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1.
J Virol ; : e0134122, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2097919

ABSTRACT

We observed the interference between two prevalent respiratory viruses, respiratory syncytial virus (RSV) and influenza A virus (IAV) (H1N1), and characterized its molecular underpinnings in alveolar epithelial cells (A549). We found that RSV induces higher levels of interferon beta (IFN-ß) production than IAV and that IFN-ß priming confers higher-level protection against infection with IAV than with RSV. Consequently, we focused on the sequential infection scheme of RSV and then IAV. Using A549 wild-type (WT), IFNAR1 knockout (KO), IFNLR1 KO, and IFNAR1-IFNLR1 double-KO cell lines, we found that both IFN-ß and IFN-λ are necessary for maximum protection against subsequent infection. Immunostaining revealed that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. Strikingly, the susceptible cells turned out to be those already compromised and efficiently expressing RSV, whereas the bystander, interferon-primed cells are resistant to IAV infection. Thus, virus-virus exclusion at the cell population level is not realized through direct competition for a shared ecological niche (single cell) but rather is achieved with the involvement of specific cytokines induced by the host's innate immune response. IMPORTANCE Influenza A virus (IAV) and respiratory syncytial virus (RSV) are common recurrent respiratory infectants that show a relatively high coincidence. We demonstrated that preinfection with RSV partitions the cell population into a subpopulation susceptible to subsequent infection with IAV and an IAV-proof subpopulation. The susceptible cells are those already compromised and efficiently expressing RSV, whereas the bystander cells are resistant to IAV infection. The cross-protective effect critically depends on IFN-ß and IFN-λ signaling and thus ensues when the proportion of cells preinfected with RSV is relatively low yet sufficient to trigger a pervasive antiviral state in bystander cells. Our study suggests that mild, but not severe, respiratory infections may have a short-lasting protective role against more dangerous respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

2.
Eur J Clin Microbiol Infect Dis ; 41(12): 1445-1449, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2085399

ABSTRACT

With the COVID-19 pandemic still ongoing, the annual season of influenza and other respiratory virus epidemics has arrived. Specimens from patients suspected of respiratory viruses infection were collected. Viral detection was performed following RNA extraction and real-time RT-PCR. During the study period, we received and tested a total of 606 specimens. Rhinovirus virus was the viral type most prevalent, detected in 186 (45.47%) specimens. The age range of patients positive for influenza A, influenza A (H1N1), and influenza B was 18 days to 13 years. With female prevalence for this viral type, cough and asthma were the main clinical manifestations presented by this viral type. Our results indicate that rhinoviruses, adenoviruses, metapneumoviruses, and influenza are among the most important agents of ARI in pediatrics. The epidemic period of respiratory infections observed in Goiânia can be useful for planning and implementing some prevention strategies.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza, Human , Respiratory Tract Infections , Viruses , Child , Humans , Female , Influenza, Human/epidemiology , Influenza A Virus, H1N1 Subtype/genetics , Prevalence , Pandemics , Viruses/genetics , Rhinovirus/genetics
3.
Non-conventional in English | WHOIRIS, Grey literature | ID: grc-754729

ABSTRACT

This is the eighth report for the 2021-2022 influenza season. The June 2022 characterization report, gave a breakdown of influenza detections across the World Health Organization (WHO) European Region reported to TESSy up to week 25/2022. As of week 30/2022, 145 913 detections had been reported (a rise of nearly 13 000 since week 20/2022) resulting from extended late season influenza activity. Of these 145 913 detections, 98% were type A viruses, with A(H3N2) still dominating (84%) over A(H1N1)pdm09 (16%), but by a lower margin than in the June report (92%:8%), and 2% type B of which only 134 were ascribed to a lineage, with all but two being B/Victoria. This represents a large increase (144 903, 144-fold) in detections compared to the 2020-2021 season, on the back of a great increase (1 926 053, 176%) in the number of samples tested. However, while there have been clear indications of an influenza epidemic in 2021-2022 with the epidemic threshold of 10% positivity within sentinel specimens having been crossed for 17 weeks as of week 25/2022 (unlike in 2020-2021), numbers of detections are reduced compared to earlier seasons (e.g., 12% reduced compared to 2019-2020). The increased testing but reduced number of influenza detections is undoubtedly related to the emergence of SARS-CoV-2 and measures introduced to combat it.

4.
Non-conventional in English | WHOIRIS, Grey literature | ID: grc-754728

ABSTRACT

This is the seventh report for the 2021-2022 influenza season. The May 2022 characterization report, gave a breakdown of influenza detections across the World Health Organization (WHO) European Region reported to TESSy up to week 20/2022. As of week 25/2022, 138 352 detections had been reported (a rise of over 5 000 since week 20/2022) resulting from extended late season influenza activity. Of these 138 352 detections, 98% were type A viruses, with A(H3N2) (92%) dominating over A(H1N1)pdm09 (8%), and 2% type B of which only 125 were ascribed to a lineage, with all but two being B/Victoria. This represents a large increase (137 418, 148-fold ) in detections compared to the 2020-2021 season, on the back of a great increase (1 900 146, 200%) in the number of samples tested. However, while there have been clear indications of an influenza epidemic in 2021-2022 with the epidemic threshold of 10% positivity within sentinel specimens having been crossed for 17 weeks as of week 25/2022 (unlike in 2020-2021), numbers of detections are reduced compared to earlier seasons (e.g., 16% reduced compared to 2019-2020). The increased testing but reduced number of influenza detections is undoubtedly related to the emergence of SARS-CoV-2 and measures introduced to combat it.

