Susceptibility to reinfection with SARS-CoV-2 virus relative to existing antibody concentrations and T cell response.

OBJECTIVES: We investigated the reinfection rate of vaccinated or convalescent immunized SARS-CoV-2 in 952 expatriate workers with SARS-CoV-2 serological antibody (Ab) patterns and surrogate T cell memory at recruitment and follow-up. METHODS: Trimeric spike, nucleocapsid, and neutralizing Abs were measured, along with a T cell stimulation assay, targeting SARS-CoV-2 memory in clusters of differentiation (CD) 4+ and CD8+ T cells. The subjects were then followed up for reinfection for up to 6 months. RESULTS: The seroprevalence positivity at enrollment was greater than 99%. The T cell reactivity in this population was 38.2%. Of the 149 (15.9%) participants that were reinfected during the follow-up period (74.3%) had nonreactive T cells at enrollment. Those who had greater than 100 binding Ab units/ml increase from the median concentration of antispike immunoglobulin G Abs had a 6% reduction in the risk of infection. Those who were below the median concentration had a 78% greater risk of infection. CONCLUSION: Significant immune protection from reinfection was observed in those who retained T cell activation memory. Additional protection was observed when the antispike was greater than the median value.

Primary Sjögren's Syndrome Presenting as Recurrent Ischemic Strokes.

Primary Sjogren's Syndrome (PSS) is an autoimmune exocrinopathy, with protean manifestations affecting multiple organ systems. Neurological manifestations are documented in about 20% of PSS cohorts in literature, with peripheral manifestations being commoner. Central nervous system manifestations of PSS (CNS-SS) encompass ischemic strokes, demyelinating lesions, aseptic meningitis, encephalitis, cerebellar ataxia, cognitive impairment and movement disorders. Ischemic stroke as presenting manifestation of PSS is extremely rare. We hereby describe a 50-year-old male, who presented for evaluation of 2 episodes of discrete focal neurological deficits over a duration of 6 weeks, with neuro-imaging findings revealing evidence of acute-subacute bihemispheric infarcts. Further evaluation revealed evidence of strongly positive anti phospholipid antibodies (aPL), indirect immunofluorescence antinuclear antibody (IIF-ANA), anti Sjögren's syndrome-A (SS-A/Ro) and anti-Ribonuclear protein (RNP) antibodies, with histopathological evidence of periductal and periacinar lymphocytic infiltration as well as acinar atrophy and interstitial fibrosis of minor salivary glands on lip biopsy, consistent with a diagnosis of Sjögren's syndrome, constituting a diagnosis of Antiphospholipid syndrome (APS) associated with PSS.

Evaluation of post-vaccination immunoglobulin G antibodies and T-cell immune response after inoculation with different types and doses of SARS-CoV-2 vaccines: A retrospective cohort study.

