Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection.

Respiratory viral infection increases host susceptibility to secondary bacterial infections, yet the precise dynamics within airway epithelia remain elusive. Here, we elucidate the pivotal role of CD47 in the airway epithelium during bacterial super-infection. We demonstrated that upon influenza virus infection, CD47 expression was upregulated and localized on the apical surface of ciliated cells within primary human nasal or bronchial epithelial cells. This induced CD47 exposure provided attachment sites for Staphylococcus aureus, thereby compromising the epithelial barrier integrity. Through bacterial adhesion assays and in vitro pull-down assays, we identified fibronectin-binding proteins (FnBP) of S. aureus as a key component that binds to CD47. Furthermore, we found that ciliated cell-specific CD47 deficiency or neutralizing antibody-mediated CD47 inactivation enhanced in vivo survival rates. These findings suggest that interfering with the interaction between airway epithelial CD47 and pathogenic bacterial FnBP holds promise for alleviating the adverse effects of super-infection.

Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.

Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.

Downregulation of endogenous nectin1 in human keratinocytes by herpes simplex virus 1 glycoprotein D excludes superinfection but does not affect NK cell function.

Many viruses downregulate their cognate receptors, facilitating virus replication and pathogenesis via processes that are not yet fully understood. In the case of herpes simplex virus 1 (HSV1), the receptor binding protein glycoprotein D (gD) has been implicated in downregulation of its receptor nectin1, but current understanding of the process is limited. Some studies suggest that gD on the incoming virion is sufficient to achieve nectin1 downregulation, but the virus-encoded E3 ubiquitin ligase ICP0 has also been implicated. Here we have used the physiologically relevant nTERT human keratinocyte cell type - which we have previously shown to express readily detectable levels of endogenous nectin1 - to conduct a detailed investigation of nectin1 expression during HSV1 infection. In these cells, nectin1, but not nectin2 or the transferrin receptor, disappeared from the cell surface in a process that required virus protein synthesis rather than incoming virus, but did not involve virus-induced host shutoff. Furthermore, gD was not only required but was sufficient for nectin1 depletion, indicating that no other virus proteins are essential. NK cells were shown to be activated in the presence of keratinocytes, a process that was greatly inhibited in cells infected with wild-type virus. However, degranulation of NK cells was also inhibited in ΔgD-infected cells, indicating that blocking of NK cell activation was independent of gD downregulation of nectin1. By contrast, a superinfection time-course revealed that the ability of HSV1 infection to block subsequent infection of a GFP-expressing HSV1 was dependent on gD and occurred in line with the timing of nectin1 downregulation. Thus, the role of gD-dependent nectin1 impairment during HSV infection is important for virus infection, but not immune evasion, which is achieved by other mechanisms.

Diagnostic, clinical management, and outcome of bone flap-related osteomyelitis after cranioplasty.

OBJECTIVES: We aimed to describe diagnostic, management, and outcome of bone flap-related osteomyelitis after cranioplasty. METHODS: Patients followed up in our tertiary care hospital for bone flap-related osteomyelitis after cranioplasty were included in a retrospective cohort (2008-2021). Determinants of treatment failure were assessed using logistic regression and Kaplan-Meier curves analysis. RESULTS: The 144 included patients (81 [56.3%] males; median age 53.4 [interquartile range [IQR], 42.6-62.5] years) mostly presented wound abnormalities (n = 115, 79.9%). All infections were documented, the main pathogens being Staphylococcus aureus (n = 64, 44.4%), Cutibacterium acnes (n = 57, 39.6%), gram-negative bacilli (n = 40, 27.8%) and/or non-aureus staphylococci (n = 34, 23.6%). Surgery was performed in 140 (97.2%) cases, for bone flap removal (n = 102, 72.9%) or debridement with flap retention (n = 31, 22.1%), along with 12.7 (IQR, 8.0-14.0) weeks of antimicrobial therapy. After a follow-up of 117.1 (IQR, 62.5-235.5) weeks, 37 (26.1%) failures were observed: 16 (43.2%) infection persistence, three (8.1%) relapses, 22 (59.5%) superinfections and/or two (1.7%) infection-related deaths. Excluding superinfections, determinants of the 19 (13.4%) specific failures were an index craniectomy for brain tumor (odds ratio = 4.038, P = 0.033) and curettage of bone edges (odds ratio = 0.342, P = 0.048). CONCLUSION: Post-craniectomy bone flap osteomyelitis are difficult-to-treat infection, necessitating prolonged antimicrobial therapy with appropriate surgical debridement, and advocating for multidisciplinary management in dedicated reference centers.

