Antibiotics daptomycin interacts with S protein of SARS-CoV-2 to promote cell invasion of Omicron (B1.1.529) pseudovirus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed enormous challenges to global public health. The use of antibiotics has greatly increased during the SARS-CoV-2 epidemic owing to the presence of bacterial co-infection and secondary bacterial infections. The antibiotics daptomycin (DAP) is widely used in the treatment of infectious diseases caused by gram-positive bacteria owing to its highly efficient antibacterial activity. It is pivotal to study the antibiotics usage options for patients of coronavirus infectious disease (COVID-19) with pneumonia those need admission to receive antibiotics treatment for bacterial co-infection in managing COVID-19 disease. Herein, we have revealed the interactions of DAP with the S protein of SARS-CoV-2 and the variant Omicron (B1.1.529) using the molecular docking approach and Omicron (B1.1.529) pseudovirus (PsV) mimic invasion. Molecular docking analysis shows that DAP has a certain degree of binding ability to the S protein of SARS-CoV-2 and several derived virus variants, and co-incubation of 1-100 µM DAP with cells promotes the entry of the PsV into human angiotensin-converting enzyme 2 (hACE2)-expressing HEK-293T cells (HEK-293T-hACE2), and this effect is related to the concentration of extracellular calcium ions (Ca2+). The PsV invasion rate in the HEK-293T-hACE2 cells concurrently with DAP incubation was 1.7 times of PsV infection alone. In general, our findings demonstrate that DAP promotes the infection of PsV into cells, which provides certain reference of antibiotics selection and usage optimization for clinicians to treat bacterial coinfection or secondary infection during SARS-CoV-2 infection.

Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia.

Acute lung injury (ALI) is generally caused by severe respiratory infection and characterized by overexuberant inflammatory responses and inefficient pathogens-containing, the two major processes wherein alveolar macrophages (AMs) play a central role. Dysfunctional mitochondria have been linked with distorted macrophages and hence lung disorders, but few treatments are currently available to correct these defects. Plant-derive nanovesicles have gained significant attention because of their therapeutic potential, but the targeting cells and the underlying mechanism remain elusive. We herein prepared the nanovesicles from Artemisia annua, a well-known medicinal plant with multiple attributes involving anti-inflammatory, anti-infection, and metabolism-regulating properties. By applying three mice models of acute lung injury caused by bacterial endotoxin, influenza A virus (IAV) and SARS-CoV-2 pseudovirus respectively, we showed that Artemisia-derived nanovesicles (ADNVs) substantially alleviated lung immunopathology and raised the survival rate of challenged mice. Macrophage depletion and adoptive transfer studies confirmed the requirement of AMs for ADNVs effects. We identified that gamma-aminobutyric acid (GABA) enclosed in the vesicles is a major molecular effector mediating the regulatory roles of ADNVs. Specifically, GABA acts on macrophages through GABA receptors, promoting mitochondrial gene programming and bioenergy generation, reducing oxidative stress and inflammatory signals, thereby enhancing the adaptability of AMs to inflammation resolution. Collectively, this study identifies a promising nanotherapeutics for alleviating lung pathology, and elucidates a mechanism whereby the canonical neurotransmitter modifies AMs and mitochondria to resume tissue homeostasis, which may have broader implications for treating critical pulmonary diseases such as COVID-19.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic.

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking. Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France. Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed. Exposure: Onset of COVID-19 pandemic. Main outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents). Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children. Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

[Identifying Novel Coronavirus Pneumonia With CT Images: A Deep Learning Approach With Detail Upsampling and Attention Guidance]. / 从CTå›¾åƒä¸­æ£€æµ‹æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“å¯¼è‡´çš„è‚ºç‚Žï¼šä¸€ç§ç»†èŠ‚ä¸Šé‡‡æ ·å’Œæ³¨æ„åŠ›å¼•å¯¼çš„æ·±åº¦å­¦ä¹ æ–¹æ³•.

