Mismanagement of SARS-CoV-2 Infection Pre Hospitalisation during the Omicron Era: Antibiotics and Steroids Instead of Early Antivirals.

The aim of this study was to assess the prevalence of inappropriate treatment among hospitalised patients affected by SARS-CoV-2 infection before hospital admission during the Omicron era. This single-centre, retrospective observational study included all the patients hospitalised because of SARS-CoV-2 infection during three periods characterised by the Italian prevalence of an Omicron variant of concern: (1) January-May 2022 (BA.1-BA.2), (2) June-October 2022 (BA.5), and (3) November 2022-March 2023 (BQ.1-XBB). Inappropriate treatment was defined as pre-hospitalisation exposure to antibiotics and/or steroids in the absence of a documented bacterial infection or the need for steroid treatment of an underlying medical condition. A total of 931 subjects were hospitalised: 394 in period 1, 334 in period 2, and 203 in period 3. Of the 157 patients undergoing inappropriate treatment (16.9%), 142 (15.3%) received antibiotics and 52 (5.6%) steroids. The proportion of inappropriately treated patients significantly decreased over time, from 23.1% in period 1 to 11.7% in period 2 and 13.3% in period 3 (p < 0.001), and there was a parallel decrease in antibiotic (p < 0.001) and steroid treatment (p < 0.013). Only 13 subjects (1.4%) received early pre-hospitalisation treatment for SARS-CoV-2. A significant proportion of hospitalised COVID-19 patients were exposed to inappropriate treatment before hospital admission.

Major Bleeding Events in Hospitalized COVID-19 Patients: A Retrospective Observational Study.

Thromboprophylaxis/anticoagulation treatment is often required in hospitalized COVID-19 patients. We aimed to estimate the prevalence of major bleeding events in hospitalized COVID-19 patients. This was a retrospective observational study including all COVID-19 hospitalized patients ≥18 years of age at one reference center in northern Italy. The crude prevalence (between February 2020-2022) of major bleeding events was estimated as the number of major bleeding episodes divided by patients at risk. Uni- and multivariable Cox models were built to assess factors potentially associated with major bleeding events. Twenty-nine (0.98%) out of 2,945 COVID-19 patients experienced a major bleeding event [prevalence of 0.55% (95%CI 0.37-0.79)], of which five were fatal. Patients who experienced a major bleeding event were older [78 years (72-84 IQR) vs. 67 years (55-78 IQR), p-value < 0.001] and more frequently exposed to anti-aggregating therapy (44.8% vs. 20.0%, p-value 0.002) when compared to those who did not. In the multivariable Cox model, age [per 1 year more AHR 1.05 (CI95% 1.02-1.09)] was independently associated with an increased risk of major bleeding events. A strict monitoring of older hospitalized COVID-19 patients is warranted due to the risk of major bleeding events.

Detection and typization of HPV genotypes in subjects with oral and upper respiratory tract lesions, Milan, Italy.

BACKGROUND: Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms. METHODS: This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included. RESULTS: Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination. CONCLUSIONS: Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted.

Bloodstream Infections in Intensive Care Unit during Four Consecutive SARS-CoV-2 Pandemic Waves.

Critically ill COVID-19 patients are at an increased risk of bloodstream infections (BSIs). We performed a retrospective observational single-center study on COVID-19 patients admitted to intensive care unit (ICU) to assess the incidence of BSIs in four consecutive periods: 21 February-31 July 2020 (W1), 1 August 2020-31 January 2021 (W2), 1 February-30 September 2021 (W3) and 1 October 2021 and 30 April 2022 (W4). BSIs that occurred 48 h after ICU admission were included. The crude incidence of BSIs was estimated by means of Poisson distribution normalized to 1000 patient-days. A total of 404 critically ill COVID-19 patients were admitted to ICU, of whom 284 (61%) developed at least one episode of BSI with an overall crude incidence of 87 events every 1000 patient-days (95% CI 77-98) without a significant difference in consecutive epidemic periods (p = 0.357). Gram-positive bacteria were the most frequent etiological agents of BSIs, contributing to 74.6% episodes. A progressive decrease in BSIs due to Enterococcus spp. was observed (W1 57.4%, W2 43.7%, W3 35.7% and W4 32.7%; p = 0.004). The incidence of BSIs remained stable during different epidemic periods. Enterococcus spp. prevalence was significantly reduced, although still accounted for one third of BSIs in more recent epidemic periods.

Clinical efficacy of the first two doses of anti-SARS-CoV-2 mRNA vaccines in solid cancer patients.