Bacterial Infection of an Alveolar Echinococcus Cyst from C. perfringens Septicemia: A Case Report and Review of the Literature.

Background and Objectives: Alveolar echinococcosis (AE) is a highly variable disease able to present as structurally diverse cysts in different organs based on the host's immunological state as well as the time between diagnosis and the primary infection. Bacterial superinfections, especially with anaerobic pathogens from the Clostridiaceae genus, can further alter the radiological findings due to pneumobilia, newly formed abscess formations, and inflammatory changes. Materials and Methods: We present a case of a 71-year-old Caucasian male admitted to our intensive care unit with septic shock, pneumobilia, and a complex cyst of the liver with calcification, as shown by an initial CT. Because of the septic shock, the patient was started on broad-band antibiotics. Clostridiaceae infection was considered an important differential diagnosis due to the presence of pneumobilia observed in the initial CT, without a history of previous endoscopy. Furthermore, serology for echinococcus was positive, and blood cultures showed growth of C. perfringens. Therefore, the patient was additionally treated with albendazole. After recovery, further staging was conducted, showing complete remission of the cyst and a left-over lesion classified as Alveolar Echinococcosis Ulm Classification (AEUC) V. In summary, the patient had a pre-existing, controlled AE infection that became superinfected with C. perfringens, likely attributable to the anaerobic necrotic tissue, leading to septicemia. Results: The anaerobic tissue within the AE cyst provided an ideal medium for C. perfringens to replicate, leading to cyst infection, which subsequently caused septic shock and pneumobilia. The initial findings from CT and MRI were confounded by the superinfection, demonstrating the diagnostic challenges of AE, especially when presenting with complications. Conclusions: Diagnosing AE remains a demanding task, even with the excellent tools available through serology, coupled with CT, FDG-PET-CT, and MRI. Notably, older superinfected cysts can pose difficulties when integrated into the appropriate diagnostic context. Prompt diagnosis is critical for the accurate treatment of echinococcosis and its complications, such as bacterial superinfections. From a clinical perspective, septicemia from Clostridiaceae and infections with C. perfringens-pathogens capable of inducing pneumobilia-should be regarded as significant differential diagnoses for pneumobilia in the absence of a recent history of endoscopy.

Mimicking superinfection exclusion disrupts alphavirus infection and transmission in the yellow fever mosquito Aedes aegypti.

Multiple viruses, including pathogenic viruses, bacteriophages, and even plant viruses, cause a phenomenon termed superinfection exclusion whereby a currently infected cell is resistant to secondary infection by the same or a closely related virus. In alphaviruses, this process is thought to be mediated, at least in part, by the viral protease (nsP2) which is responsible for processing the nonstructural polyproteins (P123 and P1234) into individual proteins (nsP1-nsP4), forming the viral replication complex. Taking a synthetic biology approach, we mimicked this naturally occurring phenomenon by generating a superinfection exclusion-like state in Aedes aegypti mosquitoes, rendering them refractory to alphavirus infection. By artificially expressing Sindbis virus (SINV) and chikungunya virus (CHIKV) nsP2 in mosquito cells and transgenic mosquitoes, we demonstrated a reduction in both SINV and CHIKV viral replication rates in cells following viral infection as well as reduced infection prevalence, viral titers, and transmission potential in mosquitoes.

Coinfection and superinfection in ICU critically ill patients with severe COVID-19 pneumonia and influenza pneumonia: are the pictures different?

