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.

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

Background: University workers undergo intense social interactions due to frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, enhanced ventilation of all premises, fomites disinfection and mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as number of cases by number of person-days (p-d) at risk. Multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, controlling for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of COVID-19 vaccines, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16;95% CI: 1.04;4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10;95% CI: 0.06;0.16) and after (aHR = 0.37;95% CI: 0.27;0.52) the Omicron transmission period. Vaccine effectiveness of the booster was 90% (=(1−0.10) × 100) before versus 63% (=(1−0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous immunization (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine). Conclusions: The incidence of SARS-CoV-2 infection in university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed the vast majority of asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between administrative and teaching staff.

Persistence of Symptoms 15 Months since COVID-19 Diagnosis: Prevalence, Risk Factors and Residual Work Ability.

Background: A proportion of patients' ailments may last after recovering from acute COVID-19, with episodic and systemic symptoms of unclear etiology potentially involving different organs. Study aim: The aim of this study was to investigate the persistence of symptoms 15 months since COVID-19 diagnosis in patients referring to the post-COVID-19 clinic in Trieste (north-eastern Italy). Methods: Two-hundred-forty-seven patients were medically examined between 8 December 2020-6 April 2021, after a median time of 49 days since first positive swab test for SARS-CoV-2. After a median time of 15 months since COVID-19 diagnosis, the same patients were contacted over the phone and investigated by standardized questionnaire collecting information on any persisting symptoms and work ability index (WAI). Four multivariable logistic regression models were fitted to investigate factors associated with persistence of any respiratory, neurological, dysautonomic, or psychiatric symptoms at first (median time 49 days since COVID-19 diagnosis) as well as second (median 15 months since COVID-19 diagnosis) follow up. A multiple linear regression was also employed to investigate factors associated with higher mean WAI, assessed only at second follow up. Additionally, factors associated with persistence of symptoms 200+ days since COVID-19 diagnosis between first and second follow-up were investigated by multivariable Generalized Estimating Equation (GEE). Results: At first follow up (median time of 49 days since COVID-19 diagnosis) symptoms more frequently reported were fatigue (80.2%), shortness of breath (69.6%), concentration deficit (44.9%), headache (44.9%), myalgia (44.1%), arthralgia (43.3%), and anosmia (42.1%). At second follow-up (median time of 15 months since COVID-19 diagnosis) 75% patients returned to their baseline status preceding COVID-19. At first follow up males were less likely to experience neurological (OR = 0.16; 95% CI: 0.08; 0.35) as well as psychiatric (OR = 0.43; 95% CI: 0.23; 0.80) symptoms as compared to females. At first follow up, the risk of neurological symptoms increased also linearly with age (OR = 1.04; 95% CI: 1.01; 1.08) and pre-existing depression was a major risk factor for persisting dysautonomic (aOR = 6.35; 95% CI: 2.01; 20.11) as well as psychiatric symptoms (omitted estimate). Consistently, at second follow up only females experience psychiatric symptoms, whereas males exhibited significantly higher mean WAI (RC = 0.50; 95% CI: 0.11; 0.88). Additionally, neurological symptoms at second follow up were more likely in patients with pre-existing comorbidities (OR = 4.31; 95% CI: 1.27; 14.7). Finally, persistence of symptoms lasting 200+ days since COVID-19 diagnosis increased linearly with age (OR = 1.03; 95% CI 1.01-1.05) and were more likely in patients affected by pre-existing depression (OR = 2.68; 95% CI 1.60; 4.49). Conclusions: Following a median time of 15 months since first positive swab test, 75% patients with symptoms returned to their baseline health status preceding COVID-19. Females had a significantly lower WAI and were more likely to experience psychiatric symptoms at second follow up (15 months since COVID-19 diagnosis). Furthermore, the risk of symptoms persisting 200+ days since COVID-19 diagnosis increased with history of depression, endorsing the hypothesis that long-COVID-19 symptoms may be at least partially explained by pre-existing psychological conditions. Patient rehabilitation and psychological support may therefore play a key role in caring patients with the so called long COVID-19 syndrome.

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020-2 April 2022.

Background: University workers undergo intense social interactions due to frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, enhanced ventilation of all premises, fomites disinfection and mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as number of cases by number of person-days (p-d) at risk. Multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, controlling for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of COVID-19 vaccines, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16; 95% CI: 1.04; 4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10; 95% CI: 0.06; 0.16) and after (aHR = 0.37; 95% CI: 0.27; 0.52) the Omicron transmission period. Vaccine effectiveness of the booster was 90% (=(1-0.10) × 100) before versus 63% (=(1-0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous immunization (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine). Conclusions: The incidence of SARS-CoV-2 infection in university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed the vast majority of asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between administrative and teaching staff.

Supporting the Aspecific Physiological Defenses of Upper Airways against Emerging SARS-CoV-2 Variants.

