Transcriptional reprogramming of infiltrating neutrophils drives lung disease in severe COVID-19 despite low viral load.

Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. Nevertheless, targeted studies within this vulnerable population are scant. Here, we applied multi-omics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, led to a persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1ß, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of a transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to ARDS in a well-defined patient population disproportionally affected by severe COVID-19.

Transcriptional reprogramming of infiltrating neutrophils drives lung disease in severe COVID-19 despite low viral load

Troubling disparities in COVID-19-associated mortality emerged early, with nearly 70% of deaths confined to Black/African American (AA) patients in some areas. Nevertheless, targeted studies within this vulnerable population are scant. Here, we applied multi-omics single-cell analyses of immune profiles from matching airways and blood samples of Black/AA patients during acute SARS-CoV-2 infection. Transcriptional reprogramming of infiltrating IFITM2+/S100A12+ mature neutrophils, likely recruited via the IL-8/CXCR2 axis, led to a persistent and self-sustaining pulmonary neutrophilia with advanced features of acute respiratory distress syndrome (ARDS) despite low viral load in the airways. In addition, exacerbated neutrophil production of IL-8, IL-1β, IL-6, and CCL3/4, along with elevated levels of neutrophil elastase and myeloperoxidase, were the hallmarks of a transcriptionally active and pathogenic airway neutrophilia. Although our analysis was limited to Black/AA patients and was not designed as a comparative study across different ethnicities, we present an unprecedented in-depth analysis of the immunopathology that leads to ARDS in a well-defined patient population disproportionally affected by severe COVID-19.

COVID-19 and plasma cells: Is there long-lived protection?

Infection with SARS-CoV-2, the etiology of the ongoing COVID-19 pandemic, has resulted in over 450 million cases with more than 6 million deaths worldwide, causing global disruptions since early 2020. Memory B cells and durable antibody protection from long-lived plasma cells (LLPC) are the mainstay of most effective vaccines. However, ending the pandemic has been hampered by the lack of long-lived immunity after infection or vaccination. Although immunizations offer protection from severe disease and hospitalization, breakthrough infections still occur, most likely due to new mutant viruses and the overall decline of neutralizing antibodies after 6 months. Here, we review the current knowledge of B cells, from extrafollicular to memory populations, with a focus on distinct plasma cell subsets, such as early-minted blood antibody-secreting cells and the bone marrow LLPC, and how these humoral compartments contribute to protection after SARS-CoV-2 infection and immunization.

Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection1 has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic2-5. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential6-10, although their origins and resolution have remained unclear11. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity12,13, as a dominant feature of severe and critical COVID-19 (refs. 14-18). Here, using single-cell B cell repertoire analysis of patients with mild and severe disease, we identify the expansion of a naive-derived, low-mutation IgG1 population of antibody-secreting cells (ASCs) reflecting features of low selective pressure. These features correlate with progressive, broad, clinically relevant autoreactivity, particularly directed against nuclear antigens and carbamylated proteins, emerging 10-15 days after the onset of symptoms. Detailed analysis of the low-selection compartment shows a high frequency of clonotypes specific for both SARS-CoV-2 and autoantigens, including pathogenic autoantibodies against the glomerular basement membrane. We further identify the contraction of this pathway on recovery, re-establishment of tolerance standards and concomitant loss of acute-derived ASCs irrespective of antigen specificity. However, serological autoreactivity persists in a subset of patients with postacute sequelae, raising important questions as to the contribution of emerging autoreactivity to continuing symptomology on recovery. In summary, this study demonstrates the origins, breadth and resolution of autoreactivity in severe COVID-19, with implications for early intervention and the treatment of patients with post-COVID sequelae.

Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH. METHODS: Clinical data abstraction from patient charts, T-cell immunophenotyping, and multiplex cytokine and chemokine profiling were performed for patients with MIS-C, patients with coronavirus disease 2019, and patients with HLH. RESULTS: We found that both patients with MIS-C and patients with HLH showed robust T-cell activation, markers of senescence, and exhaustion along with elevated TH1 and proinflammatory cytokines such as IFN-γ, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10. In comparison, the amplitude of T-cell activation and the levels of cytokines/chemokines were higher in patients with HLH when compared with patients with MIS-C. Distinguishing inflammatory features of MIS-C included elevation in TH2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as vascular endothelial growth factor A and platelet-derived growth factor. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8+ T-cell activation correlated with cardiac dysfunction parameters such as B-type natriuretic peptide and troponin and inversely correlated with platelet count. CONCLUSIONS: Overall, this study characterizes unique and overlapping immunologic features that help to define the hyperinflammation associated with MIS-C versus HLH.

