The peptide link between pathogens and human centromere proteins

This work tested the hypothesis that infection causes unexplained production of anti-centromere protein antibodies (ACA) via autoimmune cross-reactivity. To further examine the clinical origin of ACA, the overlapped peptides between human pathogens, including viruses, bacteria and fungi and centromere proteins (CENP-A, CENP-B and CENP-C) were assessed. We found a broad overlap of pathogenetic peptides with human centromere proteins. These data indicate potential immune cross-reactivity between pathogens and human centromere proteins. Additionally, the current findings corroborate a molecular and mechanistic framework for autoimmune disorders related to infection. Moreover, preliminary evidence for a potential role of infection in ACA-related autoimmune diseases was presented. © 2022 The Scandinavian Foundation for Immunology.

Assessment of Ocular Lesions in a Persian Cat Concurrently Infected with Chlamydia felis, Herpesvirus and Coronavirus

In this case report, Chlamydia felis, herpesvirus and coronavirus correlations were revealed in a Persian cat with some complaints related to the eye. Upon ophthalmological examination, there was a dark brown lesion on the right corneal surface, and some clinical signs observed in the left eye resembling limbal insufficiency. As a result of ELISA test in blood, the FCoV and chlamydia antibody titers were positive at the S4 level. Chlamydia infection was confirmed by real-time PCR analysis in blood and conjunctival samples. Tear samples were found positive upon the herpesvirus antigen test. The lesions regressed after treatment, and the test results for chlamydia were negative following the 7-week treatment period. Copyright © 2022, Veteriner Fakultesi Dergisi. All rights reserved.

Herpesviral encephalitis associated with bortezomib use in a patient with multiple myeloma and associated light-chain amyloidosis.

INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Establishment and preliminary application of a TaqMan real-time quantitative PCR method for PastV3 detection

In order to build a specific, sensitive and rapid detection method for PAstV3 detection, the PAstVB gene sequences in Genbank were used and the conserved region in ORFlb was selected to design specific primers and TaqMan probe. Clinical stool samples were collected and preliminary detected by this newly established real-time RT-PCR method after reaction systems and conditions optimization. This detection method established in this study has a good linear relationship with the standard curve, with R2 value up to 0.9971. The sensitivity is 100 times higher than conventional PCR method, The variation co-efficient of in-batch and inter-batch repeatability test is less than 2.0%, indicating good repeatability. The detection results of Clinical samples showed that the positive rate of this method is higher than conventional PCR method. The establishment of this method provides a rapid detection means for PAstV3 laboratory diagnosis and epidemiological investigation.

Clinical diagnosis and treatment of Epstein-Barr virus infection initially manifested as ocular diseases in children

Objective: To investigate the clinical. features and treatment of ophthalmopathy secondary to EB virus(EBV) infection in children.

News from the 22nd National Days of Infectious Diseases (JNI) Montpellier, August 30 and 31, 2021

This proceedings contains s on the proper use of antibiotics, multidrug-resistant infections and new molecules;influenza and COVID-19;osteoarticular infections;and pneumocystis and CMV in the immunocompromised (excluding HIV).

Coronavirus-2019 Disease with Pancytopenia with Leptospirosis and Herpes Simplex Virus Co-infection

Aim and background: COVID-19 pandemic has affected the whole world. Besides COVID, many infections may emerge during the course of the disease. Lymphopenia, use of immunosuppressants underlying comorbidities, and immune dysregulation secondary to SARS-CoV-2 could be the likely cause of the emergence such infections. We hereby describe a case of COVID-19 disease which presented with pancytopenia and was found to have Leptospirosis and Herpes Simplex Virus co-infection. Case summary: A 23-yearold postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital 2 weeks after a full-term normal vaginal delivery. She developed generalized convulsive status epilepticus on the 10th day of her delivery, which was managed elsewhere with anti-epileptic drugs (AEDs). During her hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic throughout the course of her illness and seizures remained well-controlled on AEDs. On admission to our hospital, she was fully conscious, alert with no focal neurological deficits. Notable findings on evaluation were pancytopenia with megaloblastic features, bilateral pedal edema, and hepatosplenomegaly. NCCT brain was done which was suggestive of subarachnoid hemorrhage (SAH) along bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of abdomen revealed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In the panel sent for pancytopenia workup, IgM anti-HSV 1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies were positive). Workup for tuberculosis was negative. Bone marrow workup revealed features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia with no evidence of hemophagocytosis. Subsequently, IV acyclovir, IV doxycycline, and iron replacement were added. She improved clinically after these therapies and was subsequently discharged in a stable condition. MRI brain with MR angiography and venography done before discharge showed T1 sulcal hyperintensities along bilateral parietooccipital regions suggestive of SAH which was not progressing (as compared to NCCT brain scan done at admission). On day 60 of telephonic follow-up, patient was doing well and leading normal life without any persistence or emergence of symptoms.

