Early expansion of activated adaptive but also exhausted NK cells during acute severe SARS-CoV-2 infection.

The analysis of immunological parameters during the course of a SARS-CoV-2 infection is of great importance, both to identify diagnostic markers for the risk of a severe course of COVID-19, and to better understand the role of the immune system during the infection. By using multicolor flow cytometry we compared the phenotype of Natural Killer (NK) cells from hospitalized COVID-19 patients during early SARS-CoV-2 infection with samples from recovered and SARS-CoV-2 naïve subjects. Unsupervised high-dimensional analysis of 28-color flow cytometric data revealed a strong enrichment of NKG2C expressing NK cells in response to the acute viral infection. In addition, we found an overrepresentation of highly activated NK cell subsets with an exhausted phenotype. Moreover, our data show long-lasting phenotypic changes within the NK cell compartment that did not completely reverse up to 2 months after recovery. This demonstrates that NK cells are involved in the early innate immune response against SARS-CoV-2.

Neutralizing antibody responses 300 days after SARS-CoV-2 infection and induction of high antibody titers after vaccination.

Neutralizing antibodies against SARS-CoV-2 are important to protect against infection and/or disease. Using an assay to detect antibodies directed against the receptor binding domain (RBD) of SARS-CoV-2 Spike, we identified individuals with SARS-CoV-2 infection after an outbreak at a local health institution. All but one COVID-19 patient developed detectable anti-RBD antibodies and 77% had virus neutralizing antibody titers of >1:25. Antibody levels declined slightly over time. However, we still detected virus neutralizing antibody titers in 64% of the COVID-19 patients at >300 days after infection, demonstrating durability of neutralizing antibody levels after infection. Importantly, full COVID-19 vaccination of these individuals resulted in higher antibody titers compared to fully vaccinated individuals in the absence of prior infection. These data demonstrate long-lived antibody-mediated immunity after SARS-CoV-2 infection, and a clear benefit of two vaccine doses for recovered individuals.

SARS-CoV-2 infection shortly after BNT162b2 vaccination results in high anti-spike antibody levels in nursing home residents and staff.

INTRODUCTION: One dose of a coronavirus disease 2019 (COVID-19) vaccine can elicit high antibody titers in individuals who were previously infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear how a SARS-CoV-2 infection shortly after a first COVID-19 vaccine dose affects antibody responses. METHODS: Here we investigate residents and staff of a nursing home, where a COVID-19 outbreak occurred shortly after the first BNT162b2 immunization. RESULTS AND CONCLUSIONS: Our data show that individuals who got infected as early as 10 days after their first immunization show antibody levels comparable to fully vaccinated individuals.

Clostridium difficile: A rare cause of pyogenic liver abscess.

Extra-intestinal infections due to Clostridium difficile have been reported rarely. Herein we report a case of pyogenic liver abscess from toxigenic C. difficile in an 80-year-old non-hospitalized woman with diabetes mellitus, cerebrovascular and cardiovascular diseases. The patient was admitted to the emergency department with fever and abdominal pain. There was no history of diarrhea or use of antibiotics. Laboratory parameters revealed signs of inflammation and elevated AST and ALT levels. Abdominal ultrasound and computer tomography showed multiple focal lesions in the bilateral liver lobes and hydropic gallbladder with stones. The patient underwent cholecystectomy and the liver abscesses were drained. Toxigenic C. difficile strains were isolated from the drained pus and also from the stool sample. According to repetitive-element PCR (rep-PCR) analyses both organisms were the same. The organisms were susceptible to antibiotics. Despite proper antibiotic therapy and surgical drainage, the patient succumbed to her illness.

TLR2/6 stimulation of the rat lung: effects on lymphocyte subsets, natural killer cells and dendritic cells in different parts of the air-conducting compartments and at different ages.

The composition of lymphocyte subsets in the lung has been found to be compartment-specific. To characterize the effect of age, weanling, young adult and adult rats were studied in control conditions and after a single intratracheal dose of the Toll-like receptor 2/6 (TLR2/6) agonist macrophage activating lipopeptide-2 (MALP-2). In all age groups, T, B and natural killer (NK) cells increased dramatically in the epithelium and lamina propria of the bronchi. Male adult rats were found to have responded to MALP-2 to a much greater extent than females when lymphocyte subsets were counted in the epithelium and the lamina propria. In a second series of experiments the time kinetics of regulatory T-cell (Treg) subsets and dendritic cells (DCs) in the lung was studied after local stimulation with MALP-2. Different time-dependent patterns were found in the Treg subsets CD4(+) CD25(+), CD4(+) CD25(+) neuropilin 1(+) and CD4(+) CD25(+) Foxp3(+) cells. Neutrophils and DCs also showed different patterns. Thus, the local application of a TLR agonist increased the number of lymphocyte subsets in a compartment-specific pattern. However, data should not be generalized or extrapolated from one age group, sex or lymphocyte subpopulation to another.