The Importance of CMV Reactivation in COVID-19-Related ARDS Patients

Objectives: Cytomegalovirus (CMV) reactivation is a significant cause of morbidity and mortality in critically ill patients. Existing or newly developed immunosuppression appears to be the main factor for reactivation. COVID-19 patients with acute respiratory distress syndrome can be affected by a variety of conditions that cause immunosuppression. Clarifying CMV reactivation and notably its predictive features became important during the epidemic. Method(s): This is a retrospective, observational, and cohort study. All COVID-19 patients admitted to the ICU between March 11, 2020 and March 11, 2021 were analyzed. All of the information was gathered from the hospital's electronic records. CMV reactivation was defined as CMV DNA >=1000 copies/ml in tracheal samples. The patient population was analyzed in two groups, namely, patients with CMV reactivation and patients without reactivation. Result(s): During the study period, 99 of all COVID-19 ARDS patients fulfilled the inclusion criteria, and CMV reactivation was detected in 55 (55.6%) of them. Age, BMI, APACHE-II score, hypertension, chronic respiratory disease, the usage of interleukin blockers, the duration of steroid usage, procalcitonin (PCT), and CD-8 T-cell levels differed significantly from the patients without CMV reactivation. Furthermore, the reactivation group had longer ICU stays, longer durations of mechanical ventilation, and higher mortality. Conclusion(s): CMV can be reactivated in critically ill COVID-19 ARDS patients, which appears to correlate with worse outcomes. Obesity, the usage of IL-blockers and steroids >12 days, high PCT, and low CD-8 T-cell levels appear to be risk factors. Critically ill COVID-19 patients should be closely monitored with regard to immunosuppression and CMV status.Copyright © 2022 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.

Stability of a delayed SARS-CoV-2 reactivation model with logistic growth and adaptive immune response.

This paper develops and analyzes a SARS-CoV-2 dynamics model with logistic growth of healthy epithelial cells, CTL immune and humoral (antibody) immune responses. The model is incorporated with four mixed (distributed/discrete) time delays, delay in the formation of latent infected epithelial cells, delay in the formation of active infected epithelial cells, delay in the activation of latent infected epithelial cells, and maturation delay of new SARS-CoV-2 particles. We establish that the model's solutions are non-negative and ultimately bounded. We deduce that the model has five steady states and their existence and stability are perfectly determined by four threshold parameters. We study the global stability of the model's steady states using Lyapunov method. The analytical results are enhanced by numerical simulations. The impact of intracellular time delays on the dynamical behavior of the SARS-CoV-2 is addressed. We noted that increasing the time delay period can suppress the viral replication and control the infection. This could be helpful to create new drugs that extend the delay time period.

COVID-19 infection and vaccines: potential triggers of Herpesviridae reactivation.

Since the onset of the COVID-19 outbreak, numerous articles have highlighted a possible link between COVID-19 vaccination or infection and Herpesviridae co-infection or reactivation. The authors conducted an exhaustive literature review on this topic, the results of which are presented individually for each member of the Herpesviridae family: Herpes Simplex Virus (HSV) types-1 (HSV-1) and 2 (HSV-2); Varicella-Zoster Virus (VZV); Epstein-Barr Virus (EBV); Cytomegalovirus (CMV); HHV-6; HHV-7; and HHV-8. These human herpesviruses can serve as prognostic markers for the COVID-19 infection and may even underlie some of the clinical manifestations initially attributed to SARS-CoV-2. In addition to SARS-CoV-2 infection, all corresponding vaccines approved to date in Europe appear capable of inducing herpesvirus reactivation. It is important to consider all viruses of the Herpesviridae family when managing patients infected with or recently vaccinated against COVID-19.

