Prolonged viral pneumonia and high mortality in COVID-19 patients on anti-CD20 monoclonal antibody therapy.

PURPOSE: In clinical practice, we observed an apparent overrepresentation of COVID-19 patients on anti-CD20 monoclonal antibody therapy. The aim of this study was to characterize the clinical picture of COVID-19 in these patients. METHODS: All adult patients from Turku University Hospital, Turku, Finland, with COVID-19 diagnosis and/or positive SARS-CoV-2 PCR test result up to March 2023, and with anti-CD20 therapy within 12 months before COVID-19 were included. Data was retrospectively obtained from electronic patient records. RESULTS: Ninety-eight patients were identified. 44/93 patients (47.3%) were hospitalized due to COVID-19. Patients with demyelinating disorder (n = 20) were youngest (median age 36.5 years, interquartile range 33-45 years), had less comorbidities, and were least likely to be hospitalized (2/20; 10.0%) or die (n = 0). COVID-19 mortality was 13.3% in the whole group, with age and male sex as independent risk factors. Persistent symptoms were documented in 33/94 patients (35.1%) alive by day 30, in 21/89 patients (23.6%) after 60 days, and in 15/85 after 90 days (17.6%), mostly in patients with haematological malignancy or connective tissue disease. Prolonged symptoms after 60 days predisposed to persistent radiological findings (odds ratio 64.0; 95% confidence interval 6.3-711; p < 0.0001) and persistently positive PCR (odds ratio 45.5, 95% confidence interval 4.0-535; p < 0.0001). Several patients displayed rapid response to late antiviral therapy. CONCLUSION: Anti-CD20 monoclonal antibody therapy is associated with high COVID-19 mortality and with a phenotype consistent with prolonged viral pneumonia. Our study provides rationale for retesting of immunocompromised patients with prolonged COVID-19 symptoms and considering antiviral therapy.

Biomarkers: Are They Useful in Severe Community-Acquired Pneumonia?

Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.

Influenza and Viral Pneumonia.

Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are in general nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited but there is ongoing research on the development and clinical testing of new treatment regimens and strategies.

Risk factors for SARS-CoV-2 pneumonia among renal transplant recipients in Beijing Omicron wave.

The novel coronavirus disease-19 had become an unprecedented global health emergency, quickly expanding worldwide. Omicron (B.1.1.529), as a novel variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in South Africa and Botswana. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. Thus, this study aimed to assess the incidence and risk factors of SARS-CoV-2 pneumonia that occurred in RTRs with Omicron infection. This single-center case-control study enrolled the RTRs who were diagnosed with SARS-CoV-2 infection by the SARS-CoV-2 nucleic acid test, which were divided into two groups according to the imaging features of SARS-CoV-2 pneumonia. The parameters were collected by questionnaires and analyzed using Statistical Product and Service Solutions. A total of 313 RTRs completed the questionnaires, and 131 were enrolled in this study with a mean age of 42.66 years. The incidence of SARS-CoV-2 pneumonia among the enrolled participants was 76.3%. The first symptoms included fever (89.3%), cough (93.1%), and expectoration (81.7%). From the comparison, the parameters such as age, gender, body mass index, lymphocyte count, and the percent of neutrophils and the basic serum creatinine before SARS-CoV-2 infection were significantly different between the two groups (P < 0.05). In multivariate analysis, age and the basic serum creatinine were independent risk factors for developing SARS-CoV-2 pneumonia (P < 0.05). Older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia. More randomized controlled studies are needed.IMPORTANCEThis study aimed to assess the incidence and the risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia that occurred in renal transplant recipients (RTRs) with Omicron infection. In conclusion, older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia and should be timely treated, in case of severe pneumonia.

Viral Pneumonia: From Influenza to COVID-19.

Respiratory viruses are increasingly recognized as a cause of community-acquired pneumonia (CAP). The implementation of new diagnostic technologies has facilitated their identification, especially in vulnerable population such as immunocompromised and elderly patients and those with severe cases of pneumonia. In terms of severity and outcomes, viral pneumonia caused by influenza viruses appears similar to that caused by non-influenza viruses. Although several respiratory viruses may cause CAP, antiviral therapy is available only in cases of CAP caused by influenza virus or respiratory syncytial virus. Currently, evidence-based supportive care is key to managing severe viral pneumonia. We discuss the evidence surrounding epidemiology, diagnosis, management, treatment, and prevention of viral pneumonia.