Delayed Kinetics of IgG, but Not IgA, Antispike Antibodies in Transplant Recipients following SARS-CoV-2 Infection.

BACKGROUND: Kidney transplant recipients are at increased risk of severe outcomes during COVID-19. Antibodies against the virus are thought to offer protection, but a thorough characterization of anti-SARS-CoV-2 immune globulin isotypes in kidney transplant recipients following SARS-CoV-2 infection has not been reported. METHODS: We performed a cross-sectional study of 49 kidney transplant recipients and 42 immunocompetent controls at early (≤14 days) or late (>14 days) time points after documented SARS-CoV-2 infection. Using a validated semiquantitative Luminex-based multiplex assay, we determined the abundances of IgM, IgG, IgG1-4, and IgA antibodies against five distinct viral epitopes. RESULTS: Kidney transplant recipients showed lower levels of total IgG antitrimeric spike (S), S1, S2, and receptor binding domain (RBD) but not nucleocapsid (NC) at early versus late time points after SARS-CoV-2 infection. Early levels of IgG antispike protein epitopes were also lower than in immunocompetent controls. Anti-SARS-CoV-2 antibodies were predominantly IgG1 and IgG3, with modest class switching to IgG2 or IgG4 in either cohort. Later levels of IgG antispike, S1, S2, RBD, and NC did not significantly differ between cohorts. There was no significant difference in the kinetics of either IgM or IgA antispike, S1, RBD, or S2 on the basis of timing after diagnosis or transplant status. CONCLUSIONS: Kidney transplant recipients mount early anti-SARS-CoV-2 IgA and IgM responses, whereas IgG responses are delayed compared with immunocompetent individuals. These findings might explain the poor outcomes in transplant recipients with COVID-19.

The intersection of COVID-19 and autoimmunity.

Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed.

One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses. We developed a multiplex immunoassay from serum/plasma of acutely infected and convalescent COVID-19 patients and prepandemic and postpandemic healthy adults. We measured IgA, IgG, and/or IgM against SARS-CoV-2 nucleocapsid (N), spike domain 1 (S1), S1-receptor binding domain (RBD) and S1-N-terminal domain. For diagnosis, the combined [IgA + IgG + IgM] or IgG levels measured for N, S1, and S1-RBD yielded area under the curve values ≥0.90. Virus-specific Ig levels were higher in patients with severe/critical compared with mild/moderate infections. A strong prozone effect was observed in sera from severe/critical patients-a possible source of underestimated Ab concentrations in previous studies. Mild/moderate patients displayed a slower rise and lower peak in anti-N and anti-S1 IgG levels compared with severe/critical patients, but anti-RBD IgG and neutralization responses reached similar levels at 2-4 mo after symptom onset. Measurement of the Ab responses in sera from 18 COVID-19-vaccinated patients revealed specific responses for the S1-RBD Ag and none against the N protein. This highly sensitive, SARS-CoV-2-specific, multiplex immunoassay measures the magnitude, complexity, and kinetics of the Ab response and can distinguish serum Ab responses from natural SARS-CoV-2 infections (mild or severe) and mRNA COVID-19 vaccines.