5.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166584, 2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2082535

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.

6.
J Leukoc Biol ; 111(6): 1159-1173, 2022 06.
Article in English | MEDLINE | ID: covidwho-2075036

ABSTRACT

Neutrophils play significant roles in immune homeostasis and as neutralizers of microbial infections. Recent evidence further suggests heterogeneity of neutrophil developmental and activation states that exert specialized effector functions during inflammatory disease conditions. Neutrophils can play multiple roles during viral infections, secreting inflammatory mediators and cytokines that contribute significantly to host defense and pathogenicity. However, their roles in viral immunity are not well understood. In this review, we present an overview of neutrophil heterogeneity and its impact on the course and severity of viral respiratory infectious diseases. We focus on the evidence demonstrating the crucial roles neutrophils play in the immune response toward respiratory infections, using influenza as a model. We further extend the understanding of neutrophil function with the studies pertaining to COVID-19 disease and its neutrophil-associated pathologies. Finally, we discuss the relevance of these results for future therapeutic options through targeting and regulating neutrophil-specific responses.


Subject(s)
COVID-19 , Virus Diseases , Cytokines , Humans , Inflammation Mediators , Neutrophil Activation , Neutrophils , Virus Diseases/pathology
7.
BIOpreparations. Prevention, Diagnosis, Treatment ; 22(2):170-186, 2022.
Article in Russian | EMBASE | ID: covidwho-2067593

ABSTRACT

The COVID-19 pandemic has exacerbated the public’s need for effective vaccines. Consequently, significant financial support has been provided to developers of a number of innovative vaccines, including the vaccines with saponin-based adjuvants. In 2021, the World Health Organisation recommended Mosquirix, the first malaria vaccine, which contains a saponin adjuvant. An anti-covid vaccine by Novavax is in the approval phase. A promising approach to vaccine development is presented by the use of virus-like immune-stimulating complexes (ISCOMs) containing saponins and by the creation of combinations of ISCOMs with antigens. The aim of the study was to develop, produce and characterise virus-like immune-stimulating complexes based on saponins of Quillaja saponaria, as well as similar saponins of Russian-sourced Polemonium caeruleum. Materials and methods: The ISCOM adjuvants, Matrix-BQ and Matrix-BP, were produced using liquid chromatography and examined using electron microscopy. Balb/c mice were immunised intraperitoneally and intramuscularly with ISCOM-antigen preparations. Afterwards, the immunised animals were challenged with the influenza virus strain, A/California/4/2009(H1N1)pdm09, adapted and lethal to mice. The serum samples were examined using haemagglutination inhibition (HI) tests. Results: The authors produced the ISCOMs containing saponins of Quillaja saponaria and Polemonium caeruleum. After one intramuscular injection of either of the ISCOM-antigen preparations with 1 µg of each of A/Brisbane/02/2018 (H1N1) pdm09, A/Kansas/14/2017 (H3N2), and B/Phuket/3073/2013 haemagglutinin antigens (HAs), HI tests detected serum antibody titres to the corresponding antigens of ≥1:40. Two intramuscular injections of the ISCOM-antigen preparation containing 50 ng of each of the HAs and Matrix-BQ resulted in a protective response. In some animals, two intraperitoneal injections of ISCOM-antigen preparations resulted in the maximum antibody titre to the A/Kansas/14/2017 (H3N2) vaccine strain of 1:20,480. Two intramuscular injections of a test preparation containing 5 µg, 1 µg, 200 ng, or 50 ng of each of the HAs and Matrix-BQ or a control preparation containing 5 µg, 1 µg, or 200 ng of each of the HAs (commercially available vaccines) to the mice that were afterwards infected with the lethal influenza strain protected the experimental animals from death. Conclusions: The ISCOM-based preparations had high immunostimulatory activity in the mouse-model study. The presented results indicate the potential of further studies of ISCOM-based preparations in terms of both vaccine and immunotherapeutic development.

8.
Int J Mol Sci ; 23(19)2022 Sep 28.
Article in English | MEDLINE | ID: covidwho-2066124

ABSTRACT

Influenza viruses represent a leading cause of high morbidity and mortality worldwide. Approaches for fighting flu are seasonal vaccines and some antiviral drugs. The development of the seasonal flu vaccine requires a great deal of effort, as careful studies are needed to select the strains to be included in each year's vaccine. Antiviral drugs available against Influenza virus infections have certain limitations due to the increased resistance rate and negative side effects. The highly mutative nature of these viruses leads to the emergence of new antigenic variants, against which the urgent development of new approaches for antiviral therapy is needed. Among these approaches, one of the emerging new fields of "peptide-based therapies" against Influenza viruses is being explored and looks promising. This review describes the recent findings on the antiviral activity, mechanism of action and therapeutic capability of antiviral peptides that bind HA, NA, PB1, and M2 as a means of countering Influenza virus infection.


