Analysis of pathogen detection results of upper respiratory tract specimens from fever clinic patients

Objective: To explore the pathogen composition and distribution characteristics of pathogens in respiratory samples from patients with fever of unknown origin. Methods: A total of 96 respiratory samples of patients with unknown cause fever with respiratory symptoms were collected from four hospitals above grade II in Shijiazhuang area (Hebei Provincial Hospital of Traditional Chinese Medicine, Luancheng District People's Hospital, Luquan District People's Hospital, Shenze County Hospital) from January to April 2020, and multiplex-fluorescent polymerase chain reaction(PCR)was used to detect influenza A virus, influenza B virus, enterovirus, parainfluenza virus I/II/III/IV, respiratory adenovirus, human metapneumovirus, respiratory syncytial virus, human rhinovirus, human bocavirus, COVID-19, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa, Streptococcus pneumoniae, Klebsiella pneumoniae, Group A streptococcus, Haemophilus influenzae, Staphylococcus aureus nucleic acid detection, the results were analyzed for chi-square. Results: A total of 8 pathogens were detected in the upper respiratory tract samples of 96 fever patients, including 1 kind of virus, 6 kinds of bacterias, and Mycoplasma pneumoniae. There were 12 viruses including influenza virus and parainfluenza virus, Legionella pneumophila and Chlamydia pneumoniae were not detected. The pathogen detection rates in descending order were Streptococcus pneumoniae (58/96, 60.42%), Haemophilus influenzae(38/96, 39.58%), Klebsiella pneumoniae (14/96, 14.58%), Staphylococcus aureus (10/96, 10.42%), Mycoplasma pneumoniae (8/96, 8.33%), Pseudomonas aeruginosa (6/96, 6.25%), Group A streptococcus (4/96, 4.17%) and human rhinovirus (2/96, 2.08%). The proportions of single-pathogen infection and multi-pathogen mixed infection in fever clinic patients were similar, 41.67% (40/96) and 45.83% (44/96), respectively, and 12.50% (12/96)of the cases had no pathogens detected. The infection rate of Mycoplasma pneumoniae in female patients with fever (21.43%) was higher than that in male patients with fever (2.94%) (P < 0.05). There was no statistical difference between the distribution of of other pathogens and gender and age(P > 0.05). Conclusions: The upper respiratory tract pathogens were mainly bacterial infections, and occasional human rhinovirus and Mycoplasma pneumonia infections. In clinical diagnosis and treatment, comprehensive consideration should be given to the pathogen detection.

COVID-19: comparison lung CT signs and biochemical parameters in the groups of patients with three-time positive RT-PCR and with triple negative RT-PCR test during the period of hospitalization.