INTRODUCTION: Cancer patients are frail individuals, thus the prevention of SARS-CoV-2 infection is essential. To date, vaccination is the most effective tool to prevent COVID-19. In a previous study, we evaluated the immunogenicity of two doses of mRNA-based vaccines (BNT162b2 or mRNA-1273) in solid cancer patients. We found that seroconversion rate in cancer patients without a previous exposure to SARS-CoV-2 was lower than in healthy controls (66.7% vs. 95%, p = 0.0020). The present study aimed to evaluate the clinical efficacy of the vaccination in the same population. METHODS: This is a single-institution, prospective observational study. Data were collected through a predefined questionnaire through phone call in the period between the second and third vaccine dose. The primary objective was to describe the clinical efficacy of the vaccination, defined as the percentage of vaccinated subjects who did not develop symptomatic COVID-19 within 6 months after the second dose. The secondary objective was to describe the clinical features of patients who developed COVID-19. RESULTS: From January to June 2021, 195 cancer patients were enrolled. Considering that 7 (3.59%) patients tested positive for SARS-CoV-2 and 5 developed symptomatic disease, the clinical efficacy of the vaccination was 97.4%. COVID-19 disease in most patients was mild and managed at home; only one hospitalization was recorded and no patient required hospitalization in the intensive care unit. DISCUSSION: Our study suggests that increasing vaccination coverage, including booster doses, could improve the prevention of infection, hospitalization, serious illness, and death in the frail population of cancer patients.

Concomitant diagnosis of sexually transmitted infections and human monkeypox in patients attending a sexual health clinic in Milan, Italy.

In 2022, many monkeypox (MPX) outbreaks have been documented in countries where MPX was not endemic. It spread all around the world, especially in European Union and United States. While MPX is classically considered to be transmitted through close contact with lesions, the hypothesis of sexual transmission has been proposed. This study considered a total of 49 patients suspected for MPX that were also tested for other sexually transmitted infections (STIs), including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis. The data from coinfected patients suggested that MPXV and STIs might share the same route of inoculum, corroborating the hypothesis of possible sexual transmission for the emerging poxvirus. And like any other STI, MPX should be considered without stigmatization.

Isolation of viable monkeypox virus from anal and urethral swabs, Italy, May to July 2022.

Anal and urethral samples from confirmed cases of monkeypox were screened for monkeypox virus (MPXV) by real-time PCR. Isolation of the virus was subsequently attempted in cell culture. Actively-replicating virus was demonstrated in 13 of 18 and 11 of 15 PCR-positive anal and urethral swabs, respectively, collected within 7 days from symptoms onset. Two asymptomatic secondary cases had detectable MPXV genetic material in urethral secretion and for one, MPXV was successfully isolated, supporting a potential MPXV sexual transmission hypothesis.

Challenges in Diagnosing COVID-19-Associated Pulmonary Aspergillosis in Critically Ill Patients: The Relationship between Case Definitions and Autoptic Data.

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59-72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA.

Hospitalisation for monkeypox in Milan, Italy.

During the current multi-country outbreak of human monkeypox the hospitalisation rate observed in Milan, Italy was 8.8%. Bacterial superinfection and severe perianal pain were the main cause of hospitalisation requiring antibiotic treatment and analgesic therapy. One patient was treated with Cidofovir. All hospitalised patients were discharged and the outcome was favourable with full recovery.

Mortality rates among COVID-19 patients hospitalised during the first three waves of the epidemic in Milan, Italy: A prospective observational study.

INTRODUCTION: This paper describes how mortality among hospitalised COVID-19 patients changed during the first three waves of the epidemic in Italy. METHODS: This prospective cohort study used the Kaplan-Meier method to analyse the time-dependent probability of death of all of the patients admitted to a COVID-19 referral centre in Milan, Italy, during the three consecutive periods of: 21 February-31 July 2020 (first wave, W1), 1 August 2020-31 January 2021 (second wave, W2), and 1 February-30 April 2021 (third wave, W3). Cox models were used to examine the association between death and the period of admission after adjusting for age, biological sex, the time from symptom onset to admission, disease severity upon admission, obesity, and the comorbidity burden. RESULTS: Of the 2,023 COVID-19 patients admitted to our hospital during the study period, 553 (27.3%) were admitted during W1, 838 (41.5%) during W2, and 632 (31.2%) during W3. The crude mortality rate during W1, W2 and W3 was respectively 21.3%, 23.7% and 15.8%. After adjusting for potential confounders, hospitalisation during W2 or W3 was independently associated with a significantly lower risk of death than hospitalisation during W1 (adjusted hazard ratios [AHRs]: 0.75, 95% confidence interval [CI] 0.59-0.95, and 0.58, 95% CI 0.44-0.77). Among the patients aged >75 years, there was no significant difference in the probability of death during the three waves (AHRs during W2 and W3 vs W1: 0.93, 95% CI 0.65-1.33, and 0.88, 95% CI 0.59-1.32), whereas those presenting with critical disease during W2 and W3 were at significantly lower risk of dying than those admitted during W1 (AHRs 0.61, 95% CI 0.43-0.88, and 0.44, 95% CI 0.28-0.70). CONCLUSIONS: Hospitalisation during W2 and W3 was associated with a reduced risk of COVID-19 death in comparison with W1, but there was no difference in survival probability in patients aged >75 years.