Background: Similar to influenza, coinfections and superinfections are common and might result in poor prognosis. Our study aimed to compare the characteristics and risks of coinfections and superinfections in severe COVID-19 and influenza virus pneumonia. Methods: The data of patients with COVID-19 and influenza admitted to the intensive care unit (ICU) were retrospectively analyzed. The primary outcome was to describe the prevalence and pathogenic distribution of coinfections/ICU-acquired superinfections in the study population. The secondary outcome was to evaluate the independent risk factors for coinfections/ICU-acquired superinfections at ICU admission. Multivariate analysis of survivors and non-survivors was performed to investigate whether coinfections/ICU-acquired superinfections was an independent prognostic factor. Results: In the COVID-19 (n = 123) and influenza (n = 145) cohorts, the incidence of coinfections/ICU-acquired superinfections was 33.3%/43.9 and 35.2%/52.4%, respectively. The most common bacteria identified in coinfection cases were Enterococcus faecium, Pseudomonas aeruginosa, and Acinetobacter baumannii (COVID-19 cohort) and A. baumannii, P. aeruginosa, and Klebsiella pneumoniae (influenza cohort). A significant higher proportion of coinfection events was sustained by Aspergillus spp. [(22/123, 17.9% in COVID-19) and (18/145, 12.4% in influenza)]. The COVID-19 group had more cases of ICU-acquired A. baumannii, Corynebacterium striatum and K. pneumoniae. A. baumannii, P. aeruginosa, and K. pneumoniae were the three most prevalent pathogens in the influenza cases with ICU-acquired superinfections. Patients with APACHE II ≥18, CD8+ T cells ≤90/µL, and 50 < age ≤ 70 years were more susceptible to coinfections; while those with CD8+ T cells ≤90/µL, CRP ≥120 mg/L, IL-8 ≥ 20 pg./mL, blood glucose ≥10 mmol/L, hypertension, and smoking might had a higher risk of ICU-acquired superinfections in the COVID-19 group. ICU-acquired superinfection, corticosteroid administration for COVID-19 treatment before ICU admission, and SOFA score ≥ 7 were independent prognostic factors in patients with COVID-19. Conclusion: Patients with COVID-19 or influenza had a high incidence of coinfections and ICU-acquired superinfections. The represent agents of coinfection in ICU patients were different from those in the general ward. These high-risk patients should be closely monitored and empirically treated with effective antibiotics according to the pathogen.

Evaluation of the features of cystic echinococcosis with concurrent super-infection: a retrospective study in Southern Iran.

OBJECTIVE: Superinfection of cystic echinococcosis (CE) is a life-threatening complication with significant morbidities, which can be prevented with early diagnosis and treatment. This study aims to examine the clinical characteristics, diagnostic methods, and treatment options for superinfected CE, as there is currently limited information available on the differences between superinfected and non-infected CE in terms of clinical features, serological and radiologic findings. METHODS: This cross-sectional study was conducted on hospital records of patients who were diagnosed with hydatid cysts in a 15-year period (2004 to 2018) in two main university-affiliated referral centers in Fars province, southern Iran. Patients' information regarding the demographical and clinical features related to CE, age, sex, previous history of CE or recurrence, size and location of CE, and length of hospital stay were collected. Moreover, the characteristics of concurrent infections with hydatid cysts were recorded. RESULTS: A total of 586 surgeries due to CE were performed on 501 patients, of which 67 (11.43%) had reoperations due to the recurrence of the disease. A total of 30 (5.99%) incidences of superinfection were observed. There were no statistically significant differences in terms of laboratory and imaging findings between CE patients with concurrent infections and other CE patients (p-value > 0.05). Among the patients with super-infection, four had fungal infections of the lungs. Aspergillus fumigatus was the causative pathogen in all four patients that were diagnosed with fungal superinfection. All patients underwent surgical excision with favorable long-term outcomes. CONCLUSION: Our study revealed a 5.99% incident rate of CE superinfection. Regarding the concurrent fungal infections in hydatid cysts, the patient's symptoms and laboratory and imaging findings are inconclusive and histopathological evaluation seems to be the most reliable option. Surgical resection is the gold-standard treatment option with favorable outcomes and potentially can be curative.