Research goal. Comparative characteristics of the dynamics of CT semiotics and biochemical parameters of two groups of patients: with positive RT-PCR and with triple negative RT-PCR. Reflection of the results by comparing them with the data already available in the literature. The aim of the study is to compare the dynamics of CT semiotics and biochemical parameters of blood tests in two groups of patients: with positive RT-PCR and with triple negative RT-PCR. We also reflect the results by comparing them with the data already available in the literature. Materials and methods. We have performed a retrospective analysis of CT images of 66 patients: group I (n1 = 33) consists of patients who had three- time negative RT-PCR (nasopharyngeal swab for SARS-CoV-2 RNA) during hospitalization, and group II (n2 = 33) includes patients with triple positive RT-PCR. An important selection criterion is the presence of three CT examinations (primary, 1st CT and two dynamic examinations - 2nd CT and 3rd CT) and at least two results of biochemistry (C-reactive protein (CRP), fibrinogen, prothrombin time, procalcitonin) performed in a single time interval of +/- 5 days from 1st CT, upon admission, and +/- 5 days from 3st CT. A total of 198 CT examinations of the lungs were analyzed (3 examinations per patient). Results. The average age of patients in the first group was 58 +/- 14.4 years, in the second - 64.9 +/- 15.7 years. The number of days from the moment of illness to the primary CT scan 6.21 +/- 3.74 in group I, 7.0 (5.0-8.0) in group II, until the 2nd CT scan - 12.5 +/- 4, 87 and 12.0 (10.0-15.0), before the 3rd CT scan - 22.0 (19.0-26.0) and 22.0 (16.0-26.0), respectively. In both groups, all 66 patients (100%), the primary study identified the double-sided ground-glass opacity symptom and 36 of 66 (55%) patients showed consolidation of the lung tissue. Later on, a first follow-up CT defined GGO not in all the cases: it was presented in 22 of 33 (67%) patients with negative RT-PCR (group I) and in 28 of 33 (85%) patients with the positive one (group II). The percentage of studies showing consolidation increased significantly: up to 30 of 33 (91%) patients in group I, and up to 32 of 33 (97%) patients in group II. For the first time, radiological symptoms of "involutional changes" appeared: in 17 (52%) patients of the first group and in 5 (15%) patients of the second one. On second follow-up CT, GGO and consolidations were detected less often than on previous CT: in 1 and 27 patients of group I (3% and 82%, respectively) and in 6 and 30 patients of group II (18% and 91%, respectively), although the consolidation symptom still prevailed significantly . The peak of "involutional changes" occurred on last CT: 31 (94%) and 25 (76%) patients of groups I and II, respectively.So, in the groups studied, the dynamics of changes in lung CT were almost equal. After analyzing the biochemistry parameters, we found out that CRP significantly decreased in 93% of patients (p < 0.001) in group I;in group II, there was a statistically significant decrease in the values of C-reactive protein in 81% of patients (p = 0.005). With an increase in CT severity of coronavirus infection by one degree, an increase in CRP by 41.8 mg/ml should be expected. In group I, a statistically significant (p = 0.001) decrease in fibrinogen was recorded in 77% of patients;and a similar dynamic of this indicator was observed in group II: fibrinogen values decreased in 66% of patients (p = 0.002). Such parameters as procalcitonin and prothrombin time did not significantly change during inpatient treatment of the patients of the studied groups (p = 0.879 and p = 0.135), which may indicate that it is inappropriate to use these parameters in assessing dynamics of patients with a similar course of the disease. When comparing the outcomes of the studied groups, there was a statistically significant higher mortality in group II - 30.3%, in group I - 21.2% (p = 0.043). Conclusion. According to our data, a course of the disease does not significantly differ in the groups o patients with positive RT-PCR and three-time negative RT-PCR. A negative RT-PCR analysis may be associated with an individual peculiarity of a patient such as a low viral load of SARS-CoV-2 in the upper respiratory tract. Therefore, with repeated negative results on the RNA of the virus in the oro- and nasopharynx, one should take into account the clinic, the X-ray picture and biochemical indicators in dynamics and not be afraid to make a diagnosis of COVID-19.Copyright © 2021 ALIES. All rights reserved.

A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

Physical and mental condition and medicine consumption of frontline medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019.

Objective To investigate the physical and mental condition and medicine consumption of medical staff of shelter hospitals in Shanghai during the fight against the epidemic of coronavirus disease 2019 (COVID-19). Methods A total of 144 frontline medical staff who fighting against the COVID-19 epidemic from a tertiary first-class hospital from Apr. 4 to May 12, 2022 were surveyed by questionnaires online. Their physical condition including body weight change before the medical work and one month later, sleep quality and the medicine consumption during the medical work were collected and analyzed. Results The mean body weight of frontline doctors before the medical work and one month later were (69.80+/-8.35) kg and (68.60+/-7.37) kg, while those of nurses were (55.36+/-8.27) kg and (53.80+/-7.38) kg, both showing a decreasing trend but without significant difference (all P0.05). A total of 63.89% (92/144) frontline medical staff suffered from insomnia, of which 27.08% (39/144) needed drug intervention. The top 5 common diseases among frontline medical staff were sleep disorder (63.89%, 92/144), skin injury (25.69%, 37/144), body pain (23.61%, 34/144), oral ulcer (13.19%, 19/144), and acute upper respiratory tract infection (9.72%, 14/144). A total of 155 medical staff used drugs, and the top 5 common drugs were skin application (16.77%, 26/155), Ganmao'an granule (12.26%, 19/155), zolpidem tartrate tablets (11.61%, 18/155), Kangfuxin liquid (11.61%, 18/155), and celecoxib capsules (8.39%, 13/155). Conclusion Frontline medical staff in shelter hospitals are prone to have body weight change, sleep disorder, skin injury, body pain, oral ulcer, acute upper respiratory tract infection and so on, which suggests that in future similar large-scale medical support, it is necessary to pay sufficient attention to the physical condition of frontline medical staff and provide them sufficient medicine.Copyright © 2022, Second Military Medical University Press. All rights reserved.

