Correlates of SARS-CoV-2 anti-RBD IgG antibody titers among persons experiencing homelessness in Los Angeles

Objectives

People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions.

Design

A case–control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables.

Sample

A convenience sample of 97 PEH in Skid Row, Los Angeles.

Measurements

A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions.

Results

We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 diagnosis or being vaccinated, suggesting undiagnosed and/or asymptomatic COVID-19. While anti-RBD IgG titers across vaccination categories were not statistically significant (p = .069), participants vaccinated with Janssen had the lowest mean anti-RBD IgG titers. In multivariable analysis, we found negative associations between level of SARS-CoV-2 antibody titers with the Janssen vaccine and depression; thus, a need for integrated care for PEH with depression and COVID-19.

Conclusions

Further research is warranted to confirm the immune response, initial and over time, to SARS-CoV-2 infection and to COVID-19 vaccinations, particularly among PEH whose immune systems may be impacted by multiple health conditions.     

Accelerated immune senescence and reduced response to vaccination in ovariectomized female rhesus macaques

Aging is associated with a general dysregulation in immune function, commonly referred to as “immune senescence”. Several studies have shown that female sex steroids can modulate the immune response. However, the impact of menopause-associated loss of estrogen and progestins on immune senescence remains poorly understood. To help answer this question, we examined the effect of ovariectomy on T-cell homeostasis and function in adult and aged female rhesus macaques. Our data show that in adult female rhesus macaques, ovariectomy increased the frequency of naïve CD4 T cells. In contrast, ovariectomized (ovx) aged female rhesus macaques had increased frequency of terminally differentiated CD4 effector memory T cells and inflammatory cytokine-secreting memory T cells. Moreover, ovariectomy reduced the immune response (T-cell cytokine and IgG production) following vaccination with modified vaccinia ankara in both adult and aged female rhesus macaques compared to ovary-intact age-matched controls. Interestingly, hormone therapy (estradiol alone or in conjunction with progesterone) partially improved the T-cell response to vaccination in aged ovariectomized female rhesus macaques. These data suggest that the loss of ovarian steroids, notably estradiol and progesterone, may contribute to reduced immune function in post-menopausal women and that hormone therapy may improve immune response to vaccination in this growing segment of the population.     

TMC1 but not TMC2 is responsible for autosomal recessive nonsyndromic hearing impairment in Tunisian families

Hereditary nonsyndromic hearing impairment (HI) is extremely heterogeneous. Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of nonsyndromic HI linked to the loci DFNA36 and DFNB7/B11, respectively. TMC1 is 1 member of a family of 8 genes encoding transmembrane proteins. In the mouse, MmTmc1 and MmTmc2 are both members of Tmc subfamily A and are highly and almost exclusively expressed in the cochlea. The restricted expression of Tmc2 in the cochlea and its close phylogenetic relationship to Tmc1 makes it a candidate gene for nonsyndromic HI. We analyzed 3 microsatellite markers linked to the TMC1 and TMC2 genes in 85 Tunisian families with autosomal recessive nonsyndromic HI and without mutations in the protein-coding region of the GJB2 gene. Autozygosity by descent analysis of 2 markers bordering the TMC2 gene allowed us to rule out its association with deafness within these families. However, 5 families were found to segregate deafness with 3 different alleles of marker D9S1837, located within the first intron of the TMC1 gene. By DNA sequencing of coding exons of TMC1 in affected individuals, we identified 3 homozygous mutations, c.100C-->T (p.R34X), c.1165C-->T (p.R389X) and the novel mutation c.1764G-->A (p.W588X). We additionally tested 60 unrelated deaf Tunisian individuals for the c.100C-->T mutation. We detected this mutation in a homozygous state in 2 cases. This study confirms that mutations in the TMC1 gene may be a common cause for autosomal recessive nonsyndromic HI.     

T2 laryngeal carcinoma with impaired mobility: subtypes with therapeutic implications

The aim of this study was to evaluate the outcome in the treatment of T2 laryngeal carcinoma with impaired laryngeal mobility, comparing surgical management to radiotherapy in terms of local control and survival. The files of 66 patients treated between 1988 and 1994 were retrospectively studied for tumor location, treatment and outcome. Forty-two patients were treated surgically and 24 by radiotherapy. Follow-up averaged 8.5 years. Local recurrence occurred in 12.5% of the cases treated by conservation laryngeal surgery and in 21% of the cases by radiotherapy. Ultimate laryngeal preservation was achieved in 90.9% of the cases initially treated by partial laryngectomy and in 87.5% of the cases treated by radiotherapy. Five-year actuarial survival rates were 90% and 28%, respectively. A higher rate of metastases and second primaries occurred in the group treated by radiotherapy. T2 laryngeal carcinoma amenable to partial laryngectomy had a higher local control rate than the cases not amenable to conservation surgery and treated by radiotherapy. Tumors differed in the two treatment groups in location and extensions, despite the fact that all were T2 tumors. We emphasize the limits of retrospective studies. Only prospective randomized studies will determine the true results of surgery versus radiotherapy for a homogeneous subset of T2 laryngeal tumors. Received: 17 May 2001 / Accepted: 21 August 2001     

