Mental health and the effects on methylation of stress-related genes in front-line versus other health care professionals during the second wave of COVID-19 pandemic: an Italian pilot study.

Healthcare workers experienced high degree of stress during COVID-19. Purpose of the present article is to compare mental health (depressive and Post-Traumatic-Stress-Disorders-PTSD-symptoms) and epigenetics aspects (degree of methylation of stress-related genes) in front-line healthcare professionals versus healthcare working in non-COVID-19 wards. Sixty-eight healthcare workers were included in the study: 39 were working in COVID-19 wards (cases) and 29 in non-COVID wards (controls). From all participants, demographic and clinical information were collected by an ad-hoc questionnaire. Depressive and PTSD symptoms were evaluated by the Patient Health Questionnaire-9 (PHQ-9) and the Impact of Event Scale-Revised (IES-R), respectively. Methylation analyses of 9 promoter/regulatory regions of genes known to be implicated in depression/PTSD (ADCYAP1, BDNF, CRHR1, DRD2, IGF2, LSD1/KDM1A, NR3C1, OXTR, SLC6A4) were performed on DNA from blood samples by the MassARRAY EpiTYPER platform, with MassCleave settings. Controls showed more frequent lifetime history of anxiety/depression with respect to cases (χ2 = 5.72, p = 0.03). On the contrary, cases versus controls presented higher PHQ-9 (t = 2.13, p = 0.04), PHQ-9 sleep item (t = 2.26, p = 0.03), IES-R total (t = 2.17, p = 0.03), IES-R intrusion (t = 2.46, p = 0.02), IES-R avoidance (t = 1.99, p = 0.05) mean total scores. Methylation levels at CRHR1, DRD2 and LSD1 genes was significantly higher in cases with respect to controls (p < 0.01, p = 0.03 and p = 0.03, respectively). Frontline health professionals experienced more negative effects on mental health during COVID-19 pandemic than non-frontline healthcare workers. Methylation levels were increased in genes regulating HPA axis (CRHR1) and dopamine neurotransmission (DRD2 and LSD1), thus supporting the involvement of these biological processes in depression/PTSD and indicating that methylation of these genes can be modulated by stress conditions, such as working as healthcare front-line during COVID-19 pandemic.

Intestinal ischemic manifestations of SARS-CoV-2: Results from the ABDOCOVID multicentre study.

BACKGROUND: Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (coronavirus disease 19, COVID-19). AIM: To define the clinical and histological, characteristics, as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 infection. METHODS: A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern Italy. Clinical, radiological, endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were reviewed. The diagnosis was established by consecutive analysis of all abdominal computed tomography (CT) scans performed. RESULTS: Among 2929 patients, 21 (0.7%) showed gastrointestinal ischemic manifestations either as presenting symptom or during hospitalization. Abdominal CT showed bowel distention in 6 patients while signs of colitis/enteritis in 12. Three patients presented thrombosis of main abdominal veins. Endoscopy, when feasible, confirmed the diagnosis (6 patients). Surgical resection was necessary in 4/21 patients. Histological tissue examination showed distinctive features of endothelial inflammation in the small bowel and colon. Median hospital stay was 9 d with a mortality rate of 39%. CONCLUSION: Gastrointestinal ischemia represents a rare manifestation of COVID-19. A high index of suspicion should lead to investigate this complication by CT scan, in the attempt to reduce its high mortality rate. Histology shows atypical feature of ischemia with important endotheliitis, probably linked to thrombotic microangiopathies.

Examination of the relationship between emergency department presentations and population mortality: a multicenter analysis of emergency department presentations during the COVID-19 pandemic.