The influence of the Covid-19 pandemic on the shunt revision rate

Introduction: During the first year of the Covid-19 pandemic we observed a decrease of our shunt revision rate. In order to investigate a possible correlation with an assumingly lower general infection rate in children in times of lock down and homeschooling, we performed a detailed analysis of our shunt and general pediatric patient population. Method(s): Electronic patient charts retrieval for children admitted for shunt revision or infectious diseases was performed for four time periods (study period April 2020 - March 2021, control periods from three previous years). A detailed analysis of all shunt revision and infectious cases including age and season specific evaluation followed. Possible correlations were investigated. Result(s): A total of 318 shunt revision and 13,919 pediatric cases have been evaluated. The shunt revision rate during the study period was 29% less compared to the average rate of three previous years (p 0.061), the number of pediatric cases with main diagnosis infection dropped significantly (p < 0.05), whereas other pediatric admissions remained stable. Significant age or seasonal influences did not exist. The number of shunt revisions in association with a documented systemic infection or a primary shunt infection dropped significantly during the study period (p<0.05 each). This was not the case for underdrainage, overdrainage (p>0.05 each) or other indications. In general, infections of upper and lower airways, the gastrointestinal and nervous system decreased during the pandemic, urinary infection rates remained stable. Conclusion(s): The decreased shunt revision rate during the first year of the pandemic seems correlate with a decrease of the general infection rate in children and adolescents at the same time. Infectionassociated shunt failures showed a significant decrease during this period compared to previous years.

Potential targets and traditional Chinese medicine treatment strategy of cough after SARS-CoV-2 infection.

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) Omicron variants BA.5.2 and BF.7 have become the main epidemic strains in China since the quarantine policy was lifted in 7th December 2022. Cough is one of the main symptoms induced by SARS-CoV-2 infection. SARS-CoV-2 infection-associated cough injuries the lung and upper respiratory tract, while the infected people cough out virus and liquid which forms virus-containing aerosols, a medium for quickly spreading. Furthermore, cough is one of primary sequelae of discharged patients in corona virus disease 2019 (COVID-19). By now, there are no efficacious drugs for treatment of upper respiratory tract infection associated cough induced by omicron. Traditional Chinese medicine (TCM) has a long history on treating cough. By reviewing the mechanisms of the occurrence of cough after SARS-CoV-2 infection, potential therapeutic targets and cough suppressant herbs with significant efficacy in clinical and basic research, we provide a reference for the treatment of cough after SARS-Cov-2 infection and a basis for the majority of infected patients to select appropriate herbs for cough relief under guidance of physicians.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Development of warm autoimmune hemolytic anemia after initiation of Ruxolitinib in a patient with STAT1 gain-of-function mutation