A Case Report of Coronavirus (COVID-19) Disease and Herpesviridae Viral Co-Infections: A Lethal Combination? ABS0138)

Introduction: COVID-19 pandemic has affected the whole world. Besides COVID, other viral infections may emerge during the course of the disease owing to lymphopenia, use of immunosuppressants, underlying comorbidities, and immune dysregulation, which may pose additional threats.1 We hereby describe two cases of COVID- 19 with viral co-infections belonging to the Herpesviridae family with undulating clinical course. Case 1: Cytomegalovirus (CMV) Co-infection: A 55-year-old male, COVID unvaccinated, chronic smoker, overweight and hypertensive was admitted to our ICU with a 1-week history of fever, cough, and breathlessness. SARSCoV- 2 reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive. At admission, he had hypoxaemia (SpO2 86%on room air), respiratory rate 35-40/minute, and ground-glass opacities in chest X-ray involving 50% of bilateral lung parenchyma suggestive of severe COVID-19 pneumonia. He was managed with lung-protective invasive mechanical ventilation, restrictive fluid strategy, 16-18 hour/day proning sessions (4-5), intravenous (IV) remdesivir, IV dexamethasone 6 mg 12 hourly, and enoxaparin thromboprophylaxis. After 2 weeks of ICU stay, weaning was attempted but the weaning attempts failed due to underlying neuromuscular weakness. On examination, bilateral (B/L) cranial nerve palsies, areflexia, and motor power 0/5 in bilateral upper and lower limbs were noticed. possibility of Guillain-Barre syndrome (GBS) was kept and IV immunoglobulin therapy was empirically administered for 5 days with some improvement in power up to 1/5 in upper limbs. On day 35 of hospitalization, he developed pancytopenia along with features of deranged liver function and gut dysfunction. In evaluation, PCR for CMV turned out to be positive in blood. Bone marrow aspiration and biopsy showed hemopoiesis with viral inclusion bodies and hemophagocytosis (HLH) [Figs 1 and 2]. A diagnosis of secondary HLH related to CMV was contemplated and IV ganciclovir was initiated along with steroids. Histological evidence of CMV co-infection was present and moreover, the quantitative viral load of CMV showed a decreasing trend after initiating IV gancyclovir. However, the patient continued to deteriorate and succumbed to his illness in the 8th week of the ICU stay. Case 2: Herpes Simplex Virus (HSV) Co-infection: Twenty-three years postpartum female with no comorbidities and uneventful obstetric history was referred to our hospital two weeks after a full-term normal vaginal delivery. She developed generalized status epilepticus on the 10th day of delivery, which was managed with anti-epileptic drugs (AEDs). During the hospital stay, RTPCR for COVID-19 turned out to be positive but she remained asymptomatic and seizures were well-controlled on AEDs. On admission to our hospital, she was fully conscious and alert with no neurological deficits. Notable findings were pancytopenia with megaloblastic features, B/L pedal edema, and hepatosplenomegaly. NCCT brain revealed mild subarachnoid hemorrhage (SAH) along the bilateral parietooccipital region for which conservative management was planned. 