Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life.

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multivariable logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (a woman aged 96 years) was unvaccinated and the other (a woman aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals-Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) or Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a slightly stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥5 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of COVID-19 antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST.

Hand Eczema in Apprentice Nurses during the COVID-19 Pandemic after a Skin Prevention Program.

BACKGROUND: Healthcare workers, particularly nurses and apprentice nurses, are at high risk of the development of hand eczema due to daily exposure to wet work. This study aimed to assess the occurrence of hand eczema in a group of first-, second-, and third-year apprentice nurses at the University Hospitals of Trieste (northeastern Italy) during the COVID-19 pandemic. METHODS: Two hundred forty-two Nursing School students were recruited. Data were collected using a standardized questionnaire based on the Nordic Occupational Skin Questionnaire, and all patients underwent a medical examination to evaluate their skin condition based on standard scores. Transepidermal water loss was also measured. The factors associated with hand eczema were investigated using univariate and multivariate logistic regression analyses. RESULTS: The prevalence of hand eczema was low in students both before and after the traineeship (17.9 and 21.5%, respectively), but clinical signs of mild skin damage, mainly skin dryness, were present in 52.3 and 47.2%, respectively. The factor associated with hand eczema was a personal history of atopic eczema (odd ratios 2.61, 95% confidence intervals 1.18-5.80), while exposure to irritants and glove use did not reach statistical significance. CONCLUSIONS: Our findings might be explained by the preventive measures adopted for skin protection among healthcare workers in Trieste since the apprenticeship.

Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: An individual-level analysis within 13 months in the ORCHESTRA cohort.

Short summary: We investigated changes in serologic measurements after COVID-19 vaccination in 19,422 subjects. An individual-level analysis was performed on standardized measurements. Age, infection, vaccine doses, time between doses and serologies, and vaccine type were associated with changes in serologic levels within 13 months. Background: Persistence of vaccine immunization is key for COVID-19 prevention. Methods: We investigated the difference between two serologic measurements of anti-COVID-19 S1 antibodies in an individual-level analysis on 19,422 vaccinated healthcare workers (HCW) from Italy, Spain, Romania, and Slovakia, tested within 13 months from first dose. Differences in serologic levels were divided by the standard error of the cohort-specific distribution, obtaining standardized measurements. We fitted multivariate linear regression models to identify predictors of difference between two measurements. Results: We observed a progressively decreasing difference in serologic levels from <30 days to 210-240 days. Age was associated with an increased difference in serologic levels. There was a greater difference between the two serologic measurements in infected HCW than in HCW who had never been infected; before the first measurement, infected HCW had a relative risk (RR) of 0.81 for one standard deviation in the difference [95% confidence interval (CI) 0.78-0.85]. The RRs for a 30-day increase in time between first dose and first serology, and between the two serologies, were 1.08 (95% CI 1.07-1.10) and 1.04 (95% CI 1.03-1.05), respectively. The first measurement was a strong predictor of subsequent antibody decrease (RR 1.60; 95% CI 1.56-1.64). Compared with Comirnaty, Spikevax (RR 0.83, 95% CI 0.75-0.92) and mixed vaccines (RR 0.61, 95% CI 0.51-0.74) were smaller decrease in serological level (RR 0.46; 95% CI 0.40-0.54). Conclusions: Age, COVID-19 infection, number of doses, time between first dose and first serology, time between serologies, and type of vaccine were associated with differences between the two serologic measurements within a 13-month period.

Determinants of Anti-S Immune Response at 9 Months after COVID-19 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

Background: The persistence of antibody levels after COVID-19 vaccination has public health relevance. We analyzed the determinants of quantitative serology at 9 months after vaccination in a multicenter cohort. Methods: We analyzed data on anti-SARS-CoV-2 spike antibody levels at 9 months from the first dose of vaccinated HCW from eight centers in Italy, Germany, Spain, Romania and Slovakia. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log antibody level and the corresponding 95% confidence interval (CI), and combined them in random-effects meta-analyses. Finally, we conducted a trend analysis of 1 to 7 months' serology within one cohort. Results: We included 20,216 HCW with up to two vaccine doses and showed that high antibody levels were associated with female sex (p = 0.01), age (RR = 0.87, 95% CI = 0.86-0.88 per 10-year increase), 10-day increase in time since last vaccine (RR = 0.97, 95% CI 0.97-0.98), previous infection (3.03, 95% CI = 2.92-3.13), two vaccine doses (RR = 1.22, 95% CI = 1.09-1.36), use of Spikevax (OR = 1.51, 95% CI = 1.39-1.64), Vaxzevria (OR = 0.57, 95% CI = 0.44-0.73) or heterologous vaccination (OR = 1.33, 95% CI = 1.12-1.57), compared to Comirnaty. The trend in the Bologna cohort, based on 3979 measurements, showed a decrease in mean standardized antibody level from 8.17 to 7.06 (1-7 months, p for trend 0.005). Conclusions: Our findings corroborate current knowledge on the determinants of COVID-19 vaccine-induced immunity and declining trend with time.