Introduction: STAT1 gain-of-function (GOF) disease is associated with chronic mucocutaneous candidiasis (CMC) and a broad spectrum of infectious, inflammatory, and vascular manifestations. The Janus Kinase inhibitor ruxolitinib has been used successfully for CMC and autoimmune phenomena. We describe a case of warm autoimmune hemolytic anemia (WAIHA) in a patient with STAT1 GOF disease after initiating ruxolitinib. Case report: A 36-year-old man with STAT1 c.850G>A (p.Glu284Lys) mutation presented with CMC as well as recurrent viral and bacterial infections, lymphadenopathy, enteritis, nodular regenerative hyperplasia (NRH) and splenomegaly. Immune workup confirmed a combined immunodeficiency with hypogammaglobulinemia and T-cell lymphopenia. Ruxolitinib was initiated at 5 mg twice daily (due to pre-existing thrombocytopenia) with up titration over 3 months to 20 mg twice daily. He improved with weight gain, increased energy, resolution of chronic anemia, and improved lymphadenopathy and splenomegaly on imaging. Serum CXCL9 only minimally decreased from 4660 pg/ml to 3990 pg/ml. Soon after reaching ruxolitinib 20 mg twice daily, he developed JC viremia, prompting dose reduction to 15 mg BID. Within two weeks, he developed a non-COVID upper respiratory tract infection followed by fatigue, shortness of breath with ambulation, and dark urine. Emergency evaluation revealed warm antibody positive hemolytic anemia with a hemoglobin of 5 g/dL, and worsened thrombocytopenia. He was treated with blood transfusions, pulse steroids, and high-dose IVIG with stabilization but continued hemolysis. Due to the JC viremia, there was concern to give rituximab with increased PML risk. Bone marrow showed trilineage hematopoiesis, a mild increase in megakaryocytes and RBC precursors, and a loss of B-cell progenitors with retention of mature B cells. His B and T lymphocyte numbers had increased since prior to ruxolitinib, with a predominance of Tfh1-cells (58.7% of total Tfh-cells). He was started on sirolimus with a slow taper of prednisone with continued stable hemoglobin and platelets, and resolution of hemolysis after 3 months. Conclusion(s): To our knowledge, this is the first case of a STAT1 GOF patient developing WAIHA while receiving ruxolitinib therapy. Treatment choices were complicated by the risks of PML. Sirolimus combined with ruxolitinib allowed wean of corticosteroid and subsequent resolution of hemolysis.Copyright © 2023 Elsevier Inc.

ENT Manifestation of Covid-19: An Experience at a Tertiary Care Medical Teaching Institute of Khyber Pakhtunkhwa

Aim: To determine the frequency of ear, nose and throat related disorders of covid disease in PCR proven positive Covid-19 patients. Method(s): This prospective study included 320 Covid-19 positive patients and was conducted at ENT Department of MTI Hayatabad Medical Complex, Peshawar from May 1, 2021 to April 30, 2022. The acute phase of covid-19 was taken as the time interval between the onsets of symptoms as day 1 today 30th post infection. Questions were asked about the following symptoms;flu, sore throat, sinus involvement, taste disturbances, smell disturbances, hoarseness and hearing loss. Clinical examination and relevant investigations were carried out to make a diagnosis. The data was documented on a proforma & analyzed using SPSS 26.0 for windows to determine the frequencies of signs & symptoms related to ENT. Result(s): A total of 320 patients were included in the study. The ages ranged from 18-50 years with mean age of 33.96 years. The age group 18-25 years mostly presented with symptoms related to ENT. Upper respiratory tract infection was the commonest symptom (60.6%) followed by sore throat (57.5%). Smell and taste disturbances accounted for in 46.3% & 15.3 % of the patients respectively. Fungal rhinosinusitis was observed in 6.9% of the patients. As there is a wide variation of the ENT symptoms in covid disease, it is important to know the predictive symptoms so that appropriate measures can be adopted. Identification & isolation of patients will prevent spread of disease and focused therapy and investigations. Practical implication Conclusion(s): The portal of entry for the SARS-CoV-2 is through the upper airway. It is important to know the symptoms related to ENT to make an early diagnosis and therefore, institute measures for management and prevention of further spread of the disease.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

In Vitro Potential Virucidal Effect Evaluation of Xibornol on Human Adenovirus Type 5, Human Rhinovirus Type 13, Human Coronavirus 229E, Human Parainfluenza Virus Type 1, and Human Respiratory Syncytial Virus.