2D echocardiography was normal. Ultrasonography of the abdomen showed gross splenomegaly and mild hepatomegaly with mesenteric lymphadenopathy. NCCT thorax and abdomen were unremarkable apart from hepatosplenomegaly. In pancytopenia workup, IgM anti-HSV-1 antibodies turned out to be positive in blood. In addition, tropical workup was suggestive of Leptospirosis (IgM antibodies positive). Serological evidence was suggestive of acute HSV-1 infection (based on antibody titers). Bone marrow workup had features of trilineage hematopoiesis with micronormoblastic maturation consistent with iron deficiency anemia without any evidence of hemophagocytosis. IV acyclovir, IV doxycycline, and iron replacement were added, after which she improved clinically and was discharged in stable condition. Tables 1 and 2 show a detailed description of these cases. Discussion: Herpesviridae family is the most important group of viruses responsible for persistent vi al infections in humans, of which CMV contributes to 60-90% of infections in adults, especially in developing countries.2 In healthy individuals, these viruses are kept dormant by the body's immune mechanisms but in an immunocompromised population, reactivation from the latent state can occur. SARS-CoV-2 infection predisposes patients to concomitant viral co-infections, owing to T-cell lymphopenia, decreased NK cell number, and use of immunosuppressive medications.3,4 The first case of CMV co-infection was first reported by D'Ardes and co-workers in 2020.5 Since then, many studies have been emerging in this area. In an observational study from France, 38 COVID-19 patients on >7 days of MV were studied for HSV and CMV pulmonary co-infections (by quantitative real-time PCR in tracheal samples) out of which 47% of patients had one of these infections (24% HSV, 5% CMV, 18% both).6 Another study looking for HSV-1 in patients on invasive MV found HSV-1 reactivation between days 11 and 40, which correlated with immunological markers of decreased innate immunity.7 A case series looking for CMV infection (by PCR in plasma or BAL) in COVID-19, also found CMV reactivation between day 7 and 45 of illness. Most of these patients were above 60 years of age and immunosuppressed (HIV, diabetes mellitus, medications).8 Although immunocompromised individuals are more vulnerable, healthy immunocompetent adults who are critically ill or on prolonged MV may also be susceptible to these infections.9-12 This may be explained by a state of immunoparalysis inherent to prolonged critical illness. In case 1, an ICU stay of around 9 weeks complicated with recurrent nosocomial infections, multiple blood product transfusions, and steroid usage could have the likely triggers. Whether viral co-infections are merely bystanders or truly pathogenic is difficult to comment but timely management is essential to avoid end-organ damage (EOD) which may occur directly (by enhanced viral load secondary to compromised host immunity) or indirectly (by inflammatory changes consequent to prolonged cell-mediated immunity required to maintain viral dormancy).2-4,13 It also seems imperative to study if a viral co-infection has a proclivity to develop more severe hematological anomalies (besides the inherent risk of HLH with COVID) as was seen in case 1, in which the patient had a downward spiral of illness with multiorgan dysfunction.14-15 Limitations: Dynamics of PCR trends and virology studies of samples from trachea, gut, and urine could not be analysed in our patients. Conclusion: Viral co-infections can occur in COVID-19 disease as these patients are often immunocompromised and critically ill. A high index of suspicion and prompt management is needed to improve the outcome of patients. Patients with organ dysfunctions especially hematologic abnormalities with bone marrow involvement should be worked up in detail to look for concomitant viral co-infections. In the future, large-scale research is needed to better elucidate the relationship between SARS-CoV-2 and other viral co-infections.

Establishment of interferon membrane protein IFITML knockdown cells and investigation of its effect on the replication of PRV, PCV2 and TGEV

