The protective effect of SARS-CoV-2 antibodies in Scottish healthcare workers

BACKGROUND: Healthcare workers (HCW) are believed to be at increased risk of SARS-CoV-2 infection. It is not known to what extent the natural production of antibodies to SARS-CoV-2 is protective against re-infection. METHODS: A prospective observational study of HCW's in Scotland (UK) from May to September 2020. The Siemens SARS-CoV-2 total antibody assay was used to establish seroprevalence in this cohort. Controls, matched for age and sex to the general local population, were studied for comparison. New infections (up to 2/12/2020) post antibody testing were recorded to determine if the presence of SARS-CoV-2 antibodies protect against re-infection. RESULTS: A total of 2063 health and social care workers were recruited for this study. At enrolment 300 HCW had a positive antibody test (14.5%). 11/231 control sera tested positive (4.8%). HCW therefore had an increased likelihood of a positive test (Odds ratio 3.4 95% CI 1.85–6.16, p<0.0001). Dentists were most likely to test positive. 97.3% of patients who had previously tested positive for SARS-CoV-2 by RT-PCR had positive antibodies. 18.7% had an asymptomatic infection. There were 38 new infections with SARS-CoV-2 in HCW who were previously antibody negative and one symptomatic RT-PCR positive re-infection. The presence of antibodies was therefore associated with an 85% reduced risk of re-infection with SARS-CoV-2 (HR 0.15, 95% CI 0.06 to 0.35, p=0.026). CONCLUSION: HCW were three times more likely to test positive for SARS-CoV-2 than the general population. Almost all infected individuals developed an antibody response which was 85% effective in protecting against re-infection with SARS-CoV-2

Neurofibromatosis type 1: a case highlighting pulmonary and other rare clinical manifestations.

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support

ALG11-CDG syndrome: Expanding the phenotype.

ALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy. Their fibroblasts synthesized truncated precursor glycan structures, consistent with ALG11-CDG, while also showing hypoglycosylation of a novel biomarker, GP130. Surprisingly, one patient presented with normal transferrin glycosylation profile, a feature that has not been reported previously in patients with ALG11-CDG. Together, our data expand the clinical and mutational spectrum of ALG11-CDG

De novo loss-of-function variants in STAG2 are associated with developmental delay, microcephaly, and congenital anomalies.

The cohesin complex is an evolutionarily conserved multi-subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2. Loss-of-function mutations in many of these proteins have been implicated in human developmental disorders collectively termed cohesinopathies. Through clinical exome sequencing (CES) of an 8-year-old girl with a clinical history of global developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features, we describe a heterozygous de novo variant (c.205C&gt;T; p.(Arg69*)) in the integral cohesin structural protein, STAG2. This variant is associated with decreased STAG2 protein expression. The analyses of metaphase spreads did not exhibit premature sister chromatid separation; however, delayed sister chromatid cohesion was observed. To further support the pathogenicity of STAG2 variants, we identified two additional female cases from the DECIPHER research database with mutations in STAG2 and phenotypes similar to our patient. Interestingly, the clinical features of these three cases are remarkably similar to those observed in other well-established cohesinopathies. Herein, we suggest that STAG2 is a dosage-sensitive gene and that heterozygous loss-of-function variants lead to a cohesinopathy

When moments matter: Finding answers with rapid exome sequencing

Abstract Background When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing. Methods The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed. Results Clinical rapid exome sequencing identified a definitive diagnosis in 13/41 (31.7%) and other relevant findings in 17 of the patients (41.5%). The average time to verbal report was 7 days; to written report was 11 days. Conclusions Our observations demonstrate the utility and effectiveness of rapid family‐based diagnostic exome sequencing in improving patients care