The availability of virucidal compounds to reduce the impact of respiratory viruses is a relevant topic for public health, especially during the recent coronavirus disease (COVID-19) pandemic. Antimicrobial properties of Xibornol are known since the 1970s, but its activity on viruses is currently little explored. In this study, Xibornol activity at a fixed concentration of 0.03 mg/100 ml has been evaluated on five respiratory viruses (Human Adenovirus 5, Human Rhinovirus type 13, Human Coronavirus 229E, Human Parainfluenza Virus type 1, and Human Respiratory Syncytial Virus) through in vitro experiments based on adapted European standard UNI EN 14476-20019. The experiments were carried out under two different environmental conditions, one with the addition of fetal bovine serum to simulate an in vivo condition (dirty condition) and the other without the addition of any organic substances (clean condition). The viral abatement of Xibornol (expressed as Log10 reduction - LR) was statistically significant under both clean and dirty environmental conditions. Namely, in clean condition, LR ranged from 2.67 to 3.84, while in the dirty one the abatement was slightly lower (from 1.75 to 3.03). Parainfluenza Virus and Human Adenovirus were most resistant compared to the other viruses. The obtained data confirmed Xibornol activity and its use as topic substance for viral inactivation to prevent upper respiratory tract disease.

Liver injury caused by SARS-CoV-2 delta and omicron-variant in Taiwan

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has recently emerged and spread globally. An outbreak of coronavirus disease 2019 (COVID-19) caused by the Delta variant occurred in Southern Taiwan in June 2021 and has been eliminated [1]. However, in April 2022, there was an outbreak of the Omicron variant in Taiwan. Fifteen patients with Omicron variant were admitted to our hospital from April 26 to May 1, 2022. We compared the clinical characteristics of the patients with the Delta variant in June 2021 and the Omicron variant in April 2022 (Table 1). These laboratory data were the first laboratory data at admission, and no anti-COVID-19 therapy was prescribed before these data. There were no differences in age (59.9 vs. 57.1 years, P = 0.96), male gender (63.6 vs. 60.0%, P = 1.00), diabetes ratio (27.3 vs. 35.7%, P = 1.00), body mass index (25.0 vs. 26.0 kg/m2, P = 1.00), pneumonia ratio (18.2 vs. 40.0%, P = 0.40) between the Delta and Omicron variants. There were also no differences in serum levels of aspartate aminotransferase (AST) (40.1 vs. 25.8 IU/L, P = 0.24) and alanine aminotransferase (ALT) (26.3 vs. 27.2 IU/L, P = 0.64) between the two groups. All the patients with the Omicron variant were symptomatic. The most common symptoms were upper respiratory tract infections (60.0%) (Supplementary Table 1). Six patients developed pneumonia without mechanical ventilator support requirement during admission (40.0%). Remdesivir, Paxlovid, or Molnupiravir were prescribed to patients according to their clinical conditions. Among the patients with the Omicron variant, nine (60.0%) had past medical history of diabetes, four (26.7%) had hypertension, three had chronic kidney disease (20.0%), and three had malignancy history (20.0%). COVID-19 might cause liver injury and lead to a more unfavorable prognosis [2]. In this study, about one-fifth of the patients suffered from liver injury, which was similar to previous studies [3]. There was no difference in liver injury between the Delta and Omicron variants in our study, which echoes previous research [4]. COVID-19 vaccination might protect against symptomatic diseases caused by the Omicron variant [5]. Vaccination rates have increased since 2021. In the study, over ninety percent of the patients have received at least two doses of vaccination. In conclusion, we demonstrated no difference in liver injury ratio between the Delta and Omicron variants. To our knowledge, this is the first report that compares the Delta and Omicron variants in Taiwan.

