Potential of MicroRNAs As Biomarkers and Therapeutic Targets in Respiratory Viruses: A Literature Review.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through recognition of cognate sequences and interference of transcriptional, translational, or epigenetic processes. Hundreds of miRNA genes have been found in diverse viruses, and many of these are phylogenetically conserved. Respiratory viruses are the most frequent causative agents of disease in humans, with a significant impact on morbidity and mortality worldwide. Recently, the role of miRNAs in respiratory viral gene regulation, as well as host gene regulation during disease progression, has become a field of interest. This review highlighted the importance of various miRNAs and their potential role in fighting with respiratory viruses as therapeutic molecules with a focus on COVID-19.

New Insights into the Role of the Complement System in Human Viral Diseases.

The complement system (CS) is part of the human immune system, consisting of more than 30 proteins that play a vital role in the protection against various pathogens and diseases, including viral diseases. Activated via three pathways, the classical pathway (CP), the lectin pathway (LP), and the alternative pathway (AP), the complement system leads to the formation of a membrane attack complex (MAC) that disrupts the membrane of target cells, leading to cell lysis and death. Due to the increasing number of reports on its role in viral diseases, which may have implications for research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this review aims to highlight significant progress in understanding and defining the role of the complement system in four groups of diseases of viral etiology: (1) respiratory diseases; (2) acute liver failure (ALF); (3) disseminated intravascular coagulation (DIC); and (4) vector-borne diseases (VBDs). Some of these diseases already present a serious global health problem, while others are a matter of concern and require the collaboration of relevant national services and scientists with the World Health Organization (WHO) to avoid their spread.

Microarray-Based Detection of Antibodies against SARS-CoV-2 Proteins, Common Respiratory Viruses and Type I Interferons.

A microarray-based assay to detect IgG and IgM antibodies against betacoronaviruses (SARS-CoV-2, SARS, MERS, OC43, and HKU1), other respiratory viruses and type I interferons (IFN-Is) was developed. This multiplex assay was applied to track antibody cross-reactivity due to previous contact with similar viruses and to identify antibodies against IFN-Is as the markers for severe COVID-19. In total, 278 serum samples from convalescent plasma donors, COVID-19 patients in the intensive care unit (ICU) and patients who recovered from mild/moderate COVID-19, vaccine recipients, prepandemic and pandemic patients with autoimmune endocrine disorders, and a heterogeneous prepandemic cohort including healthy individuals and chronically ill patients were analyzed. The anti-SARS-CoV-2 microarray results agreed well with the ELISA results. Regarding ICU patients, autoantibodies against IFN-Is were detected in 10.5% of samples, and 10.5% of samples were found to simultaneously contain IgM antibodies against more than two different viruses. Cross-reactivity between IgG against the SARS-CoV-2 nucleocapsid and IgG against the OC43 and HKU1 spike proteins was observed, resulting in positive signals for the SARS-CoV-2 nucleocapsid in prepandemic samples from patients with autoimmune endocrine disorders. The presence of IgG against the SARS-CoV-2 nucleocapsid in the absence of IgG against the SARS-CoV-2 spike RBD should be interpreted with caution.

Comparison of Clinical Findings in SARS-CoV-2 with Other Respiratory Viruses in Critically Ill Children during the COVID-19 Pandemic.