Analysis of PERV-C superinfection resistance using HA-tagged viruses.

BACKGROUND: Using pigs as organ donors has advanced xenotransplantation to the point that it is almost ready for clinical use. However, there is still a zoonotic risk associated with xenotransplantation, and the potential transmission of porcine endogenous retroviruses needs to be surveyed. Despite significant attempts to eliminate this risk, by the selection of PERV-C free pigs with low expression of PERV-A, -B, and by the genome-wide inactivation of PERV using CRISPR/Cas9, the impact of superinfection resistance (SIR) was not investigated. SIR is a viral trait that prevents reinfection (superinfection). For PERV, the underlying mechanism is unclear, whether and how cells, that harbor functional PERV, are protected. Using PERV-C(5683) as a reference virus, we investigated SIR in a newly developed in vitro model to pursue the mechanism and confirm its protective effect. RESULTS: We developed three PERV-C constructs on the basis of PERV-C(5683), each of which carries a hemagglutinin tag (HA-tag) at a different position of the envelope gene (SP-HA, HA-VRA, and RPep-HA), to distinguish between primary infection and superinfection. The newly generated PERV-C(5683)-HA viruses were characterized while quantifying the viral RNA, reverse transcriptase activity, protein expression analysis, and infection studies. It was demonstrated that SP-HA and RPep-HA were comparable to PERV-C(5683), whereas HA-VRA was not replication competent. SP-HA and RPep-HA were chosen to challenge PERV-C(5683)-positive ST-IOWA cells demonstrating that PERV-C-HA viruses are not able to superinfect those cells. They do not integrate into the genome and are not expressed. CONCLUSIONS: The mechanism of SIR applies to PERV-C. The production of PERV-C particles serves as a defense mechanism from superinfection with exogenous PERV-C. It was demonstrated by newly generated PERV-C(5683)-HA clones that might be used as a cutting-edge tool. The HA-tagging of PERV-C is novel, providing a blueprint for the tagging of other human tropic PERV viruses. The tagged viruses are suitable for additional in vitro and in vivo infection studies and will contribute, to basic research on viral invasion and pathogenesis. It will maintain the virus safety of XTx.

P3 and NIa-Pro of Turnip Mosaic Virus Are Independent Elicitors of Superinfection Exclusion.

Superinfection exclusion (SIE) is an antagonistic interaction between identical or closely related viruses in host cells. Previous studies by us and others led to the hypothesis that SIE was elicited by one or more proteins encoded in the genomes of primary viruses. Here, we tested this hypothesis using Turnip mosaic virus (TuMV), a member of the genus Potyvirus of the family Potyviridae, with significant economic consequences. To this end, individual TuMV-encoded proteins were transiently expressed in the cells of Nicotiana benthamiana leaves, followed by challenging them with a modified TuMV expressing the green fluorescent protein (TuMV-GFP). Three days after TuMV-GFP delivery, these cells were examined for the replication-dependent expression of GFP. Cells expressing TuMV P1, HC-Pro, 6K1, CI, 6K2, NIa-VPg, NIb, or CP proteins permitted an efficient expression of GFP, suggesting that these proteins failed to block the replication of a superinfecting TuMV-GFP. By contrast, N. benthamiana cells expressing TuMV P3 or NIa-Pro did not express visible GFP fluorescence, suggesting that both of them could elicit potent SIE against TuMV-GFP. The SIE elicitor activity of P3 and NIa-Pro was further confirmed by their heterologous expression from a different potyvirus, potato virus A (PVA). Plants systemically infected with PVA variants expressing TuMV P3 or NIa-Pro blocked subsequent infection by TuMV-GFP. A +1-frameshift mutation in P3 and NIa-Pro cistrons facilitated superinfection by TuMV-GFP, suggesting that the P3 and NIa-Pro proteins, but not the RNA, are involved in SIE activity. Additionally, deletion mutagenesis identified P3 amino acids 3 to 200 of 352 and NIa-Pro amino acids 3 to 40 and 181 to 242 of 242 as essential for SIE elicitation. Collectively, our study demonstrates that TuMV encodes two spatially separated proteins that act independently to exert SIE on superinfecting TuMV. These results lay the foundation for further mechanistic interrogations of SIE in this virus.