To establish a J2-KD (knockdown) cell line stably expressing interfered IFITM1 and study the effect of interference with IFITMI gene on the infection of PCV2, PRV and TGEV. Gene cloning tech- niques were used to constructed pLKO. l-EGFP-Puro-IFITMI recombinant vector, which was co-transfected into 293 FT cells with lentiviral packaging plasmids psPAXZ and pMDZ. G to produce green fluorescent protein labeled lentiviruses expression IFITMlshRNA, the viral supernatant was collected at 48 hours after post transfection. J2 cells were infected with the harvested lentiviruses, screened by puromycin and cloned via cell limited dilution. Real-time PCR identify that the cell lines with stable interference with IFITMl gene were obtained, and via MTT method verify that interference with IFITMI expression had no effect on the growth of J2 cells, the successfully constructed J2 stable cell line interfere with IFITMl expression was named as JZ-KD. PRV, PCV2 and TGEV infected J2-KD cells, respectively. Using real-time fluorescence quantitative PCR detect virus replication. The results showed that J2-KD cell line was successfully generated with interfered IFITMl expression;the copy number of PCV2 and TGEV were in- creased, while PRV was decreased in J'Z-KD cell. Indicating that the interference of IFITMI gene expression markedly inhibited the replication of PRV while promoted that. of TGEV and PCV2, providing a basis for further study on the function of porcine IFITMI protein and elucidates its antiviral mechanism.

Research progress of histone deacetylases inhibitors in antiviral drugs discovery

Histone deacetylases (HDACs) are a class of key enzymes that regulate epigenetics. There are 5 small-molecule HDACs inhibitors having been approved for anti-cancer therapy on the market. In recent years, there have been more and more studies on the antiviral aspects of HDACs inhibitors. This article classifies viruses into human immunodeficiency virus 1 (HIV-1), new coronavirus (SARS-CoV-2), Epstein-Barr virus (EBV) and other viruses, systematically summarizes the recent advances of antiviral effects of the HDACs inhibitors from the perspective of medicinal chemistry. This review aims to provide the researchers the convenience of accessing the latest advances of the antiviral effects of HDACs inhibitors, and to analyze the challenges and prospects of this field in future drug discovery.

INFECTIOUS HYPOTHESIS OF NEURODEGENERATIVE DISEASES. WHAT WAITS US AFTER THE COVID-19 PANDEMIC?

Since the description of the first clinical cases of the most common neurodegenerative diseases, numerous hypotheses have been proposed for their development. At the same time, the failure of therapeutic strategies in various directions of clinical research indicates the fallacy of most theories. In this regard, in recent years, various infectious agents are increasingly considered as a trigger of neuronal inflammation and a factor inducing the onset of the neurodegenerative process. Infectious agents differ in their mechanisms of invasion into the central nervous system and can even enter the brain perineurally. Reactivation of latent viral infection induces the production of viral proteins and the accumulation of abnormal proteins that are markers of Alzheimer's disease and Parkinson's disease. Both bacterial (chlamydia, causative agents of chronic periodontitis, E. coli) and viral (herpes viruses, noroviruses) infectious agents are considered. However, for the development of neurodegeneration, it is not enough just a simple invasion and reactivation of the infectious process: the genetic characteristics of the main histocompatibility complex also play a huge role. Currently, several studies have been initiated on the possible efficacy of antibacterial and antiviral drugs in Alzheimer's disease. Data obtained over the past year suggests that the brain may act as a target for SARS-CoV-2. Neurological manifestations of COVID-19 can occur as a result of both the direct cytopathic action of the pathogen and the activation of neuroinflammation, accompanied by a violation of the integrity of the blood-brain barrier. Further study of the molecular and cellular mechanisms of neuroinflammation and neurodegeneration in COVID-19 will form the basis for the development of treatments for neurological complications.

A Novel Host-Targeted Viral Assembly Inhibitor Blocks SARS-CoV-2 in Airway Epithelial Cells