Objective: To construct a deep learning-based target detection method to help radiologists perform rapid diagnosis of lesions in the CT images of patients with novel coronavirus pneumonia (NCP) by restoring detailed information and mining local information. Methods: We present a deep learning approach that integrates detail upsampling and attention guidance. A linear upsampling algorithm based on bicubic interpolation algorithm was adopted to improve the restoration of detailed information within feature maps during the upsampling phase. Additionally, a visual attention mechanism based on vertical and horizontal spatial dimensions embedded in the feature extraction module to enhance the capability of the object detection algorithm to represent key information related to NCP lesions. Results: Experimental results on the NCP dataset showed that the detection method based on the detail upsampling algorithm improved the recall rate by 1.07% compared with the baseline model, with the AP50 reaching 85.14%. After embedding the attention mechanism in the feature extraction module, 86.13% AP50, 73.92% recall, and 90.37% accuracy were achieved, which were better than those of the popular object detection models. Conclusion: The feature information mining of CT images based on deep learning can further improve the lesion detection ability. The proposed approach helps radiologists rapidly identify NCP lesions on CT images and provides an important clinical basis for early intervention and high-intensity monitoring of NCP patients.

Outcome of pregnant women admitted to critical care unit with confirmed severe COVID-19: A center experience.

OBJECTIVES: To explore the traits and risk factors of pregnant women admitted to intensive care units (ICUs) with COVID-19. Moreover, the study classifies outcomes based on differing levels of required respiratory support during their intensive care stay. METHODS: This retrospective and descriptive study included all pregnant women with COVID-19 admitted to the adult critical care unit at a specialized tertiary hospital in Riyadh, Saudi Arabia. Between January 2020 and December 2022. A total of 38 pregnant women were identified and were eligible for our study. RESULTS: The mean age of the patients was 32.9 (19-45) years, and the average Acute Physiology and Chronic Health Evaluation IV (APACHI IV) score was 49.9 (21-106). Approximately 60.5% of the patients suffered from superimposed infections during their ICU stay. Approximately 81.6% patients were delivered by C-section, 33 of the newborns survived, and 5 died. The crude mortality rate among pregnant women in our cohort was 15.8%. Patients treated with high-flow nasal cannula (HFNC) were mostly discharged or delivered normally, while the mechanical ventilation (MV) and extracorporeal membrane oxygenation groups mostly underwent C-sections. Most of the surviving newborns were on HFNC and MV. Patients with multiple infections had the longest ICU stay and had the highest risk of death. CONCLUSION: The results of this study highlight the characteristics of pregnant women admitted to the ICU at a specialized tertiary healthcare center in Saudi Arabia. The APACHI IV scores accurately predicted patient's mortality, duration of MV, and length of ICU stay. In our study, we shared our experience of managing severe COVID-19 infections in pregnant patients.

The effect of malnutrition on adult Covid-19 patient's ICU admission and mortality in Covid-19 isolation and treatment centers in Ethiopia: A prospective cohort study.