Value of Combined Detection of PCT, CRP, and FIB in Differentiating Viral Infection from Bacterial Infection in Severe Pneumonia.

BACKGROUND: The aim was to explore the value of combined detection of PCT, CRP, and FIB in differentiating severe pneumonia from viral infection and bacterial infection. METHODS: A total of 100 patients with severe pneumonia admitted to Hebei General Hospital from August 2020 to November 2021 were selected as the research objects, including 50 patients with viral pneumonia (as the viral group, n = 50) and 50 patients with bacterial pneumonia (as the bacterial group, n = 50). At the same time, the clinical data of 50 healthy people in the hospital were selected as the healthy group (n = 50). All the subjects in the three groups were tested for PCT, CRP, and FIB. The difference of each index level among the three groups was compared. The diagnostic efficacy of each index for pneumonia was analyzed by drawing receiver operating characteristic curves, and the independent predictors of pneumonia were determined by logistic regression model. RESULTS: There were no statistically significant differences in gender, age, course of disease, body mass index (BMI), and other general data among the three groups (p > 0.05). Compared with the healthy group, the levels of serum PCT, CRP, and FIB in the viral group and the bacterial group were significantly increased, and the levels of serum PCT, CRP, and FIB in the bacterial group were significantly higher than those in the viral group, and the differences were statistically significant (p < 0.05). The positive rates of FIB, CRP, and PCT in bacterial group and viral group were increased in turn, and the differences were statistically significant (p < 0.05), and the positive rates of combined detection in the two groups were significantly higher than the positive rates of single index detection (p < 0.05). Taking etiological examination as the gold standard, the sensitivity (92.59%) and specificity (90.17%) of the three combined detection methods were significantly higher than those of PCT, CRP, and FIB alone. Kappa test showed that the results of the combined detection and etiological examination were in good agreement (Kappa value = 0.847, p < 0.05). ROC curve analysis showed that the AUC of combined prediction of the three was 0.964, which was higher than that of single detection of 0.859, 0.832, and 0.871. Logistic regression analysis showed that serum PCT, CRP, and FIB were independent predictors of bacterial pneumonia, and the differences were statistically significant (p < 0.05). Pearson's correlation analysis showed that FIB level in the bacterial group was positively correlated with PCT and CRP. PCT was positively correlated with CRP. CONCLUSIONS: Compared with viral pneumonia, the levels of serum PCT, CRP, and FIB in patients with bacterial pneumonia are higher. Biochemical indexes can be used as independent predictors for the diagnosis of bacterial pneumonia, and have high diagnostic value. The combined detection of the three has the highest diagnostic efficiency, which is conducive to the clinical differential diagnosis of the early types of pneumonia infection.

Uncoupling of the center-to-periphery arterial stiffness gradient and pulse pressure amplification in viral pneumonia infection.

OBJECTIVES: Arterial stiffness is a common manifestation of viral pneumonia infections, including COVID-19. Nevertheless, the relationship between the center-to-periphery arterial stiffness gradient and pulse pressure amplification (PPA) in infectious diseases remains unclear. This study aimed to investigate this relationship utilizing arterial pressure volume index (API) and arterial velocity pulse index (AVI) ratio. METHODS: API/AVI and PPA were measured in 219 participants with COVID-19 and 374 normal participants. Multiple linear regression was used to assess the association of API/AVI and PPA, and restricted cubic spline was used to investigate the non-linear relationship between API/AVI and PPA. Receiver operating characteristic curve (ROC) analysis was used to evaluate the effects of API/AVI in identifying COVID-19 infection and severe stage. RESULTS: There was a significant J-shaped relationship between API/AVI and PPA in COVID-19 group, while a M-shaped relationship was observed in normal group. API/AVI decreased rapidly as PPA decreased until API/AVI decreased slowly at PPA of 1.07, and then API/AVI decreased slowly again at PPA of 0.78. ROC results showed that API/AVI demonstrated excellent accuracy in identifying COVID-19 infection (AUC = 0.781) and a high specificity (84.88%) in identifying severe stage. CONCLUSIONS: There was a J-shaped association between the API/AVI and PPA in viral infected patients, while a M-shaped relationship in the normal participants. API/AVI is better for identifying infected and uninfected patients, with a high specificity in identifying those in severe stages of the disease. The attenuation or reversal of API/AVI may be associated with the loss of PPA coupling.