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...].

Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy).

Background. Allergic patients may develop reactions following COVID-19 vaccination more frequently than non-allergic individuals. The aim of our study was to assess the risk of reactions in high-risk allergic patients vaccinated for COVID-19 at the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (northeastern Italy). Methods. Patients were considered at high risk for allergic reactions in case of: prior anaphylactic reaction to any drug/vaccine; multiple drug allergy; intolerance to polyethylene glycol (PEG) or polysorbate 80 (PS80) containing drugs; and mast cell disorders. High-risk allergic patients were immunized in hospital by a dedicated allergy team supported by resuscitation staff. Patients were interviewed over the phone one month after vaccination to complete a structured questionnaire investigating signs and symptoms developed after immunization. Results. From March 2021 to February 2022, 269 patients with a history of severe allergic reactions were assessed, of whom 208 (77.3%) eventually received COVID-19 vaccination, 50 (18.6%) refused to be immunized, 10 (3.7%) were deferred for medical reasons and one was declared exempted due to testing positive for PS80. Mild reactions (urticaria, angioedema, rhinitis, erythema) to COVID-19 vaccines were reported by 30.3% of patients, 8.7% within 4 h and 21.6% > 4 h after immunization. No anaphylactic events were observed. Although they were 80 times (3.8%) more prevalent than in COVID-19 vaccinees from the general population (0.047%), vaccine allergic reactions in high-risk patients were mainly mild and late, more likely affecting women (OR = 3.05; 95% CI 1.22-7.65). Conclusions. High-risk allergic patients with urticaria and angioedema may experience mild flare-ups of mast cell activation-like symptoms following COVID-19 vaccination, supporting antihistamine premedication before vaccination and to be continued for one week afterwards.

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran).

Background: Several reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19. Methods: Herein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth; hospital admission; AKI onset; ICU admission; hospital discharge; death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death). Results: In this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients. Conclusions: Since the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications.

Primary SARS-CoV-2 Infections, Re-infections and Vaccine Effectiveness during the Omicron Transmission Period in Healthcare Workers of Trieste and Gorizia (Northeast Italy), 1 December 2021-31 May 2022.

Objective: To evaluate the incidence of primary and recurrent COVID-19 infections in healthcare workers (HCWs) routinely screened for SARS-CoV-2 by nasopharyngeal swabs during the Omicron wave. Design: Dynamic Cohort study of HCWs (N = 7723) of the University Health Agency Giuliano Isontina (ASUGI), covering health services of the provinces of Trieste and Gorizia (Northeast Italy). Cox proportional hazard model was employed to estimate the risk of primary as well as recurrent SARS-CoV-2 infection from 1 December 2021 through 31 May 2022, adjusting for a number of confounding factors. Results: By 1 December 2021, 46.8% HCWs of ASUGI had received the booster, 37.2% were immunized only with two doses of COVID-19 vaccines, 6.0% only with one dose and 10.0% were unvaccinated. During 1 March 2020-31 May 2022, 3571 primary against 406 SARS-CoV-2 recurrent infections were counted among HCWs of ASUGI, 59.7% (=2130/3571) versus 95.1% (=386/406) of which occurring from 1 December 2021 through 31 May 2022, respectively. All HCWs infected by SARS-CoV-2 during 1 December 2021 through 31 May 2022 presented mild flu-like disease. Compared to staff working in administrative services, the risk of primary as well as recurrent SARS-CoV-2 infection increased in HCWs with patient-facing clinical tasks (especially nurses and other categories of HCWs) and in all clinical wards but COVID-19 units and community health services. Regardless of the number of swab tests performed during the study period, primary infections were less likely in HCWs immunized with one dose of COVID-19 vaccine. By contrast, the risk of SARS-CoV-2 re-infection was significantly lower in HCWs immunized with three doses (aHR = 0.58; 95%CI: 0.41; 0.80). During the study period, vaccine effectiveness (VE = 1-aHR) of the booster dose declined to 42% against re-infections, vanishing against primary SARS-CoV-2 infections. Conclusions: Though generally mild, SARS-CoV-2 infections and re-infections surged during the Omicron transmission period. Compared to unvaccinated colleagues, the risk of primary SARS-CoV-2 infection was significantly lower in HCWs immunized just with one dose of COVID-19 vaccines. By Italian law, HCWs immunized only with one dose were either suspended or re-assigned to job tasks not entailing patient facing contact; hence, while sharing the same biological risk of unvaccinated colleagues, they arguably had a higher level of protection against COVID-19 infection. By contrast, SARS-CoV-2 re-infections were less likely in HCWs vaccinated with three doses, suggesting that hybrid humoral immunity by vaccination combined with natural infection provided a higher level of protection than vaccination only. In this stage of the pandemic, where SARS-CoV-2 is more infectious yet much less pathogenic, health protection measures in healthcare premises at higher biological risk seem the rational approach to control the transmission of the virus.