BACKGROUND: A new coronavirus was first identified in Wuhan, China in December 2019. Since the times of the 1918 influenza pandemic, malnutrition has been known as a risk factor for severity and mortality from viral pneumonia. Similarly, the recently identified SARS-Cov2 infection (COVID-19) and related pneumonia may be closely linked to malnutrition. Therefore, this study will contribute to new knowledge and awareness of the recording and evaluation of each COVID-19 patient's nutritional status by assessing the effect of malnutrition on ICU admission and death of COVID-19 patients in developing countries. METHOD: We conducted a prospective cohort study in adult COVID-19 patients admitted to selected COVID-19 Isolation and Treatment Centers, Addis Ababa, Ethiopia. Baseline data of the patients were collected using interviewer-administered structured questionnaire and data on the adverse outcomes of follow up were extracted from follow up chart. The main clinical outcomes (ICU admission and death) were captured every week of follow up. We ran a multivariate Cox's regression analysis to determine the relationship between malnutrition at admission and its effect on ICU admission and death. RESULTS: A total of 581 COVID-19 patients were enrolled. From the total of recruited patients, 346 (59.6%) were males and 235 (40.4%) were females. The mean age of the respondents was 55 years (16.45) years. The Cox proportional hazard model controlled for sex, age group, number of co-morbidities, and number of medications found that malnutrition at admission was associated with ICU admission and death. When compared to well-nourished patients, the rate of ICU admission was significantly associated and found to be higher among underweight [(adjusted hazard ratio (AHR) = 10.02, 95% CI: (8.64-12.10)] and overweight [(AHR = 7.7, 95% CI: (6.41-9.62)] patients. The rate of survival probability was significantly associated and was found to be better among well-nourished patients (AHR = 0.06, 95% CI : (0.01-0.44) when compared with malnourished COVID-19 patients. CONCLUSION: Malnutrition at the time of admission was shown to increase the risk of ICU admission and mortality among COVID-19 patients. Therefore, it is vital to evaluate patients' nutritional condition early in their admission and provide timely intervention to minimize the effects on patients and the healthcare system.

Point-of-care lung ultrasound predicts hyperferritinemia and hospitalization, but not elevated troponin in SARS-CoV-2 viral pneumonitis in children.

SARS-CoV-2 often causes viral pneumonitis, hyperferritinemia, elevations in D-dimer, lactate dehydrogenase (LDH), transaminases, troponin, CRP, and other inflammatory markers. Lung ultrasound is increasingly used to diagnose and stratify viral pneumonitis severity. We retrospectively reviewed 427 visits in patients aged 14 days to 21 years who had had a point-of-care lung ultrasound in our pediatric emergency department from 30/November/2019 to 14/August/2021. Lung ultrasounds were categorized using a 6-point ordinal scale. Lung ultrasound abnormalities predicted increased hospitalization with a threshold effect. Increasingly abnormal laboratory values were associated with decreased discharge from the ED and increased admission to the ward and ICU. Among patients SARS-CoV-2 positive patients ferritin, LDH, and transaminases, but not CRP or troponin were significantly associated with abnormalities on lung ultrasound and also with threshold effects. This effect was not demonstrated in SARS-CoV-2 negative patients. D-Dimer, CRP, and troponin were sometimes elevated even when the lung ultrasound was normal.

Enhancing pediatric pneumonia diagnosis through masked autoencoders.

Pneumonia, an inflammatory lung condition primarily triggered by bacteria, viruses, or fungi, presents distinctive challenges in pediatric cases due to the unique characteristics of the respiratory system and the potential for rapid deterioration. Timely diagnosis is crucial, particularly in children under 5, who have immature immune systems, making them more susceptible to pneumonia. While chest X-rays are indispensable for diagnosis, challenges arise from subtle radiographic findings, varied clinical presentations, and the subjectivity of interpretations, especially in pediatric cases. Deep learning, particularly transfer learning, has shown promise in improving pneumonia diagnosis by leveraging large labeled datasets. However, the scarcity of labeled data for pediatric chest X-rays presents a hurdle in effective model training. To address this challenge, we explore the potential of self-supervised learning, focusing on the Masked Autoencoder (MAE). By pretraining the MAE model on adult chest X-ray images and fine-tuning the pretrained model on a pediatric pneumonia chest X-ray dataset, we aim to overcome data scarcity issues and enhance diagnostic accuracy for pediatric pneumonia. The proposed approach demonstrated competitive performance an AUC of 0.996 and an accuracy of 95.89% in distinguishing between normal and pneumonia. Additionally, the approach exhibited high AUC values (normal: 0.997, bacterial pneumonia: 0.983, viral pneumonia: 0.956) and an accuracy of 93.86% in classifying normal, bacterial pneumonia, and viral pneumonia. This study also investigated the impact of different masking ratios during pretraining and explored the labeled data efficiency of the MAE model, presenting enhanced diagnostic capabilities for pediatric pneumonia.

