Congenital Infantile Fibrosarcoma Involving Pelvic Wall and Thigh Soft Tissues and Placenta, Presenting with Coagulopathy.

Infantile fibrosarcoma (IF) is a well characterized pediatric malignancy marked by gene rearrangements involving members of the NTRK family. In this report, we present a case of IF that presented in the inguinal region-proximal thigh and was initially thought to be a kaposiform hemangioendothelioma (KHE) because it presented with a bleeding diathesis thought to be Kasabach-Merritt phenomenon (KMP). Subsequently, the placental examination showed a neoplasm in the perivascular-subendothelial space of stem villi, initially thought to be myofibromatosis. Ultimately, a biopsy of the thigh mass showed IF with an NTRK3-ETV6 fusion. Subsequent FISH analysis of the placenta showed an ETV6 rearrangement confirming that it was also IF. Review of the laboratory studies suggests that disseminated intravascular coagulation may have been more likely than KMP, highlighting the difficulty in making this distinction in some cases. We believe this to be the first report of an IF presenting in a soft tissue site and the placenta, and discuss the possible mechanisms that could have allowed the IF in the leg to spread to the placenta.

SARS-CoV-2 seroprevalence among healthcare workers.

BACKGROUND: Monitoring COVID-19 infection risk among health care workers (HCWs) is a public health priority. We examined the seroprevalence of SARS-CoV-2 among HCWs following the fall infection surge in Minnesota, and before and after COVID-19 vaccination. Additionally, we assessed demographic and occupational risk factors for SARS-CoV-2 infection. METHODS: We conducted two rounds of seroprevalence testing among a cohort of HCWs: samples in round 1 were collected from 11/22/20-02/21/21 and in round 2 from 12/18/20-02/15/21. Demographic and occupational exposures assessed with logistic regression were age, sex, healthcare role and setting, and number of children in the household. The primary outcome was SARS-CoV-2 IgG seropositivity. A secondary outcome, SARS-CoV-2 infection, included both seropositivity and self-reported SARS-CoV-2 test positivity. RESULTS: In total, 459 HCWs were tested. 43/454 (9.47%) had a seropositive sample 1 and 75/423 (17.7%) had a seropositive sample 2. By time of sample 2 collection, 54% of participants had received at least one vaccine dose and seroprevalence was 13% among unvaccinated individuals. Relative to physicians, the odds of SARS-CoV-2 infection in other roles were increased (Nurse Practitioner: OR[95%CI] 1.93[0.57,6.53], Physician's Assistant: 1.69[0.38,7.52], Nurse: 2.33[0.94,5.78], Paramedic/EMTs: 3.86[0.78,19.0], other: 1.68[0.58,4.85]). The workplace setting was associated with SARS-CoV-2 infection (p = 0.04). SARS-CoV-2 seroprevalence among HCWs reporting duties in the ICU vs. those working in an ambulatory clinic was elevated: OR[95%CI] 2.17[1.01,4.68]. CONCLUSIONS: SARS-CoV-2 seroprevalence in HCW increased during our study period which was consistent with community infection rates. HCW role and setting-particularly working in the ICU-is associated with higher risk for SARS-CoV-2 infection.

Identification of Natural SARS-CoV-2 Infection in Seroprevalence Studies Among Vaccinated Populations.

Most SARS-CoV-2 antibody assays cannot distinguish between antibodies that developed after natural infection and those that developed after vaccination. We assessed the accuracy of a nucleocapsid-containing assay in identifying natural infection among vaccinated individuals. A longitudinal cohort composed of health care workers in the Minneapolis/St. Paul area was enrolled. Two rounds of seroprevalence studies separated by 1 month were conducted from November 2020 to January 2021 among 81 participants. Capillary blood from rounds 1 and 2 was tested for IgG antibodies against spike proteins by enzyme-linked immunosorbent assay (spike-only assay). During round 2, IgGs reactive to SARS-CoV-2 nucleocapsid protein (nucleocapsid-containing assay) were assessed. Vaccination status at round 2 was determined by self-report. Area under the curve was computed to determine the discriminatory ability of the nucleocapsid-containing assay for identification of recent infection. Participants had a mean age of 40 years (range, 23 to 66 years); 83% were female. Round 1 seroprevalence was 9.5%. Before round 2 testing, 46% reported vaccination. Among those not recently infected, in comparing vaccinated vs unvaccinated individuals, elevated levels of spike 1 (P<.001) and spike 2 (P=.01) were observed, whereas nucleocapsid levels were not statistically significantly different (P=.90). Among all participants, nucleocapsid response predicted recent infection with an area under the curve of 0.93 (95% CI, 0.88 to 0.99). Among individuals vaccinated more than 10 days before antibody testing, the specificity of the nucleocapsid-containing assay was 92%, whereas the specificity of the spike-only assay was 0%. An IgG assay identifying reactivity to nucleocapsid protein is an accurate predictor of natural infection among a partially vaccinated population, whereas a spike-only assay performed poorly.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) screening among symptom-free healthcare workers.

Transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is possible among symptom-free individuals. Patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. We screened 489 symptom-free healthcare workers for SARS-CoV-2 and found no positive results, strongly suggesting that the prevalence of SARS-CoV-2 was <1%.

Identification of natural SARS-CoV-2 infection in seroprevalence studies among vaccinated populations.