Diagnosis and Management of Hepatitis Delta Virus Infection.

Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.

Neumonía lipoidea exógena crónica y sobreinfección por Mycobacterium tuberculosis / Chronic Exogenous Lipoid Pneumonia and Superinfection by Mycobacterium Tuberculosis

Introducción: la neumonía lipoidea exógena es una enfermedad pulmonar inflamatoria poco común, desencadenada por la inhalación o aspiración de material graso de origen animal, vegetal o mineral. El diagnóstico se establece a través de confirmación histo-patológica, por la presencia de macrófagos cargados de lípidos en muestras respirato-rias, asociado a las características clínicas específicas al momento de su presentación.Requiere de un alto nivel de sospecha y una adecuada anamnesis de los antecedentes exposicionales del paciente debido a que muchos casos son subdiagnosticados y trat-ados como neumonía adquirida en la comunidad, lo que retrasa su diagnóstico y mane-jo, sumado a la ausencia de guías disponibles para su tratamiento.Se han reportado pocos casos de sobreinfección por tuberculosis en pacientes con neu-monía lipoidea exógena crónica. Caso clínico: femenino 33 años, con antecedentes de exposición crónica a sustancias desinfectantes de características aceitosas sin protección de vía aérea, con cuadro de tos y dolor torácico. Conclusión: el diagnóstico temprano, asociado a tratamiento de soporte, general-mente conservador, favorece la mejoría clínica y radiológica, y de esta manera dis-minuye la morbimortalidad. (AU)

Introduction: exogenous lipoid pneumonia is a rare inflammatory lung disease, trigge-red by inhalation or aspiration of fatty material of animal, vegetable or mineral origin. The diagnosis is established through histological confirmation by the presence of lipid-laden macrophages in respiratory samples, associated with the specific clinical charac-teristics at the time of presentation. It requires a high level of suspicion and an adequate anamnesis of the patient's expo-sure history, since many cases are underdiagnosed and treated as community-acquired pneumonia, what delays its diagnosis and management, added to the absence of avai-lable guidelines for its treatment. Few cases of tuberculosis superinfection have been reported in patients with exoge-nous lipoid pneumonia.Clinical case: 33-year-old female, with a history of chronic exposure to oily disinfectant substances without airway protection, with symptoms of cough and chest pain.Conclusion: early diagnosis, associated with supportive treatment, generally conser-vative, favors clinical and radiological improvement, thus reducing morbidity and mor-tality. (AU)

What do we know about pathological mechanism and pattern of lung injury related to SARS-CoV-2 Omicron variant?

Pulmonary damage in SARS-CoV-2 is characterized pathologically by diffuse alveolar damage (DAD) and thrombosis. In addition, nosocomial bacterial superinfections and ventilator-induced lung injury (VILI) are likely to occur. The SARS-CoV-2 Omicron variant have manifested itself as a more diffusive virus which mainly affects the upper airways, such as the nose and pharynx. The mechanism leading to a lung injury with a complex clinical course for the Omicron SARS-CoV-2 variant remains unclear. A key question is whether the organ damage is due to direct organ targeting of the virus or downstream effects such as an altered immune response. An immune escape process of Omicron variant is being studied, which could lead to prolonged viral shedding and increase hospitalization times in patients with comorbidities, with an increased risk of pulmonary co-infections/superinfections and organ damage. This brief commentary reports the current knowledge on the Omicron variant and provides some useful suggestions to the scientific community.

Analysis of risk factors of fungal superinfections in viral pneumonia patients: A systematic review and meta-analysis.

BACKGROUND: Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta-analysis. OBJECTIVE: This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta-analysis. METHODS: We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses. RESULTS: In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001). CONCLUSIONS: Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluid Aspergillus antigen testing, culture, and biopsy.

Acute gastrointestinal graft-versus-host disease with cytomegalovirus and Epstein-Barr virus superinfection in a patient with COVID-19.