Analysis of viral pneumonia and risk factors associated with severity of influenza virus infection in hospitalized patients from 2012 to 2016.

BACKGROUND: Influenza viruses cause pneumonia in approximately one-third of cases, and pneumonia is an important cause of death. The aim was to identify risk factors associated with severity and those that could predict the development of pneumonia. METHODS: This retrospective, observational study included all adult patients with confirmed influenza virus infection admitted to Son Espases University Hospital during four influenza seasons in Spain (October to May) from to 2012-2016. RESULTS: Overall, 666 patients with laboratory-confirmed influenza were included, 93 (14%) of which were severe; 73 (10.9%) were admitted to Intensive Care Unit (ICU), 39 (5.8%) died, and 185 (27.7%) developed pneumonia. Compared to less severe cases, patients with severe disease: were less vaccinated (40% vs. 28%, p = 0.021); presented with more confusion (26.9% vs. 6.8%), were more hypoxemic (Horowitz index (PaO2/FiO2) 261 vs. 280), had higher C-reactive protein (CRP) (12.3 vs. 4.0), had more coinfections (26.8% vs. 6.3%) and had more pleural effusion (14% vs. 2.6%) (last six all p < 0.001). Risk factors significantly associated with severity were pneumonia [OR (95% CI) = 4.14 (2.4-7.16)], history of heart disease (1.84, 1.03-3.28), and confusion at admission (4.99, 2.55-9.74). Influenza vaccination was protective (0.53, 0.28-0.98). Compared to those without pneumonia, the pneumonia group had higher CRP (11.3 vs. 4.0, p < 0.001), lower oxygen saturation (92% vs. 94%, p < 0.001), were more hypoxic (PaO2/FiO2 266 vs. 281, p < 0.001), and incurred more mechanical ventilation, septic shock, admission to the ICU, and deaths (all four p < 0.001). Higher CRP and lower oxygen saturation were independent variables for predicting the development of pneumonia. CONCLUSIONS: Pneumonia, history of heart disease, confusion and no influenza vaccination were independent variables to present complications in patients admitted with influenza infection.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review.

OBJECTIVE: To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. METHODS: This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. RESULTS: The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. CONCLUSION: This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

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.

Radiographic findings of adenoviral pneumonia in children.

OBJECTIVE: Adenovirus pneumonia is a common cause of community-acquired pneumonia in children and can mimic bacterial pneumonia, but there are few publications on its radiographic features. This study has evaluated the chest radiography findings of community-acquired adenovirus pneumonia in children. The frequency of radiological findings mimicking bacterial pneumonia was investigated. The clinical features of patients with adenovirus pneumonia possessing radiological findings mimicking bacterial pneumonia were also evaluated. MATERIALS AND METHODS: The chest radiographs of patients diagnosed with adenovirus pneumonia were retrospectively reviewed. The chest radiographs were interpreted independently by a pediatric infectious disease specialist and a pediatric radiologist. Chest radiography findings mimicking bacterial pneumonia (bacterial-like) were specified as consolidation +/- pleural effusion. Other findings on chest radiography or a completely normal chest X-ray were specified as findings that were compatible with "typical viral pneumonia". RESULTS: A total of 1407 patients were positive for adenovirus with respiratory multiplex PCR. The 219 patients who met the study criteria were included in the study. Chest radiographs were normal in 58 (26.5 %) patients. The chest radiograph findings mimicked bacterial pneumonia in 41 (18.7 %) patients. CONCLUSION: Adenovirus pneumonia occurs predominantly in children aged five years and younger, as with other viral pneumonias. The radiographic findings in adenovirus pneumonia are predominantly those seen in viral pneumonia. Increasing age and positivity for only adenovirus without other viruses on respiratory multiplex PCR were associated with the chest radiograph being more likely to be "bacterial-like". Adenovirus may lead to lobar/segmental consolidation at a rate that is not very rare.

Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle delivery.

Macrophages are integral components of the innate immune system, playing a dual role in host defense during infection and pathophysiological states. Macrophages contribute to immune responses and aid in combatting various infections, yet their production of abundant proinflammatory cytokines can lead to uncontrolled inflammation and worsened tissue damage. Therefore, reducing macrophage-derived proinflammatory cytokine release represents a promising approach for treating various acute and chronic inflammatory disorders. However, limited macrophage-specific delivery vehicles have hindered the development of macrophage-targeted therapies. In this study, we screened a pool of 112 lipid nanoparticles (LNPs) to identify an optimal LNP formulation for efficient siRNA delivery. Subsequently, by conjugating the macrophage-specific antibody F4/80 to the LNP surface, we constructed MacLNP, an enhanced LNP formulation designed for targeted macrophage delivery. In both in vitro and in vivo experiments, MacLNP demonstrated a significant enhancement in targeting macrophages. Specifically, delivery of siRNA targeting TAK1, a critical kinase upstream of multiple inflammatory pathways, effectively suppressed the phosphorylation/activation of NF-kB. LNP-mediated inhibition of NF-kB, a key upstream regulator in the classic inflammatory signaling pathway, in the murine macrophage cell line RAW264.7 significantly reduced the release of proinflammatory cytokines after stimulation with the viral RNA mimic Poly(I:C). Finally, intranasal administration of MacLNP-encapsulated TAK1 siRNA markedly ameliorated lung injury induced by influenza infection. In conclusion, our findings validate the potential of targeted macrophage interventions in attenuating inflammatory responses, reinforcing the potential of LNP-mediated macrophage targeting to treat pulmonary inflammatory disorders.

Functional decline at 1 year in hospitalized elderly pneumonia with SARS-CoV-2 Omicron variant: Comparison with the ancestral strain and Alpha variant.

In the SARS-CoV-2 Omicron period, the pattern of pneumonia changed from primarily viral pneumonia to pneumonia mixed with bacteria in the elderly. We investigated functional outcomes at 1 year after hospital discharge in patients with primary Omicron pneumonia and pneumonia mixed with bacteria, mainly aspiration pneumonia. Functional decline rates calculated using the Barthel Index at 1 year after hospital discharge were significantly higher in the pneumonia mixed with bacteria group than the primary viral pneumonia group (42.6% vs. 20.5%, p < 0.0001). It is necessary to consider early rehabilitation and treatment in elderly patients even when the predominant strain is the Omicron variant.

Prevalence and progression of pneumonia in immunocompetent adults with varicella.

Pneumonia is the most common complication of varicella infections. Although previous studies have tended to focus mainly on immunocompromised patients, varicella pneumonia can also occur in healthy adults. Therefore, in this study, we aimed to assess the progression of varicella pneumonia in immunocompetent hosts. This retrospective study involved immunocompetent adult outpatients with varicella who attended the adult Fever Emergency facility of Peking University Third Hospital from April 1, 2020, to October 31, 2022. Varicella pneumonia was defined as a classic chickenpox-type rash in patients with infiltrates on chest computed tomography. The study included 186 patients, 57 of whom had a contact history of chickenpox exposure. Antiviral pneumonia therapy was administered to 175 patients by treating physicians. Computed tomography identified pneumonia in 132 patients, although no deaths from respiratory failure occurred. Seventy of the discharged patients were subsequently contacted, all of whom reported being well. Follow-up information, including computed tomography findings, was available for 37 patients with pneumonia, among whom 24 reported complete resolution whereas the remaining 13 developed persistent calcifications. Notably, we established that the true incidence of varicella pneumonia is higher than that previously reported, although the prognosis for immunocompetent hosts is generally good.