OBJECTIVES: The aim of this study was to compare the clinical and laboratory findings in SARS-CoV-2 (COVID-19) with those of other respiratory viruses in critically ill children. METHODS: It is a single center retrospective descriptive study conducted in a 32-bed pediatric intensive care unit (PICU). Our study was performed in Ankara City Hospital, Ankara, Turkey, between 1 March 2020, and 1 March 2021. Demographic and clinical characteristics of the patients were collected and we recorded the antibiotic use, antiviral treatments, respiratory and extracorporeal supports, PICU stay and survival rates. RESULTS: A total of 202 pediatric patients who tested positive for either COVID-19 or for another respiratory virus panel (RVP) were included in the study. Seventy-two patients were COVID-19 positive. The median age of COVID-19 positive patients and RVP positive patients was 97 and 17 months, respectively. Hypoxia was much more common in patients with RVP than in COVID-19 patients. Low oxygen saturation in arterial blood (SaO2), increased oxygen saturation index (OSI) and fraction of inspired oxygen (FiO2) needs were more significant in RVP patients than in COVID-19 patients. Respiratory support therapies, such as high-flow nasal cannula and non-invasive ventilation (NIV), were used more frequently in RVP patients than in COVID-19 patients. CONCLUSION: It is important to distinguish between COVID-19 and RVP cases in order to prioritize intensive care needs in these patients. In addition, non-Covid diseases should not be left aside in the pandemic and appropriate care should be provided to them.

COVID-19 originated in Wuhan, China, at the end of 2019 and has since spread around the world. During the key period of the pandemic from 1 March 2020, to 1 March 2021, the pediatric intensive care unit registered a total of 72 patients testing positive for SARS-CoV-2 and 130 patients positive for RVP on the respiratory virus panel. In this single-center study, we compared the clinical differences and course of the disease in pediatric intensive care patients infected with SARS-CoV-2 with patients diagnosed with respiratory tract viruses during the COVID-19 outbreak. Unlike previous studies, this is the first to compare the clinical manifestations of COVID-19 with other respiratory pathogens requiring intensive care. Respiratory support therapy, such as high-flow nasal cannula (HFNC) and NIV, was prescribed more frequently in RVP patients than in COVID-19 patients. In our study, low oxygen saturation in the arterial blood (SaO2), increased OSI and increased fraction of inspired oxygen (FiO2) requirements were more significant in RVP patients than in COVID-19 patients. In parallel, the need for mechanical ventilation was higher in RVP patients than in COVID-19 patients. Therefore, we believe that RVP patients should be followed more carefully during this pandemic period.

Comparison of 11 respiratory pathogens among hospitalized children before and during the COVID-19 epidemic in Shenzhen, China.

BACKGROUND: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children. METHODS: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children's Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (during the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed. RESULTS: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019.The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001). CONCLUSIONS: Successful containment of seasonal influenza as a result of COVID-19 control measures will ensure we are better equipped to deal with future outbreaks of both influenza and COVID-19.Caused by virus competition, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased in Shenzhen,that reminds us we need to take further monitoring and preventive measures in the next epidemic season.

Population Decline in COPD Admissions During the COVID-19 Pandemic Associated with Lower Burden of Community Respiratory Viral Infections.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has led to widespread implementation of public health measures, such as stay-at-home orders, social distancing, and masking mandates. In addition to decreasing spread of severe acute respiratory syndrome coronavirus 2, these measures also impact the transmission of seasonal viral pathogens, which are common triggers of chronic obstructive pulmonary disease (COPD) exacerbations. Whether reduced viral prevalence mediates reduction in COPD exacerbation rates is unknown. METHODS: We performed retrospective analysis of data from a large, multicenter health care system to assess admission trends associated with community viral prevalence and with initiation of COVID-19 pandemic control measures. We applied difference-in-differences analysis to compare season-matched weekly frequency of hospital admissions for COPD prior to and after implementation of public health measures for COVID-19. Community viral prevalence was estimated using regional Centers for Disease Control and Prevention test positivity data and correlated to COPD admissions. RESULTS: Data involving 4422 COPD admissions demonstrated a season-matched 53% decline in COPD admissions during the COVID-19 pandemic, which correlated to community viral burden (r = 0.73; 95% confidence interval, 0.67-0.78) and represented a 36% greater decline over admission frequencies observed in other medical conditions less affected by respiratory viral infections (incidence rate ratio 0.64; 95% confidence interval, 0.57-0.71, P < .001). The post-COVID-19 decline in COPD admissions was most pronounced in patients with fewer comorbidities and without recurrent admissions. CONCLUSION: The implementation of public health measures during the COVID-19 pandemic was associated with decreased COPD admissions. These changes are plausibly explained by reduced prevalence of seasonal respiratory viruses.