Introduction: The induction and speed of production of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune biomarkers may vary by type and number of inoculated vaccine doses. This study aimed to explore variations in SARS-CoV-2 anti-spike (anti-S), anti-nucleocapsid (anti-N), and neutralizing immunoglobulin G (IgG) antibodies, and T-cell response by type and number of SARS-CoV-2 vaccine doses received. Methods: In a naturally exposed and SARS-CoV-2-vaccinated population, we quantified the anti-S, anti-N, and neutralizing IgG antibody concentration and assessed T-cell response. Data on socio-demographics, medical history, and history of SARS-CoV-2 infection and vaccination were collected. Furthermore, nasal swabs were collected to test for SARS-CoV-2 infection. Confounder-adjusted association between having equal or more than a median concentration of the three IgG antibodies and T-cell response by number and type of the inoculated vaccines was quantified. Results: We surveyed 952 male participants with a mean age of 35.5 years ± 8.4 standard deviations. Of them, 52.6% were overweight/obese, and 11.7% had at least one chronic comorbidity. Of the participants, 1.4, 0.9, 20.2, 75.2, and 2.2% were never vaccinated, primed with only one dose, primed with two doses, boosted with only one dose, and boosted with two doses, respectively. All were polymerase chain reaction-negative to SARS-CoV-2. BBIBP-CorV (Sinopharm) was the most commonly used vaccine (92.1%), followed by rAd26-S + rAd5-S (Sputnik V Gam-COVID-Vac) (1.5%) and BNT162b2 (Pfizer-BioNTech) (0.3%). Seropositivity to anti-S, anti-N, and neutralizing IgG antibodies was detected in 99.7, 99.9, and 99.3% of the study participants, respectively. The T-cell response was detected in 38.2% of 925 study participants. Every additional vaccine dose was significantly associated with increased odds of having ≥median concentration of anti-S [adjusted odds ratio (aOR), 1.34; 95% confidence interval (CI): 1.02-1.76], anti-N (aOR, 1.35; 95% CI: 1.03-1.75), neutralizing IgG antibodies (aOR, 1.29; 95% CI: 1.00-1.66), and a T-cell response (aOR, 1.48; 95% CI: 1.12-1.95). Compared with boosting with only one dose, boosting with two doses was significantly associated with increased odds of having ≥median concentration of anti-S (aOR, 13.8; 95% CI: 1.78-106.5), neutralizing IgG antibodies (aOR, 13.2; 95% CI: 1.71-101.9), and T-cell response (aOR, 7.22; 95% CI: 1.99-26.5) although not with anti-N (aOR, 0.41; 95% CI: 0.16-1.08). Compared with priming and subsequently boosting with BBIBP-CorV, all participants who were primed with BBIBP-CorV and subsequently boosted with BNT162b2 had ≥median concentration of anti-S and neutralizing IgG antibodies and 14.6-time increased odds of having a T-cell response (aOR, 14.63; 95% CI: 1.78-120.5). Compared with priming with two doses, boosting with the third dose was not associated, whereas boosting with two doses was significantly associated with having ≥median concentration of anti-S (aOR, 14.20; 95% CI: 1.85-109.4), neutralizing IgG (aOR, 13.6; 95% CI: 1.77-104.3), and T-cell response (aOR, 7.62; 95% CI: 2.09-27.8). Conclusion: Achieving and maintaining a high blood concentration of protective immune biomarkers that predict vaccine effectiveness is very critical to limit transmission and contain outbreaks. In this study, boosting with only one dose or with only BBIBP-CorV after priming with BBIBP-CorV was insufficient, whereas boosting with two doses, particularly boosting with the mRNA-based vaccine, was shown to be associated with having a high concentration of anti-S, anti-N, and neutralizing IgG antibodies and producing an efficient T-cell response.

Evaluation of three commercial SARS-CoV-2 serology assays in a tertiary care hospital in the United Arab Emirates.

BACKGROUND: Serology assays have the potential to support RT-PCR in the diagnosis of SARS-CoV-2 infection. We studied three commercially available immunoassays for their diagnostic accuracy from blood specimens collected from 93 patients. METHODS: Blood samples from patients with confirmed COVID-19 infection were analysed using three different Immunoassays (Roche total antibody assay, Abbott IgG assay and Euroimmun IgG assay). Sensitivity, specificity, precision and time of seroconversion were evaluated. RESULTS: The sensitivity of Roche, Abbott and Euroimmun assays was 38.7%, 35.5% and 25.0% respectively for specimens collected <10 days and 84.4%, 84.4% and 70.0% respectively for specimens collected ≥10 days after the first positive RT-PCR. The specificity of all the three assays in this study was 100%. The timing of seroconversion occurred at day 1, 7 or 14. CONCLUSIONS: The assays evaluated in this study have different sensitivities for detecting antibodies in SARS-CoV-2 infection. Sensitivity for detecting antibodies for all three assays was higher for specimens collected ≥10 days after first positive PCR compared with specimens collected <10 days. Time of seroconversion is variable and assay-dependent.