Molecular diagnostic approaches for SARS-CoV-2 detection and pathophysiological consequences.

SARS-CoV-2, a novel coronavirus within the Coronaviridae family, is the causative agent behind the respiratory ailment referred to as COVID-19. Operating on a global scale, COVID-19 has led to a substantial number of fatalities, exerting profound effects on both public health and the global economy. The most frequently reported symptoms encompass fever, cough, muscle or body aches, loss of taste or smell, headaches, and fatigue. Furthermore, a subset of individuals may manifest more severe symptoms, including those consistent with viral pneumonitis, which can be so profound as to result in fatalities. Consequently, this situation has spurred the rapid advancement of disease diagnostic technologies worldwide. Predominantly employed in diagnosing COVID-19, the real-time quantitative reverse transcription PCR has been the foremost diagnostic method, effectively detecting SARS-CoV-2 viral RNA. As the pandemic has evolved, antigen and serological tests have emerged as valuable diagnostic tools. Antigen tests pinpoint specific viral proteins of SARS-CoV-2, offering swift results, while serological tests identify the presence of antibodies in blood samples. Additionally, there have been notable strides in sample collection methods, notably with the introduction of saliva-based tests, presenting a non-invasive substitute to nasopharyngeal swabs. Given the ongoing mutations in SARS-CoV-2, there has been a continuous need for genomic surveillance, encompassing full genome sequencing and the identification of new variants through Illumina technology and, more recently, nanopore metagenomic sequencing (SMTN). Consequently, while diagnostic testing methods for COVID-19 have experienced remarkable progress, no test is flawless, and there exist limitations with each technique, including sensitivity, specificity, sample collection, and the minimum viral load necessary for accurate detection. These aspects are comprehensively addressed within this current review.

Condition of the Right Heart in Patients With COVID-19­Associated Pneumonia: Follow-Up During Hospitalization.

Aim      Dynamic assessment of the right heart in patients with COVID-19-associated pneumonia of different severity during regression of the systemic inflammatory response (SIR).Material an methods    This single-center prospective study included 46 patients with the novel coronavirus infection COVID-19 and viral pneumonia according to chest multispiral computed tomography (CT). Laboratory and echocardiographic examinations of patients were performed.Results Based on the results of evaluation with the Clinical Condition Scale (CCS-COVID), patients were divided into two groups: group A, patients with a score from 6 to 9 and group B, patients with a score from 10 to 14. The study results of both groups were evaluated twice: on day 10±2.5 from the onset of symptoms (groups A10 and B10, respectively) and again on day 17±1.8 (groups A17 and B17, respectively). Patients of group B10 had more pronounced SIR (C-reactive protein, 111.38±52.5 mg / l) and a larger volume of ground-glass opacity (38.3±9.6 %). At the first stage, higher values of right ventricular global longitudinal strain (RV GLS) were detected in group B10 compared to group A10 (23.2±4.8 % vs. 19.9±3.5 %, р=0.048). During the regression of SIR intensity and the positive dynamics of CT, lower values of Е / А were observed in group B17 (1.0 [0.98; 1.2]) vs. group А17 (1.4 [1.18; 1.5, p=0.015), and е' / a' in group B17 (0.66 [0.58; 0.85]) vs. 0.95 [0.79; 1.12] in group B17 (p=0.010). Е / А and е' / a' ratios were correlated with total lactate dehydrogenase fraction (r= -0.452 and p=0.006; r= -0.334 and p=0.050, respectively).Conclusion      In patients with severe COVID-19-associated pneumonia during regression of SIR intensity, changes in the parameters that reflected RV diastolic dysfunction were observed.

Development and validation of a hybrid deep learning-machine learning approach for severity assessment of COVID-19 and other pneumonias.