Virus load and incidence of olfactory, gustatory, respiratory, gastrointestinal disorders in COVID-19 patients: A retrospective cohort study.

OBJECTIVES: This study investigated the relationship between viral load and the incidence of olfactory and gustatory dysfunction (OD and GD), the incidence of respiratory and gastrointestinal symptoms and the recovery of OD and GD in COVID-19 patients. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: This study was conducted on 599 outpatients' cases in Golestan province between February and June 2020. MAIN OUTCOME MEASURES: The incidence, severity (complete or partial) and recovery time of OD and GD and their associations with cycle threshold (CT) values of SARS-CoV-2 polymerase chain reaction were assessed. RESULTS: The mean age of patients was 38.27 ± 13.62 years. The incidence of general symptoms included myalgia 70.1%, headache 51.8%, fever 47.7% and dyspnoea 21.4%. 41.9% of patients had gastrointestinal symptoms, including abdominal pain 26.5%, diarrhoea 25.2%, nausea 20.5% and vomiting 12.9%. 12.2% of patients had comorbidity. The trimester recovery rates of OD and GD were 93.94% and 94.74% respectively. The mean recovery time of OD and GD was 14.56 ± 13.37 and 13.8 ± 3.77 days respectively. The mean CT value in all patients was 27.45 ± 4.55. There were significant associations between the mean of CT value with headache (p = 0.04), GD (p = 0.002) and OD (p = 0.001). CONCLUSIONS: The finding of this study indicates a possible association between viral load with incidence of OD and GD in COVID-19 patient's cases and assures the recovery of OD/GD in these patients.

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.

BACKGROUND: Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. OBJECTIVE: We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. METHODS: This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. RESULTS: Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). CONCLUSION: Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. CLINICALTRIALSGOV IDENTIFIER: NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

The Role of Sialylation in Respiratory Viral Infection and Treatment.

Respiratory infections caused by viruses such as influenza and coronavirus are a serious global problem due to their high infection rates and potential to spark pandemics, such as the current COVID-19 pandemic. Although preventing these infections by using vaccines has been the most successful strategy to date, effective vaccines are not always available. Therefore, developing broad-spectrum anti-viral drugs to treat such infections is essential, especially in the case of immunocompromised patients or for outbreaks of novel virus strains. Sialic acids have been highlighted as a key molecule in the viral infection cycle, with terminally sialylated glycans acting as a target for several viral proteins involved in infection, particularly respiratory infection. Inhibitors of one such protein, neuraminidase, are the only anti-influenza drugs currently on the market. Problems with neuraminidase inhibitors, including the development of resistance and a relatively narrow spectrum of activity, drive the need for an improved understanding of the viral infection cycle and the development of more resilient, broader-spectrum anti-viral treatments. Hence, this review outlines the various roles played by sialic acids in respiratory viral infection and provides examples of drugs that exploit sialic acids to inhibit viral infections. It has been concluded that drugs targeting host cell expression of sialic acid could be especially well suited to inhibiting a broad spectrum of respiratory infections. This warrants the continued design and improvement of such drugs in an attempt to lessen the burden of respiratory infections.

Opportunities for respiratory disease transmission from people to chimpanzees at an East African tourism site.

