Long Covid.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), refers to a constellation of persistent symptoms and health issues that continue beyond the acute phase of COVID-19. This chapter provides an overview of the pathogenesis, risk factors, manifestations, major findings, and diagnosis and treatment strategies associated with Long COVID. Hypotheses regarding the pathogenesis of Long COVID are discussed, encompassing various factors such as persistent viral reservoirs, immune dysregulation with or without reactivation of herpesviruses (e.g., Epstein-Barr Virus and human herpesvirus), dysbiosis, autoimmunity triggered by infection, endothelial dysfunction, microvessel blood clotting, and dysfunctional brainstem and/or vagal signaling. The chapter also highlights the risk factors associated with Long COVID and its occurrence in children. The major findings of Long COVID, including immune dysregulation, vessel and tissue damage, neurological and cognitive pathology, eye symptoms, endocrinal issues, myalgic encephalomyelitis and chronic fatigue syndrome, reproductive system involvement, respiratory and gastrointestinal symptoms, and the chronology of symptoms, are thoroughly explored. Lastly, the chapter discusses the challenges and current approaches in the diagnosis and treatment of Long COVID, emphasizing the need for multidisciplinary care and individualized management strategies.

B cell responses to SARS-CoV-2.

This chapter provides an overview of B cell responses in COVID-19, highlighting the structure of SARS-CoV-2 and its impact on B cell immunity. It explores the production and maturation of SARS-CoV-2-specific B cells, with a focus on the two distinct phases of the humoral immune response: the extrafollicular (EF) phase and the germinal center (GC) phase. Furthermore, the interplay between B cells, follicular T helper cells, CD4+ T cells, and plasma cells is discussed, emphasizing their collaborative role in mounting an effective humoral immune response against SARS-CoV-2. The concept of immunological memory is explored, highlighting the roles of plasma cells and B memory cells in providing long-term protection. The chapter delves into the antibody response during SARS-CoV-2 infection, categorizing the types of antibodies generated. This includes a detailed analysis of neutralizing antibodies, such as those directed against the receptor-binding domain (RBD) and the N-terminal domain (NTD), as well as non-neutralizing antibodies. The role of mucosal antibodies, cross-reactive antibodies, and auto-reactive antibodies is also discussed. Factors influencing the dynamics of anti-SARS-CoV-2 antibodies are examined, including the duration and strength of the humoral response. Additionally, the chapter highlights the impact of the Omicron variant on humoral immune responses and its implications for vaccine efficacy and antibody-mediated protection.

COVID-19 pathogenesis.

The pathogenesis of COVID-19 involves a complex interplay between host factors and the SARS-CoV-2 virus, leading to a multitude of clinical manifestations beyond the respiratory system. This chapter provides an overview of the risk factors, genetic predisposition, and multisystem manifestations of COVID-19, shedding light on the underlying mechanisms that contribute to extrapulmonary manifestations. The chapter discusses the direct invasion of SARS-CoV-2 into various organs as well as the indirect mechanisms such as dysregulation of the renin-angiotensin-aldosterone system (RAAS), immune response dysfunctions within the innate and adaptive immune systems, endothelial damage, and immunothrombosis. Furthermore, the multisystem manifestations of COVID-19 across different organ systems, including the cardiovascular, renal, gastrointestinal, hepatobiliary, nervous, endocrine and metabolic, ophthalmic, ear-nose-throat, reproductive, hematopoietic, and immune systems are discussed in detail. Each system exhibits unique manifestations that contribute to the complexity of the disease.

Diagnostic therapeutic assistance pathway (PDTA) of type 2 chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a complex and heterogeneous disorder whose etiopathogenetic picture is not yet completely known and is classically divided into CRS with (CRSwNP) and without nasal polyps (CRSsNP). But today the distinction is made with type 2 and nontype 2 variants. A rational and defined pathway for the diagnosis of chronic rhinosinusitis is an indispensable means to be able to arrive at a correct identification of the patient. This typing is essential to be able to arrive at the correct course of treatment, which turns out to be different for different types of patients. For this reason, the realization of a diagnostic therapeutic pathway represents a fundamental way for the otolaryngologist specialist but not only, since today diagnostics has a multidisciplinary framework. In the present work, precise indications have been developed to arrive at a correct diagnosis. The various diagnostic pathways and processes to arrive at a correct therapeutic framing have been highlighted. Therapy ranging from medical therapy to surgical therapy without neglecting the new biological therapies. It does not represent a guideline but a diagnostic method that can be adapted to all the various territorial realities.

Coexistence of proboscis lateralis and multiple craniofacial, neurological, cardiac and spinal deformities: a one-of-a-kind case report.