Seroprevalence of COVID-19 infection in the Emirate of Abu Dhabi, United Arab Emirates: a population-based cross-sectional study.

BACKGROUND: The United Arab Emirates (UAE) was the first country in the Middle East to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serosurveys are essential to understanding the extent of virus transmission. This cross-sectional study aims to assess the seroprevalence of SARS-CoV-2 infection in the Emirate of Abu Dhabi. METHODS: Between 19 July and 14 August 2020, 4487 households were selected using a random sample stratified by region and citizenship of the head of household (UAE citizen or non-citizen). A cluster sample of 40 labour camps was selected. Data on socio-demographic characteristics, risk factors and symptoms compatible with coronavirus disease 2019 (COVID-19) were collected. Each participant was first tested by Roche Elecsys® Anti-SARS-CoV-2 assay, followed, when reactive, by the LIAISON® SARS-CoV-2 S1/S2 IgG assay. RESULTS: Among 8831 individuals from households, seroprevalence was 10·4% [95% confidence intervals (CIs) 9·5-11·4], with higher seroprevalence in Abu Dhabi and Al Ain regions compared with those in Al Dhafra. In households, we found no sex difference and UAE citizens had lower seroprevalence compared with those of other nationalities. Among 4855 workers residing in labour camps, seroprevalence was 68·6% (95% CI 61·7-74·7), with higher seroprevalence among workers from Southeast Asia. In households, individuals with higher body mass indexes demonstrated higher seroprevalences than individuals with normal weight. Anosmia and ageusia were strongly associated with seropositivity. CONCLUSIONS: The majority of household populations in the Emirate of Abu Dhabi remained unexposed to SARS-CoV-2. In labour camps, SARS-CoV-2 transmission was high. Effective public health measures should be maintained.

Saliva as an Alternative Specimen for Molecular COVID-19 Testing in Community Settings and Population-Based Screening.

PURPOSE: With the easing of restriction measures, repeated community-based sampling for tracking new COVID-19 infections is anticipated for the next 6 to 12 months. A non-invasive, self-collected specimen like saliva will be useful for such public health surveillance. Investigations on the use of saliva for SARS-CoV-2 RT-PCR have largely been among COVID-19 in-pa\tients and symptomatic ambulatory patients with limited work in a community-based screening setting. This study was carried out to address this paucity of data and reported discrepancies in diagnostic accuracy for saliva samples. PATIENTS AND METHODS: From 29th June to 14th July 2020, adults presenting for COVID-19 testing at a community-based screening facility in Dubai, United Arab Emirates were recruited. Clinical data, nasopharyngeal swab in universal transport media and drooling saliva in sterile containers were obtained. Reverse transcriptase PCR amplification of SARS-CoV-2 RdRp and N genes was used to detect the presence of the SARS-CoV-2 virus. RESULTS: Of the 401 participants, 35 (8.7%) had viral detection in at least one specimen type and the majority (n=20/35; 57.1%) were asymptomatic. Both swab and saliva were positive in 19 (54.2%) patients, while 7 (20.0%) patients had swab positive/saliva negative results. There were 9 (25.7%) patients with saliva positive/swab negative result and this included 5 asymptomatic COVID-19 patients undergoing repeat screening. Using the swab as the reference gold standard, the sensitivity and specificity of saliva were 73.1% (95% CI 52.2-88.4%) and 97.6% (95% CI 95.5-98.9%) while the positive and negative predictive values were 67.9% (95% CI 51.5-80.8%) and 98.1% (95% CI 96.5-99.0%), respectively. CONCLUSION: The findings suggest good diagnostic accuracy for saliva and feasibility of utilization of specimen without transport media for SARS-CoV-2 RT-PCR. Saliva represents a potential specimen of choice in community settings and population-based screening.

Subcutaneous efalizumab is not effective in the treatment of alopecia areata.