Subject(s)
Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Orthomyxoviridae , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Neuraminidase , Peptides/pharmacology , Peptides/therapeutic use
9.
American Journal of Transplantation ; 22(Supplement 3):638-639, 2022.
Article in English | EMBASE | ID: covidwho-2063546

ABSTRACT

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

10.
Tissue Engineering - Part A ; 28:324-325, 2022.
Article in English | EMBASE | ID: covidwho-2062832

ABSTRACT

Purpose/Objectives: <Most used lower respiratory tract models consist of cell monolayers which lack of tissue and organ level response and of in-vivo phenotype. Ex-vivo lung tissues have short viability and limited availability. Lung organoids, which recapitulates better the 3D cellular complex structures, architecture, and in-vivo function, fail to reach maturity even after 85 -185 days of culture. Therefore, these models have a limited use to study fetal lung diseases. Other lung models, consist of only one structure of the lower track, such as bronchial tubes or alveoli, but fail to recapitulate the whole organ structure. In this work, cell microenvironment was used to promote the self-organization of epithelial and mesenchymal cells into macro-structures, aiming to mimic the whole and adult lower respiratory tract model> Methodology: <Different parts of the microenvironment were considered to create a compliant matrix. Alginate-Gelatin hydrogels were used for 3D encapsulation of mesenchymal origin cells. This hydrogel provided a stiffness like the one on the lung. Base membrane zone proteins were used to induce the attachment and guidance of epithelial cells into 3D structures. The interactions between both cell types, further guided them into lung fate. The morphology of resulting organoids was analyzed using immunostaining and confocal microscopy, LSM710, with the purpose of evaluate polarization, protein markers, and different cell populations. Quantitative PCR was performed to evaluate and compare the expression of lung fate genes with traditional cell monocultures.> Results: <The engineered microenvironment and protocol development done in this work resulted in macro-scale structures, in which branching morphogenesis occurred at day 21. Different structures were identified in the organoid including bronchial tube, bronchioles, and alveoli. Polarization of the organoids was confirmed by visualization of E-cadherin, and ZO-1. Expression of Surfactant Protein B and C into the organoids confirmed the presence of alveolar type II cells, which are only present in the later development stage. Surfactant Protein B, Transmembrane protease, serine 2, TMPRSS-2, and Angiotensin-converting enzyme 2, ACE2 were found to be significantly higher expressed into the organoids in comparison with traditional epithelial cells monolayers.> Conclusion/Significance: <Growth factors are normally used to induce the fate of stem cells into lung organoids;however, these fail to reach maturity. Here, we developed a new methodology to induce the formation of the organoids based on the cell microenvironment. The resulting organoids require less time for development. The initial stage of adult cells can be modulated through culture conditions induce a 3D structure like the adult lung. As such, these organoids have the potential to be used for modeling adult diseases and to develop specific models from patient cells, which is one step forward to personalized medicine. SFTPB is one of the main proteins which facilitates the breathing process. Its high expression into our model may indicate that breathing occurs into our lung organoids. The higher expression of TMPRSS-2 and ACE2 into the organoids has a major significance in the field of virology since both proteins are the mainly entrance of SARS-CoV-2, and influenza H1N1.>.

11.
Journal of Cardiac Critical Care ; 6(2):103-107, 2022.
Article in English | EMBASE | ID: covidwho-2062347

ABSTRACT

Introduction Respiratory extracorporeal membrane oxygenation (ECMO) is well established and its popularity has increased during coronavirus disease 2019 (COVID-19) time. The efficacy of ECMO has been proved in refractory respiratory failure with varied etiology. More than 85,000 respiratory ECMO cases (neonatal, pediatric, adult) registered as per Extracorporeal Life support Organization (ELSO) statistics April 2022 report, with survived to discharge or transfer ranging from 58 to 73%. Early initiation of ECMO is usually associated with shorter ECMO run and better outcome. Many patient factors have been associated with mortality while on ECMO. Pre-ECMO patient pH and arterial partial pressure of carbon dioxide (paCO2) have been associated with poor outcome. We designed a retrospective study from a single tertiary care center and analyzed our data of all respiratory ECMO (neonatal, pediatric, and adult) to understand the effect of pre ECMO, paCO2, and arterial pH to ECMO outcome. Methods It is a retrospective analysis of data collected of patients with acute respiratory failure managed on ECMO from January 2010 to December 2021. Pre-ECMO (1-6 hours before initiation), paCO2, and arterial pH level were noted and analyzed with primary and secondary outcome. Primary outcome goal was survivor and discharged home versus nonsurvivor, while secondary goal was the number of ECMO days and incidence of neurological complications. The statistical analysis was done for primary outcome and incidences of neurological complications and p-value obtained by using chi-squared method. Meta-analysis was done by classifying the respiratory ECMO cases in three major category-COVID-19, H1N1 non-COVID-19, and H1N1 respiratory failure. Results The total 256 patients of respiratory failure were treated with ECMO during specified period by Riddhi Vinayak Multispecialty Hospital ECMO team. Data analysis of 251 patients (5 patients were transferred for lung transplant, hence been not included in study) done. Patients were divided on the basis of pH level less than 7.2 and more than 7.2 and analyzed for primary and secondary outcome. Similarly, patients were divided on the basis of paCO2 level of less than 45 and more than 45. Patient with pre-ECMO pH level more than 7.2 has statistically better survived extracorporeal life support (ECLS) (p-value: 0.008) and survival to discharge home (p-value: 0.038) chances. Pre-ECMO paCO2 level of less than 45 also showed better survival chance of survived ECLS (46.67 vs. 36.02) and survived to discharge home (42.22 vs. 31.06) but not statistically significant (p-value: 0.15 and 0.18, respectively). There was no significant difference in average number of ECMO days in patient survived to discharge home with paCO2 less than 45 and more than 45 (15.7 vs. 11.1 days), and also in pH more than 7.2 and pH less than 7.2 (15.8 vs. 11.6). The incidence of neurological complications was also found lower in patient with pH more than 7.2 (7.5 vs. 17.3%, p-value: 0.034) and in paCO2 level of less than 45 (4.4 vs. 12.65, p-value: 0.15). Conclusion Pre-ECMO arterial pH of more than 7.2 (statistically significant) and paCO2 of less than 45 (statistically not significant) have definitely better survival chances and have lesser incidences of neurological complications. There was no significance difference in the number of ECMO days in either group. Authors recommends early initiation of ECMO for mortality and morbidity benefits.