Introduction: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many monoclonal antibody therapies illustrates the need for anti-viral treatments with low susceptibility to evolutionary escape. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly. This compound has minimal host toxicity, including once daily oral dosing in rats that achieves >200-fold of the 90% effective concentration (EC90) in blood. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low suceptability to evolutionary escape. We hypothesized that PAV-104 would be active against SARSCoV- 2 variants in human airway epithelial cells. Methods: Airway epithelial cells were differentiated from lung transplant tissue at air-liquid interface (ALI) for four weeks prior to challenge with Alpha (Pango lineage designation B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) SARS-CoV-2 variants. Viral replication was determined by quantitative PCR measurement of the SARS-CoV-2 nucleocapsid (N) gene. Dose-dependent virus inhibition and cytotoxicity of PAV-104 in the Calu-3 airway epithelial cell line was determined by PCR and MTT assay. Student's t-tests were used to evaluate statistical significance. Results: Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 showed comparable infectivity in human primary airway epithelial cells at ALI (N=3 donors), 47- to 550-fold higher than the parent (USA-WA1/2020) strain. PAV-104 reached 50% cytotoxicity in Calu-3 cells at 240 nM (Fig. 1A). Dose-response studies in Calu-3 cells demonstrated PAV-104 has a 6 nM 50% inhibitory concentration (IC50) for blocking replication of SARS-CoV-2 (USA-WA1/2020) (Fig.1B). In primary cells at ALI from 3 donors tested, there was >99% inhibition of infection by SARS-CoV-2 Gamma variant (N=3, MOI 0.1, P <0.01) with 100 nM PAV-104 (Fig. 1C). Addition of 100 nM PAV-104 2-hours post-infection, but not pre-infection, resulted in >99% suppression of viral replication, indicating a post-entry drug mechanism. PAV-104 bound a small subset of the known allosteric modulator 14-3-3, itself implicated in the interactome of SARS-CoV-2. Conclusion: PAV-104 is a host-targeted, orally bioavailable, pan-viral small molecule inhibitor with promising activity against SARS-CoV-2 variants in human primary airway epithelial cells. (Figure Presented).

Integrated pipeline using ANCHOR tagged autofluorescent viruses for accelerated discovery of antiviral molecules

As successive pandemics have shown that antiviral discovery and validation should be done as a continuous process and all viruses should be considered as a potential threat. For this purpose, we have, we have developed a visualization technique called ANCHORTM that allows us to visualize directly in real-time in living cells infection, localization, replication and cell-to-cell spread of any kind of viruses having a dsDNA phase. This technology has been successfully used to image different kinds of viruses, including herpesviruses, adenovirus, poxviruses and retroviruses. Combined with an automatic pipetting robot and high content microscopy, the technology allows the screening of a large number of molecules or conditions very rapidly and efficiently without any fixation, extraction or reagent. Based on our expertise, we have also developed an image-based screening pipeline for RNA viruses such as RSV, influenza virus and SARS-CoV-2. With a collection of around 30 viruses impacting the human, animal and biodefense markets, we propose one of the most integrated antiviral screening pipelines so far, from early discovery to animal testing in A3 conditions. Two antiviral molecules discovered in the lab will be presented, the first one impacting the animal market and the second one funded by a large grant from the French Ministry of Armed Forces.

Research progress on association between COVID-19 and herpes zoster

The infection caused by SARS-CoV-2 may result in a series of skin damages. In addition, some patients report the re-activation of the varicella-zoster virus, which might be related to T cell immune dysfunction caused by SARS-CoV-2 infection. Recently, studies reported herpes zoster occurrence after inoculating the COVID-19 vaccine. At present, the mechanism of interaction between COVID-19, COVID-19 vaccine and herpes zoster remains unclear, and more high-quality studies are required to further define the relationship.

Quarterly report of investigations of suspected exotic diseases: July to September 2021

Exotic pest and disease investigations are managed and reported by the Ministry for Primary Industries' (MPI's) Diagnostic and Surveillance Directorate. This article presents a summary of investigations of suspect exotic and emerging pests and diseases in New Zealand during the period from July to September 2021.

"Fuzheng Quxie" and antiviral effect of Ganoderma (Lingzhi)

"Fuzheng Quxie" is an important theory of TCM related to prevention and cure of diseases. By enhancing the body immunity, Ganoderma (Lingzhi) indirectly inhibits the virus invasion, proliferation and destruction in the human body ("Fuzheng" means strengthening and consolidating body resistance). It can also directly inhibit and kill viruses ("Quxie" means dispelling evil). Lingzhi and its active components have antiviral effects on influenza virus, herpes virus, hepatitis B virus, human immunodeficiency virus, Newcastle disease virus, dengue virus and enterovirus. Lingzhi preparations alone or with antiviral drugs can treat hepatitis B, herpes zoster, recurrent genital herpes, condyloma acuminatum, infectious mononucleosis of children, cervical papillomavirus infection and AIDS. In addition, the possibility of preventing and treating COVID-19 (corona virus disease 2019) with Lingzhi was discussed.