The Coronavirus Disease 2019 (COVID-19) is transitioning into the endemic phase. Nonetheless, it is crucial to remain mindful that pandemics related to infectious respiratory diseases (IRDs) can emerge unpredictably. Therefore, we aimed to develop and validate a severity assessment model for IRDs, including COVID-19, influenza, and novel influenza, using CT images on a multi-centre data set. Of the 805 COVID-19 patients collected from a single centre, 649 were used for training and 156 were used for internal validation (D1). Additionally, three external validation sets were obtained from 7 cohorts: 1138 patients with COVID-19 (D2), and 233 patients with influenza and novel influenza (D3). A hybrid model, referred to as Hybrid-DDM, was constructed by combining two deep learning models and a machine learning model. Across datasets D1, D2, and D3, the Hybrid-DDM exhibited significantly improved performance compared to the baseline model. The areas under the receiver operating curves (AUCs) were 0.830 versus 0.767 (p = 0.036) in D1, 0.801 versus 0.753 (p < 0.001) in D2, and 0.774 versus 0.668 (p < 0.001) in D3. This study indicates that the Hybrid-DDM model, trained using COVID-19 patient data, is effective and can also be applicable to patients with other types of viral pneumonia.

Evaluation of Severe Acute Respiratory Syndrome surveillance caused by respiratory viruses in a pediatric unit, 2013 to 2019.

OBJECTIVE: To evaluate severe acute respiratory syndrome surveillance in a pediatric unit. METHODS: Descriptive study of reported severe acute respiratory syndrome cases with the detection of respiratory viruses in the nasopharyngeal sample of patients hospitalized between 2013 and 2019, in a reference hospital in the Federal District, Brazil. RESULTS: A total of 269 children had one or more viruses detected, resulting in 280 viruses, of which 152 (54%) were respiratory syncytial virus. The detection of respiratory syncytial virus was higher during the autumn-winter period. Children´s median age was 6.9 months, 156 (58%) were male, 104 (39%) had comorbidity, 197 (73%) required mechanical ventilation, 241 (90%) received antibiotics, and 146 (54%) oseltamivir. There were 19 (7%) deaths. The median time from symptom onset to sample collection was 5 days and the median time from sample collection to final results was 6 days. CONCLUSIONS: The system needs to reduce the time to deliver results so that inappropriate use of antibiotics and antivirals can be avoided. Moreover, the burden of viral pneumonia was relevant and the system must be flexible enough to include emerging viruses in order to be useful in responding to public health emergencies caused by respiratory viruses.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study.

PURPOSE: The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. METHODS: We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. RESULTS: Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p=0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p=0.04), respiratory failure (59.3% vs 42.8%, p=0.001), ICU admission (17.8% vs 7%, p=0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p=0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06-6.73). CONCLUSIONS: Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection.

[Prognostic scale for in-hospital mortality in patients with COVID-19 viral pneumonia]. / Escala pronóstica para mortalidad intrahospitalaria en pacientes con neumonía viral COVID-19.

Background: The COVID-19 pandemic represented a challenge in medical care. A tool would be very useful to establish the prognosis of in-hospital death that is reliable and can be applied to the Mexican population entitled to the IMSS. Objective: To propose a prognostic scale to stratify patients with viral pneumonia COVID-19 in the emergency services. Material and methods: A nested case-control study was conducted in a cohort of patients who were consecutively admitted to the emergency department with viral pneumonia COVID-19. The cases were those patients who died, and the controls were those who were discharged due to health improvement. An association analysis was performed between the variables with significant differences between groups. Subsequently, the association was adjusted using a multivariate logistic regression model, from which the prognostic scale was developed. Results: A total of 70 subjects with COVID-19 were included, 34 cases and 36 controls. Chronic diseases, smoking, severe pulmonary involvement diagnosed by tomography, leukocytosis, and pulse oximetry less than 80% with were associated with in-hospital mortality; Odds Ratio (OR) of >1.1. Vaccination was a protective factor (OR = 0.04, CI95%: 0.01-0.16). A score greater than 3 points on the prognostic scale predicts in-hospital mortality with a specificity of 0.86 and a sensitivity of 0.73. Conclusions: The proposed prognostic scale can be a useful tool in the classification of patients with COVID-19 viral pneumonia in the emergency room services of secondary care level Hospitals.