12.
Virology ; 576: 105-110, 2022 11.
Article in English | MEDLINE | ID: covidwho-2061964

ABSTRACT

As SARS-CoV-2 and influenza viruses co-circulate, co-infections with these viruses generate an increasing concern to public health. To evaluate the prevalence and clinical impacts of SARS-CoV-2 and influenza A virus co-infections during the 2021-2022 influenza season, SARS-CoV-2-positive samples from 462 individuals were collected from October 2021 to January 2022. Of these individuals, 152 tested positive for influenza, and the monthly co-infection rate ranged from 7.1% to 48%. Compared to the Delta variant, individuals infected with Omicron were less likely to be co-infected and hospitalized, and individuals who received influenza vaccines were less likely to become co-infected. Three individuals had two samples collected on different dates, and all three developed a co-infection after their initial SARS-CoV-2 infection. This study demonstrates high prevalence of co-infections in central Missouri during the 2021-2022 influenza season, differences in co-infection prevalence between the Delta and the Omicron waves, and the importance of influenza vaccinations against co-infections.


Subject(s)
COVID-19 , Coinfection , Influenza A virus , Influenza Vaccines , Influenza, Human , Humans , Influenza, Human/epidemiology , SARS-CoV-2 , Coinfection/epidemiology , Cross-Sectional Studies , Seasons , Missouri/epidemiology , COVID-19/epidemiology , Influenza A virus/genetics
13.
Chest ; 162(4):A2250, 2022.
Article in English | EMBASE | ID: covidwho-2060920

ABSTRACT

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Amyloidosis of the respiratory tract is rare. We present a case of tracheobronchial amyloid presenting as multifactorial cough with syncope. CASE PRESENTATION: The patient is a 65-year-old man with history of hypertension, hyperlipidemia, and allergic rhinitis who presented to the ED after a syncopal event. Two weeks prior, he had a new-onset myalgias and severe persistent cough, not resolving with over-the-counter medications. During a coughing paroxysm, he experienced a brief loss of consciousness. On arrival, his vital signs and physical exam were within normal limits except for Mallampati II, BM of 38.8 kg/m2. Basic laboratory testing was also unremarkable except for troponin T of 251 nl/dL and NT-ProBNP of 1181 pg/mL. NP swab for Sars-CoV-19 (PCR), Influenza A and B were not detected. CT of the chest revealed an area of circumferential mural soft tissue thickening in the left lower lobe bronchi. Cardiac MRI showed an area of subepicardial delayed enhancement, suggestive of myocardial inflammation or edema. Flexible bronchoscopy confirmed that the left lower lobe bronchus and proximal subsegmental bronchi had an infiltrative process with a friable, erythematous irregular mucosal surface. Forceps biopsy sampling and staining with Congo red, sulfate Alcian blue and Trichome stain were positive for amyloid deposits. Immunostain revealed predominantly CD3 positive T-Cells. Mass spectometry showed AL (lamda)-type amyloid deposition. GMS and AFB stains were negative. Telemetry showed 2-3 second pauses, correlated with episodes of cough. DISCUSSION: Amyloidosis is a disorder caused by misfolding of proteins and fibril accumulation in the extracellular space. It can present as a diffuse or localized process to one organ system. Several patterns of lung involvement have been described: nodular pulmonary, diffuse alveolar-septal, cystic, pleural, and tracheobronchial amyloidosis. Tracheobronchial amyloidosis is usually limited and not associated with systemic disease or hematologic malignancy. It can be asymptomatic, or can present with cough, dyspnea or signs of obstruction, including postobstructive pneumonia. Congo Red stained samples reveal green birefringence under polarized light microscopy. Further analysis of proteins usually reveals localized immunoglobulin light chains (AL). Cough syncope is due to increased intrathoracic pressure, decreased venous return and cardiac output, stimulation of baroreceptors, decreased chronotropic response, arterial hypotension and decreased cerebral perfusion. Our patient presented with multifactorial cough (possible viral infection, upper airway cough syndrome, amyloidosis) causing sinus pauses and syncope, on underlying myocarditis. CONCLUSIONS: Amyloid infiltration of the respiratory system is rare, but it should be considered in the differential diagnosis of airway disorders, nodular or cystic lung diseases, and pleural processes. Reference #1: Milani P, Basset M, Russo F, et al. The lung in amyloidosis. Eur Respir Rev 2017;26: 170046 [https://doi.org/10.1183/16000617.0046-2017]. Reference #2: Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996 Feb 15;124(4):407-13. doi: 10.7326/0003-4819-124-4-199602150-00004 Reference #3: Dicpinigaitis PV, Lim L, Farmakidis C. Cough syncope. Respir Med. 2014 Feb;108(2):244-51. doi: 10.1016/j.rmed.2013.10.020. Epub 2013 Nov 5. PMID: 24238768. DISCLOSURES: No relevant relationships by Amarilys Alarcon-Calderon No relevant relationships by Ashokakumar Patel

