Self-administered, remote assessment of SARS-CoV-2 seroprevalence in health care workers.

BACKGROUND: Our objective was to safely and remotely assess longitudinal SARS-CoV-2 seroprevalence in at-risk health care workers at the onset of the epidemic. METHODS: Self-administered serologic testing was performed every 30 days up to 5 times using a point-of-care, lateral flow SARS-CoV-2 nucleocapsid IgG immunoassay in a cohort of at-risk health care workers (n = 339) and lower-risk controls (n = 100). RESULTS: Subjects were enrolled between 4/14/20-5/6/20 and most were clinicians (41%) or nurses (27%). Of 20 subjects who reported confirmed SARS-CoV-2 infection prior to (n = 5, 1%) or during the study (n = 15, 3%), half (10/20) were seropositive. Five additional subjects were seropositive and did not report documented infection. Estimated infection rates in health care workers did not differ from concurrent community rates. CONCLUSIONS: This remotely conducted, contact-free study did not identify serologic evidence of widespread occupational SARS-CoV-2 infection in health care workers.

Candidal endocarditis presenting with bilateral lower limb ischemia.

The incidence of fungal endocarditis is increasing. While the pathogenic mechanisms are not fully understood, infection is associated with underlying heart disease and is most often attributable to Candida species. Candidal endocarditis complications include heart damage, inflammation, and emboli with resulting ischemia and tissue death. Candidal endocarditis is difficult to diagnose as blood cultures are often negative. Treatment includes surgical intervention and antifungal therapy. This case study describes a 41-year-old female complaining of acute onset of pain with numbness and tingling in both lower extremities. Prior history was significant for mycotic valve aneurysm and replacement secondary to culture-negative endocarditis. Evidence of limb-threatening ischemia led to a bilateral thrombectomy. During the thrombectomy white debris, later identified as Candida albicans, was encountered. A transesophogeal echocardiogram revealed a pedunculated mass which was determined to be the source of infection. The patient was placed on micafungin and voriconazole and discharged with a diagnosis of C. albicans fungal infection with descending aorta fungal mass. This case study illustrates an unusual presentation of candidal endocarditis with discussion of disease epidemiology, pathogenesis, diagnosis, and treatment.

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces.

Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [(3)H]proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-α(1)(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production.

Expression in SPARC-null mice of collagen type I lacking the globular domain of the α1(I) N-propeptide results in abdominal hernias and loss of dermal collagen.

The sequence encoding the N-propeptide of collagen I is characterized by significant conservation of amino acids across species; however, the function of the N-propeptide remains poorly defined. Studies in vitro have suggested that one activity of this propeptide might be to act as a feedback inhibitor of collagen I synthesis. To determine whether the N-propeptide contributed to decreased collagen content in SPARC-null mice, mice carrying a deletion of exon 2, which encodes the globular domain of the N-propeptide of collagen I, were crossed to SPARC-null animals. Mice lacking SPARC and expressing collagen I without the globular domain of the N-propeptide were viable and fertile. However, a significant number of animals developed abdominal hernias within the first 2 months of life with an approximate 20% penetrance (~35% of males). The dermis of SPARC-null/exon 2-deleted mice was thinner and contained fewer large collagen fibers in comparison with wild-type or in either single transgenic animal. The average collagen fibril diameter of exon 2-deleted mice did not significantly differ from wild-type mice (WT: 87.9 nm versus exon 2-deleted: 88.2 nm), whereas SPARC-null/exon 2-deleted fibrils were smaller than that of SPARC-null dermis (SPARC-null: 60.2 nm, SPARC-null/exon 2-deleted: 40.8 nm). As measured by hydroxyproline analysis, double transgenic skin biopsies contained significantly less collagen than those of wild-type, those of exon 2-deleted, and those of SPARC-null biopsies. Acetic acid extraction of collagen from skin biopsies revealed an increase in the proportion of soluble collagen in the SPARC-null/exon 2-deleted mice. These results support a function of the N-propeptide of collagen I in facilitating incorporation and stabilization of collagen I into the insoluble ECM and argue against a primary function of the N-propeptide as a negative regulator of collagen synthesis.