Introducción: la pandemia por COVID-19 representó un reto en la atención médica. Sería de gran utilidad una herramienta para establecer el pronóstico de muerte intrahospitalaria que sea confiable y pueda aplicarse a la población mexicana derechohabiente del Instituto Mexicano del Seguro Social. Objetivo: proponer una escala pronóstica para estratificar a los pacientes con neumonía viral por COVID-19 en los servicios de urgencias de los hospitales de segundo nivel. Material y métodos: se realizó un estudio de casos y controles anidado en una cohorte de pacientes adultos que fueron admitidos consecutivamente en el servicio de Urgencias con diagnóstico de neumonía viral por COVID-19. Los casos fueron aquellos pacientes que fallecieron y los controles aquellos que fueron egresados de la unidad por mejoría. Se realizó un análisis de asociación ente las variables con diferencias significativas entre ambos grupos, se ajustó la asociación mediante un modelo de regresión logística multivariada a partir del cual se elaboró la escala pronóstica. Resultados: se incluyeron en total 70 personas con COVID-19, 34 casos y 36 controles. Se asociaron a la mortalidad intrahospitalaria: las enfermedades crónicas, el tabaquismo, la afectación pulmonar severa diagnosticada por tomografía, la leucocitosis y la oximetría de pulso menor a 80% con una razón de Momios (RM) de > 1.1. La vacunación fue un factor protector (RM: 0.29, IC95%: 0.11-0.80). Un puntaje mayor a 3 puntos en la escala pronóstica predice la mortalidad intrahospitalaria (sensibilidad: 0.73, especificidad: 0.86). Conclusiones: la escala pronóstica propuesta puede ser una herramienta útil en la clasificación de los pacientes con neumonía viral por COVID-19 en los servicios de urgencias de los hospitales de segundo nivel de atención.

Epidemiología de la COVID-19 entre el personal de centros sanitarios y sociosanitarios del área sanitaria de A Coruña y Cee / COVID-19 epidemiology in health and social health workers in the health area of A Coruña and Cee

Objetivo Desde el comienzo de la pandemia ha sido necesario conocer la evolución epidemiológica del SARS-CoV-2. Es por ello que el objetivo de este estudio fue describir las características de la casuística de la COVID-19 en el personal de centros sanitarios y sociosanitarios del área sanitaria de A Coruña y Cee durante la primera ola epidémica, así como determinar la asociación entre el cuadro clínico y/o la duración del mismo y la condición de repositivizar la RT-PCR. Material y métodos En el periodo de estudio se diagnosticaron 210 casos de COVID-19 entre el personal sanitario y sociosanitario del área sanitaria de A Coruña y Cee. Se llevó a cabo un análisis descriptivo de los factores sociodemográficos, así como la búsqueda de asociación entre el cuadro clínico y la duración de la detección de una RT-PCR positiva. Resultados Las categorías profesionales más afectadas fueron enfermería (33,3%) y auxiliares de enfermería (16,2%). El tiempo medio que los casos tardaron en negativizar la RT-PCR fue de 18,3±9,1 días, con una mediana de 17 días. Se observó que 26 casos (13,8%) volvían a obtener un resultado positivo en alguna RT-PCR posterior, sin cumplir criterios de reinfección. La existencia de manifestaciones cutáneas y artralgias se asoció con la repositivización tras ajustar por edad y sexo (OR=4,6 y OR=6,5; respectivamente). Conclusiones En los profesionales sanitarios diagnosticados con COVID-19 durante la primera ola, los síntomas disnea, manifestaciones cutáneas y artralgias determinaron la repositivización de la RT-PCR tras un resultado negativo previo y sin cumplir criterios de reinfección (AU)

Objective Since the beginning of the pandemic, it has become necessary to know the epidemiological evolution of SARS-CoV-2. Therefore, this study aims to describe the characteristics of the casuistry of COVID-19 in health and social-health workers in the health area of A Coruña and Cee during the first epidemic wave, as well as to determine the association between the clinical profile and/or its duration and the condition of RT-PCR repositivization. Materials and methods During the study period, 210 cases belonging to healthcare and social-healthcare workers from the healthcare area of A Coruña and Cee were diagnosed. A descriptive analysis of sociodemographic factors was carried out, as well as the search for association between the clinical picture and the duration of detection of a positive RT-PCR. Results The most affected categories were nursing (33.3%) and nursing assistants (16.2%). The mean time taken for cases to become RT-PCR negative was 18.3±9.1 days, with a median of 17. It was observed that 26 cases (13.8%) had a positive result in a subsequent RT-PCR, without meeting criteria for reinfection. The existence of skin manifestations and arthralgias was associated with repositivization after adjusting for age and sex (OR=4.6 and OR=6.5, respectively). Conclusions In healthcare professionals diagnosed with COVID-19 during the first wave, symptoms such as dyspnea, skin manifestations and arthralgias led to RT-PCR repositivization after a previous negative result and without meeting criteria for reinfection (AU)

Early Detection of Aspergillus Species in Lower Respiratory Tract is Associated with Higher Mortality in Viral Community-Acquired Pneumonia: A Multicenter Prospective Cohort Study in China.