14.
Chest ; 162(4):A2163, 2022.
Article in English | EMBASE | ID: covidwho-2060904

ABSTRACT

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Fat embolism is a syndrome that can occur during orthopedic procedures or fractures of the long bones, especially the femur and tibia. It can affect multiple organs, including the brain, skin, and lungs, causing the triad of altered mentation, petechiae, and hypoxemia. Here, we present a case of a 54-year-old woman at risk for graft versus host disease (GVHD) who presented with dyspnea a few weeks after an orthopedic procedure. Initial chest radiograph was notable for parenchymal infiltrates, and she was initially treated with antibiotics without improvement. CASE PRESENTATION: A 54-year-old woman with a history of leukemia, stem cell transplantation years ago, GVHD (skin liver, ocular, oral, joints (not lung), with clinical and cytogenetic remission underwent total hip arthroplasty. Two weeks later, she developed lethargy and dyspnea and presented to the emergency department. She was found to have an elevated WBC of x19.5 k/ul (normal 4.1-9.3k/uL) with a left upper lobe consolidation on the chest radiograph (Figure 1). She was treated empirically for pneumonia and discharged with a 7-day course of levofloxacin. Despite completing the course of antibiotics, her dyspnea worsened, and she presented to the emergency department two weeks later with worsening hypoxemia. Computed tomography (CT) of the chest showed bilateral diffuse ground-glass opacities (GGOs) with patchy consolidations in a broncho-vascular distribution (Figure 2). She was negative for COVID-19, Influenza A, B and Legionella urinary antigen. The differential diagnosis included infection and GVHD among others. She underwent bronchoalveolar lavage (BAL). The Gram stain and the culture did not suggest an infection. Pathology from BAL returned significant for reactive bronchial and squamous cells with lipid-laden macrophages. She was started on steroids. Her clinical status improved dramatically, and she was eventually discharged. At a 3-month follow-up her symptoms had improved. Her CT scan also showed significant improvement (Figure 3). DISCUSSION: Our case highlights the successful diagnosis of fat embolism in the lungs in a patient with complicated medical history. Fat embolism usually presents as ground glass opacities. However, the diagnosis was more challenging in this case due to a significant time lapse between her surgery and her presentation to the hospital. She also lacked the other common signs of fat embolism including altered mentation and skin changes. Therefore, other etiologies, such as GVHD, bacterial or viral infection were initially strongly considered. CONCLUSIONS: The diagnosis of fat embolism syndrome condition should still be suspected despite a delay from the initial surgery. Diagnosis in immunocompromised patients requires a detailed workup to rule out other etiologies. Reference #1: Johnson, M. J., & Lucas, G. L. (1996). Fat embolism syndrome. Orthopedics, 19(1), 41-49. Reference #2: Newbigin, K., Souza, C. A., Torres, C., Marchiori, E., Gupta, A., Inacio, J., … & Peña, E. (2016). Fat embolism syndrome: state-of-the-art review focused on pulmonary imaging findings. Respiratory medicine, 113, 93-100. Reference #3: Swiatek, K., Kordic, G., & Jordan, K. (2018). An Unlikely Presentation of Fat Embolism Syndrome. Chest, 154(4), 686A. DISCLOSURES: No relevant relationships by Raheel Anwar No relevant relationships by Boris Medarov