Cirugía de urgencia en urología durante la pandemia Covid-19

INTRODUCCIÓN: La crisis del coronavirus SARS-CoV-2 causante del COVID-19 está poniendoa prueba los sistemas sanitarios de todo el mundo. En un gran esfuerzo por estandarizar las pautas de manejo y tratamiento, las distintas autoridades sanitarias y asociaciones científicas han tratado de dictar unas recomendaciones sobre como actuar en este nuevo y complejo escenario. OBJETIVO: Sintetizar la evidencia y recomendaciones existentes acerca de la cirugía de urgencia urológica durante la situación de pandemia COVID-19. Además, proponemos un protocolo de actuación general para estos pacientes. MATERIAL Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/Cov-2 y la experiencia de los autores en el manejo de COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Madrid y País Vasco. Se realizó una búsqueda web y en PubMed utilizando las palabras clave "SARSCoV-2", "COVID19", "COVID Urology", "COVID19 surgery"y "emergency care". Se realizó una revisión narrativa de la literatura hasta el día 30 de Abril de2020 incluyendo solo artículos y documentos escritos en lengua española e inglesa. Tras técnica de grupo nominal modificada debido a las restricciones extraordinarias se realizó un primer borrador para unificar criterios. Finalmente, se realizó una versión definitiva, consensuada por todos los autores el 12 Mayo 2020. RESULTADOS: Se exponen unos principios generales de actuación, así como unas recomendaciones específicas para los procedimientos urológicos urgentes más frecuentes. CONCLUSIONES: Dado el carácter excepcional de la situación, existe un déficit de evidencia respecto al óptimo manejo del paciente con patología urológica urgente. La información es cambiante, según avanza el conocimiento epidemiológico de la enfermedad. Es recomendable el establecimiento de comités multidisciplinares quirúrgicos que desarrollen e implementen protocolos de actuación adecuados a los distintos recursos y situaciones particulares de cada centro. Del mismo modo, estos comités deben evaluar de forma individualizada cada posible situación de urgencia quirúrgica urológica y velar por el cumplimiento de las medidas de protección para el paciente y resto del personal sanitario INTRODUCTION: The crisis in the SARSCoV-2 coronavirus causing COVID-19 is putting health systems around the world to the test. In a great effort to standardize the management and treatment guidelines, the different health authorities and scientific associations have tried to issue recommendations on how to act in this new and complex scenario. OBJECTIVE: To synthesize the existing evidence and recommendations about urological emergency surgery during the COVID-19 pandemic situation. Furthermore, we propose a general action protocol for these patients. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in the management of COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Madrid and the Basque Country. A web and PubMed search was performed using the keywords "SARS-CoV-2", "COVID19", "COVID Urology", "COVID19 surgery"and "emergency care". A narrative review of the literature was carried out until April 30, 2020, including only articles and documents written in Spanish and English. After the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria. Finally, a definitive version was made, agreed by all the authors on May 12, 2020. RESULTS: General principles of action are set out, as well as specific recommendations for the most frequent urgent urological procedures. CONCLUSIONS: Given the exceptional nature of the situation, there is a lack of evidence regarding the optimal management of the patient with urgent urological pathology. The information is changing, as the epidemiological knowledge of the disease advances. The establishment of multidisciplinary surgical committees that develop and implement action protocols appropriate to the different resources and particular situations of each center is recommended. Likewise, these committees must individually assess each possible urological surgical emergency situation and ensure compliance with rotective measures for the patient and other healthcare personnel

Cáncer de próstata y la pandemia Covid-19 Recomendaciones ante una nueva realidad

OBJETIVO: El objetivo de esta publicaciónes proporcionar recomendaciones en el manejo del cáncer de próstata (CP) en el marco de la nueva realidad que supone la presencia de la COVID-19. MATERIALES Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/CoV-2 y la experiencia de los autores en el manejo de la COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Cataluña, Madrid y Comunidad Valenciana. RESULTADOS: Los autores definieron diferentes prioridades para los distintos supuestos clínicos en CP. Emergencia/urgencia (riesgo vital o urgencia aún en situación de normalidad), alta prioridad/urgencia electiva (potencialmente peligrosa si se pospone más de 1mes), prioridad intermedia/electiva (se recomienda no retrasar más de 6 meses), baja prioridad/demorable (se puede posponer más de 6 meses). Acorde a esta clasificación, el grupo de trabajo consensuó la distribución de los diferentes escenarios diagnósticos, terapéuticos y de seguimiento del CP. El riesgo de morbilidad grave como resultado de la infección por SARS-CoV-2puede superar el riesgo de morbi-mortalidad por CP en muchos hombres;por lo tanto, a corto plazo es pocoprobable que los retrasos en el diagnóstico o tratamiento conduzcan a peores resultados oncológicos. CONCLUSIONES: La pandemia COVID-19 ha resultado en un desafío para nuestro sistema de salud, lo que plantea varias consideraciones en el tratamiento de pacientes con CP. La planificación de los procedimientos quirúrgicos en función de los grados de prioridades imprescindible durante el periodo de pandemia y transición a la nueva normalidad. La reorganización de las consultas incluyendo la adaptación a las medidas de seguridad para profesionales y pacientes y el desarrollo de un programa de telemedicina es altamente recomendable OBJECTIVE: The objective of this publication is to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS: The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), high priority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/elective priority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may outweigh the risk of PC morbidity/mortality in many men;therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS: The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, and the development of a telemedicine program is highly recommended