MISSED TB DIAGNOSIS DURING THE COVID-19 PANDEMIC: MYTH OR REAL

SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Miliary Tuberculosis (TB) is a rare disorder caused by the hematogenous dissemination of Mycobacterium tuberculosis. Patients infected with Mycobacterium tuberculosis can develop Miliary TB from primary infection or reactivation of a latent infection. Many patients with Miliary TB will present with symptoms of classic tuberculosis and in the pandemic time overlaps with symptoms of Covid-19. Since the Covid-19 pandemic the reported TB diagnosis fell 20% in 2020 and remained 13% lower in 2021 as compared to pre-COVID-19 pandemic. Decrease in cases may be due to pandemic-related mitigation efforts, such as social distancing and wearing masks. CASE PRESENTATION: This patient is a 23-year-old undocumented male who presented to the ED, originally in January of 2021, with complaints of generally not feeling well. He reported feeling feverish and having a poor appetite for the past 2 weeks. At this visit, the patient received testing for COVID-19, Influenza and strep;all of which were negative. He was then discharged home and instructed to follow-up outpatient. In July of 2021, the patient again presented to the ED with complaints of weakness, fevers, cough, and weight loss that have progressively worsened. A chest x-ray and CT chest were performed at this time which were positive for innumerable bilateral upper lobe predominant peri-bronchial vascular nodular airspace opacities and patchy areas of consolidation with central cavitation, highly suspicious for tuberculosis. A QuantiFERON gold test was ordered and the patient underwent bronchoscopy. After 2 weeks of hospitalization, a NAAT test came back positive for Tuberculosis. At this point, the patient was immediately started on rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE). The patient received 2 weeks of RIPE treatment and after being hospitalized for 1 month, he was then discharged home on RIPE therapy with strict instructions to follow-up outpatient. DISCUSSION: Similarities in symptoms of TB and COVID-19 may mean that some people who have TB are being evaluated for COVID-19, but not tested for TB. The case was very unusual in that the infection of TB went undiagnosed during his initial emergency department (ED) during the Pandemic surges. It had not been discovered until presenting to the ED 5 months later with worsening symptoms. In presenting this case, we hope to further education on Miliary TB and prevent future missed diagnoses given the extremely infectious nature of the disease. CONCLUSIONS: The 2020 and 2021 declines may be related to factors associated with the COVID-19 pandemic like similarities in symptoms between COVID-19 and TB disease may have led to missed TB diagnoses;widespread disruptions to healthcare during the COVID-19 pandemic may have delayed TB diagnoses;and Efforts to prevent COVID-19, such as wearing masks and staying six feet away from others, may also reduce the spread of TB. Reference #1: Masahiro Narita, Grace Hatt, Katelynne Gardner Toren, Kim Vuong, Monica Pecha, John A Jereb, Neela D Goswami, Delayed Tuberculosis Diagnoses During the Coronavirus Disease 2019 (COVID-19) Pandemic in 2020—King County, Washington, Clinical Infectious Diseases, Volume 73, Issue Supplement_1, 15 July 2021, Pages S74–S76, https://doi.org/10.1093/cid/ciab387 Reference #2: Cleverley J, Piper J, Jones MM. The role of chest radiography in confirming COVID-19 pneumonia. BMJ 2020;370 : m2426. Reference #3: https://www.cdc.gov/media/releases/2022/s0324-tuberculosis-covid-19.html DISCLOSURES: No relevant relationships by Nawal Aamir No relevant relationships by Gabrielle Gerbino

