Gastrointestinal Manifestations and Their Association with Neurologic and Sleep Problems in Long COVID-19 Minority Patients: A Prospective Follow-Up Study.

BACKGROUND: Long-COVID is a condition post SARS-CoV-2 infection with persistent or recurring symptoms affecting multiple organs, and may involve viral persistence, changes to the microbiome, coagulopathies, and alterations to neuro-immune interactions. These factors can disrupt the Gut-Brain Axis, which is a complex system involving bidirectional communication between the central nervous system and the gastrointestinal (GI) system. As a result of these disruptions, individuals with long-COVID may develop post-infectious functional GI disorders, which can cause a range of symptoms affecting the digestive system. AIM: To understand frequency of GI manifestations of Long-COVID and to determine association with sleep or neurological symptoms in a predominantly minority population. METHODS: We included patients with positive SARS-CoV-2 PCR (n = 747) who were hospitalized from Feb. 2020 to May 2021 at Howard University Hospital and followed between 6 and 12 months from discharge. GI, sleep, and neurological symptoms (via the Montreal Cognitive Assessment (MoCA) scoring system) were assessed using a standardized questionnaire. Linear regression analysis, χ2 and Fisher's exact test were utilized to determine the statistical significance of correlations of GI/Neuro/COVID. RESULTS: The mean age of patients was 58, with 51.6% females and a predominant African American ethnicity (73.6%, n = 550). A total of 108 patients died during their initial hospital stay, with the remaining 639 patients followed-up. Three hundred fifty (350) patients responded to the questionnaire (57 patients died during the follow-up period). Overall, 39 (13.3%) patients reported GI-related symptoms, out of which 19 (6.4%) had persistent symptoms and 20 (6.8%) developed new onset GI symptoms. Nausea and vomiting were the most common 24/39 (61.5%), followed by abdominal pain 7/39 (18%), diarrhea 5/39 (12.8%), and others 3/39 (7.6%). Patients who presented with vomiting during acute SARS-CoV-2 infection were more likely to have Long-COVID GI manifestations (P = 0.023). Use of ACE inhibitors, abnormal lymphocyte count and elevated ferritin are other variables that showed significant associations with Long-COVID GI manifestations (P = 0.03, 0.006 and 0.03, respectively). During follow-up, a total of 28 (9.5%) patients reported difficulty with sleep and 79 (27%) patients had abnormal MoCA assessment. With further analysis, there was a trend between presentation of GI symptoms on admission with abnormal MoCA assessment, and an association between abnormal LFTs and history of liver disease during hospitalization with subsequent sleep problems. Baseline characteristics, clinical comorbidities, other laboratory values, hospital length of stay, mechanical ventilation, medications during hospitalization, re-admission and Flu or COVID-19 vaccination have not shown any association with Long-COVID GI symptoms in our cohort. CONCLUSION: Dyspeptic symptoms were common GI manifestations in the acute and post COVID periods. GI symptoms, abnormal LFTs and a history of liver disease during the acute infectious phase associates with abnormal MoCA and sleep problems during follow-up. Further large population studies are needed to determine if COVID-19 leads to a GI symptoms-associated Long-COVID phenotypes and other symptoms through the Gut-Brain-Axis.

A Case of a Thrombotic Storm (Arterial and Venous) in Nephrotic Syndrome.

Nephrotic syndrome is a condition characterized by proteinuria, hypoalbuminemia, edema, hyperlipidemia, and a hypercoagulable state. Nephrotic syndrome may lead to several complications, including, but not limited to, increased risk of infection, respiratory distress, and thromboembolism. There are several etiologies of nephrotic syndrome with various predisposing factors ranging from idiopathic, autoimmune diseases, infections (human immunodeficiency virus, hepatitis C virus, hepatitis B virus), drugs, and heavy metal poisoning. Here, we report the case of a 37-year-old male who presented with worsening exertional dyspnea and bilateral lower extremity swelling. He was found to have simultaneous multiple acute thromboses in both the venous and arterial systems in the setting of worsening renal function. Further investigation revealed that the patient had membranous nephropathy. Initiation of anticoagulation and immunosuppression made a significant difference in his survival. Vascular thromboembolic (VTE) complications may be the initial presentation that prompts patients with nephrotic syndrome to seek medical care. As such, clinicians must have a high index of suspicion in patients presenting with concurrent VTE and nephrotic-range proteinuria. In addition, given that treatment modalities for the various etiologies of nephrotic syndrome differ considerably, it is also essential to distinguish the type of nephrotic syndrome in a patient, which dictates the treatment algorithm.

Intrahepatic microbes govern liver immunity by programming NKT cells.

The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity.