Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to 2 Years Following COVID-19.

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

Chronic viral coinfections differentially affect the likelihood of developing long COVID.

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).

Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID.

The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. In a cohort of 280 adults with prior SARS-CoV-2 infection, we observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4 months following initial diagnosis were independently associated with serological evidence of recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen IgG levels, but not with ongoing EBV viremia. Evidence of EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52) and tended to have less severe (>5 symptoms reported) LC (OR 0.44). Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted. SUMMARY: The authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence of recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with a decreased risk of Long COVID.

Síndrome RS3PE en paciente con cáncer de próstata en estadio IV / RS3PE Syndrome in a Patient with Stage IV Prostate Cancer

La polisinovitis aguda edematosa benigna del anciano, también llamada síndrome RS3PE (acrónimo de remitting seronegative symmetrical synovitis with pitting edema), es una enfermedad reumatológica heterogénea que forma parte de las artritis inflamatorias y es de causa desconocida. Se presenta de forma exclusiva en la población de adultos mayores con afección poliarticular asociada a edema, tumefacción y limitación funcional que tiene por lo general buen pronóstico. Se describe el caso de un hombre de 70 años que cumple con seis de los siete criterios diagnósticos para esta enfermedad(AU)

Acute benign edematous polysynovitis in the elderly, also called RS3PE syndrome (acronym for remitting seronegative symmetrical synovitis with pitting edema), is a heterogeneous rheumatologic disease that is part of inflammatory arthritis and whose cause is unknown. It is presented exclusively in the population of aged adults with polyarticular affection associated with edema, swelling and functional limitation and has, in general, a good prognosis. We describe the case of a 70-year-old man who presents six of the seven diagnostic criteria for this disease(AU)

Endoloop hecho en casa / Homemade Endoloop

La polipectomía es un procedimiento muy común en endoscopia que no está exento de complicaciones; la más frecuente es el sangrado posterior al procedimiento por lo que se han desarrollado para su prevención numerosas estrategias; una de ellas es el uso de endoloop que ha mostrado buenos resultados para pólipos de pedículo muy largo o grueso. Sin embargo, los kits comerciales para realizar este procedimiento son muy costosos y poco disponibles, lo que hace que en nuestro medio se use muy poco. Aquí presentamos un diseño artesanal de bajo costo diseñado (por el grupo del doctor Sakai en Sao Pablo, Brasil) y la experiencia en nuestro servicio con este.

Although polypectomies are very common procedures in endoscopy, they are not without complications. The most common complication is bleeding following the procedure. Numerous strategies have been developed to prevent bleeding. One of these, the use of an endoloop, has had good results for polyps with very long or thick pedicles. Nevertheless, since commercial endoloop kits for this procedure are very expensive and in short supply, they are not widely used in Colombia. In this article we present a low cost design developed by Dr. Sakai in Sao Paul Brazil for an endoloop that can be made in house, and we present our experience with this tool.

Síndrome de Boerhaave: a propósito de dos casos / Two Case Reports of Boerhaave’s Syndrome

El síndrome de Boerhaave es un tipo de ruptura esofágica barogénica, causada por un aumento rápido en la presión intraluminal en un esófago previamente sano, habitualmente, en su tercio distal. Esta enfermedad es muy rara y tiene una alta mortalidad, con muy pocas series de casos reportados en la literatura. Las tasas de mortalidad estimadas van hasta el 40%; aunque el manejo en manos experimentadas en un cuadro diagnosticado a tiempo ha mostrado impactar positivamente el pronóstico de los pacientes. Desafortunadamente, debido a la baja frecuencia de la enfermedad, aún no hay un consenso claro respecto al mejor enfoque terapéutico. Aquí presentamos el cuadro clínico de dos pacientes que fueron diagnosticados en nuestra institución, se describe el cuadro clínico, se presentan las imágenes diagnósticas y se realiza una revisión de tema.

Boerhaave’s syndrome is a type of esophageal rupture caused by a rapid increase in intraluminal pressure in a previously healthy esophagus. The rupture usually occurs in the distal third of the esophagus. This condition has a high mortality rate and is very rare with very few cases reported in the literature. Estimates of mortality rates range as high as 40%, but management by experienced physicians combined with early diagnosis early has been shown to positively impact patients’ prognoses. Unfortunately due to the condition´s low frequency, no clear consensus exists regarding the best therapeutic approach. Here we present the clinical features of two patients who were diagnosed at our institution, present diagnostic images, and review the topic.