COVID-19 and Breast Cancer: Analysis of Surgical Management of a Large Referral Center during the 2020-2021 Pandemic Period.

BACKGROUND: Coronavirus disease-19 (COVID-19) has spread worldwide since December 2019 and was officially declared a pandemic in March 2020. Due to the rapid transmission and the high fatality rate, drastic emergency restrictions were issued, with a negative impact on routine clinical activities. In particular, in Italy, many authors have reported a reduction in the number of breast cancer diagnoses and critical problems in the management of patients who accessed the breast units during the dramatic first months of the pandemic. Our study aims to analyze the global impact of COVID-19 in the two years of the pandemic (2020-2021) on the surgical management of breast cancer by comparing them with the previous two years. METHODS: In our retrospective study, we analyzed all cases of breast cancer diagnosed and surgically treated at the breast unit of "Città della Salute e della Scienza" in Turin, Italy, making a comparison between the 2018-2019 pre-pandemic period and the 2020-2021 pandemic period. RESULTS: We included in our analysis 1331 breast cancer cases surgically treated from January 2018 to December 2021. A total of 726 patients were treated in the pre-pandemic years and 605 in the pandemic period (-121 cases, 9%). No significant differences were observed regarding diagnosis (screening vs. no screening) and timing between radiological diagnosis and surgery for both in situ and invasive tumors. There were no variations in the breast surgical approach (mastectomy vs. conservative surgery), while a reduction in axillary dissection compared to the sentinel lymph node in the pandemic period was observed (p-value < 0.001). Regarding the biological characteristics of breast cancers, we observed a greater number of grades 2-3 (p-value = 0.007), pT stage 3-4 breast cancer surgically treated without previous neoadjuvant chemotherapy (p-value = 0.03), and a reduction in luminal B tumors (p-value = 0.007). CONCLUSIONS: Overall, we report a limited reduction in surgical activity for breast cancer treatment considering the entire pandemic period (2020-2021). These results suggest a prompt resumption of surgical activity similar to the pre-pandemic period.

The humoral and cellular response to mRNA SARS-CoV-2 vaccine is influenced by HLA polymorphisms.

Host genetic variability contributes to susceptibility to SARS-CoV-2 infection and COVID-19 evolution and the role of HLA system has not clearly emerged, suggesting the involvement of other factors. Studying response to vaccination with Spyke protein mRNA represents an ideal model to highlight whether the humoral or cellular responses are influenced by HLA. Four hundred and sixteen workers, vaccinated with Comirnaty beginning 2021, were selected within the Azienda Ospedaliera Universitaria "Città della Salute e della Scienza di Torino." The humoral response was determined with the LIAISON® kit, while the analysis of the cellular response was performed with the Quantiferon SARS-CoV-2 assay, for the S1 (receptor-binding domain; Ag1) and S1 and S2 (Ag2) subunits of the Spyke protein. Six HLA loci were typed by next-generation sequencing. Associations between HLA and vaccine response were performed with univariate and multivariate analyses. An association was found between A*03:01, B*40:02 and DPB1*06:01 and high antibody concentration and between A*24:02, B*08:01 and C*07:01 and low humoral responses. The haplotype HLA-A*01:01 ~ B1*08:01 ~ C*07:01 ~ DRB1*03:01 ~ DQB1*02:01 conferred an increased risk of low humoral response. Considering cellular responses, 50% of the vaccinated subjects responded against Ag1 and 59% against Ag2. Carriers of DRB1*15:01 displayed a higher cellular response both to Ag1 and Ag2 compared to the rest of the cohort. Similarly, DRB1*13:02 predisposed to a robust cellular response to Ag1 and Ag2, while DRB1*11:04 showed an opposite trend. Cellular and humoral responses to Comirnaty are influenced by HLA. Humoral response is mainly associated to class I alleles, with A*03:01, previously associated to protection against severe COVID-19, and response to vaccination, standing out. Cellular response predominantly involves class II alleles, with DRB1*15:01 and DPB1*13:01 prevailing. Affinity analysis for Spyke peptides is generally in line with the association results.

Cellular Immune Response to BNT162b2 mRNA COVID-19 Vaccine in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital.