Historical perspective: other human coronavirus infectious diseases, SARS and MERS

Alphacoronaviruses (HCoV-229E and HCoV-NL63) and betacoronaviruses (HCoV-OC43 and HCoV-HKU1) are common causes of upper respiratory tract infection in humans. SARS-CoV-1 and MERS-CoV emerged in 2002 and 2012, respectively, with the potential of causing severe and lethal disease in humans, termed SARS and MERS, respectively. Bats appear to be the common natural source of SARS-like coronaviruses including SARS-CoV-1, but their role in MERS-CoV is less clear. Civet cats and dromedary camels are the intermediary animal sources for SARS-CoV-1 and MERS-CoV, respectively. Nosocomial outbreaks are hallmarks of SARS and MERS. MERS patients with comorbidities or immunosuppression tend to progress more rapidly to respiratory failure and have a higher case fatality rate than SARS patients. SARS has disappeared since 2004, while there are still sporadic cases of MERS in the Middle East. Continued global surveillance is essential for SARS-like coronaviruses and MERS-CoV to monitor changing epidemiology due to viral variants.Copyright © ERS 2021.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children

Background: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. Objectives: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. Search methods: We searched CENTRAL (2022, Issue 3), including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 16 March 2022), Embase (2010 to 16 March 2022), CINAHL (1981 to 16 March 2022), AMED (1985 to 16 March 2022), CAMbase (searched 16 March 2022), and British Homeopathic Library (searched 26 June 2013- no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov (16 March 2022), checked references, and contacted study authors to identify additional studies. Selection criteria: We included double-blind randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: In this 2022 update, we identified three new RCTs involving 251 children, for a total of 11 included RCTs with 1813 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for ARTIs. All studies focused on upper respiratory tract infections (URTIs), with only one study including some lower respiratory tract infections (LRTIs). Six treatment studies examined the effect on URTI recovery, and five studies investigated the effect on preventing URTIs after one to four months of treatment. Two treatment and three prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products, with dilutions ranging from 1 x 10-4 to 1 x 10-200. We identified several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many studies had additional domains with unclear risk of bias. Four studies received funding from homeopathy manufacturers;one study support from a non-government organisation;two studies government support;one study was co-sponsored by a university;and three studies did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products, whilst trials at unclear or high risk of bias reported beneficial effects. For the comparison of individualised homeopathy versus placebo or usual care for the prevention of ARTIs, two trials reported on disease severity;due to heterogeneity the data were not combined, but neither study demonstrated a clinically significant difference. We combined data from two trials for the outcome need for antibiotics (OR 0.79, 95% CI 0.35 to 1.76;low-certainty evi

Smell disorders associated with COVID-19 infection

Background: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, nose, anosmia, hyposmia, smell, olfactory, ORL, different ENT related symptoms. We reviewed published and peer-reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. Main text: Within the included 2549 COVID-19 laboratory-confirmed positive patients, smell affection was reported in 1453 patients (57%). The other reported ENT manifestations were taste disorder (49.2%), headache (42.8%), nasal blockage (26.3%), sore throat (25.7%), runny nose or rhinorrhea (21.3%), upper respiratory tract infection (URTI) (7.9%), and frequent sneezing (3.6%). Conclusion(s): Smell affection in COVID-19 is common and could be one of the red flag signs in COVID-19 infection. With a sensitivity of utilized questionnaire in smell identification, a homogenous universal well-defined COVID-19 questionnaire is needed to make the COVID-19 data collection more sensible.Copyright © 2021, The Author(s).

Does Covid-19 Increase the Risk of Atrial Fibrillation? A Retrospective Analysis of a Large Administrative Claims Database of Commercially Insured Non-Elderly and Medicare Advantage Beneficiaries in the United States