15.
Chest ; 162(4):A1578, 2022.
Article in English | EMBASE | ID: covidwho-2060843

ABSTRACT

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Pneumatoceles are air-filled cavitary lesions that are rarely seen in the lung after infection, trauma, or as part of a more diffuse cystic disease process. Several infectious agents have been associated with pneumatoceles, one of them being Pneumocystis Jirovecii, a potentially life-threatening fungus commonly seen as an opportunistic infection in immunocompromised patients. We present a case of bilateral extensive pneumatocele in a newly diagnosed HIV patient found to be positive for Pneumocystis pneumonia CASE PRESENTATION: A 52-year-old female presented to the emergency room for 2 months of shortness of breath, body aches, and chills. She was saturating at 86% on room air on arrival. Initial chest x-ray showed bilateral airspace disease. Had additional history of daily smoking, polysubstance abuse, and poor follow-up with doctors’ appointments due to social issues. She was started on oxygen support, steroids, antibiotics, and IV fluids. Labs were notable for normal overall WBC count but low lymphocyte count of 0.4. A CT Angiogram of the chest showed moderate to severe diffuse bilateral gas-filled cystic structures throughout the lungs, consistent with pneumatoceles. Infectious workup performed: COVID PCR, Influenza A/B antigen, legionella antigen, strep. pneumoniae antigen, B-D-glucan assay, histoplasma and blastomyces antigens, and HIV antibody. HIV antibody, strep pneumo antigen, and B-D-glucan assay came positive. She did not have a known diagnosis of HIV prior to this admission. Antibiotic regimen was changed to ceftriaxone, azithromycin, Bactrim, and fluconazole. Bronchoscopy with lavage was performed. Lavage samples were sent for cytology and found to be positive for Pneumocystis on GMS stain HIV viral load was checked and found to be at 1.4 million copies. CD4 count was less than 25 Patient was started on antiretroviral therapy in addition to prolonged course of Bactrim. She was ultimately discharged from the hospital in stable condition with pulmonary and infectious disease follow-up. At this time her pneumatoceles have improved on follow-up imaging. DISCUSSION: Pneumatoceles can rarely present as a complication of PCP pneumonia and can be a marker of more advanced disease. In our patient, pneumatoceles were identified first followed by diagnosis of HIV and PCP pneumonia. Overall incidence of post-infectious pneumatoceles is low at 2-8%. Prompt treatment and careful monitoring is needed due to risk of mortality from underlying infection and progression to pneumothorax. CONCLUSIONS: HIV with PCP infection complicated by pneumatocele formation is much less common due to improvements in HIV detection and screening for opportunistic infection, but should remain an important consideration in patients with unexplained cystic lung disease patterns, especially in patients without established outpatient follow-up or who don't see medical providers often. Reference #1: Thomas CF Jr, Limper AH: Pneumocystis pneumonia. N Engl J Med. 2004;350: pp. 2487-2498. Reference #2: Albitar, Hasan and Saleh, Omar M. Pneumocystis Pneumonia Complicated by Extensive Diffuse Pneumatoceles. Am J Med. 2019 May;132(5):e562-e563. Epub 2019 Jan 16. Reference #3: Ryu, Jay et al. Diffuse Cystic Lung Diseases. Frontiers of Medicine volume 7, pages 316–327 (2013) DISCLOSURES: No relevant relationships by Clifford Hecht

16.
Chest ; 162(4):A1265, 2022.
Article in English | EMBASE | ID: covidwho-2060791

ABSTRACT

SESSION TITLE: Diagnosis of Lung Disease through Pathology Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Usual interstitial pneumonia (UIP) is a histological term used to describe a pattern of interstitial fibrosis with alternating areas of the normal lung with temporal fibrosis and architectural alteration due to chronic scarring or honeycomb change. It is a subset of idiopathic interstitial pneumonias (IPF) that usually presents in the sixth and seventh decades of life with progressive dyspnea on exertion and productive cough. CASE PRESENTATION: We present a 46 y/o man with a history of thyroid disease, hypertension and a former smoker of 20 pack-year smoking. Presented to ED complaining of low oxygen saturation with pulse oximetry at home with readings between 60-80%. Accompanied with progressive dyspnea on exertion and unintentional weight loss of 80 pounds in the last year. Also referred productive cough of white sputum that was worse in the morning. Home nebulized Albuterol therapy did not provide improvement. Denied recent viral respiratory infections, night sweats, environmental exposures nor family history of lung disease. DISCUSSION: Physical exam demonstrated bilateral expiratory dry crackles and pulse oximetry oxygen saturation at room air of 78%. RBBB evidenced on EKG. Bloodwork showed polycythemia with hemoglobin of 17.8;ABG's with pH: 7.40, Pco2: 42.2, PO2: 59.8, HCO3: 26, O2 sat: 90.8 and ideal PO2: 85.6 consistent with metabolic alkalosis with BMP CO2 of 30, A/a gradient: 43.0. Mycoplasma IgM, Influenza A & B and COVID-19 antigen test were negative. CXR with increased vascular markings, chest CT demonstrated small pericardial effusion, bilateral coarse interstitial pulmonary markings and bronchiectasis suggestive of chronic interstitial lung disease with no specific pattern. Left heart catheterization revealed right ventricular hypertrophy, normal EF >55%, and no evidence of coronary disease. Alpha-1 antitrypsin: 158, EPO: 6.5, HIV, and hepatitis panel were all negative. Rheumatology work up with only an ANA antibody positive, with titer 1:160. Patient underwent VATS procedure with wedge biopsy of the right upper and middle lobe that revealed usual interstitial pneumonia pattern. Patient improved and was discharged on home oxygen 3L. At follow-up, treatment was started with Nintedanib and Sildenafil Citrate. He had clinical improvement and oxygen requirements decreased to intermittent oxygen. CONCLUSIONS: Patients with interstitial pulmonary fibrosis experience slow progressive decline with typical clinical presentation over 60 years of age. This case remarks the importance of the need for stratification of interstitial lung disease classification, when pattern and history are non specific, with the use of VATS procedure for early start of treatment. Our patient with no environmental exposure or connective tissue disease had an uncommon early presentation of usual interstitial pneumonia. Reference #1: Tibana, R.C.C., Soares, M.R., Storrer, K.M. et al. Clinical diagnosis of patients subjected to surgical lung biopsy with a probable usual interstitial pneumonia pattern on high-resolution computed tomography. BMC Pulm Med 20, 299 (2020). https://doi.org/10.1186/s12890-020-01339-9 DISCLOSURES: No relevant relationships by Jesse Aleman No relevant relationships by Carlos Martinez Crespí no disclosure submitted for Jean Ramos;No relevant relationships by Alexandra Rodriguez Perez No relevant relationships by Paola Vazquez No relevant relationships by Nahomie Veguilla Rivera