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.

Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial.

Background: COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods: We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results: During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions: Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

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.

A Prospective Study on Risk Factors for Acute Kidney Injury and All-Cause Mortality in Hospitalized COVID-19 Patients From Tehran (Iran)

Background Several reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19. Methods Herein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth;hospital admission;AKI onset;ICU admission;hospital discharge;death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death). Results In this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients. Conclusions Since the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications.

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.

On Therapeutic Plasma Exchange Against Severe COVID-19-Associated Pneumonia: An Observational Clinical Study

Background There is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs and vaccines. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill patients with COVID-19 is still provisional, and further investigations are needed to confirm its eventual beneficial effects. Aims To assess the effect of TPE on the risk of mortality in patients with COVID-19-associated pneumonia, using three statistical procedures to rule out any threats to validity. Methods We therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with the diagnosis of COVID-19-associated pneumonia confirmed by real-time polymerase chain reaction (RT-qPCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir), and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 l of patients' plasma by a solution, 50% of normal plasma, and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint. Results Deaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of structural equation modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name “severity”). Disease severity was lower (Wilkinson rank-sum test p < 0.001) among patients with COVID-19 undergoing TPE (median: −2.82;range: −5.18;7.96) as compared to those not receiving TPE (median: −1.35;range: −3.89;8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as the covariate in Cox regression models. The univariate hazard ratio (HR) of 0.68 (95%CI: 0.26;1.80;p = 0.441) for TPE turned to 1.19 (95%CI: 0.43;3.29;p = 0.741) after adjusting for severity. Conclusions In this study sample, the lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than the TPE effects.

Chronic Kidney Disease Major Risk Factor for COVID-19 Severity and Mortality, A Scoping Review

A growing body of evidence points out at chronic kidney disease (CKD) as a major risk factor for severe COVID-19, increasing also the respective mortality risk. Preventive measures, rapid monitoring organ function and interventions capable of preventing multiorgan failures are of great importance to reduce adverse outcomes in COVID-19 patients with CKD. While efforts are underway to carry out indirect protection interventions and large-scale vaccination to achieve herd immunity in the general population, direct protection of patients with CKD through rapid vaccination trials are necessary since uraemia and immunosuppressive agents could have a negative impact on vaccination responses of CDK patients. More epidemiological data are needed for in-depth understanding of the course and outcome of COVID-19 in CKD patients, supporting clinical decision-making. DOI: 10.52547/ijkd.6797

Violence Against Healthcare: A Public Health Issue beyond Conflict Settings.

A 3-year analysis released in August 2021 by the WHO indicated that more than 700 healthcare workers and patients have died (2,000 injured) as a result of attacks against health facilities since 2017. The COVID-19 pandemic has made the risks even worse for doctors, nurses, and support staff, unfortunately. According to the latest figures from the International Committee of the Red Cross, 848 COVID-19-related violent incidents were recorded in 2020, and this is likely an underrepresentation of a much more widespread phenomenon. In response to rises in COVID-19-related attacks against healthcare, some countries have taken action. In Algeria, for instance, the penal code was amended to increase protection for healthcare workers against attacks and to punish individuals who damage health facilities. In the United Kingdom, the police, crime, sentencing, and courts bill proposed increased the maximum penalty from 12 months to 2 years in prison for anyone who assaults an emergency worker. Measures taken by countries represent a good practical way to counteract this crisis within COVID-19. However, we stress the importance of primary prevention with the use of communication: social media and other communication channels are fundamentally important to combat violence against health professionals, both to inform the population with quality data and to disseminate campaigns to prevent these acts.

Are "cases", "waves", "tests" and "modeling" deceiving indicators to describe the COVID-19 pandemic?

This commentary elaborates on different methodological aspects complicating the interpretation of epidemiological data related to the current COVID-19 pandemic, thus preventing reliable within and across-country estimates. Firstly, an inaccuracy of epidemiological data maybe arguably be attributed to passive surveillance, a relatively long incubation period during which infected individuals can still shed high loads of virus into the surrounding environment and the very high proportion of cases not even developing signs and/or symptoms of COVID-19. The latter is also the major reason for the inappropriateness of the abused "wave" wording, which gives the idea that health system starts from scratch to respond between "peaks". Clinical data for case-management on the other hand often requires complex technology in order to merge and clean data from health care facilities. Decision-making is often further derailed by the overuse of epidemiological modeling: precise aspects related to transmissibility, clinical course of COVID-19 and effectiveness of the public health and social measures are heavily influenced by unbeknownst and unpredictable human behaviors and modelers try to overcome missing epidemiological information by relying on poorly precise or questionable assumptions. Therefore the COVID-9 pandemic may provide a valuable opportunity to rethink how we are dealing with the very basic principles of epidemiology as well as risk communication issues related to such an unprecedented emergency situation.

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.