BACKGROUND: Proboscis lateralis (PL) is an uncommon congenital facial deformity marked by the protrusion of a primitive tubular structure made up of skin and soft tissue that generally emerges from the eye's medial canthus and is associated with some craniofacial deformities. We report the first case of PL with multiple craniofacial, neurological, cardiac, and spinal anomalies. CASE PRESENTATION: A full-term female baby delivered by cesarean section cried immediately at birth. The mother reported having a normal pregnancy but has a history of x-ray during her first trimester. The baby was born with a rare presentation of proboscis lateralis which was accompanied by multiple anomalies, including but not limited to bilateral colpocephaly, corpus callosum agenesis, complex cyanotic congenital heart disease, and hemivertebra of the T10 body. CONCLUSION: PL is an uncommon congenital condition that causes a variety of craniofacial abnormalities. Multiple additional defects affecting various organ systems should also be evaluated in a person diagnosed with PL.

Long-term persistence of IgG antibodies in recovered COVID-19 individuals at 18 months post-infection and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response: Analysis using fixed-effects linear regression model.

This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG response over 18 months in n = 36 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer-BioNTech) vaccination on the antibody responses of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on these responses. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG levels in recovered individuals 161 times, this "boost" was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals.

International consensus statement on allergy and rhinology: Olfaction.

BACKGROUND: The literature regarding clinical olfaction, olfactory loss, and olfactory dysfunction has expanded rapidly over the past two decades, with an exponential rise in the past year. There is substantial variability in the quality of this literature and a need to consolidate and critically review the evidence. It is with that aim that we have gathered experts from around the world to produce this International Consensus on Allergy and Rhinology: Olfaction (ICAR:O). METHODS: Using previously described methodology, specific topics were developed relating to olfaction. Each topic was assigned a literature review, evidence-based review, or evidence-based review with recommendations format as dictated by available evidence and scope within the ICAR:O document. Following iterative reviews of each topic, the ICAR:O document was integrated and reviewed by all authors for final consensus. RESULTS: The ICAR:O document reviews nearly 100 separate topics within the realm of olfaction, including diagnosis, epidemiology, disease burden, diagnosis, testing, etiology, treatment, and associated pathologies. CONCLUSION: This critical review of the existing clinical olfaction literature provides much needed insight and clarity into the evaluation, diagnosis, and treatment of patients with olfactory dysfunction, while also clearly delineating gaps in our knowledge and evidence base that we should investigate further.

The mechanisms of action of ivermectin against SARS-CoV-2-an extensive review.

Considering the urgency of the ongoing COVID-19 pandemic, detection of new mutant strains and potential re-emergence of novel coronaviruses, repurposing of drugs such as ivermectin could be worthy of attention. This review article aims to discuss the probable mechanisms of action of ivermectin against SARS-CoV-2 by summarizing the available literature over the years. A schematic of the key cellular and biomolecular interactions between ivermectin, host cell, and SARS-CoV-2 in COVID-19 pathogenesis and prevention of complications has been proposed.

Longitudinal observation of antibody responses for 14 months after SARS-CoV-2 infection.

Better understanding of antibody responses against SARS-CoV-2 after natural infection might provide valuable insights into the future implementation of vaccination policies. Longitudinal analysis of IgG antibody titers was carried out in 32 recovered COVID-19 patients based in the Umbria region of Italy for 14 months after Mild and Moderately-Severe infection.Two FDA-approved immunoassays against SARS-CoV-2 Nucleocapsid protein (NCP) and anti-spike-receptor binding domain (S-RBD) were used for sequential serological tests at different time points. The demographics,clinical history and symptom profile associated with the magnitude and longevity of antibody responses were also analyzed. Anti-S-RBD IgG persisted in 96.8% (31 of 32) subjects at 14 months. Patients reporting loss of smell and taste during the clinical course of the disease developed significantly higher antibody titers. Anti-NCP IgG seronegative patients(n=7) at 10 months, tested positive for anti-S-RBD IgG at 12,13 and 14 months emphasizing on a higher false-negative rate for NCP protein-based antibody assays. This study also highlights the importance of adopting specific immunoassays for routine estimation of antibody titers and the decreased rate of re-infections in recovered patients.

Sinus and anterior skull base surgery during the COVID-19 pandemic: systematic review, synthesis and YO-IFOS position.

