 pandemic. We explore the impact on both the acute and elective corneal services during the first wave of this pandemic. METHODS: A retrospective review of the proportion of corneal transplants and anterior segment trauma repairs was performed during the period of March 23rd to July 1st 2020 compared with an identical period in 2019. Data were acquired from our in-house electronic patient records. RESULTS: A 92% reduction in corneal elective work was observed during the lockdown period compared with an identical period in 2019, with only 10 elective cases in total being performed. In addition, 91 corneal cross-linking and 76 therapeutic lasers were cancelled. There were 15 cases of primary repair for anterior segment trauma compared with 6 cases pre-COVID-19. A similar scenario occurs with removal of foreign body (4 cases during COVID-19 period versus no cases during pre-COVID-19 era) and with traumatic lens aspirations (6 cases during COVID-19 compared with 2 pre-COVID-19). Interestingly, a statistical difference (p=0.03) was found in the time interval from presentation of symptoms to emergency corneal surgery. During the COVID-19 period, a delay of 1.5 days ± 2.29 (range 0-10 days) occurred compared with 0.8 days ± 1.54 (range 0-6 days) pre-COVID-19. CONCLUSION: Stringent risk stratification reduced elective corneal surgery capacity during the lockdown thereby preserving social distancing requirements. However, an apparent increase in emergency corneal surgery seen is likely attributed to centralisation of ophthalmic services during the pandemic crisis, alongside increased domestic injuries. Despite the challenges posed, successful delivery of corneal surgery occurred whilst helping to identify lessons in preparations for future pandemics and current inefficiencies in healthcare delivery.

Impact of the COVID-19 pandemic on emergency department: Early findings from a hospital in Madrid.

INTRODUCTION: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyze the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. PATIENTS AND METHODS: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. RESULTS: A total of 1666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. CONCLUSIONS: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms.

INTRODUCCIÓN: SARS-CoV-2, responsable de la enfermedad por coronavirus 2019 (COVID-19), fue detectado por primera vez en España el 31 de enero de 2020. El 14 de marzo fue declarado el estado de alarma con el objetivo de controlar la pandemia. El objetivo de este estudio es analizar las consecuencias de esta crisis sanitaria sobre el patrón de demanda asistencial, así como el manejo y las características de los pacientes con sospecha de COVID-19 en el Servicio de Urgencias Pediátricas. PACIENTES Y MÉTODOS: Estudio retrospectivo observacional en niños y adolescentes menores de 18 años, atendidos en nuestro Servicio de Urgencias Pediátricas durante el periodo comprendido desde el 14 de marzo hasta el 17 de abril de 2020. RESULTADOS: Durante el periodo de estudio se atendieron 1.666 pacientes, un 65,4% menos que en el mismo periodo de 2019. La edad media fue de 5,4 años y el 51,2% eran varones. El 39,9% fueron clasificados con niveles de alta prioridad, un 6,5% más que en 2019. Los principales motivos de consulta fueron fiebre (26,5%), síntomas respiratorios (16,1%) y traumatismos (15,2%). Un total de 218 pacientes (13%) fueron diagnosticados de posible COVID-19, confirmándose la infección en el 18,4%. El 44% (96/218) fueron diagnosticados de infección respiratoria inferior y el 33,9% (74/218), superior. El 23,8% (52/218) fueron hospitalizados. CONCLUSIONES: Durante el brote epidémico SARS-CoV-2 disminuyó la demanda de asistencia pediátrica urgente, aumentando la proporción de casos con niveles de triaje de alta prioridad. La mayoría de los pacientes con sospecha o confirmación microbiológica de COVID-19 cursaron con clínica respiratoria leve.

[Impact of the COVID-19 pandemic on emergency department: Early findings from a hospital in Madrid]. / Impacto de la pandemia COVID-19 en urgencias: primeros hallazgos en un hospital de Madrid.

INTRODUCTION: SARS-CoV-2, coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in Spain on 31 January 2020. On 14 March 2020, a state of emergency was declared in Spain in a bid to control the spread of the COVID-19 pandemic in the country. The aim of our study is to analyse the impact on emergency medicine attendance after the national lockdown, as well as the clinical presentation and the management of patients with suspected COVID-19 in the Paediatric Emergency Department. PATIENTS AND METHODS: This retrospective observational study included children and adolescents under the age of 18, attended in our Paediatric Emergency Department during the period March 14 to April 17, 2020. RESULTS: A total of 1,666 patients were attended during the study period, 65.4% less than in the same period of 2019. Just over half (51.2%) were males, and mean age was 5.4 years. In triage, 39.9% were high priority levels, 6.5% more than 2019. Most frequent reasons for consultation at the Paediatric Emergency Department were fever (26.5%), respiratory symptoms (16.1%), and trauma (15.2%). A total of 218 patients (13%) received a diagnosis of possible COVID-19, with SARS-CoV-2 infection confirmed in 18.4%, and 23.8% (52/218) were hospitalised. At discharge, 44% (96/218) were diagnosed with lower, and 33.9% (74/218) with upper respiratory infection. CONCLUSIONS: During the SARS-CoV-2 outbreak, the demand for urgent paediatric care decreased, with the proportion of cases with high priority triage levels increasing. Most of the patients with suspected or microbiological confirmation of COVID-19 had mild respiratory symptoms.