BACKGROUND: In the spring of 2020, Italy experienced a significant reduction in the number of emergency department (ED) presentations during the first wave of the COVID-19 pandemic. If ED access has an impact on patients' prognosis, such a reduction in ED presentations would be expected to correlate with a parallel increase in the mortality rate of the corresponding population. The aim of the present study was to evaluate the impact of reduced ED presentations on the all-cause mortality of the general population. METHODS: Absolute and relative variation in ED accesses from March 1 to April 30 of both 2019 and 2020 in three hub hospitals in areas with different COVID-19 prevalence and age-standardized mortality data from January 1 to June 30 in 2019 and 2020 of the same areas were evaluated. RESULTS: During March and April 2020, ED consults were decreased of approximately 50% in all three hospitals, as compared with the same months in 2019. There was a marked increase in cumulative mortality in Milan (high SARS-CoV2 infection spread zone) compared with the same period in 2019. In the other two municipalities (Ferrara and Perugia), which had intermediate and low levels of infection spread, the mortality in 2020 was not substantially changed from that of 2019. CONCLUSIONS: Taking into account the increase in mortality due to SARS-CoV-2, reductions in ED access did not seem to affect death rates. If this finding will be confirmed, ED organization and access would need to be reconsidered.

Laryngotracheal aspiration test reduce the false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative nasopharyngeal swab.

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.

Variations in volume of emergency surgeries and emergency department access at a third level hospital in Milan, Lombardy, during the COVID-19 outbreak.

BACKGROUND: During the recent outbreak of COVID-19 (coronavirus disease 2019), Lombardy was the most affected region in Italy, with 87,000 patients and 15,876 deaths up to May 26, 2020. Since February 22, 2020, well before the Government declared a state of emergency, there was a huge reduction in the number of emergency surgeries performed at hospitals in Lombardy. A general decrease in attendance at emergency departments (EDs) was also observed. The aim of our study is to report the experience of the ED of a third-level hospital in downtown Milan, Lombardy, and provide possible explanations for the observed phenomena. METHODS: This retrospective, observational study assessed the volume of emergency surgeries and attendance at an ED during the course of the pandemic, i.e. immediately before, during and after a progressive community lockdown in response to the COVID-19 pandemic. These data were compared with data from the same time periods in 2019. The results are presented as means, standard error (SE), and 95% studentized confidence intervals (CI). The Wilcoxon rank signed test at a 0.05 significance level was used to assess differences in per-day ED access distributions. RESULTS: Compared to 2019, a significant overall drop in emergency surgeries (60%, p < 0.002) and in ED admittance (66%, p ≅ 0) was observed in 2020. In particular, there were significant decreases in medical (40%), surgical (74%), specialist (ophthalmology, otolaryngology, traumatology, and urology) (92%), and psychiatric (60%) cases. ED admittance due to domestic violence (59%) and individuals who left the ED without being seen (76%) also decreased. Conversely, the number of deaths increased by 196%. CONCLUSIONS: During the COVID-19 outbreak the volume of urgent surgeries and patients accessing our ED dropped. Currently, it is not known if mortality of people who did not seek care increased during the pandemic. Further studies are needed to understand if such reductions during the COVID-19 pandemic will result in a rebound of patients left untreated or in unwanted consequences for population health.

Utility of hospitalization for elderly individuals affected by COVID-19.

BACKGROUND: During the COVID-19 pandemic, the number of individuals needing hospital admission has sometimes exceeded the availability of hospital beds. Since hospitalization can have detrimental effects on older individuals, preference has been given to younger patients. The aim of this study was to assess the utility of hospitalization for elderly affected by COVID-19. We hypothesized that their mortality decreases when there is greater access to hospitals. METHODS: This study examined 1902 COVID-19 patients consecutively admitted to three large hospitals in Milan, Italy. Overall mortality data for Milan from the same period was retrieved. Based on emergency department (ED) data, both peak and off-peak phases were identified. The percentage of elderly patients admitted to EDs during these two phases were compared by calculating the standardized mortality ratio (SMR) of the individuals younger than, versus older than, 80 years. RESULTS: The median age of the patients hospitalized during the peak phase was lower than the median age during the off-peak phase (64 vs. 75 years, respectively; p <0.001). However, while the SMR for the younger patients was lower during the off-peak phase (1.98, 95% CI: 1.72-2.29 versus 1.40, 95% CI: 1.25-1.58, respectively), the SMR was similar between both phases for the elderly patients (2.28, 95% CI: 2.07-2.52 versus 2.48, 95% CI: 2.32-2.65, respectively). CONCLUSIONS: Greater access to hospitals during an off-peak phase did not affect the mortality rate of COVID-19-positive elderly patients in Milan. This finding, if confirmed in other settings, should influence future decisions regarding resource management of health care organizations.