IMPORTANCE: Identification of SARS-CoV-2 infection via antibody assays is important for monitoring natural infection rates. Most antibody assays cannot distinguish natural infection from vaccination. OBJECTIVE: To assess the accuracy of a nucleocapsid-containing assay in identifying natural infection among vaccinated individuals. DESIGN: A longitudinal cohort comprised of healthcare workers (HCW) in the Minneapolis/St. Paul metropolitan area was enrolled. Two rounds of seroprevalence studies separated by one month were conducted from 11/2020-1/2021. Capillary blood from round 1 and 2 was tested for IgG antibodies against SARS-CoV-2 spike proteins with a qualitative chemiluminescent ELISA (spike-only assay). In a subsample of participants (n=82) at round 2, a second assay was performed that measured IgGs reactive to SARS-CoV-2 nucleocapsid protein (nucleocapsid-containing assay). Round 1 biospecimen collections occurred prior to vaccination in all participants. Vaccination status at round 2 was determined via self-report. SETTING: The Minneapolis/St. Paul, Minnesota metropolitan area. PARTICIPANTS: HCW age 18-80 years. EXPOSURES: Round 1 recent SARS-CoV-2 infection assessed via a spike-only assay and participant self-report. OUTCOMES: Round 2 SARS-CoV-2 infection assessed via the nucleocapsid-containing assay. Area under the curve (AUC) was computed to determine the discriminatory ability of round 2 IgG reactivity to nucleocapsid for identification of recent infection determined during round 1. RESULTS: Participants had a mean age of 40 (range=23-66) years, 83% were female, 46% reported vaccination prior to the round 2 testing. Round 1 seroprevalence was 9.5%. Among those not recently infected, when comparing vaccinated vs. unvaccinated individuals, elevated levels of spike 1 (p<0.001) and spike 2 (p=0.01) were observed while nucleocapsid levels were not statistically significantly different (p=0.90). Among all participants, nucleocapsid response predicted recent infection with an AUC(95%CI) of 0.93(0.88,0.99). Among individuals vaccinated >10 days prior to antibody testing, the specificity of the nucleocapsid-containing assay was 92% and while the specificity of the spike-only assay was 0%. CONCLUSIONS AND RELEVANCE: An IgG assay identifying reactivity to nucleocapsid protein is an accurate predictor of natural infection among vaccinated individuals while a spike-only assay performed poorly. In the era of SARS-CoV-2 vaccination, seroprevalence studies monitoring natural infection will require assays that do not rely on spike-protein response alone.

SARS-CoV-2 Screening Among Symptom-Free Healthcare Workers.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possible among symptom-free individuals and some patients are avoiding medically necessary healthcare visits for fear of becoming infected in the healthcare setting. Limited data are available on the point prevalence of SARS-CoV-2 infection in symptom-free U.S. healthcare workers (HCW). METHODS: A cross-sectional convenience sample of symptom-free HCWs from the metropolitan area surrounding Minneapolis and St. Paul, Minnesota was enrolled between April 20 th and June 24 th , 2020. A participant self-collected nasopharyngeal swab (NPS) was obtained. SARS-CoV-2 infection was assessed via polymerase chain reaction. Participants were queried about their willingness to repeat a self-collection NPS for diagnostic purposes. We had >95% power to detect at least one positive test if the true underlying prevalence of SARS-CoV2 was ≥1%. RESULTS: Among n=489 participants 80% were female and mean age±SD was 41±11. Participants reported being physicians (14%), nurse practitioners (8%), physician's assistants (4%), nurses (51%), medics (3%), or other which predominantly included laboratory technicians and administrative roles (22%). Exposure to a known/suspected COVID-19 case in the 14 days prior to enrollment was reported in 40% of participants. SARS-CoV-2 was not detected in any participant. Over 95% of participants reported a willingness to repeat a self-collected NP swab in the future. CONCLUSIONS: The point prevalence of SARS-CoV-2 infection was likely <1% in a convenience sample of symptom-free Minnesota healthcare workers from April 20 th and June 24 th , 2020. Self-collected NP swabs are well-tolerated and a viable alternative to provider-collected swabs to preserve PPE.

The Role of Hematopoietic Cell Transplant in the Glycoprotein Diseases.

The glycoprotein disorders are a group of lysosomal storage diseases (α-mannosidosis, aspartylglucosaminuria, ß-mannosidosis, fucosidosis, galactosialidosis, sialidosis, mucolipidosis II, mucolipidosis III, and Schindler Disease) characterized by specific lysosomal enzyme defects and resultant buildup of undegraded glycoprotein substrates. This buildup causes a multitude of abnormalities in patients including skeletal dysplasia, inflammation, ocular abnormalities, liver and spleen enlargement, myoclonus, ataxia, psychomotor delay, and mild to severe neurodegeneration. Pharmacological treatment options exist through enzyme replacement therapy (ERT) for a few, but therapies for this group of disorders is largely lacking. Hematopoietic cell transplant (HCT) has been explored as a potential therapeutic option for many of these disorders, as HCT introduces functional enzyme-producing cells into the bone marrow and blood along with the engraftment of healthy donor cells in the central nervous system (presumably as brain macrophages or a type of microglial cell). The outcome of HCT varies widely by disease type. We report our institutional experience with HCT as well as a review of the literature to better understand HCT and outcomes for the glycoprotein disorders.