The Importance of CMV Reactivation in COVID-19-Related ARDS Patients

Objectives: Cytomegalovirus (CMV) reactivation is a significant cause of morbidity and mortality in critically ill patients. Existing or newly developed immunosuppression appears to be the main factor for reactivation. COVID-19 patients with acute respiratory distress syndrome can be affected by a variety of conditions that cause immunosuppression. Clarifying CMV reactivation and notably its predictive features became important during the epidemic. Methods: This is a retrospective, observational, and cohort study. All COVID-19 patients admitted to the ICU between March 11, 2020 and March 11, 2021 were analyzed. All of the information was gathered from the hospital’s electronic records. CMV reactivation was defined as CMV DNA ≥1000 copies/ml in tracheal samples. The patient population was analyzed in two groups, namely, patients with CMV reactivation and patients without reactivation. Results: During the study period, 99 of all COVID-19 ARDS patients fulfilled the inclusion criteria, and CMV reactivation was detected in 55 (55.6%) of them. Age, BMI, APACHE-II score, hypertension, chronic respiratory disease, the usage of interleukin blockers, the duration of steroid usage, procalcitonin (PCT), and CD-8 T-cell levels differed significantly from the patients without CMV reactivation. Furthermore, the reactivation group had longer ICU stays, longer durations of mechanical ventilation, and higher mortality. Conclusion: CMV can be reactivated in critically ill COVID-19 ARDS patients, which appears to correlate with worse outcomes. Obesity, the usage of IL-blockers and steroids >12 days, high PCT, and low CD-8 T-cell levels appear to be risk factors. Critically ill COVID-19 patients should be closely monitored with regard to immunosuppression and CMV status. (English) [ FROM AUTHOR] Amaç: Sitomegalovirüs reaktivasyonu, kritik hastalarda önemli bir morbidite ve mortalite nedeni olarak karşımıza çıkmaktadır. Reaktivasyon için en önemli faktörlerden biri yeni gelişmiş veya var olan immünsüpresyondur. Akut solunum sıkıntısı sendromu olan koronavirüs hastalığı-19 (COVID-19) hastaları, immünsüpresyona neden olan çeşitli koşullardan etkilenebilir. Sitomegalovirüs reaktivasyonunun ve özellikle tahmin edici özelliklerinin netleştirilmesi, özellikle pandemi döneminde önem kazandı. Yöntem: Bu çalışma, retrospektif ve gözlemsel bir kohort çalışmasıdır. 11 Mart 2020 ile 11 Mart 2021 tarihleri arasında yoğun bakım ünitesine kabul edilen COVID-19 hastaları değerlendirildi. Tüm hasta bilgileri hastanenin elektronik kayıtlarından elde edildi. Trakeal örneklerde CMV DNA’nın ≥ 1000 kopya/mL olarak saptanması sitomegalovirüs reaktivasyonu olarak tanımlandı. Hastalar sitomegalovirüs reaktivasyonu olan ve olmayan hastalar olarak iki grupta değerlendirildi. Bulgular: Çalışma süresi boyunca, tüm COVID-19 akut solunum sıkıntısı sendromu hastalarından sadece 99'u çalışmaya dahil edilme kriterlerini karşıladı ve 55 hastada (%55,6) sitomegalovirüs reaktivasyonu tespit edildi. Sitomegalovirüs reaktivasyonu saptanan hastalarda, yaş, beden kitle indeksi, APACHE-II skoru, hipertansiyon, kronik solunum yolu hastalığı, interlökin bloker kullanımı, steroid kullanım süresi, prokalsitonin ve T hücre düzeyi (CD-8) sitomegalovirüs reaktivasyonu olmayan hastalardan önemli ölçüde farklıydı. Ayrıca, sitomegalovirüs reaktivasyon grubundaki hastaların daha uzun yoğun bakım ve mekanik ventilasyon süresi ve daha yüksek mortaliteye sahip oldukları gözlemlendi. Sonuç: COVID-19 ilişkili akut solunum sıkıntısı sendromu hastalarında sitomegalovirüs reaktivasyonu görülebilir ve bu durumun daha kötü sonuçlarla ilişkili olduğu tespit edilmiştir. Ínterlökin veya 12 günden fazla steroid kullanımı, obezite, yüksek prokalsitonin ve düşük CD-8 T lenfosit düzeyleri reaktivasyon için risk faktörleridir. Yoğun bakımda COVID-19 hastaları immünsüpresyon ve sitomegalovirüs reaktivasyonu açısından yakın izlenmelidir. (Turkish) [ FROM AUTHOR] Copyright of Journal of the Society of Thoracic Carido-Vascular Anaesthesia & Intensive Care is the property of Gogus Kalp Damar Anestezi ve Yogun Bakim Dernegi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Therapeutic Effect of Subunit Vaccine AEC/BC02 on Mycobacterium tuberculosis Post-Chemotherapy Relapse Using a Latent Infection Murine Model