A 60-year-old female was diagnosed with acute myeloid leukemia. After initial remission with chemotherapy, she relapsed and underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two months later, she presented to emergency department with watery diarrhea, abdominal pain and fever. She also tested positive for SARS-CoV2 on nasopharyngeal swab by polymerase chain reaction (PCR) and both cytomegalovirus (CMV) and Epstein-Barr virus (EBV) were detected in peripheral blood. Flexible sigmoidoscopy showed diffuse edema, erythema and loss of vascular pattern with interspersed segments of mucosal denudation and exudate and bBiopsies revealed epithelial cell apoptosis, diffuse crypt atrophy and dropout, with ulceration and both CMV and EBV were detected in colon mucosa, consistent with acute severe gastrointestinal graft-versus-host disease complicated by CMV and EBV superinfection. Despite starting therapy with methylprednisolone, ganciclovir and rituximab,she presented unfavorable evolution and died after 5 weeks.

Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused widespread morbidity and mortality since its onset in late 2019. Here, we demonstrate that prior infection with human cytomegalovirus (HCMV) substantially increases infection with SARS-CoV-2 in vitro. HCMV is a common herpesvirus carried by 40%-100% of the population, which can reactivate in the lung under inflammatory conditions, such as those resulting from SARS-CoV-2 infection. We show in both endothelial and epithelial cell types that HCMV infection upregulates ACE2, the SARS-CoV-2 cell entry receptor. These observations suggest that HCMV reactivation events in the lung of healthy HCMV carriers could exacerbate SARS-CoV-2 infection and subsequent COVID-19 symptoms. This effect could contribute to the disparity of disease severity seen in ethnic minorities and those with lower socioeconomic status, due to their higher CMV seroprevalence. Our results warrant further clinical investigation as to whether HCMV infection influences the pathogenesis of SARS-CoV-2.

Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections.

OBJECTIVE: Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo. DESIGN: A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer. RESULTS: The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection. CONCLUSION: The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.

Neumatocele traumático: una presentación inusual del trauma cerrado de tórax en paciente de 21 años / Traumatic pneumatocele: an unusual presentation of blunt chest trauma in a 21-year-old patient

El neumatocele traumático, o pseudoquiste pulmonar traumático, es una complicación infrecuente del trauma cerrado de tórax, caracterizada por lesiones cavitadas únicas o múltiples de paredes fibrosas bien delimitadas, sin revestimiento epitelial. Representa un reto diagnóstico ante la prevalencia de etiologías más frecuentes de cavitación pulmonar, presentación clínica inespecífica y el carácter subreportado de la patología. Se presenta el caso de un paciente de 21 años, con cuadro clínico de fiebre y dolor torácico posterior a traumatismo contuso por accidente en motocicleta, con identificación de una lesión cavitada rodeada de vidrio esmerilado, ubicada en lóbulo superior derecho en tomografía de tórax. Se ofreció tratamiento antibiótico ante la sospecha clínica de sobreinfección. Sin embargo, se atribuyó la alteración pseudoquística pulmonar al antecedente traumático. En ocasiones las cavitaciones pulmonares postrauma no son identificadas en la atención inicial, por ende, es fundamental la evaluación clínica e imagenológica subsecuente.

Traumatic pneumatocele, or traumatic pulmonary pseudocyst, is a rare complication of blunt chest trauma, characterized by multiple or unique cavitary lesions, with well-defined fibrous walls without epithelial lining. It represents a diagnostic challenge due to the higher prevalence of other etiologies of lung cavities, nonspecific clinical features and the under-reported nature of this pathology. We present the case of a 21-year-old male with fever and chest pain after a blunt chest trauma in a motorcycle accident, with identification of a cavity in the right upper lobe, surrounded by ground glass opacities. Antibiotic therapy was administered after clinical suspicion of superinfection, however, the cavitary lesion was attributed to the trauma. Occasionally, traumatic pulmonary pseudocysts are not identified during initial assessment, therefore, clinical and imagenologic follow-up is essential.