Respiratory illnesses, including COVID-19, present a serious threat to endangered wild chimpanzee (Pan troglodytes) populations. In some parts of sub-Saharan Africa, chimpanzee tracking is a popular tourism activity, offering visitors a chance to view apes in their natural habitats. Chimpanzee tourism is an important source of revenue and thus benefits conservation; however, chimpanzee tracking may also increase the risk of disease transmission from people to chimpanzees directly (e.g., via aerosol transmission) or indirectly (e.g., through the environment or via fomites). This study assessed how tourist behaviors might facilitate respiratory disease transmission at a chimpanzee tracking site in Kibale National Park, Uganda. We observed tourists, guides, and student interns from the time they entered the forest to view the chimpanzees until they left the forest and noted behaviors related to disease transmission. Common behaviors included coughing, sneezing, and urinating, which respectively occurred during 88.1%, 65.4%, and 36.6% of excursions. Per excursion, individuals touched their faces an average of 125.84 ± 34.45 times and touched large tree trunks or branches (which chimpanzees might subsequently touch) an average of 230.14 ± 108.66 times. These results show that many pathways exist by which pathogens might move from humans to chimpanzees in the context of tourism. Guidelines for minimizing the risk of such transmission should consider tourist behavior and the full range of modes by which pathogen transmission might occur between tourists and chimpanzees.

Coronavirus disease 2019 (COVID-19), human erythrocytes and the PKC-alpha/-beta inhibitor chelerythrine -possible therapeutic implication.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. Until now, diverse drugs have been used for the treatment of COVID-19. These drugs are associated with severe side effects, e.g. induction of erythrocyte death, named eryptosis. This massively affects the oxygen (O2) supply of the organism. Therefore, three elementary aspects should be considered simultaneously: (1) a potential drug should directly attack the virus, (2) eliminate virus-infected host cells and (3) preserve erythrocyte survival and functionality. It is known that PKC-α inhibition enhances the vitality of human erythrocytes, while it dose-dependently activates the apoptosis machinery in nucleated cells. Thus, the use of chelerythrine as a specific PKC-alpha and -beta (PKC-α/-ß) inhibitor should be a promising approach to treat people infected with SARS-CoV-2.

Risk for In-Hospital Complications Associated with COVID-19 and Influenza - Veterans Health Administration, United States, October 1, 2018-May 31, 2020.

Coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, although increasing evidence indicates that infection with SARS-CoV-2, the virus that causes COVID-19, can affect multiple organ systems (1). Data that examine all in-hospital complications of COVID-19 and that compare these complications with those associated with other viral respiratory pathogens, such as influenza, are lacking. To assess complications of COVID-19 and influenza, electronic health records (EHRs) from 3,948 hospitalized patients with COVID-19 (March 1-May 31, 2020) and 5,453 hospitalized patients with influenza (October 1, 2018-February 1, 2020) from the national Veterans Health Administration (VHA), the largest integrated health care system in the United States,* were analyzed. Using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, complications in patients with laboratory-confirmed COVID-19 were compared with those in patients with influenza. Risk ratios were calculated and adjusted for age, sex, race/ethnicity, and underlying medical conditions; proportions of complications were stratified among patients with COVID-19 by race/ethnicity. Patients with COVID-19 had almost 19 times the risk for acute respiratory distress syndrome (ARDS) than did patients with influenza, (adjusted risk ratio [aRR] = 18.60; 95% confidence interval [CI] = 12.40-28.00), and more than twice the risk for myocarditis (2.56; 1.17-5.59), deep vein thrombosis (2.81; 2.04-3.87), pulmonary embolism (2.10; 1.53-2.89), intracranial hemorrhage (2.85; 1.35-6.03), acute hepatitis/liver failure (3.13; 1.92-5.10), bacteremia (2.46; 1.91-3.18), and pressure ulcers (2.65; 2.14-3.27). The risks for exacerbations of asthma (0.27; 0.16-0.44) and chronic obstructive pulmonary disease (COPD) (0.37; 0.32-0.42) were lower among patients with COVID-19 than among those with influenza. The percentage of COVID-19 patients who died while hospitalized (21.0%) was more than five times that of influenza patients (3.8%), and the duration of hospitalization was almost three times longer for COVID-19 patients. Among patients with COVID-19, the risk for respiratory, neurologic, and renal complications, and sepsis was higher among non-Hispanic Black or African American (Black) patients, patients of other races, and Hispanic or Latino (Hispanic) patients compared with those in non-Hispanic White (White) patients, even after adjusting for age and underlying medical conditions. These findings highlight the higher risk for most complications associated with COVID-19 compared with influenza and might aid clinicians and researchers in recognizing, monitoring, and managing the spectrum of COVID-19 manifestations. The higher risk for certain complications among racial and ethnic minority patients provides further evidence that certain racial and ethnic minority groups are disproportionally affected by COVID-19 and that this disparity is not solely accounted for by age and underlying medical conditions.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19.