BACKGROUND: Alopecia areata (AA) is a T-cell-mediated autoimmune disease. Efalizumab is a T-cell-targeted therapy approved for the treatment of psoriasis. OBJECTIVE: To assess the efficacy and safety of efalizumab in the treatment of moderate-to-severe AA. METHODS: Sixty-two patients were enrolled into this phase II, placebo-controlled trial. The trial consisted of three 12-week periods-a double-blind treatment period, an open-label efalizumab treatment period, and a safety follow-up. RESULTS: There were no statistical differences between treatment groups in percent hair regrowth, quality-of-life measures, or changes in biologic markers of disease severity after 12 or 24 weeks. In both groups, there was an approximately 8% response rate for hair regrowth (at 12 weeks). Efalizumab was well tolerated. LIMITATIONS: Numbers were too small for certain analyses. CONCLUSION: A 3- to 6-month trial of efalizumab was not effective in promoting hair regrowth in this small cohort of patients with moderate-to-severe AA.

Undifferentiated carcinoma of the endometrium.

Undifferentiated carcinoma arising in the endometrium is considered a rare neoplasm with only a few studies published thus far. This limited number of studies is most likely a reflection of the underrecognition of this tumor because of a lack of diagnostic criteria to separate it from endometrial endometrioid adenocarcinoma, FIGO grade 3. In this study, we present the clinicopathologic features of 16 cases of endometrial undifferentiated carcinoma. In addition, we review the clinicopathologic features of 33 cases of endometrial endometrioid adenocarcinoma, FIGO grade 3, and compare them with the undifferentiated cases. The age of the 16 patients with undifferentiated carcinoma of the endometrium ranged from 40 and 69 years (mean, 59 years). Stage was known in 13 patients. Six (46%) patients presented with early stage disease (4 stage I and 2 stage II). Seven (54%) patients presented with advanced stage disease (2 stage III and 5 stage IV). Staging information was not available for 3 patients. Undifferentiated carcinoma was characterized by a proliferation of medium-sized, monotonous, epithelial cells growing in solid sheets with no specific pattern. Glands were not identified. Keratin immunostaining was focally positive in 11 of 12 cases, and EMA was focally positive in all 12 cases. The age of the 33 patients with endometrial endometrioid carcinoma, FIGO grade 3, ranged from 40 to 90 years (mean, 68 years). Twenty-three (70%) patients presented with early stage disease (21 stage I and 2 stage II), and 10 (30%) patients presented with advanced stage disease (8 stage III and 2 stage IV). Focal glandular differentiation was seen in all cases. The solid component was different from the one seen in the undifferentiated carcinomas because well demarcated trabeculae, cords, or groups of cells were identified in all cases. The tumor cells in the solid areas resembled the cells in the glandular component of the tumor. Immunoperoxidase studies for keratin and EMA were positive in 23 of 23 cases. Twelve of the 16 (75%) patients with undifferentiated carcinoma died of disease; 10 (62.5%) of them within 5 years after diagnosis. In contrast, 13 of 33 (39.4%) patients with endometrial endometrioid carcinoma, FIGO grade 3, died of disease. Twelve (36.4%) died within 5 years after diagnosis. In summary, undifferentiated carcinoma of the endometrium appears to be more aggressive than endometrial endometrioid adenocarcinoma, FIGO grade 3. Its proper recognition is important for prognosis and potentially for therapy.