SARS-CoV-2 Infection in Health Care Workers of Trieste (North-Eastern Italy), 1 October 2020-7 February 2022: Occupational Risk and the Impact of the Omicron Variant.

Vaccination coverage against COVID-19 among health care workers (HCWs) of the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (North-eastern Italy) by 1 January 2022 was 90.4% with at least one vaccine dose, 84.9% with at least 2 doses, and 75.1% with 3 doses, 98.2% with Comirnaty (Pfizer BioNtech, New York, NY, USA) versus 1.8% with Spikevax (Moderna, Cambridge, MA, USA). From 1 October 2020 to 7 February 2022, 1652 SARS-CoV-2 infections were notified in HCWs of ASUGI Trieste. Although the overall risk of SARS-CoV-2 contagion increased over time, the rate of occupational infections progressively declined, from 42.5% during the second COVID-19 wave to 15.6% in the fifth. Between 1 January-7 February 2022 (a period dominated by the Omicron variant), albeit no COVID-19-associated hospitalizations were recorded in HCWs of ASUGI Trieste, 669 SARS-CoV-2 infections were counted against 367 cases observed from 1 October to 31 December 2020, the 3 months preceding the implementation of the vaccination campaign against COVID-19. Job tasks and health care settings turned out to be the most significant risk factors for SARS-CoV-2 infection. However, the effect of workplace prevailed over job task on the biological risk, with greater rates of SARS-CoV-2 infections observed among HCWs operating in areas with higher levels of circulation of the virus, particularly COVID-19 dedicated units.

COVID-19 susceptibility and vaccination coverage for measles, rubella and mumps in students and healthcare workers in Trieste hospitals (NE Italy).

BACKGROUND: Measles, mumps, and rubella (MMR) vaccines have been suggested as preventive measures to protect subjects from the worst sequelae of COVID-19 infection because neutralizing antibodies can cross-react with other viruses. AIM: To verify COVID-19 infection in MMR vaccinated and non-vaccinated healthcare workers and medical students in Trieste Hospitals. RESULTS: Nurse aids resulted in significantly more infections than structured physicians (OR 1.80; 95% CI 1.14-2.80) while students resulted in less infections (OR, 0.66; 95% CI 0.43-1.01). The presence of an MMR vaccination was inversely associated with COVID-19 (OR, 0.77; 95% CI 0.61-0.96) but only in univariate analysis. In the multivariable logistic regression analysis, MMR vaccination lost statistical significance (OR, 0.86; 95%CI 0.62-1.20).On 13 HCWs hospitalized for COVID-19, 11 resulted not vaccinated for MMR. DISCUSSION: Our study found a mild, non-significant reduction in SARS-CoV-2 infections in workers vaccinated with MMR.

Incidence of COVID-19 infection in hospital workers from March 1, 2020 to May 31, 2021 routinely tested, before and after vaccination with BNT162B2.

To evaluate the incidence of COVID-19 infection in health care workers from the start of the COVID-19 pandemic in NE Italy, vaccination with BNT162b2. This was a retrospective cohort study. Healthcare workers were routinely tested for SARS-CoV-2 infection using real-time polymerase chain reaction tests in nasopharyngeal swabs. Logistic regression was used to calculate the incidence rate ratios (IRRs) of the factors associated with COVID-19. A total of 4251 workers were followed up, and the prevalence of COVID-19 was 13.6%. In March 2021 the incidence of infection was 4.88 and 103.55 cases for 100,000 person-days in vaccinated and non-vaccinated workers, respectively, with an adjusted IRRs of 0.05 (95% CI 0.02-0.08). Our study evaluated the monthly incidence in health care workers in Trieste hospitals before and after vaccination, finding an estimated vaccine effectiveness of 95% in health care workers routinely tested.