Recomendaciones de actuación en cirugía reconstructiva urológica durante la pandemia Covid-19

OBJETIVOS: Establecer unas recomendaciones o guía de actuación durante la evolución de la pandemia COVID-19 en cuanto al diagnóstico, tratamiento y seguimiento en el campo de la Urología Reconstructiva. MATERIAL y MÉTODO: El documento se basa en la evidencia sobre SARS/Cov-2 y la experiencia de los autores en el manejo de COVID-19 en sus instituciones, incluyendo especialistas de Andalucía, Madrid, Cantabria, Comunidad Valenciana y Cataluña. Se realizó una búsqueda web y en PubMed utilizando "SARS-CoV-2", "COVID-19", "COVID-19 Urology", "COVID19 urology complications", "COVID-19 reconstructive surgery". Se realizó una revisión narrativa de la literatura (17/5/2020) y tras la técnica de grupo nominal modificada debido a las restricciones extraordinarias, se realizó un primer borrador para unificar criterios y llegar a un rápido consenso. Finalmente, se realizó una versión definitiva, consensuada por todos los autores el 22/5/2020. RESULTADOS: Los autores definieron para la Cirugía Urológica Reconstructiva las siguientes prioridades quirúrgicas: Emergencia/Urgencia (Riesgo vital o urgencias aún en situación de normalidad), Urgencia Electiva/Alta prioridad (Patología potencialmente peligros asi se pospone más de 1 mes), Cirugía Electiva/Prioridad intermedia (Patología con poca probabilidad de ser peligrosa pero se recomienda no retrasar más de 6 meses), Cirugía demorable/Baja prioridad (Patología no peligrosa si se pospone más de 6 meses). Acorde a esta clasificación, el Grupo de Trabajo consensuó la distribución de los diferentes escenarios quirúrgicos de la Urología Reconstructiva. Además, se llegó a consenso sobre recomendaciones en cuanto al diagnóstico y seguimiento de la patología en el ámbito de la Urología Reconstructiva. CONCLUSIONES: Deben implementarse mecanismos que faciliten la agrupación de la visita médica y pruebas diagnósticas. La redistribución de los procedimientos quirúrgicos en función de los grados de prioridad es imprescindible durante el periodo de pandemia y de transición. El empleo de la telemedicina es necesario para el seguimiento, mediante vía informática, telefónica o videoconferencia OBJECTIVES: Offer some recommendations or guidelines during the evolution of the COVID-19 pandemic in terms of diagnosis, treatment and follow-up in the field of Reconstructive Urology. MATERIAL AND METHOD: The document is based on the evidence on SARS/Cov-2 and the authors'experience in managing COVID-19 in their institutions, including specialists from Andalusia, Madrid, Cantabria, the Valencian Community and Catalonia. A web and PubMed search was performed using "SARS-CoV-2", "COVID-19", "COVID-19 Urology", "COVID19 urology complications", "COVID-19 reconstructive surgery". A narrative review of the literature was carried out (5/17/2020) and after the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria and reach a quick consensus. Finally, a definitive version was made, agreed by all the authors (5/22/2020). RESULTS: The authors defined the following surgical priorities for Urological Reconstructive Surgery: Emergency/ Urgency (life-threatening or emergencies still in a normal situation), Elective Urgency/High priority (potentially dangerous pathology if postponed for more than 1 month), Elective Surgery/Intermediate priority (pathology with little probability of being dangerous but it is recommended not to delay more than 6 months), Delayed surgery/Low priority (non-dangerous pathology if it is postponed for more than 6 months). According to this classification, the Working Group agreed on the distribution of the different surgical scenarios of Reconstructive Urology. In addition, consensus was reached on recommendations regarding the diagnosis and follow-up of pathology in the field of Reconstructive Urology. CONCLUSIONS: Tools should be implemented to facilitate the gathering of the medical visit and diagnostic tests. Redistribution of surgical procedures based on priority degrees is necessary during the pandemic and transition period. The use of telemedicine is essential for follow-up, by computer, telephone or videoconference

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection, Atlanta, Georgia, USA, 2020.

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.

Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein.

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes on the basis of their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of advanced antibody discovery platforms.

[Emergency surgery during COVID-19 pandemia.]