Tuberculosis (TB), caused by the human pathogen Mycobacterium tuberculosis (Mtb), is an infectious disease that presents a major threat to human health. Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, is ineffective against latent TB infection, necessitating the development of further TB drugs or therapeutic vaccines. Herein, we evaluated the therapeutic effect of a novel subunit vaccine AEC/BC02 after chemotherapy in a spontaneous Mtb relapse model. Immunotherapy followed 4 weeks of treatment with isoniazid and rifapentine, and bacterial loads in organs, pathological changes, and adaptive immune characteristics were investigated. The results showed slowly increased bacterial loads in the spleen and lungs of mice inoculated with AEC/BC02 with significantly lower loads than those of the control groups. Pathological scores for the liver, spleen, and lungs decreased accordingly. Moreover, AEC/BC02 induced antigen-specific IFN-γ-secreting or IL-2-secreting cellular immune responses, which decreased with the number of immunizations and times. Obvious Ag85b- and EC-specific IgG were observed in mice following the treatment with AEC/BC02, indicating a significant Th1-biased response. Taken together, these data suggest that AEC/BC02 immunotherapy post-chemotherapy may shorten future TB treatment.

Global stability of a delayed SARS-CoV-2 reactivation model with logistic growth, antibody immunity and general incidence rate

Mathematical models have been considered as a robust tool to support biological and medical studies of the coronavirus disease 2019 (COVID-19). This new disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This paper develop a within-host SARS-CoV-2 dynamics model with logistic growth for healthy epithelial cells, humoral (antibody) immune response and general SARS-CoV-2-target incidence rate. The model is incorporated with four mixed (distributed/discrete) time delays, delay in the formation of latent infected epithelial cells, delay in the formation of active infected epithelial cells, delay in the activation of latent infected epithelial cells, and maturation delay of new SARS-CoV-2 particles. The model is formulated as a system of delay differential equations (DDEs). We establish that the model’s solutions are non-negative and ultimately bounded. We deduce that the model has three equilibria and their existence and stability are perfectly determined by two threshold parameters. We prove the global stability of the model’s equilibria by utilizing the Lyapunov method and applying the LaSalle’s invariance principle. To support and illustrate our theoretical findings we present numerical simulations for the model with a special form of the general incidence rate function. The effect of time delays on the SARS-CoV-2 dynamics is addressed. We observe that increasing time delays values can have the same impact as drug therapies in suppressing viral progression.

Comparative analysis of the COVID-19 sequences in India and investigate the trialogue relationship between the miR- NA with Coronavirus and Gut Microbiota

Background: The Coronavirus disease 2019 (COVID -19), an infectious disease caused by newly discovered Novel Coro- navirus. COVID-19 has spread worldwide causing a pandemic, with maximum death -cases. Hence there is an urgent need for vaccines and treatments to be developed to combat the COVID -19. To overcome this Micro RNA (miRNA) based therapy will be an effective option in controlling infection. The miRNA is a noncoding single -stranded RNA that is smaller in size (17-24nucleotides). They are also able to regulate the Gut Microbiota, an essential factor of host immune response. The usage of miRNA instead of other techniques has many advantages that include early detection, improved pathogen identification, detection of latent infection, personalized medicine. Methods: Selective COVID 19 genome sequences with special reference from India by NCBI genome database and Nextstrain.org. Coronavirus subtyping and Mutation analysis carried out by Genome Detective Coronavirus Typing Tool (version 1.1.3) and CLUSTAL OMEGA software. The prediction of antiviral miRNA are performed online by Tar- getscan.org Results: This study integrated selective bioinformatics tools and databases to investigate the COVID -19 sequences in India and the trialogue relationship between the miRNA with Coronavirus and Gut Microbiota. The miRNA is found to be a potential biomarker and also therapeutics for diseases in viral diseases. Conclusions: The miRNA has been extensively documented for their key roles in combating the disease and it is still an unexplored area. As the miRNA regulates the gene of the target, altering the expression can bring in a desired therapeu- tic outcome.

Tuberculosis

Tuberculosis (TB) is a communicable, airborne infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). A quarter of the world's population is infected with TB, affecting all age groups. Infection with MTB results in latent or active disease. Latent infection is associated with a 10% lifetime risk of developing active disease, but this is much higher in those with concurrent immunosuppression. Despite being both preventable and curable, TB remains the leading cause of global death from a single infectious agent. Active disease most commonly affects the lungs but can spread to cause extrapulmonary disease anywhere in the body. Over half of individuals in the UK now present with features of extrapulmonary TB, those with HIV being at particular risk. In all cases, obtaining samples for TB culture is absolutely vital. Standard treatment is with quadruple therapy for 6 months, extended in TB meningitis and often TB bone infection. Adjunctive corticosteroids have proven benefit in TB meningitis and TB pericarditis, and can be considered in other circumstances, such as paradoxical reactions to starting treatment in miliary TB. Despite recent gains in diagnosing and treating TB cases worldwide, the global COVID-19 pandemic is likely to have significantly affected recent progress.

