Robust SARS-CoV-2-specific and heterologous immune responses in vaccine-naïve residents of long-term care facilities who survive natural infection.

We studied humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 152 long-term care facility staff and 124 residents over a prospective 4-month period shortly after the first wave of infection in England. We show that residents of long-term care facilities developed high and stable levels of antibodies against spike protein and receptor-binding domain. Nucleocapsid-specific responses were also elevated but waned over time. Antibodies showed stable and equivalent levels of functional inhibition against spike-angiotensin-converting enzyme 2 binding in all age groups with comparable activity against viral variants of concern. SARS-CoV-2 seropositive donors showed high levels of antibodies to other beta-coronaviruses but serostatus did not impact humoral immunity to influenza or other respiratory syncytial viruses. SARS-CoV-2-specific cellular responses were similar across all ages but virus-specific populations showed elevated levels of activation in older donors. Thus, survivors of SARS-CoV-2 infection show a robust and stable immunity against the virus that does not negatively impact responses to other seasonal viruses.

Profile of humoral and cellular immune responses to single doses of BNT162b2 or ChAdOx1 nCoV-19 vaccines in residents and staff within residential care homes (VIVALDI): an observational study.

BACKGROUND: Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff. METHODS: From the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination. FINDINGS: Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35·5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (r s=0·076, p=0·70). In participants without evidence of previous infection, titres were negatively correlated with age (r s=-0·434, p<0·0001) and were 8·2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (r s=-0·207, p=0·20; n=40), in contrast to samples taken after 0-21 days (r s=-0·774, p=0·0043; n=12) or 22-42 days (r s=-0·437, p=0·0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (r s=-0·439, p<0·0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0·010) and the P.1 variant (23% [14-97], p<0·0001) than against the original strain (58% [27-100]). By contrast, a single dose of vaccine resulted in around 100% inhibition of the spike-ACE2 interaction against all variants in people with a history of infection. INTERPRETATION: History of SARS-CoV-2 infection impacts the magnitude and quality of antibody response after a single dose of COVID-19 vaccine in LTCF residents. Residents who are infection-naive have delayed antibody responses to the first dose of vaccine and should be considered for an early second dose where possible. FUNDING: UK Government Department of Health and Social Care.

Monomicrobial necrotizing fasciitis complicating pregnancy and puerperium.

BACKGROUND: Necrotizing fasciitis is an uncommon, rapidly progressive, life-threatening infection involving the subcutaneous tissue and fascia. Usually, it is a synergistic polymicrobic infection that occurs in patients with coexisting factors predisposing them to bacterial inoculation and the spread of infection. CASES: We report a monomicrobial variant of necrotizing fasciitis affecting three otherwise healthy pregnant or postpartum women. The necrotizing fasciitis involved either the lower extremity or the abdominal wall. The causative bacteria were Streptococcus pyogenes (two cases) and Staphylococcus aureus (one). All patients presented with an acute fulminant infection, including one woman who died from overwhelming sepsis. CONCLUSION: These cases raise a question about the possible role of increased bacterial virulence and the immunologic changes of pregnancy as potential predisposing factors in the development of necrotizing fasciitis.

Adenoid cystic carcinoma of the trachea.

OBJECTIVE: Primary tracheal tumors are rare, occurring in 0.2 per 100,000 persons per year. Adenoid cystic carcinoma (ACC) is the second most common histologic type of tracheal malignancy. Its clinical behavior is different from the other tracheal neoplasms and thus should be studied separately. STUDY DESIGN/METHODS: Retrospective review of the medical records of six patients with tracheal ACC who were treated at University Hospitals of Cleveland between 1971 and 1996 and literature review. RESULTS/CONCLUSION: Tracheal ACC is an indolent tumor that affects people at any age but has a peak incidence in the fifth decade. There is a nearly equal male-to-female ratio. Almost half of tracheal ACCs occur in the proximal trachea, accounting for the most common presenting symptoms: dyspnea, cough, and hoarseness. Because of the hoarseness, patients are often referred to an otolaryngologist. Complete resection provides the best chance for increased survival. Neutron beam radiotherapy holds promise for adjuvant therapy.

Epiglottic hypoplasia associated with lacrimo-auriculo-dental-digital syndrome.