INTRODUCTION: The crisis in the SARSCoV-2 coronavirus causing COVID-19 is putting health systems around the world to the test. In a great effort to standardize the management and treatment guidelines, the different health authorities and scientific associations have tried to issue recommendations on how to act in this new and complex scenario. OBJECTIVE: To synthesize the existing evidence and recommendations about urological emergency surgery during the COVID-19 pandemic situation. Furthermore, we propose a general action protocol for these patients. MATERIAL AND METHODS: The document is based ont he scarce evidence on SARS / Cov-2 and the experience of the authors in the management of COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Madrid and the Basque Country. A web and PubMed search was performed using the keywords "SARS-CoV-2", "COVID19", "COVID Urology", "COVID19 surgery" and "emergency care". A narrative review of the literature was carried out until April 30, 2020, including only articles and documents written in Spanish and English. After the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria. Finally, a definitive version was made, agreed by all the authors on May 12, 2020. RESULTS: General principles of action are set out, as well as specific recommendations for the most frequent urgent urological procedures. CONCLUSIONS: Given the exceptional nature of the situation, there is a lack of evidence regarding the optimal management of the patient with urgent urological pathology. The information is changing, as the epidemiological knowledge of the disease advances. The establishment of multidisciplinary surgical committees that develop and implement action protocols appropriate to the different resources and particular situations of each center is recommended. Likewise, these committees must individually assess each possible urological surgical emergency situation and ensure compliance with protective measures for the patient and other healthcare personnel.

[Prostate cancer and COVID-19 pandemia: Current recommendations.]

OBJECTIVE: The objective of this publicationis to provide recommendations in the management of prostate cancer (PC) in a new reality framework based on the presence of COVID-19 disease. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in handling COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Catalonia, Madrid and the Valencian Community. RESULTS: The authors defined different priorities for the different clinical situations in PC. Emergency/urgency (life-threatening or urgent even in normal situation), highpriority/elective urgency (potentially dangerous if postponed for more than 1 month), intermediate/electivepriority (it is recommended not to delay more than 6 months), low priority/delayed (can be postponed more than 6 months). According to this classification, the working panel agreed on the distribution of the different diagnostic, therapeutic and follow-up scenarios for PC. The risk of severe morbidity as a result of SARS-CoV-2 infection may out weigh the risk of PC morbidity/mortalityin many men;therefore, in the short term it is unlikely that delays in diagnosis or treatment can led to worse cancer outcomes. CONCLUSIONS: The COVID-19 pandemic has resulted in a challenge for our health system, which raises several considerations in the treatment of patients with PC. The redistribution of surgical procedures according to the degrees of priority is essential during the period of the pandemic and the transition to the new normality. The change of the out-clinics with the adequate security measures for healthcare practitioners and patients, andt he development of a telemedicine program is highly recommended.

[Reconstructive surgery protocol recommendations during COVID-19 pandemia.]

OBJECTIVES: Offer some recommendations or guidelines during the evolution of the COVID-19 pandemic in terms of diagnosis, treatment and follow-upin the field of Reconstructive Urology. MATERIAL AND METHOD: The document is based on the evidence on SARS/Cov-2 and the authors' experience in managing COVID-19 in their institutions, including specialists from Andalusia, Madrid, Cantabria,the Valencian Community and Catalonia. A web and PubMed search was performed using "SARS-CoV-2", "COVID-19", "COVID-19 Urology", "COVID19 urology complications", "COVID-19 reconstructive surgery".A narrative review of the literature was carried out (5/17/2020) and after the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria and reach a quick consensus. Finally, a definitive version was made, agreed by all the authors (5/22/2020). RESULTS: The authors defined the following surgical priorities for Urological Reconstructive Surgery: Emergency/Urgency (life-threatening or emergencies still in anormal situation), Elective Urgency/High priority (potentially dangerous pathology if postponed for more than 1month), Elective Surgery/Intermediate priority (pathology with little probability of being dangerous but it is recommended not to delay more than 6 months), Delayed surgery/Low priority (non-dangerous pathology if it is postponed for more than 6 months). According to this classification, the Working Group agreed on the distribution of the different surgical scenarios of Reconstructive Urology. In addition, consensus was reached on recommendations regarding the diagnosis and follow-up of pathology in the field of Reconstructive Urology. CONCLUSIONS: Tools should be implemented to facilitate the gathering of the medical visit and diagnostic tests. Redistribution of surgical procedures based on priority degrees is necessary during the pandemic and transition period. The use of telemedicine is essential forfollow-up, by computer, telephone or videoconference.