MANIFESTAÇÕES DE TAFRO EM PACIENTE COM DOENÇA DE CASTLEMAN MULTICÊNTRICA POSITIVA PARA HERPES VIRUS HUMANO TIPO 8

Doença de Castleman ou hiperplasia linfoide angiofolicular é uma doença linfoproliferativa, não maligna e relativamente rara. Possui duas variantes: Unicêntrica (DCU) e Multicêntrica (DCM). A DCU manifesta-se em idade mais precoce (em média aos 33 anos), com predominância da variante hialino-vascular e localização preferencial na região da cabeça/pescoço e retroperitôneo. Cerca de 90% dos doentes são assintomáticos e o tratamento de primeira linha consiste na excisão curativa da lesão. Em contra-partida, sua forma multicêntrica envolve um grupo de entidades linfoproliferativas policlonais secundárias a um aumento na secreção de interleucinas, principalmente IL-6. Pode se apresentar de forma idiopática, estar relacionada ao Herpes virus humano (HHV-8) ou a Síndrome POEMS. Quando associada ao HHV-8, manifesta-se clinicamente com sintomas constitucionais (febre, sudorese noturna, perda ponderal), sintomas respiratórios, linfonodomegalias e esplenomegalia. Laboratorialmente pode ter anemia, trombocitopenia, hipoalbuminemia e hipergamaglobulinemia, com aumento de PCR. Apesar da extensa diversidade de manifestações tanto clínico como histopatológicas, há um consenso no “international working group”de que sua forma idiopática (sem HHV8) pode ainda ser subdividida conforme o fenótipo, com ou sem TAFRO - trombocitopenia (T), anasarca (A), febre (F), mielofibrose (R), organomegalia (O). No presente caso, porém, relata-se um paciente com DCM e HHV8 positivo com manifestações que mimetizaram TAFRO. Trata-se de paciente de 28 anos, branco, masculino, HIV positivo com carga viral indetectável e diagnóstico prévio de Sarcoma de Kaposi já tratado. Um ano antes do diagnóstico de DCM, iniciou quadro intermitente de febre, astenia, sintomas respiratórios, gastrointestinais e pancitopenia. Possuia esplenomegalia e linfonodopatias difusas e após biópsia recebeu diagnóstico de Doença de Castleman. O anatomopatológico mostrou-se compatível com variante intermediária entre espectros hialino vascular e plasmacítica. Teve pesquisa de HHV8 positiva na peça e no PCR sérico. Seis meses após este diagnóstico, doença entrou novamente em atividade e foi tratada com corticoterapia e etoposídeo, com resposta mínima. Trocada quimioterapia por esquema alternativo (contendo ciclofosfamida, talidomida e prednisona), cursou com remissões e recaídas, inclusive com recidiva do Sarcoma de Kaposi. Passados 3 anos do diagnóstico de Castleman, paciente manifestou anasarca, ascite, fibrose em biópsia da medula óssea, além de sintomas constitucionais, progressão de linfonodomegalia, esplenomegalia e excesso de IL-6. Assim paciente contemplou todos os cincos critérios maiores do diagnóstico de TAFRO. Na indisponibilidade de rituximabe e anticorpo monoclonal anti-IL-6, optou-se por pulsoterapia com corticoide e CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona). Após o primeiro ciclo complicou com hematotoxicidade, sepse urinária por KPC e infecção por SARS-CoV-2. Recebeu suporte clínico, com melhora lenta, discreta e momentânea, evoluindo com pancitopenia grave, icterícia. Agregou múltiplas disfunções e foi a óbito, exemplificando como realmente essa etidade rara, ainda pouco compreendida e de difícil diagnóstico se comporta de maneira extremamente agressiva.

Epidemiological characteristics of associated epidemics in Tongzhou district, Beijing, 2015-2020

Objective: To analyze the characteristics of the associated epidemics in Tongzhou district of Beijing from 2015 to 2020, identify the risk factors and provide scientific basis for the early warning, prevention and control of infectious disease epidemics.