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1.
Viruses ; 16(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38932130

ABSTRACT

The COVID-19 pandemic has been one of the most impactful events in our lifetime, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multiple SARS-CoV-2 variants were reported globally, and a wide range of symptoms existed. Individuals who contract COVID-19 continue to suffer for a long time, known as long COVID or post-acute sequelae of COVID-19 (PASC). While COVID-19 vaccines were widely deployed, both unvaccinated and vaccinated individuals experienced long-term complications. To date, there are no treatments to eradicate long COVID. We recently conceived a new approach to treat COVID in which a 15-amino-acid synthetic peptide (SPIKENET, SPK) is targeted to the ACE2 receptor binding domain of SARS-CoV-2, which prevents the virus from attaching to the host. We also found that SPK precludes the binding of spike glycoproteins with the receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) of a coronavirus, murine hepatitis virus-1 (MHV-1), and with all SARS-CoV-2 variants. Further, SPK reversed the development of severe inflammation, oxidative stress, tissue edema, and animal death post-MHV-1 infection in mice. SPK also protects against multiple organ damage in acute and long-term post-MHV-1 infection. Our findings collectively suggest a potential therapeutic benefit of SPK for treating COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , SARS-CoV-2/drug effects , Humans , COVID-19/therapy , COVID-19/virology , Animals , Spike Glycoprotein, Coronavirus/metabolism , Spike Glycoprotein, Coronavirus/genetics , Mice , Post-Acute COVID-19 Syndrome , Angiotensin-Converting Enzyme 2/metabolism , Peptides/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment
2.
Viruses ; 16(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38932125

ABSTRACT

The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.


Subject(s)
COVID-19 , Disease Models, Animal , Murine hepatitis virus , SARS-CoV-2 , Animals , Mice , COVID-19/pathology , COVID-19/virology , COVID-19/immunology , Murine hepatitis virus/pathogenicity , SARS-CoV-2/pathogenicity , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intestines/pathology , Intestines/virology , Intestine, Small/virology , Intestine, Small/pathology , Female
3.
Clin Infect Dis ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38666408

ABSTRACT

This study describes the largest cohort to date (n=147) of pregnant patients living with HIV on bictegravir (BIC). BIC in pregnancy was associated with high levels of viral suppression and similar perinatal outcomes to published literature. These findings support consideration for use of BIC in management of HIV during pregnancy.

4.
Obstet Gynecol ; 141(5): 949-955, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37103535

ABSTRACT

OBJECTIVE: To conduct a cohort study to estimate risk for readmission through 1 year postpartum and the most common readmission diagnoses for individuals with and without severe maternal morbidity (SMM) at delivery. METHODS: Using national health care claims data from IBM MarketScan Commercial Research Databases (now known as Merative), we identified all delivery hospitalizations for continuously enrolled individuals 15-49 years of age that occurred between January 1, 2016, and December 31, 2018. Severe maternal morbidity at delivery was identified using diagnosis and procedure codes. Individuals were followed for 365 days after delivery discharge, and cumulative readmission rates were calculated for up to 42 days, up to 90 days, up to 180 days, and up to 365 days. We used multivariable generalized linear models to estimate adjusted relative risks (aRR), adjusted risk differences, and 95% CIs for the association between readmission and SMM at each of the timepoints. RESULTS: The study population included 459,872 deliveries; 5,146 (1.1%) individuals had SMM during the delivery hospitalization, and 11,603 (2.5%) were readmitted within 365 days. The cumulative incidence of readmission was higher in individuals with SMM than those without at all timepoints (within 42 days: 3.5% vs 1.2%, aRR 1.44, 95% CI 1.23-1.68; within 90 days: 4.1% vs 1.4%, aRR 1.46, 95% CI 1.26-1.69); within 180 days: 5.0% vs 1.8%, aRR 1.48, 95% CI 1.30-1.69; within 365 days: 6.4% vs 2.5%, aRR 1.44, 95% CI 1.28-1.61). Sepsis and hypertensive disorders were the most common reason for readmission within 42 and 365 days for individuals with SMM (35.2% and 25.8%, respectively). CONCLUSION: Severe maternal morbidity at delivery was associated with increased risk for readmission throughout the year after delivery, a finding that underscores the need for heightened awareness of risk for complications beyond the traditional 6-week postpartum period.


Subject(s)
Patient Readmission , Postpartum Period , Female , Pregnancy , Humans , Cohort Studies , Risk Factors , Hospitalization , Retrospective Studies , Morbidity
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