We present a case of a young boy with clinical manifestations of lacrimo-auriculo-dental-digital syndrome (LADD) with the additional finding of a hypoplastic epiglottis that caused airway obstruction at birth. We also reviewed the 30 cases of LADD that have been reported since 1967. It is a rare syndrome that includes lacrimal system, aural, digital, and dental anomalies. Our patient has lacrimal duct obstruction, deficient tissue in the inferior portion of the ear pinnae, and a hypoplastic epiglottis with collapse of the supraglottic tissue. Many findings of LADD are recognizable at birth. The clinical spectrum has widened with more case reports. Our patient adds a life-threatening airway abnormality, a hypoplastic epiglottis, to the clinical spectrum of LADD.

Adult intussusception.

OBJECTIVE: The objectives were to review adult intussusception, its diagnosis, and its treatment. SUMMARY BACKGROUND DATA: Adult intussusception represents 1% of all bowel obstructions, 5% of all intussusceptions, and 0.003%-0.02% of all hospital admissions. Intussusception is a different entity in adults than it is in children. METHODS: The records of all patients 18 years and older with the postoperative diagnosis of intussusception at the Massachusetts General Hospital during the years 1964 through 1993 were reviewed retrospectively. The 58 patients were divided into those with benign enteric, malignant enteric, benign colonic, and malignant colonic lesions associated with their intussusception. The diagnosis and treatment of each were reviewed. RESULTS: In 30 years at the Massachusetts General Hospital, there are 58 cases of surgically proven adult intussusception. The patients' mean age was 54.4 years. Most patients presented with symptoms consistent with bowel obstruction. There were 44 enteric and 14 colonic intussusceptions. Ninety-three percent of the intussusceptions were associated with a pathologic lesion. Forty-eight percent of the enteric lesions were malignant and 52% were benign. Forty-three percent of the colonic lesions were malignant and 57% were benign. CONCLUSIONS: Intussusception occurs rarely in adults. It presents with a variety of acute, intermittent, and chronic symptoms, thus making its preoperative diagnosis difficult. Computed tomography scanning proved to be the most useful diagnostic radiologic method. The diagnosis and treatment of adult intussusception are surgical. Surgical resection of the intussusception without reduction is the preferred treatment in adults, as almost half of both colonic and enteric intussusceptions are associated with malignancy.

The middle ear bioelectronic microphone for a totally implantable cochlear hearing device for profound and total hearing loss.

BACKGROUND: A bioelectronic middle ear microphone (BMEM) has been developed in a laboratory bench model and successfully tested in fresh human temporal bones. A transducer actually has been bench-tested in our laboratory; it was implanted in chronic animal experiments (cats) as well as in humans for a period of 1 year as a driver of a semi-implantable electromagnetic middle ear hearing device (IDE, FDA approved). This BMEM is the result of the use of this same electromagnetic transducer used in a reverse mode. The applicability of the BMEM is for the development of a totally implantable cochlear implant using the eardrum as a diaphragm that transmits vibrations to a magnet cemented to the ossicles. This BMEM is to be powered by a lithium-ion implantable, rechargeable battery. MATERIALS AND METHODS: To test the efficacy of this BMEM, the experiment was divided into two parts: (1) bench model, and (2) fresh human temporal bones, using an air-core electromagnetic (EM) coil and a ferrite core EM coil for comparison. RESULTS: In the bench model, the average displacement at 3 kHz was 0.95 microns (peak) for 4 V p-p and 1.65 microns (peak) for 10 V p-p. At 5 kHz, the measurements were somewhat higher. In fresh human temporal bones, with sound source in the ear canal (60 dB HL and 90 dB HL), the result was better with the magnet implanted on the head of the malleus with the incus removed. The ferrite core EM coil with the magnet implanted on the malleus with the incus removed was compared with the air-core EM coil. At 60 dB HL, the ferrite core EM coil yielded more than four times the amplitude of the EM coil. At 90 dB HL, the ferrite core EM coil produced more than five times the amplitude compared with the air-core coil. CONCLUSION: This BMEM using an EM ferrite coil and a permanent magnet on the head of the malleus is more efficient when compared with an EM air-core coil. This BMEM may be applicable to the construction of a totally implantable cochlear implant. Further research is necessary to integrate this BMEM with the other components of the design concept of the totally implantable cochlear implant.