Multidrug resistance in Klebsiella pneumoniae: multicenter study

The extensive use of broad spectrum antibiotics, especially the third generation cephalosporins (C3G), was followed by the emergence of newer plasmid mediated betalactamases called extended spectrum betalactamases (ESBLs). To assess the impact of K. pneumoniae resistant to 3GC in Tunisia, this study was conducted in 3 teaching hospitals. A total of 1110 strains of K pneumoniae was collected. The antibiotics susceptibilities were tested by diffusion method using Mueller-Hinton agar. The quality control was regularly performed. I ESBLs producing solates were detected using the double-disc synergy test. Data analysis was done using the Whonet 4 software. 23.6% K. pneumoniae isolates showed phenotype pattern of ESBLs producers. The double-disc synergy test was positive in 75% of the cases. These isolates were recovered from hospitalized patients in different wards but mainly from pediatrics (23.6%), medicine (23.2%), surgery (22.9%), intensive care units (11%) and neonatology (11%). 54% were isolated from urines, 22% from blood cultures. These isolates remained susceptible to imipenem (100%) and most of them to cefoxitin (96.4%) but all had associated resistance to aminoglycosides, quinolones and trimethoprim-sulfamethoxazole. The prevalence of multidrug resistant K. pneumoniae is high. This resistance can be minimized by the implementation of infection control measures including handwashing and isolation procedures.     

Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogenous disorder reported in Quebec caused by mutations in the SACS gene (chromosome 13q12). Recently, we identified a Tunisian kindred demonstrating linkage to the ARSACS locus. OBJECTIVE: To report clinical, neurophysiological, and nerve biopsy findings in patients with autosomal recessive cerebellar ataxia related to the SACS gene in Tunisia. PATIENTS AND METHODS: Genetic linkage analysis of patients with early-onset autosomal recessive cerebellar ataxia allowed the identification of 4 families from which 18 patients demonstrated linkage to the ARSACS locus. The patients were evaluated according to the International Cooperative Ataxia Rating Scale. Peripheral nerve conduction, sensory evoked potentials, and nerve biopsy were performed in most patients. RESULTS: The mean age at onset was 4.5 years. The clinical phenotype was stereotyped and associated with a progressive cerebellar syndrome, a pyramidal syndrome with brisk knee reflexes, and Babinski sign and absent ankle reflexes. The course of the disease varied among patients. Sensory evoked potentials showed severe posterior column involvement. Peripheral nerve investigations demonstrated axonal and demyelinating neuropathy. Four mutations, 2 missense and 2 nonsense, were found. CONCLUSION: In Tunisia, autosomal recessive cerebellar ataxia related to the SACS gene demonstrated a homogenous phenotype and heterogeneous allelic mutations.     

Bcl-2 and immunoglobulin gene rearrangements in patients with malaria related chronic splenomegaly

Two cases of malaria related chronic splenomegaly, one with tropical splenic lymphoma with villous lymphocytes (TSLVL) and the other with hyperreactive malarial splenomegaly (HMS) were analyzed by cytology, histology, karyotyping, immunophenotyping, and polymerase chain reaction (PCR) for detection of bcl-2/JH and FR3/JH rearrangements on blood and bone marrow samples, at diagnosis and 12 months after malarial prophylaxis. The reported data suggest that the detection of FR3/JH rearrangement might contribute to the diagnosis of TSLVL in patients with malaria related chronic splenomegaly, for whom bcl-2/JH rearrangement may be a common molecular event.     

Abdomino-pelvic actinomycosis. Report of 2 cases

Actinomycosis is a chronic, granulomatous, suppurative and fistulasing infection related to a gram-positive bacteria (actinomyces israeli). Cervico-facial actinomycosis is the most common localization. The prevalence of abdomino-pelvic actinomycosis is increasing mainly with the increase of the use of intrauterin device. Its clinical presentation is variable and may mimic cancer or tuberculosis. The diagnosis of abdomino-pelvic actinomycosis is hard and most of the cases are detected during surgical exploration. We report two cases of abdomino-pelvic actinomycosis; in the first case, the disease was extended to the caecum and the abdominal wall. The skin biopsies made the diagnosis of actinomycosis, avoiding surgery. In the second case, the diagnosis of actinomycosis is made post operatively because of high suspicion of pelvic cancer. Through these two observations, we review pathogenesis of the disease, its clinical aspects and its diagnostic and therapeutic means.     

Structural basis for the restoration of TCR recognition of an MHC allelic variant by peptide secondary anchor substitution

Major histocompatibility complex (MHC) class I variants H-2K(b) and H-2K(bm8) differ primarily in the B pocket of the peptide-binding groove, which serves to sequester the P2 secondary anchor residue. This polymorphism determines resistance to lethal herpes simplex virus (HSV-1) infection by modulating T cell responses to the immunodominant glycoprotein B(498-505) epitope, HSV8. We studied the molecular basis of these effects and confirmed that T cell receptors raised against K(b)-HSV8 cannot recognize H-2K(bm8)-HSV8. However, substitution of Ser(P2) to Glu(P2) (peptide H2E) reversed T cell receptor (TCR) recognition; H-2K(bm8)-H2E was recognized whereas H-2K(b)-H2E was not. Insight into the structural basis of this discrimination was obtained by determining the crystal structures of all four MHC class I molecules in complex with bound peptide (pMHCs). Surprisingly, we find no concerted pMHC surface differences that can explain the differential TCR recognition. However, a correlation is apparent between the recognition data and the underlying peptide-binding groove chemistry of the B pocket, revealing that secondary anchor residues can profoundly affect TCR engagement through mechanisms distinct from the alteration of the resting state conformation of the pMHC surface.