The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer-BioNTech Vaccine.

The aim of this study was to analyze the profiles of IgG subclasses in COVID-19 convalescent Puerto Rican subjects and compare these profiles with those of non-infected immunocompetent or immunocompromised subjects that received two or more doses of an mRNA vaccine. The most notable findings from this study are as follows: (1) Convalescent subjects that were not hospitalized developed high and long-lasting antibody responses. (2) Both IgG1 and IgG3 subclasses were more prevalent in the SARS-CoV-2-infected population, whereas IgG1 was more prevalent after vaccination. (3) Individuals that were infected and then later received two doses of an mRNA vaccine exhibited a more robust neutralizing capacity against Omicron than those that were never infected and received two doses of an mRNA vaccine. (4) A class switch toward the "anti-inflammatory" antibody isotype IgG4 was induced a few weeks after the third dose, which peaked abruptly and remained at high levels for a long period. Moreover, the high levels of IgG4 were concurrent with high neutralizing percentages against various VOCs including Omicron. (5) Subjects with IBD also produced IgG4 antibodies after the third dose, although these antibody levels had a limited effect on the neutralizing capacity. Knowing that the mRNA vaccines do not prevent infections, the Omicron subvariants have been shown to be less pathogenic, and IgG4 levels have been associated with immunotolerance and numerous negative effects, the recommendations for the successive administration of booster vaccinations to people should be revised.

Pneumocystis jirovecii pneumonia in HIV-1-infected patients in the late-HAART era in developed countries.

BACKGROUND: In developed countries with free access to health care, primary chemoprophylaxis with co-trimoxazole, and antiretroviral treatment, Pneumocystis pneumonia (PCP) in HIV-infected subjects should be restricted to undiagnosed late presenters. METHODS: We retrospectively identified confirmed PCP hospital admissions in HIV-1 patients (period 1986-2010) and examined their characteristics and factors associated with mortality. RESULTS: Three hundred and twelve episodes (median CD4 27 cells/µl) were identified during 3 periods: pre-HAART (1986-1995), 49%; early-HAART (1996-1999), 17.3%; and late-HAART (2000-2010), 33.7%. PCP was the initial AIDS-defining diagnosis in only 86 (27.6%). Thirty-four (10.9%) patients died during their hospital stay, without a significant reduction in mortality in recent periods (p = 0.311). However, the 12-month mortality decreased through the periods (33.3% to 16.2%; p = 0.003). Drug users (p = 0.001) and those naïve to HAART (p < 0.001) decreased in the late-HAART era, while heterosexuals (p = 0.001), immigrants (p < 0.001), and HAART initiation before hospital discharge (p < 0.001) increased. A partial pressure of oxygen (PaO2) ≤ 55 (p = 0.04), intensive care admission (p < 0.001), and the absence of HAART initiation before discharge (p = 0.02) were correlated with mortality. CONCLUSIONS: The epidemiology and 12-month mortality of HIV-1-infected subjects with PCP have changed significantly in the late-HAART era, while mortality during hospital stay has remained unchanged. HIV diagnosed individuals lost to follow-up in care have emerged as the main driver of PCP in developed countries. Like HIV late presenters, they are more likely to have AIDS-defining illnesses, to be hospitalized, and to die. This finding has important implications for the design of better strategies to retain HIV-1-infected individuals in care.

Grade 3 Severe Liver Injury Secondary to Pembrolizumab.

Over the last years, pembrolizumab has been one of the checkpoint inhibitors that have revolutionized the management of unresectable malignancies given its successful rate of disease control. This drug has become part of the standard of care in several types of cancers, however, the side effects are an emerging concern for physicians managing patients with cancer. Immune mediated injury of these drugs can target virtually any organ. Liver injury is an important side effect of these drugs that can be life threatening and needs to be well recognized. Here we report a case of an 85-year-old male with medical history of stage 3 laryngeal carcinoma who presented with severe liver injury secondary to pembrolizumab.

Endoscopic Ultrasound-Guided Cholecystoenterostomy for Acute Hemorrhagic Cholecystitis Drainage.

Hemorrhagic cholecystitis is a rare entity with few cases reported in the literature. We report a case of a 42-year-old man with cirrhosis who presented to the hospital with abdominal pain in the right upper quadrant radiating to the back. Computed tomography scan showed findings consistent with acute cholecystitis. Owing to decompensated cirrhosis, he was not a good candidate for cholecystectomy. Endoscopic ultrasound-guided cholecystoenterostomy was performed that immediately yielded a large amount of old blood with clots along with some bile consistent with acute hemorrhagic cholecystitis. After the drainage, he had an uneventful hospitalization.

Inefficient Induction of Neutralizing Antibodies against SARS-CoV-2 Variants in Patients with Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy after Receiving a Third mRNA Vaccine Dose.

Management of inflammatory bowel disease (IBD) often relies on biological and immunomodulatory agents for remission through immunosuppression, raising concerns regarding the SARS-CoV-2 vaccine's effectiveness. The emergent variants have hindered the vaccine neutralization capacity, and whether the third vaccine dose can neutralize SARS-CoV-2 variants in this population remains unknown. This study aims to evaluate the humoral response of SARS-CoV-2 variants in patients with IBD 60 days after the third vaccine dose [BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna)]. Fifty-six subjects with IBD and 12 healthy subjects were recruited. Ninety percent of patients with IBD (49/56) received biologics and/or immunomodulatory therapy. Twenty-four subjects with IBD did not develop effective neutralizing capability against the Omicron variant. Seventy percent (17/24) of those subjects received anti-tumor necrosis factor therapy [10 = adalimumab, 7 = infliximab], two of which had a history of COVID-19 infection, and one subject did not develop immune neutralization against three other variants: Gamma, Epsilon, and Kappa. All subjects in the control group developed detectable antibodies and effective neutralization against all seven SARS-CoV-2 variants. Our study shows that patients with IBD might not be protected against SARS-CoV-2 variants, and more extensive studies are needed to evaluate optimal immunity.