PURPOSE: Community-acquired pneumonia (CAP) is a leading cause of adult mortality worldwide and poses a significant global burden. Previous studies have indicated a tendency for viral pneumonia, particularly severe influenza virus pneumonia, to be complicated by Aspergillus superinfection. However, the clinical features and prognostic implications of Aspergillus detection in early-onset viral CAP remain unclear. METHODS: We conducted a prospective multicenter observational cohort study in China involving CAP patients. Adult patients with CAP from six hospitals were enrolled between January 2017 and October 2018. Within 72 h of admission, lower respiratory tract specimens, including sputum and alveolar lavage fluid, were collected. Comprehensive pathogenic testing, utilizing molecular biology techniques, was performed on the collected specimens, encompassing bacteria, atypical pathogens, viruses, and fungi. Patient clinical data were collected through a unified electronic medical record website system. RESULTS: A total of 382 adult CAP patients were included in the study. The viral detection rate was 38% (145/382), with Aspergillus identified in 11.0% (16/145) of viral CAP cases. Mortality among Aspergillus-positive patients was significantly higher (25%, 4/16) compared to Aspergillus-negative patients (5.4%, 7/129) in viral CAP (P = 0.021). Multivariable logistic regression models demonstrated that the presence of Aspergillus at admission might increase the mortality risk in viral CAP [OR (95%CI) = 7.34 (0.92-58.65), P = 0.06]. Furthermore, Aspergillus-positive patients exhibited a significantly lower lymphocyte count than Aspergillus-negative patients (P = 0.047). CONCLUSION: Positive detection of Aspergillus in lower respiratory tract specimens might be associated with higher mortality in early-onset viral CAP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03093220. Registered retrospectively on 28 March 2017.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

NEUROPROTECTIVE AND ANTIOXIDANT POTENTIAL OF MONTELUKAST-ACETYLCYSTEINE COMBINATION THERAPY FOR BRAIN PROTECTION IN PATIENTS WITH COVID-19 INDUCED PNEUMONIA.

Direct critical attack of the coronavirus on the alveoli and the excessive release of a large number of cytokines (IL-6, IL-1, TNF-α, etc.) provides suitable conditions for the further development of acute respiratory distress syndrome (ARDS) and severe acute respiratory failure. Serious decrease in blood oxygenation often lead to the deterioration of macro- and microcirculation, irreversible brain damage and hence, persistent neurological and mental disorders despite background intensive therapy and adequate respiratory support. Therefore, the aim of our open prospective observational study was to investigate the neuroprotective and antioxidant effectiveness of montelukast-acetylcysteine combination therapy for brain protection in patients with COVID-19 viral pneumonia. A study was performed for five hundred seventy-eight (n=578) outpatients who were tested positive for novel coronavirus (SARS-CoV-2) by nasopharyngeal swap. The median age of patients was 62±17.45 years. In addition to clinical features and RT-PCR results, chest CT and chest X-ray (CXR) with high sensitivity were also very helpful for the early identification of viral pneumonia and COVID-19 disease assessment. Considering the severity of Covid-19 pneumonia and the level of arterial oxygen saturation (transcutaneous hemoglobin oxygen saturation) on room air, all patients were divided into three major groups. Group 1 (n=288) consisted of patients with a mild shift in oxygen saturation (SpO2 ≥ 95%) and well-defined pulmonary lesions (within 1-2 segments) without concomitant diseases; the second group (Group 2, n=250) included patients with clinical manifestations of moderate severity associated with a current saturation of 90-95% (SpO2) and small pulmonary lesions on chest X-ray in the presence of concomitant diseases: arterial hypertension (stage III) or CHF (FC/NYHA-2), coronary heart disease or type 2 diabetes, cancer, tuberculosis, etc. Most of the patients in third group (Group 3, n=48), during imaging studies, showed bilateral lung affection with low and peripheral distribution (with both - either ground glass opacities or multiple pulmonary nodules) and cardiomegaly. The respiratory failure of stage II-III (current oxygen saturation SpO2 75-90%), high respiratory rate (≥25 per minute), hemodynamic impairment (BP≤100/60 mm Hg. Art., heart rate ≥125/min) were the most common objective clinical findings seen in this subset of patients. Laboratory changes included leukopenia less than 4.0x109/L or leukocytosis (≥10.0X109/L). Background respiratory support with low-flow oxygen therapy and combined pharmacotherapy, where, along with montelukast and acetylcysteine, patients were prescribed a cephalosporin, a fluoroquinolone, an antifungal drug, a histamine blocker, an antiplatelet agent, a complex of B vitamins, led to a significant improvement in symptoms and laboratory parameters during the course of the disease. The mean values of the blood biomarkers (CRP - 21.46±4.43 mg/l, LDH - 410.71±40.63 U/l, procalcitonin - 1.08±0.31 ng/ml, and ferritin - 270.43±27.23 ng/ml) return to normal by the 20th day after the fever subsides. Laboratory parameters before and after treatment course showed statistically significant differences between variables (p<0.05). No patient in Group 3 received JAK inhibitors (tofacitinib and baricitinib), IL-6 (olokizumab), IL-17A (netakimab) and glucocorticosteroids, however, recovery rates were completely good. Assessment of the patient's neurological status (based on the NIHSS scores) revealed no signs of neurological changes. Thus, based on the data given, it can be concluded that the high efficacy of the acetylcysteine/montelukast combination (as neuroprotectors) in pneumonia caused by COVID-19 is due to the effect of drugs on key mechanisms of pathogenesis: reduction of oxidative stress as drugs (combination) ensuring the free radical scavenging; stimulation of glutathione synthesis; suppression of cytokine storm; reduction of bronchospasm, mucus secretion and airway edema; lowering of BBB permeability and the ability to improve cerebral microcirculatory perfusion in the presence of antiplatelet agents. In conclusion, the combination of montelukast and acetylcysteine may provide an effective, safe, multicomponent approach to the prevention of hypoxic brain injury in patients with COVID-19 pneumonia.

[Community-acquired pneumonia]. / Ambulant erworbene Pneumonie.

RISK FACTORS FOR SEVERE COURSES: The CRB-65 score is recommended as a risk predictor, as well as consideration of unstable comorbidities and oxygenation. GROUPING OF COMMUNITY-ACQUIRED PNEUMONIA: Community-acquired pneumonia is divided into 3 groups: mild pneumonia, moderate pneumonia, severe pneumonia. Whether there is a curative vs palliative treatment goal should be determined early. DIAGNOSTIC RECOMMENDATION: An X-ray chest radiograph is recommended to confirm the diagnosis, also in the outpatient setting if possible. Sonography of the thorax is an alternative, asking for additional imaging if negative. Streptococcus pneumoniae remains the most common bacterial pathogen. THERAPY: Community-acquired pneumonia continues to be associated with high morbidity and lethality. Prompt diagnosis and prompt initiation of risk-adapted antimicrobial therapy are essential measures. However, in times of COVID-19, as well as the current influenza and RSV epidemic, purely viral pneumonias must also be expected. At least with COVID-19, antibiotics can often be avoided. Antiviral and anti-inflammatory drugs are used here. POST-ACUTE COURSE: Patients after community-acquired pneumonia have increased acute and long-term mortality due to cardiovascular events in particular. The focus of research is on improved pathogen identification, a better understanding of the host response with the potential of developing specific therapeutics, the role of comorbidities, and the long-term consequences of the acute illness.

[SARS-CoV-2-Infection and Interstitial Lung Disease: Position paper of the German Respiratory Society]. / SARS-CoV-2-Infektion und interstitielle Lungenerkrankungen ­ Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin.

The SARS-CoV-2 pandemic had a tremendous impact on diagnosis and treatment of interstitial lung diseases (ILD). Especially in the early phase of the pandemic, when the delta variant was prevailling, a huge number of viral pneumonias were observed, which worsened pre-existing, triggered de novo occurence or discovery of previously subclincal interstitial lung diseases. The effect of SARS-CoV-2 infection - without or with accompanying viral pneumonia - on the further development of pre-existing ILD as well of new pulmonary inflitrates and consolidiations is difficult to predict and poses a daily challenge to interdisciplinary ILD boards. This position paper of the German Respiratory Society (DGP e.V.) provides answers to the most pressing questions based on current knowledge.