Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.

Objective: Staff surveillance is crucial during the containment phase of a pandemic to help reduce potential healthcare-associated transmission and sustain good staff morale. During an outbreak of SARS-COV-2 with community transmission, our institution used an integrated strategy for early detection and containment of COVID-19 cases among healthcare workers (HCWs).Methods: Our strategy comprised 3 key components: (1) enforcing reporting of HCWs with acute respiratory illness (ARI) to our institution's staff clinic for monitoring; (2) conducting ongoing syndromic surveillance to obtain early warning of potential clusters of COVID-19; and (3) outbreak investigation and management.Results: Over a 16-week surveillance period, we detected 14 cases of COVID-19 among HCWs with ARI symptoms. Two of the cases were linked epidemiologically and thus constituted a COVID-19 cluster with intrahospital HCW-HCW transmission; we also detected 1 family cluster and 2 clusters among HCWs who shared accommodation. No transmission to HCWs or patients was detected after containment measures were instituted. Early detection minimized the number of HCWs requiring quarantine, hence preserving continuity of service during an ongoing pandemic.Conclusions: An integrated surveillance strategy, outbreak management, and encouraging individual responsibility were successful in early detection of clusters of COVID-19 among HCWs. With ongoing local transmission, vigilance must be maintained for intrahospital spread in nonclinical areas where social mingling of HCWs occurs. Because most individuals with COVID-19 have mild symptoms, addressing presenteeism is crucial to minimize potential staff and patient exposure.

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Moraxella catarrhalis ubiquitous surface protein (Usp) A1 has been reported to bind fibronectin and is involved in adherence. In this study, using M. catarrhalis mutants derived from clinical isolates, we show that both UspA1 and UspA2 bind fibronectin. Recombinant truncated UspA1/A2 proteins, together with smaller fragments spanning the entire molecule, were tested for binding to fibronectin. Both UspA1 and UspA2 bound fibronectin, and the fibronectin-binding domains were located within UspA1(299-452) and UspA2(165-318). These 2 truncated proteins inhibited binding of M. catarrhalis to Chang conjunctival epithelial cells to an extent similar to that by anti-human fibronectin antibodies. Our observations show that both UspA1 and UspA2 are involved in adherence to epithelial cells via cell-associated fibronectin. The biologically active sites within UspA1(299-452) and UspA2(165-318) have therefore been suggested to be potential candidates to be included in a future vaccine against M. catarrhalis.

Objectives: Patients with COVID-19 may present with respiratory syndromes indistinguishable from those caused by common viruses. Early isolation and containment is challenging. Although screening all patients with respiratory symptoms for COVID-19 has been recommended, the practicality of such an effort has yet to be assessed.Methods: Over a 6-week period during a SARS-CoV-2 outbreak, our institution introduced a "respiratory surveillance ward" (RSW) to segregate all patients with respiratory symptoms in designated areas, where appropriate personal protective equipment (PPE) could be utilized until SARS-CoV-2 testing was done. Patients could be transferred when SARS-CoV-2 tests were negative on 2 consecutive occasions, 24 hours apart.

Moraxella catarrhalis ubiquitous surface proteins A1 and A2 (UspA1/A2) interfere with the classical pathway of the complement system by binding C4b-binding protein. In this study we demonstrate that M. catarrhalis UspA1 and A2 noncovalently and in a dose-dependent manner bind both the third component of complement (C3) from EDTA-treated serum and methylamine-treated C3. In contrast, related Moraxella subspecies (n = 13) or other human pathogenic bacteria (n = 13) do not bind C3 or methylamine-treated C3. Experiments with recombinant proteins and M. catarrhalis mutants devoid of UspA1/A2 revealed that UspA1/A2 exert their actions by absorbing and neutralizing C3 from serum and restrain complement activation. UspA2 was responsible for most of the effect, and the Moraxella mutant lacking UspA2 was more sensitive to the lytic effect of human serum compared with the wild type. Interestingly, among the large number of bacteria analyzed, only M. catarrhalis has this unique ability to interfere with the innate immune system of complement by binding C3.

Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex immunohistochemistry and immunofluorescence for tumor-infiltrating immune cells. Through whole-genome sequencing (n = 18), 50% of the cutaneous head and neck angiosarcomas exhibited higher tumor mutation burden (TMB) and UV mutational signatures; others were mutationally quiet and non-UV driven. NanoString profiling revealed 3 distinct patient clusters represented by lack (clusters 1 and 2) or enrichment (cluster 3) of immune-related signaling and immune cells. Neutrophils (CD15 +), macrophages (CD68 +), cytotoxic T cells (CD8 +), Tregs (FOXP3 +), and PD-L1 + cells were enriched in cluster 3 relative to clusters 2 and 1. Likewise, tumor inflammation signature (TIS) scores were highest in cluster 3 (7.54 vs. 6.71 vs. 5.75, respectively; P < 0.0001). Head and neck angiosarcomas were predominant in clusters 1 and 3, providing the rationale for checkpoint immunotherapy, especially in the latter subgroup with both high TMB and TIS scores. Cluster 2 was enriched for secondary angiosarcomas and exhibited higher expression of DNMT1, BRD3/4, MYC, HRAS, and PDGFRB, in keeping with the upregulation of epigenetic and oncogenic signaling pathways amenable to targeted therapies. Molecular and immunological dissection of angiosarcomas may provide insights into opportunities for precision medicine.