Liver transplant-associated graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) is an important, underdiagnosed cause of mortality associated with liver transplantation. We identified 12 cases of GVHD among 1,082 liver transplantations performed in patients at our institution between 1991 and 1998. Patients typically developed fever, skin rash, diarrhea, or pancytopenia within 2 to 6 weeks after their transplant. Treatment generally involved increased immune suppression and hematopoietic cytokines (granulocyte colony stimulating factor, granulocyte monocyte colony stimulating factor); however, all but one patient died, most often from sepsis. Early in its course, GVHD was difficult to distinguish from cytomegalovirus disease or drug reactions. The diagnosis was confirmed by demonstration of substantial donor lymphoid chimerism. METHODS: To identify risk factors for severe GVHD, a retrospective analysis was performed comparing index cases with the rest of the cases in our institutional experience. RESULTS: Closely matched human leukocyte antigen recipients, those older than 65 years, and recipients with donors more than 40 years younger were at higher risk for GVHD. One case occurred in a patient with a congenital immunodeficiency. CONCLUSIONS: Liver transplant-associated GVHD is a progressive and fatal disease. Future approaches should focus on prevention and might include avoidance of closely matched human leukocyte antigen donors, treatment of the donor to reduce the number of lymphocytes, or reduction of immunosuppression in the early posttransplant period.

Spindle basaloid squamous carcinoma of the upper aerodigestive tract: immunohistochemical and clinicopathological study of three cases.

We describe the clinicopathological and immunohistochemical features of three spindle (sarcomatoid) basaloid squamous carcinomas in three men aged 73, 69, and 59 years with a history of tobacco and alcohol abuse. Two tumors were located in the hypopharynx and one was located in the nasal cavity. The three tumors have a pedunculated polypoid appearance. Histologically, they were composed of conventional basaloid squamous carcinomas with extensive malignant spindle cell proliferation, comprising more than 50% of the tumor. The sarcomatoid component demonstrated immunoreactivity with one or more epithelial markers. One case in addition expressed CD99 and Bcl-2 and was originally diagnosed as monophasic synovial sarcoma; however, a subsequent biopsy disclosed basaloid squamous cell carcinoma with sarcomatoid stroma. Two patients were treated with surgery and radiation whereas one refused therapy. The patients were alive 14 (case patient 1), 10 (case patient 2), and 8 (case patient 3) months after diagnosis. In the absence of evidence from immunohistochemical or electron microscopy studies, a polypoid malignant spindle cell tumor of a mucosal surface of the upper aerodigestive tract should be considered a sarcomatoid carcinoma until proven otherwise. The type of epithelial component would determine the subtype of sarcomatoid carcinoma.

Radiofrequency thermal ablation of hepatocellular carcinoma before liver transplantation--a clinical and histological examination.

BACKGROUND: Radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) is an optional treatment for patients awaiting liver transplantation (LTX). The study evaluates the efficacy of RFA in the explanted liver and its effect on patient outcome. MATERIAL AND METHOD: Forty-seven patients underwent RFA and were listed for transplant between January 1998 and May 2003. The patients were divided into two groups: transplanted and non-transplanted. Both groups were evaluated in terms of tumor characteristics, recurrence, mortality rate, and time on the waiting list. The ablation sites in the explanted livers were examined for percentage of necrosis by Hematoxylin & Eosin (H&E) stain and by TUNEL stain. RESULTS: Transplantation was carried out in 35 patients (74.5%). Ten patients (21.3%) died before transplant or were removed from the wait list, while two patients (4.2%) are still listed. Mortality and tumor-related mortality were significantly higher in the non-transplanted group. The time spent on the waiting list was longer in the non-transplanted patients (350 vs. 186 d average, p = 0.0345). Thirty-eight ablation sites were examined in the explanted livers. The percentage of tumor necrosis by TUNEL staining was 19.6% higher than that reported by H&E staining. After TUNEL staining, 28 sites (73.7%) had more than 90% necrosis, eight sites (21.0%) had 50-90%, and two sites (5.3%) had less than 50% necrosis. CONCLUSIONS: RFA and LTX can be used successfully in HCC patients, and in most cases, tumor necrosis can be achieved with ultrasound-guided RFA. H&E stain tends to under-represent the amount of tumor necrosis on the ablation sites. Survival of RFA patients after LTX is excellent.

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node.

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size < 2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34-83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micro-metastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.