Disseminated Kaposi sarcoma following COVID-19 in a 61-year-old Albanian immunocompetent man: a case report and review of the literature.

BACKGROUND: COVID-19 and its related anti-inflammatory treatment (steroids, immunomodulators) may induce the reactivation of latent bacterial, parasitic, and viral infections. According to our knowledge, no case of disseminated HHV-8-related Kaposi sarcoma (KS) after COVID-19 and its treatment has been described so far. Only one case of cutaneous KS concurrently with COVID-19 has been previously reported. CASE PRESENTATION: We describe a case of disseminated KS in a 61-year-old immunocompetent Albanian man after hospitalization for COVID-19. METHODS FOR LITERATURE RESEARCH: We used PubMed as biomedical database for the literature research. We selected keyword combinations including "Kaposi sarcoma," "HHV-8," "immunocompetent," "COVID-19," "SARS-CoV-2," and "steroids." No time or language limitation was set. Titles and abstracts of selected articles were systematically screened. Articles were included in the examination if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 15 articles. RESULTS: We describe a case of KS in COVID-19 patient and postulate that Interleukin-6 (IL-6) activity and steroid-induced immunodeficiency may play a major role in KS emergence. No published case of disseminated KS following COVID-19 in otherwise healthy individuals was found through the systematic literature review, despite the high incidence of COVID-19 in areas with medium-high prevalence of HHV-8 infection. This observation might be explained by the role of individual genetic susceptibility factors. CONCLUSIONS: SARS-CoV-2 infection and its treatment may lead to reactivation of several latent infections, including HHV-8 and its related clinical syndrome, Kaposi sarcoma.

Long non-coding RNAs in Epstein-Barr virus-related cancer.

Epstein Barr-virus (EBV) is related to several cancers. Long non-coding RNAs (lncRNAs) act by regulating target genes and are involved in tumourigenesis. However, the role of lncRNAs in EBV-associated cancers is rarely reported. Understanding the role and mechanism of lncRNAs in EBV-associated cancers may contribute to diagnosis, prognosis and clinical therapy in the future. EBV encodes not only miRNAs, but also BART lncRNAs during latency and the BHLF1 lncRNA during both the latent and lytic phases. These lncRNAs can be targeted regulate inflammation, invasion, and migration and thus tumourigenesis. The products of EBV also directly and indirectly regulate host lncRNAs, including LINC00312, NORAD CYTOR, SHNG8, SHNG5, MINCR, lncRNA-BC200, LINC00672, MALATI1, LINC00982, LINC02067, IGFBP7-AS1, LOC100505716, LOC100128494, NAG7 and RP4-794H19.1, to facilitate tumourigenesis using different mechanisms. Additionally, lncRNAs have been previously validated to interact with microRNAs (miRNAs), and lncRNAs and miRNAs mutually suppress each other. The EBV-miR-BART6-3p/LOC553103/STMN1 axis inhibits EBV-associated tumour cell proliferation. Additionally, H. pylori-EBV co-infection promotes inflammatory lesions and results in EMT. HPV-EBV co-infection inhibits the transition from latency to lytic replication. KSHV-EBV co-infection aggravates tumourigenesis in huNSG mice. COVID-19-EBV co-infection may activate the immune system to destroy a tumour, although this situation is rare and the mechanism requires further confirmation. Hopefully, this information will shed some light on tumour therapy strategies tumourigenesis. Additionally, this strategy benefits for infected patients by preventing latency to lytic replication. Understanding the role and expression of lnRNAs in these two phases of EBV is critical to control the transition from latency to the lytic replication phase. This review presents differential expressed lncRNAs in EBV-associated cancers and provides resources to aid in developing superior strategies for clinical therapy.