Risk of Vaccine Breakthrough SARS-CoV-2 Infection and Associated Factors in Healthcare Workers of Trieste Teaching Hospitals (North-Eastern Italy).

Background: Healthcare workers (HCWs) are particularly exposed to biological risk, including SARS-CoV-2 infection. In order to contrast the current pandemic and alleviate the burden of the disease on the healthcare system, a mass vaccination campaign against COVID-19 has been launched worldwide. Aim To evaluate the impact of COVID-19 vaccination in HCWs exposed to SARS-CoV-2, to describe the clinical presentation of COVID-19 in infected HCWs, and to investigate clinical and occupational risk factors for breakthrough infection. Design: Retrospective cohort study. Methods: The cohort of HCWs of Trieste Hospitals were followed up from 1 March 2020, to 30 November 2021 (21 months). All HCWs were periodically screened for SARS-CoV-2 infection by real-time PCR (RT-PCR) analysis. Clinical data were obtained through routine medical surveillance records. Risk factors for SARS-CoV-2 infection were investigated by univariable as well as multivariable logistic regression analysis. Results: Among 4394 HCWs routinely screened for SARS-CoV-2 by PCR on nasopharyngeal swab, a total of 800 incident cases were identified during the entire study period (1 March 2020 to 30 November 2021). Five hundred and sixty-four cases occurred before, and 236 after the start of the vaccination campaign against COVID-19, of whom 155 received a complete vaccination scheme before SARS-CoV-2 infection. Breakthrough infection was featured by mild or no symptoms and was significantly associated with the male sex, BMI > 25, and diabetes mellitus. Some categories of HCWs (physicians and nurse aids/auxiliary personnel) were at a higher risk of breakthrough infection. Conclusions: Fully vaccinated HCWs were less likely to acquire symptomatic as well as asymptomatic SARS-CoV-2 infection. Risk factors for SARS-CoV-2 infection after a full COVID-19 vaccination scheme included the male gender, diabetes mellitus, and overweight. HCWs with higher exposure to COVID-19 patients were at higher risk of breakthrough infection.

Occupational Risk Factors for SARS-CoV-2 Infection in Hospital Health Care Workers: A Prospective Nested Case-Control Study.

Introduction: Health Care Workers (HCWs) are at a particular high risk of SARS-CoV-2 infection due to direct and indirect exposure to COVID-19 patients and Aerosol-Generating Procedures (AGPs). The aim of the study was to assess the risk factors for SARS-CoV-2 infection in HCWs exposed to COVID-19 patients, to evaluate the adherence and effectiveness of Infection Prevention and Control (IPC) measures, to describe the clinical presentation for SARS-CoV-2 infection in HCWs and to determine serological responses in HCWs. Methods: HCWs exposed to COVID-19 patients during the previous 14 days with a confirmed case status were recruited as cases; HCWs exposed to COVID-19 patients during the previous 14 days in the same ward without a suspected/probable/confirmed case status were recruited as controls. Serum samples were collected as soon as possible and after 21-28 days from all participants. Data were collected with a WHO standardized questionnaire as soon as possible and after 21-28 days. Results: All social, occupational and personal variables considered were not associated with an increased risk of SARS-CoV-2 infection. Conclusions: Our study showed a high knowledge of IPC measures and very high PPE use among HCWs.

Epidemiology of SARS-CoV-2 among healthcare workers in North-Eastern Italy from March 1, 2020 to May 10, 2020.

BACKGROUND: During major epidemic outbreaks, the preparedness of public health systems is challenged and -healthcare workers (HCWs) are at the frontline. Italy was among the first- and worst-hit countries by COVID-19. AIM: To analyze the prevalence and incidence of infection among HCWs in Friuli Venezia Giulia region (north-eastern Italy) from March 1 to the end of the Italian lock-down, May 10, 2020. METHODS: HCWs exposed to COVID-19 patients were actively surveyed and all HCWs were routinely tested with nasopharyngeal and oropharyngeal swab for RNA virus detection (n. 54,670). RESULTS: Infected HCWs (n. 595) represented the 32.3% of all COVID-19 cases in the region under 65 years of age, and incidence of infection was 11.4 cases/1000 workers. HCWs accounted for a significant proportion of coronavirus infection and experienced high infection incidence after unprotected contact. CONCLUSIONS: HCWs' knowledge of SARS-CoV-2 epidemiology and proper infection control practices are critical to the control of the disease.