Background: Studies have suggested that myocardial damage due to severe acute respiratory syndrome-2 (SARS-CoV-2), commonly referred to as COVID-19, may increase the risk of arrhythmias. Objective(s): To compare the one-year incidence of atrial fibrillation (AF) among patients with COVID-19 as compared to patients with non-COVID-19 acute upper respiratory infection (AURI). Method(s): The Optum Clinformatics database, an administrative claims databaseof commercially insured beneficiaries in the United States (US), was used for study purposes. Three cohorts of patients were identified: patients with COVID-19 diagnosis in any setting (April 2020-June 2021);patients with AURI in the pandemic period (April 2020-June 2021);and patients with AURI in the pre-pandemic period (January 2018-December 2018). Patients with prior AF diagnosis were excluded from each cohort. Three sets of analysis comparing AF incidence were performed: COVID-19 cohort vs AURI pandemic cohort;COVID-19 cohort vs AURI pre-pandemic cohort;and AURI pandemic cohort vs AURI pre-pandemic cohort. For each of the three comparisons, a matching weight method was used to help ensure balance among groups on baseline socio-demographic and clinical comorbidities. Logistic regression was used to assess the odds of 1-year incident AF among matched patients. Result(s): When comparing the matched COVID-19 (n=102,227) and AURI pandemic (n=102,101) cohorts, one-year incidence of AF was significantly higher in the COVID-19 cohort (2.2% vs 1.2%;p<0.001), who were 83% more likely to develop AF (odds ratio [OR] 1.83;95% confidence interval [CI] 1.72-1.95) as compared to the AURI group. COVID-19 patients were also observed to have significantly higher risk of incident AF as compared to AURI pre-pandemic cohort (2.7% vs 1.6%;p<0.001;OR 1.70, 95% CI 1.63-1.78). No significant difference was observed in AF incidence among the AURI pandemic versus AURI pre-pandemic cohort (1.1% vs 1.2%;p=0.133;OR 0.95, 95% CI 0.90-1.01). Figure 1 depicts differences in AF incidence across the comparator cohorts. Conclusion(s): Patients with COVID-19 were observed to have a higher incidence of AF as compared to those with upper respiratory infections. Awareness amongst clinicians of an increased AF incidence in COVID-19 affected patients appears warranted. [Formula presented] French language not detected for EMBFRA articles source xmlCopyright © 2023

Epidemiological Characteristics of Community-Acquired Pneumonia during the Covid-19 Epidemic in the Russian Federation

COVID-19 belongs to the group of acute respiratory infections and it is often complicated with pneumonia. This study aimed to investigate manifestations of community-acquired pneumonia (CAP) epidemic process during the COVID-19 epidemic in the Russian Federation. We analyzed the official statistical data reporting the incidence of CAP in the Russian Federation in 2013-2020 and incidence of COVID-19 as registered in March-July 2020. The mean average annual CAP incidence rate that we calculated and the 2020 CAP incidence prediction allowed assessing the relationship between CAP and COVID-19. It is shown that the long-term dynamics of the incidence of CAP in the Russian Federation is characterized by a pronounced upward trend with an average annual growth rate of 6.4%. The share of adult population among the CAP cases is the largest;on average, it is 64.7% (95% CI [63.1;66.3]). In 2020, against the background of SARS-CoV-2 circulation, the discrepancy between the actual incidence of CAP and the predicted figures reached and exceeded 558% (in July 2020). As the COVID-19 epidemic developed, the incidence of CAP was registered to increase. There was established a direct and significant correlation between the incidence of CAP and COVID-19 (rxy = 0.932;p <0.01).Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

Week 48 results of a phase 3 randomized controlled trial of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) vs dolutegravir 1 emtricitabine/tenofovir disoproxil fumarate (DTG 1 F/TDF) as initial treatment in HIV-1/HBV-coinfected adults (ALLIANCE)

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.

Deep learning model for binary classification of COVID-19 based on Chest X-Ray

COVID-19 is a novel virus infecting the upper respiratory tract and lungs. On a scale of the global pandemic, the number of cases and deaths had been increasing each day. Chest X-ray (CXR) images proved effective in monitoring a variety of lung illnesses, including the COVID-19 disease. In recent years, deep learning (DL) has become one of the most significant topics in the computing world and has been extensively applied in several medical applications. In terms of automatic diagnosis of COVID-19, those approaches had proven to be very effective. In this research, a DL technology based on convolution neural networks (CNN) models had been implemented with less number of layers with tuning parameters that will take less time for training for binary classification of COVID-19 based on CXR images. Experimental results had shown that the proposed model for training had achieved an accuracy of 96.68%, Recall of 94.12%, Precision of 93.49%, Specificity of 97.61%, and F1 Score of 93.8%. Those results had shown the high value of utilizing DL for early COVID-19 diagnosis, which can be utilized as a useful tool for COVID-19 screening. © 2023 IEEE.