The nasal viromes of cattle on arrival at western Canadian feedlots and their relationship to development of bovine respiratory disease.

Bovine respiratory disease (BRD) has a complex pathogenesis and aetiology, being the costliest disease affecting the cattle industry in North America. In this study, we applied Nanopore-based viral metagenomic sequencing to explore the nasal virome of cattle upon arrival at feedlot and related the findings to the development of BRD. Deep nasal swabs (DNS) from 310 cattle for which BRD outcomes were known (155 cattle developed BRD within 40 days and 155 remained healthy) were included. The most prevalent virus in on-arrival samples was bovine coronavirus (BCV) (45.2%, 140/310), followed by bovine rhinitis virus B (BRBV) (21.9%, 68/310), enterovirus E (EVE) (19.6%, 60/310), bovine parainfluenza virus 3 (BPIV3) (10.3%, 32/310), ungulate tetraparvovirus 1 (UTPV1) (9.7%, 30/310) and influenza D virus (7.1%, 22/310). No relationship was found between BRD development and the number of viruses detected, the presence of any specific individual virus or combination of viruses. Bovine kobuvirus (BKV) was detected in 2.6% of animals (8/310), being the first report of this virus in Canada. Results of this study demonstrate the diversity of viruses in bovine DNS collected upon arrival at feedlot and highlights the need for further research into prediction of BRD development in the context of mixed infections.

Viruses in Bovine Respiratory Disease in North America: Knowledge Advances Using Genomic Testing.

Advances in viral detection in bovine respiratory disease (BRD) have resulted from advances in viral sequencing of respiratory tract samples. New viruses detected include influenza D virus, bovine coronavirus, bovine rhinitis A, bovine rhinitis B virus, and others. Serosurveys demonstrate widespread presence of some of these viruses in North American cattle. These viruses sometimes cause disease after animal challenge, and some have been found in BRD cases more frequently than in healthy cattle. Continued work is needed to develop reagents for identification of new viruses, to confirm their pathogenicity, and to determine whether vaccines have a place in their control.

Pandemic with COVID-19 and Families with Children with Chronic Respiratory Diseases.

COVID-19 pandemic has provoked a huge change in daily functioning in millions of people worldwide. The epidemiological measures in prevention of possible infection have increased the possible risks on the mental and physical health. We have conducted a survey in order to investigate the needs and challenges of families with children with chronic respiratory diseases. In this order, we have created a questionnaire with general information about the family, general information about the child with chronic respiratory disease, overall physical and mental health before and during the pandemic, needs and mental health condition of the parents/caregivers. This survey showed that this group of families of children with respiratory disorders have suffered financially in significant way and has changed the way they perform professional and educational patterns due to the pandemic. Most of the children were stable in their physical health, but their mental health has deteriorated. This is probably due to the regular contact with the medical staff, but not with the mental health professionals. This group of children has a significant reduction in their physical activity and increase the hours in front of TV screens. The further effect on the physical and mental health is to be investigated.

A descriptive study of acute outbreaks of respiratory disease in Norwegian fattening pig herds.