Quality of Life, Insomnia and Coping Strategies during COVID-19 Pandemic in Hospital Workers. A Cross-Sectional Study.

COVID-19 became a pandemic in a few months, leading to adverse health outcomes, reducing the quality of life, affecting the sleep/wake cycle, and altering coping strategies, especially among hospital personnel. Life quality, insomnia, and coping strategies were thus assessed among hospital personnel during the first wave of the COVID-19 pandemic in Italy. This cross-sectional study was conducted from May to November 2020 through an online survey. There were 558 participants (28.5% males and 71.5% females) enrolled in two different metropolitan areas (in North and South of Italy, respectively). Three standardized questionnaires were administered: European Quality of life-5 Dimensions (EQ-5D), Athens Insomnia Scale (AIS), and Brief COPE. Differences in sociodemographic characteristics and work-related factors were also investigated in order to identify possible predictors through a generalized linear model and logistic regression analysis. Results showed good perceived life quality and high insomnia prevalence. After sample stratification, the statistical analysis highlighted that personal (gender, age, educational level) and work-related factors (employment in COVID wards, remote working) played different roles in predicting quality of life, insomnia, and coping attitude. Active, Planning, and Acceptance were the most frequently adopted coping strategies. Despite women confirming their attitude in reacting to the difficulties, adopting emotion-focused coping strategies, they showed a higher probability to develop insomnia, so a gender perspective should be considered in the health protection of this working category. An integrated approach should be implemented at individual, interpersonal and organizational levels aiming to monitor psychological distress, favor regular sharing and communication between peers, and also allow conciliation of work with family life. At the organizational level, preventive and protective measures adequate to work-related risk to COVID-19 should be adopted.

Low sensitivity of rapid tests detecting anti-CoV-2 IgG and IgM in health care workers' serum for COVID-19 screening.

BACKGROUND: the sensitivity and specificity of a rapid antibody test were investigated for the screening of healthcare workers. METHODS: the serum of 389 health care workers exposed to COVID-19 patients or with symptoms, were analysed. All workers underwent monthly the screening for SARS-CoV-2 with detection of viral RNA in nasopharyngeal swabs by RT-PCR. IgG antibody detection in serum was performed by Chemiluminescence Immunoassay (CLIA) and by the Rapid test (KHB diagnostic kit for SARS CoV-2 IgM/IgG antibody after a median of 7.6 weeks (25°-75° percentiles 6.6-11.5). RESULTS: the rapid test resulted positive in 31/132 (23.5%), 16/135 (11.8%) and 0/122 cases in COVID-19 positive individuals, in those with only SARS-CoV-2 IgG antibodies and in those negative for both tests, respectively. Sensitivity was 17.6% (CI95% 13.2-22.7) and 23.5% (CI95% 16.5-31.6), and specificity was 100% (CI95% 97-100) and 100% (CI95% 97-100) considering Rapid test vs CLIA IgG or Rapid test vs SARS-CoV-2 positive RNA detection, respectively. CONCLUSION: the KHB Rapid test is not suitable for the screening of workers with previous COVID-19 infection.

Community Use of Face Masks against the Spread of COVID-19.

The role of face masks to prevent and control COVID-19 is critical, especially since asymptomatic or pre-symptomatic infected individuals can shed high loads of SARS-CoV-2 in the surrounding environment. In addition to being a two-way barrier to protect against virions droplets both in terms of "source control" (for the benefits of the community) and "physical protection" (for wearer), face masks also allow maintaining physiological temperatures and humidity of the nasal cavity and mouth, independently from the external environmental conditions. Beyond compromising the viral transmission speed, exposure to cold environments could have a detrimental effect on the host's susceptibility to SARS-CoV-2. The innate human immune system becomes in fact weaker with cooler nose temperatures and thus more vulnerable to viral replication. Furthermore, there is evidence that warm, humid climates are associated with reduced spread of SARS-CoV-2, while cold dry conditions favor its stability and transmissibility. In the early stage of a viral infection, a physiological body temperature in the upper airways supports the innate immune system, endorsing the muco-ciliary clearance, inhibiting, or deactivating any first settlement of viruses. Face masks are therefore strongly recommended also outdoors, especially under cold weather conditions, not only as a physical barrier against the transmission of SARS-CoV-2, but also to prevent the rapid cooling of the nasal mucosa and the inhibition of the human innate defense of the upper airways.