17.
Chest ; 162(4):A590, 2022.
Article in English | EMBASE | ID: covidwho-2060640

ABSTRACT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Over the past 2 years, SARS-CoV-2 has been undergoing research regarding its immunopathology, with its understanding continuously evolving. We present a case of severe respiratory failure from viral co-infection with SARS-CoV-2, parainfluenza virus III, influenza A, and adenovirus. CASE PRESENTATION: A 42-year-old female with no respiratory or immunological comorbidities, was admitted with respiratory failure that progressed within days to severe septic shock and refractory hypoxemia requiring venovenous extracorporeal membrane oxygenation (VV-ECMO). On initial laboratory evaluation, her nasopharyngeal swab sample tested positive for SARS-CoV-2, Parainfluenza virus III, Influenza A, and Adenovirus on our institute's ROCHE PCR detection test. This was then confirmed with an endotracheal sample and a BAL sample, each of which tested positive for the above 4 viruses. The patient had no prior history of lung disease, autoimmune disorder, immunodeficiency, or malignancy. Serum immunoglobulin levels were within normal range, and the patient tested negative for HIV. She was not on any immunomodulators, and had no known contacts with individuals with polyviral infection. Her presentation had been usual, with 6 days of fever, shortness of breath, extreme fatigue, coughing, and diarrhea. She had initially received treatment with remdesivir, tocilizumab, and dexamethasone. But these tests were noted to be positive prior to her receiving any therapies. Her hospital course was complicated by septic shock, refractory hypoxemia, secondary ventilator associated pneumonia, and fungemia, requiring invasive mechanical ventilation, inhaled nitric oxide, vasopressors, broad spectrum antimicrobials, and eventually rescue by VV-ECMO. She slowly recovered over 6 weeks, received a tracheostomy and was discharged to a long-term acute care hospital for continued rehabilitation and weaning from mechanical ventilation. At 1 year follow up, she has made a full recovery with no residual respiratory limitation. DISCUSSION: Co-infection is defined as infection at diagnosis within 7 days of initial primary infection, whereas, secondary infection develops after 7 days. Co-infection of respiratory viruses, though uncommon, has been reported. Their detection has improved with the use of PCR testing. Simultaneous infection of COVID-19 and usual respiratory viruses has also been documented. Effect of co-infection on disease severity is a result of interaction of viruses among themselves and with the host. CONCLUSIONS: COVID-19 research has mainly focused on SARS-CoV-2 effects on the human host, but with it evolving into an endemic, its interaction and co- and superinfection with other pathogens is imperative. Further research into such interactions of SARS-CoV2 are required to help develop preventative and therapeutic measures. Reference #1: Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with covid-19: A systematic review and meta-analysis. SSRN Electronic Journal. 2020. Reference #2: Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-COV-2 and other respiratory pathogens. JAMA. 2020;323(20):2085. Reference #3: DaPalma T, Doonan BP, Trager NM, Kasman LM. A systematic approach to virus–virus interactions. Virus Research. 2010;149(1):1-9. DISCLOSURES: No relevant relationships by Vinita Kusupati No relevant relationships by Jyoti Lenka No relevant relationships by Rachel Tan

18.
Chest ; 162(4):A430, 2022.
Article in English | EMBASE | ID: covidwho-2060595

ABSTRACT

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Since the onset of the COVID-19 pandemic, vaccines were introduced to mitigate the spread of the virus. Depending on the COVID-19 vaccine, regimens consist of one dose (ie, J&J) or two doses (ie, Pfizer and Moderna) and is followed by a third dose/booster (for immunocompromised/immunocompetent individuals). Here, we present a case of COVID-19 infection in a triple vaccinated patient with concurrent rheumatoid arthritis (RA) receiving disease modifying antirheumatic drugs (DMARDs) who was unable to mount an adequate immune response to the vaccine. CASE PRESENTATION: Patient is a 67 year old male with PMH of RA (on DMARDs) presented to the ED with complaints of shortness of breath. He was on treatment for RA with leflunomide, rituximab and prednisone. He was COVID-19 triple vaccinated. In ED, the patient was found to be hypoxic, saturating at 87% on room air with a respiratory rate of 18. Physical examination was significant for coarse breath sounds bilaterally and remaining vitals were unremarkable. Patient was initially placed on 3 L oxygen via NC but due to persistent hypoxia, was transitioned to high-flow nasal cannula. Further investigations revealed that the patient was COVID-19 positive. He was treated with remdesivir and dexamethasone. His oxygen requirements continued to escalate and he was ultimately intubated. While in the ICU, the patient's hypoxia continued to worsen despite optimal medical and ventilatory management and he subsequently died. DISCUSSION: DMARDs are a group of medications used to slow the progression of rheumatoid arthritis. They work by reducing the immune response of B cells, T cells and cytokines. Our patient was on two commonly prescribed medications for rheumatoid arthritis, leflunomide and rituximab. The former acts by inhibiting the pyrimidine synthesis pathway, thereby decreasing T lymphocyte production and the latter depletes CD-20 positive B cells. While there is limited data on COVID-19 vaccine, it has been established that patients on DMARDs have reduced antibody titres after immunization against influenza and pneumonia vaccinations [1, 2]. A study assessing the effectiveness of a third vaccine dose in patients taking rituximab vs placebo found a significant difference in seroconversion (78.8% vs 18.2%, p=<0.0001) and neutralizing activity (80.0% vs 21.9%, p=<0.0001) [3]. In our case, the patient was on two immunosuppressive drugs which suppressed both the humoral and cell mediated immunity, resulting in an inadequate immune response and subsequently developing COVID. CONCLUSIONS: This case highlights patients on immunosuppressant therapy failing to mount an adequate immune response to the COVID-19 vaccine, warranting more booster doses in patients on DMARDs. Reference #1: Adler S, Krivine A, Weix J et al. Protective effect of A/ H1N1 vaccination in immune-mediated disease–a prospectively controlled vaccination study. Rheumatology 2012;51:695–700. Reference #2: Franca ILA, Ribeiro ACM, Aikawa NE et al. TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients. Rheumatology 2012;51:2091–8. Reference #3: David S, Koray T, Filippo F et al. Efficacy and safety of SARS-CoV-2 revaccination in non-responders with immune-mediated inflammatory disease. http://dx.doi.org/10.1136/annrheumdis-2021-221554 DISCLOSURES: No relevant relationships by Gursharan Kaur No relevant relationships by Aishwarya Krishnaiah No relevant relationships by sandeep mandal