BACKGROUND: Respiratory diseases are major health concerns in the pig production sector worldwide, contributing adversely to morbidity and mortality. Over the past years there was a rise in reported incidents of respiratory disease in pigs in Norway, despite population wide freedom from Aujeszky´s disease, porcine reproductive and respiratory syndrome, porcine respiratory corona virus and enzootic pneumonia. The main objective of this study was to investigate acute outbreaks of respiratory disease in conventional Norwegian fattening pig herds. The study included 14 herds. In seven herds with reported outbreaks of acute respiratory disease, data on clinical signs was recorded and samples for laboratory examination were collected. Diagnostic protocols were compared by parallel analysis of clinically healthy pigs from seven non-outbreak herds. RESULTS: The most commonly reported clinical signs were sudden deaths and dyspnea. An average compartment morbidity of 60%, mortality of 4% and case fatality of 9% was recorded in the outbreak herds. Post-mortem examinations revealed acute lesions resembling porcine pleuropneumonia in all 28 pigs investigated from the outbreak herds and in 2 of the 24 (8%) pigs from the non-outbreak herds. Chronic lesions were recorded in another 2 pigs (8%) from the non-outbreak herds. Actinobacillus pleuropneumoniae serovar 8 was isolated from lungs and/or pleura from all tested pigs (n = 28) in the outbreak herds, and from 2 out of 24 pigs (8%) in the non-outbreak herds, one pig with an acute and another pig with a chronic infection. No other significant bacterial findings were made. Seroconversion to A. pleuropneumoniae antibodies was detectable in all outbreak herds analyzed and in six out of seven non-outbreak herds, but the risk ratio for seroconversion of individual pigs was higher (risk ratio 2.3 [1.50- 3.43 95% CI; P < 0.001]) in the outbreak herds. All herds tested positive for porcine circovirus type 2 and negative for influenza A viruses on oral fluid RT-qPCR. CONCLUSION: The main etiological pathogen found during acute outbreaks of respiratory disease was A. pleuropneumoniae serovar 8. All pigs from outbreak herds had typical lesions of acute porcine pleuropneumonia, and only A. pleuropneumoniae serovar 8 was identified. Co-infections were not found to impact disease development.

Respiratory and Gastrointestinal COVID-19 Phenotypes in Kidney Transplant Recipients.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a large cohort of KT recipients with COVID-19. METHODS: Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery. RESULTS: The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery. CONCLUSIONS: COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality.

Viral Infections of the Upper Airway in the Setting of COVID-19: A Primer for Rhinologists.

BACKGROUND: Viral respiratory tract infections are associated with a significant burden of disease and represent one of the leading causes of mortality worldwide. The current Coronavirus Disease 2019 (COVID-19) pandemic highlights the devastating toll that respiratory viruses have on humanity and the desperate need to understand the biological characteristics that define them in order to develop efficacious treatments and vaccines. To date, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected nearly 600 times more people and resulted in 200 times more deaths relative to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) combined. OBJECTIVE: Through this review, we aim to summarize the key characteristics of respiratory viruses that hold global significance, with a focus on SARS-CoV-2. Our goal is to disseminate our current knowledge of these infectious agents to otolaryngologists, in particular rhinologists, practicing in the COVID-19 era. METHODS: The general and clinical characteristics of selected respiratory viruses along with available viral treatments and vaccines are reviewed. RESULTS: There has been significant progress in our understanding of the epidemiology and pathogenesis of various respiratory viruses. However, despite the advancement in knowledge, efficacious vaccines and antiviral treatments remain elusive for most respiratory viruses. The dire need for these scientific discoveries is highlighted by the recent COVID-19 pandemic, which has prompted investigators worldwide to conduct clinical trials at an accelerated timeline in an effort to reduce the morbidity and mortality associated with SARS-CoV-2 infection. Rhinologists will continue to remain on the front-lines of pandemics associated with respiratory viruses. CONCLUSION: In light of these unprecedented times, the need to understand the nuances of these viral respiratory pathogens, especially SARS-CoV-2, cannot be overemphasized. This knowledge base is of particular importance to otolaryngologists, whose expertise in the upper airway coincides with the anatomic tropism of these infectious agents.