The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured neutralization of the Omicron BA.1 variant pseudovirus by post-vaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. We also evaluated eighteen clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

Abstract. Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy.

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule—a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

This study demonstrated that the bacterial communities from all regions sampled were not only metabolically active with the capacity to utilize several different compounds as energy sources but also were genetically diverse. This study is the first to focus on the overall bacterial community, providing insight into this vital component of stream ecosystems. Understanding the bacterial components of aquatic systems such as the Anacostia River will increase our knowledge of the overall structure and function of the ecological communities in polluted systems, subsequently enhancing our ability to improve the health of this important tidal river.

Temporal and spatial changes in the molecular operational taxonomic unit (OTU) compositions of bacteria harboring genes for nitrification and denitrification were assessed using denaturing gradient gel electrophoresis (DGGE), clone-based DNA sequencing of selected PCR products, and analyses of ammonium and organic matter concentrations. Sediment, overlying water, and pore-water samples were taken from different vegetated sites of Jug Bay National Estuarine Research Reserve, Maryland, during spring, summer, and fall 2006. OTU richness and the diversities of nitrifiers and denitrifiers were assessed by the presence of bands on DGGE gels, both ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) were seasonally dependent. AOB OTU richness was highest in the summer when NOB richness was decreased, whereas NOB richness was highest in the spring when AOB richness was decreased. The OTU diversities of nitrifiers did not correlate with ammonium concentrations, organic matter concentrations, or the presence of vegetation. The OTU diversities of denitrifiers possessing either the nirK or nosZ genes were not seasonally dependent but were positively correlated with organic matter content (p = 0.0015, r2 = 0.27; p < 0.0001, r2 = 0.39, respectively). Additionally, the presence of vegetation significantly enhanced nosZ species richness (Wilcoxon/Kruskal-Wallis test, p < 0.008), but this trend was not seen for nirK OTU richness. Banding patterns for nirK OTUs were more similar within sites for each season compared with any of the other genes. Over all seasons, nirK OTU richness was highest and AOB and nosZ OTU richness were lowest (Wilcoxon/Kruskal-Wallis test, p < 0.0001). High levels of sequence divergence among cloned nirK PCR products indicate a broad diversity of nirK homologs in this freshwater estuary.