19.
Bioactive Materials ; 21:576-594, 2023.
Article in English | EMBASE | ID: covidwho-2060443

ABSTRACT

Viral infections cause damage to various organ systems by inducing organ-specific symptoms or systemic multi-organ damage. Depending on the infection route and virus type, infectious diseases are classified as respiratory, nervous, immune, digestive, or skin infections. Since these infectious diseases can widely spread in the community and their catastrophic effects are severe, identification of their causative agent and mechanisms underlying their pathogenesis is an urgent necessity. Although infection-associated mechanisms have been studied in two-dimensional (2D) cell culture models and animal models, they have shown limitations in organ-specific or human-associated pathogenesis, and the development of a human-organ-mimetic system is required. Recently, three-dimensional (3D) engineered tissue models, which can present human organ-like physiology in terms of the 3D structure, utilization of human-originated cells, recapitulation of physiological stimuli, and tight cell-cell interactions, were developed. Furthermore, recent studies have shown that these models can recapitulate infection-associated pathologies. In this review, we summarized the recent advances in 3D engineered tissue models that mimic organ-specific viral infections. First, we briefly described the limitations of the current 2D and animal models in recapitulating human-specific viral infection pathology. Next, we provided an overview of recently reported viral infection models, focusing particularly on organ-specific infection pathologies. Finally, a future perspective that must be pursued to reconstitute more human-specific infectious diseases is presented. Copyright © 2022 The Authors

20.
Investigative Ophthalmology and Visual Science ; 63(7):2671, 2022.
Article in English | EMBASE | ID: covidwho-2058291

ABSTRACT

Purpose : SARS-CoV-2, the viral infection that causes COVID-19, is known to induce a hypercoagulable state in patients. While there have been isolated reports of retinal vascular occlusion among patients with a pre-existing COVID-19 infection, research into this topic remains scant. Therefore, the purpose of this study is to investigate the shortterm prevalence and risk for retinal vascular occlusion between COVID-19 and influenza A patients. Methods : TrinetX is a national, federated database that was utilized in this retrospective cohort analysis. At the time of the study, electronic medical records from over 80 million patients across 57 healthcare organizations were analyzed to create two cohorts of patients. At the time of the analysis, 1,224,770 patients with a previous history for COVID19 were compared to 61,555 patients with a previous history for influenza A. Then, 1:1 propensity score matching (PSM) was utilized to balance each cohort by demographics and comorbidities (age, sex, BMI, history of hypertension, chronic lower respiratory disease, diabetes mellitus, nicotine dependence, heart failure, and alcohol related disorders). Adjusted risk ratios (aRR) using 95% confidence intervals (CI) were used to assess risk of retinal vascular occlusion 120 days after initial diagnosis for COVID-19 or influenza A. Results : Before PSM, COVID-19 patients were at significantly lesser risk for retinal vascular occlusion within 120 days of initial diagnosis than influenza A patients (aRR [95% CI] = 0.58 [0.42,0.8];p<0.001). However, the incidence for influenza patients to develop retinal vascular occlusion was very small (0.1%). After PSM, two balanced cohorts of 61,555 patients were compared to one another and revealed that there is no significant difference in developing a retinal vascular occlusion after a previous diagnosis of COVID19 or influenza A (0.92 [0.58,1.46];p=0.725). Likewise, the incidence for retinal vascular occlusion remained very small (0.1% between both cohorts) (Table 1). Conclusions : This is the first large-scale study investigating the risk of retinal vascular occlusion among COVID-19 and influenza A patients. We found that each cohort was at similar risk for developing retinal vascular occlusion within 120 days. Likewise, the incidence for retinal vascular occlusion was miniscule among patients in this study.

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