We describe the results of a T-cell immunity evaluation performed after a median elapsed time of 7 months from second-dose BNT162b2 vaccine administration, in a representative sample of 419 subjects from a large cohort of hospital workers. Overall, the Quantiferon SARS-CoV-2 assay detected a responsive pattern in 49.9%, 59.2% and 68.3% of subjects to three different antigenic stimuli from SARS-CoV-2, respectively, with 72.3% of positivity to at least one antigenic stimulus. Potential predictors of cellular response were explored by multivariable analyses; factors associated with positivity to cellular response (to Ag1 antigenic stimulus) were a previous SARS-CoV-2 infection (OR = 4.24, 95% CI 2.34-7.67, p < 0.001), increasing age (per year: OR = 1.03 95% CI 1.01-1.06, p = 0.019 and currently smoking (compared to never smoking) (OR = 1.93, 95% CI 1.11-3.36, p = 0.010). Increasing time interval between vaccine administration and T-cell test was associated with decreasing cellular response (per week of time: OR = 0.94, 95% CI 0.91-0.98, p = 0.003). A blood group A/AB/B (compared to group O) was associated with higher levels of cellular immunity, especially when measured as Ag2 antigenic stimulus. Levels of cellular immunity tended to be lower among subjects that self-reported an autoimmune disorder or an immunodeficiency and among males. Further studies to assess the protective significance of different serological and cellular responses to the vaccine toward the risk of reinfection and the severity of COVID-19 are needed to better understand these findings.

Factors Influencing Level and Persistence of Anti SARS-CoV-2 IgG after BNT162b2 Vaccine: Evidence from a Large Cohort of Healthcare Workers.

We aimed at evaluating quantitative IgG response to BNT162b2 COVID-19 vaccine among health care workers (HCW), and exploring the role of demographic, clinical, and occupational factors as predictors of IgG levels. On May 2021, among 6687 HCW at the largest tertiary care University-Hospital of Northwestern Italy, at a median of 15 weeks (Interquartile range-IQR 13.6-16.0) after second-dose, serological response was present in 99.8%. Seropositivity was >97% in all the subgroups, except those self-reporting immunodeficiency (94.9%). Overall, the median serological IgG value was 990 BAU/mL (IQR 551-1870), with most of subjects with previous SARS-CoV-2 infection or with shorter time lapse (2-8 weeks) between vaccination and serology with values in the highest quintile (>2080). At multivariable analysis, significant predictors of lower values were increasing age, male, current smoking, immunodeficiency, recent occupational contacts, and increasing time lapse from vaccination; conversely, previous infection and recent household contacts were significantly associated with higher IgG levels. Subjects with previous infection kept a very high level (around 2000 BAU/mL) up to 120 days. These results, besides supporting a high serological response up to 4-5 months, suggest predictive factors of faster decay of IgG levels that could be useful in tailoring vaccination strategies.

Spectrum of Kidney Injury Following COVID-19 Disease: Renal Biopsy Findings in a Single Italian Pathology Service.

The onset of coronavirus disease (COVID-19) as a pandemic infection, has led to increasing insights on its pathophysiology and clinical features being revealed, such as a noticeable kidney involvement. In this study, we describe the histopathological, immunofluorescence, and ultrastructural features of biopsy-proven kidney injury observed in a series of SARS-CoV-2 positive cases in our institution from April 2020 to November 2021. We retrieved and retrospectively reviewed nine cases (two pediatric and seven adults) that experienced nephrotic syndrome (six cases), acute kidney injury (two cases), and a clinically silent microhematuria and leukocyturia. Kidney biopsies were investigated by means of light microscopy, direct immunofluorescence, and electron microscopy. The primary diagnoses were minimal change disease (four cases), acute tubular necrosis (two cases), collapsing glomerulopathy (two cases), and C3 glomerulopathy (one case). None of the cases showed viral or viral-like particles on ultrastructural analysis. Novel and specific histologic features on kidney biopsy related to SARS-CoV-2 infection have been gradually disclosed and reported, harboring relevant clinical and therapeutic implications. Recognizing and properly diagnosing renal involvement in patients experiencing COVID-19 could be challenging (due to the lack of direct proof of viral infection, e.g., viral particles) and requires a proper integration of clinical and pathological data.

The Adverse Impact of the COVID-19 Pandemic on Abdominal Emergencies: A Retrospective Clinico-Pathological Analysis.

The COVID-19 pandemic has caused a worldwide significant drop of admissions to the emergency department (ED). The aim of the study was to retrospectively investigate the pandemic impact on ED admissions, management, and severity of three abdominal emergencies (appendicitis, diverticulitis, and cholecystitis) during the COVID-19 pandemic using 2017-2019 data as a control. The difference in clinical and pathological disease severity was the primary outcome measure while differences in (i) ED admissions, (ii) triage urgency codes, and (iii) surgical rates were the second ones. Overall, ED admissions for the selected conditions decreased by 34.9% during the pandemic (control: 996, 2020: 648) and lower triage urgency codes were assigned for cholecystitis (control: 170/556, 2020: 66/356, p < 0.001) and appendicitis (control: 40/178, 2020: 21/157, p = 0.031). Less surgical procedures were performed in 2020 (control: 447, 2020: 309), but the surgical rate was stable (47.7% in 2020 vs. 44.8% in 2017-2019). Considering the clinical and pathological assessments, a higher percentage of severe cases was observed in the four pandemic peak months of 2020 (control: 98/192, 2020: 87/109; p < 0.001 and control: 105/192, 2020: 87/109; p < 0.001). For the first time in this study, pathological findings objectively demonstrated an increased disease severity of the analyzed conditions during the early COVID-19 pandemic.