PURPOSE: The COVID-19 pandemic has caused significant confusion about healthcare providers' and patients' pandemic-specific risks related to surgery. The aim of this systematic review is to summarize recommendations for sinus and anterior skull base surgery during the COVID-19 pandemic. METHODS: PubMed/MEDLINE, Google Scholar, Scopus and Embase were searched by two independent otolaryngologists from the Young Otolaryngologists of IFOS (YO-IFOS) for studies dealing with sinus and skull base surgery during COVID-19 pandemic. The review also included unpublished guidelines edited by Otolaryngology-Head and Neck Surgery or Neurosurgery societies. Perioperative factors were investigated including surgical indications, preoperative testing of patients, practical management in operating rooms, technical aspects of surgery and postoperative management. The literature review was performed according to PRISMA guidelines. The criteria for considering studies or guidelines for the review were based on the population, intervention, comparison, outcome, timing and setting (PICOTS) framework. RESULTS: 15 International publications met inclusion criteria. Five references were guidelines from national societies. All guidelines recommended postponing elective surgeries. An algorithm is proposed that classifies endonasal surgical procedures into three groups based on the risk of postponing surgery. Patients' COVID-19 status should be preoperatively assessed. Highest level of personal protective equipment (PPE) is recommended, and the use of high-speed powered devices should be avoided. Face-to-face postoperative visits must be limited. CONCLUSIONS: Sinus and skull base surgeries are high-risk procedures due to potential aerosolization of SARS-CoV-2 virus. Protection of health care workers by decreasing exposure and optimizing the use of PPE is essential with sinus and anterior skull base surgery.

International registry of otolaryngologist-head and neck surgeons with COVID-19.

BACKGROUND: It has become clear that healthcare workers are at high risk, and otolaryngology has been theorized to be among the highest risk specialties for coronavirus disease 2019 (COVID-19). The purpose of this study was to detail the international impact of COVID-19 among otolaryngologists, and to identify instructional cases. METHODS: Country representatives of the Young Otolaryngologists-International Federation of Otolaryngologic Societies (YO-IFOS) surveyed otolaryngologists through various channels. Nationwide surveys were distributed in 19 countries. The gray literature and social media channels were searched to identify reported deaths of otolaryngologists from COVID-19. RESULTS: A total of 361 otolaryngologists were identified to have had COVID-19, and data for 325 surgeons was available for analysis. The age range was 25 to 84 years, with one-half under the age of 44 years. There were 24 deaths in the study period, with 83% over age 55 years. Source of infection was likely clinical activity in 175 (54%) cases. Prolonged exposure to a colleague was the source for 37 (11%) surgeons. Six instructional cases were identified where infections occurred during the performance of aerosol-generating operations (tracheostomy, mastoidectomy, epistaxis control, dacryocystorhinostomy, and translabyrinthine resection). In 3 of these cases, multiple operating room attendees were infected, and in 2, the surgeon succumbed to complications of COVID-19. CONCLUSION: The etiology of reported cases within the otolaryngology community appear to stem equally from clinical activity and community spread. Multiple procedures performed by otolaryngologists are aerosol-generating procedures (AGPs) and great care should be taken to protect the surgical team before, during, and after these operations.

Septal Flip Flap for Anterior Skull Base Reconstruction After Endoscopic Transnasal Craniectomy: Long-Term Outcomes.

BACKGROUND: Endoscopic endonasal anterior skull base malignant sinonasal tumor resection and reconstruction remains a challenge. We describe our septal flip flap (SFF) reconstruction, a new surgical technique for repairing anterior skull base defects and report our outcomes. METHODS: We retrospectively reviewed the clinical data of 24 patients who underwent skull base reconstruction using a SFF following endoscopic resection with transnasal craniectomy. We raise the SFF from the contralateral nasal septum based on the septal branches of the anterior and posterior ethmoidal arteries; the SFF is then rotated laterally for anterior skull base reconstruction after transnasal resection with craniectomy. RESULTS: The SFF was used for multiple tumor types including, most commonly, intestinal-type adenocarcinoma, followed by olfactory neuroblastoma, squamous cell carcinoma, sinonasal undifferentiated carcinoma, and other types. All of the cases had either preoperative or postoperative radiation therapy. All flaps remained viable postoperatively. Postoperatively, nasal crusting was significantly reduced with faster healing of the surgical cavity. CONCLUSIONS: The SFF adds to the clinical armamentarium the opportunity to provide vascularized mucosal coverage extending from the frontal recess back to the planum sphenoidalis. The use of SFF requires careful consideration when dealing with paranasal sinus cancers so as not to infringe oncologic principles.

Combined External-Endoscopic Endonasal Assisted Removal of a Nail Gun.

Management of penetrating trauma to the paranasal sinuses with retained foreign bodies represents a challenge due to the proximity to vital neurovascular structures. The authors report the successful treatment of a patient with a work-related nail gun injury, carried out by means of a combined endoscopic endonasal external assisted procedure.A transnasal endoscopic approach was planned to minimize inadvertent movements of the nail during surgery and in case necessary to repair the orbit or skull base. No major bleeding or neurovascular complication was observed after surgery and a computed tomography scan was performed after surgery confirming the complete removal of the nail and with no damage of the orbit nor the skull base.