Prevalence, Persistence, and Factors Associated with SARS-CoV-2 IgG Seropositivity in a Large Cohort of Healthcare Workers in a Tertiary Care University Hospital in Northern Italy.

This observational study evaluated SARS-CoV-2 IgG seroprevalence and related clinical, demographic, and occupational factors among workers at the largest tertiary care University-Hospital of Northwestern Italy and the University of Turin after the first pandemic wave of March-April 2020. Overall, about 10,000 individuals were tested; seropositive subjects were retested after 5 months to evaluate antibodies waning. Among 8769 hospital workers, seroprevalence was 7.6%, without significant differences related to job profile; among 1185 University workers, 3.3%. Self-reporting of COVID-19 suspected symptoms was significantly associated with positivity (Odds Ratio (OR) 2.07, 95%CI: 1.76-2.44), although 27% of seropositive subjects reported no previous symptom. At multivariable analysis, contacts at work resulted in an increased risk of 69%, or 24% for working in a COVID ward; contacts in the household evidenced the highest risk, up to more than five-fold (OR 5.31, 95%CI: 4.12-6.85). Compared to never smokers, being active smokers was inversely associated with seroprevalence (OR 0.60, 95%CI: 0.48-0.76). After 5 months, 85% of previously positive subjects still tested positive. The frequency of SARS-COV-2 infection among Health Care Workers was comparable with that observed in surveys performed in Northern Italy and Europe after the first pandemic wave. This study confirms that infection frequently occurred as asymptomatic and underlines the importance of household exposure, seroprevalence (OR 0.60, 95%CI: 0.48-0.76).

Placenta histopathology in SARS-CoV-2 infection: analysis of a consecutive series and comparison with control cohorts.

Infection by SARS-CoV-2 has been shown to involve a wide range of organs and tissues, leading to a kaleidoscope of clinical conditions. Within this spectrum, an involvement of the fetal-maternal unit could be expected, but, so far, the histopathological evaluation of placentas delivered by women with SARS-CoV-2 infection did not show distinct hallmarks. A consecutive series of 11 placentas, delivered by 10 women with COVID-19 admitted to our Obstetrics and Gynecology clinic have been investigated and compared to a control cohort of 58 pre-COVID-19 placentas and 28 placentas delivered by women who had a previous cesarean section. Four out of eleven placentas showed changes consistent with chronic villitis/villitis of unknown etiology (VUE), while in one case, chronic histiocytic intervillositis was diagnosed. Thrombo-hemorrhagic alterations were observed in a subset of cases. Compared to the control cohort, chronic villitis/VUE (p < 0.001), chronic deciduitis (p = 0.023), microvascular thrombosis (p = 0.003), presence of infarction areas (p = 0.047) and of accelerated villous maturation (p = 0.005) showed higher frequencies in placentas delivered by women with COVID-19. Chronic villitis/VUE (p = 0.003) and accelerated villous maturation (p = 0.019) remained statistically significant by restricting the analysis to placentas delivered after a previous cesarean section. The observed differences in terms of pathological findings could be consistent with SARS-CoV-2 pathogenesis, but just a subset of alterations remained statistically significant after adjusting for a previous cesarean section. A careful consideration of potential confounders is warranted in future studies exploring the relationship between COVID-19 and pregnancy.

Impact of COVID-19 lockdown measures on oncological surgical activity: Analysis of the surgical pathology caseload of a tertiary referral hospital in Northwestern Italy.

BACKGROUND AND OBJECTIVES: Italy was severely affected by the severe acute respiratory syndrome coronavirus 2 pandemic. Our Institution, Piedmont's largest tertiary referral center, was designated as a non-COVID-19 hospital and activities were reorganized to prioritize critical services like oncological care. The aim of this study was to investigate the efficacy in preserving the oncological surgical practice at our Institution during the most critical months of the COVID-19 epidemic by analyzing the surgical pathology activity. METHODS: The number of oncological surgical resections submitted to histopathological examination from 9th March 2020 to 8th May 2020 were collected as well staging/grading data and compared with the previous three pre-COVID-19 years (2017-2019). RESULTS: Overall, no decrease was observed for most tumor sites (5/9) while breast resections showed the largest drop (109 vs. 160; -31.9%), although a full recovery was already noticed during the second half of the period. Conversely, the selected control benchmarks showed a sharp decrease (-80.4%). Distribution of pathological TNM stages (or tumor grades for central nervous system tumors) showed no significant differences during the lockdown compared with previous years (p > .05). CONCLUSIONS: The present data suggest the possibility of preserving this cornerstone oncological activity during an evolving public health emergency thanks to a prompt workflow reorganization.