The Dynamic Risk of COVID-19-Related Events in Vaccinated Healthcare Workers (HCWs) from a Tertiary Hospital in Bucharest, Romania: A Study Based on Active Surveillance Data.

Our study describes the frequency and severity of COVID-19 in HCWs and estimates the dynamic risk of COVID-19-related events. We actively surveyed all HCWs from a tertiary infectious disease hospital from 26 February 2020 to 31 May 2023. Of 1220 HCWs, 62.9% (767) had at least one COVID-19 episode. The under 29 years (p = 0.0001) and 40-49 years (p = 0.01) age groups, nurses (p = 0.0001), and high-risk departments (p = 0.037) were characteristics significantly more frequent in HCWs with COVID-19 history. A higher percentage of boosters (53.2%; p < 0.0001) were registered in the uninfected group. The second episode of COVID-19 was significantly milder than the first. Data regarding clinical outcomes from 31 January 2021 to 31 May 2023 were analyzed in a follow-up study to determine the risk of COVID-19-related events. The Cox regression analysis revealed that HCWs with booster shots had a lower risk of COVID-19 across all events, symptomatic events, and moderate to severe events as adjusted hazard ratio (aHR) were: 0.71 (95%CI: 0.54-0.96), 0.23 (95%CI: 0.12-0.46), and 0.17 (95%CI: 0.07-0.43), respectively. Within the vaccinated subgroup, the HCWs with hybrid immunity and booster had aHR for all followed-up events of 0.42 (95%CI: 0.30-0.58), for symptomatic events of 0.52 (95%CI: 0.36-0.74), and 0.15 (95%CI: 0.03-0.66) for moderate to severe events. The risk of COVID-19 clinical events was lower for HCWs with at least one booster than those completely vaccinated.

Vaccination and Factors Related to the Clinical Outcome of COVID-19 in Healthcare Workers-A Romanian Front-Line Hospital's Experience.

The study aims to describe the frequency of COVID-19 in healthcare workers (HCWs) in a designated hospital for COVID-19 treatment in Bucharest, Romania, and to explore COVID-19 vaccination and other factors associated with the clinical outcome. We actively surveyed all HCWs from 26 February 2020 to 31 December 2021. Cases were laboratory-confirmed with RT-PCR or rapid test antigen. Epidemiological, demographic, clinical outcomes, vaccination status, and co-morbidities data were collected. Data were analyzed using Microsoft Excel, SPSS, and MedCalc. A total of 490 cases of COVID-19 in HCWs were diagnosed. The comparison groups were related to the severity of the clinical outcome: the non-severe group (279, 64.65%) included mild and asymptomatic cases, and the potentially severe group included moderate and severe cases. Significant differences between groups were registered for high-risk departments (p = 0.0003), exposure to COVID-19 patients (p = 0.0003, vaccination (p = 0.0003), and the presence of co-morbidities (p < 0.0001). Age, obesity, anemia, and exposure to COVID-19 patients predicted the severity of the clinical outcomes (χ2 (4, n = 425) = 65.69, p < 0.001). The strongest predictors were anemia and obesity (OR 5.82 and 4.94, respectively). In HCWs, mild COVID-19 cases were more frequent than severe cases. Vaccination history, exposure, and individual risk influenced the clinical outcome suggesting that measures to protect HCWs and occupational medicine are important for pandemic preparedness.

Therapeutic developments for SARS-CoV-2 infection-Molecular mechanisms of action of antivirals and strategies for mitigating resistance in emerging variants in clinical practice.

This article systematically presents the current clinically significant therapeutic developments for the treatment of COVID-19 by providing an in-depth review of molecular mechanisms of action for SARS-CoV-2 antivirals and critically analyzing the potential targets that may allow the selection of resistant viral variants. Two main categories of agents can display antiviral activity: direct-acting antivirals, which act by inhibiting viral enzymes, and host-directed antivirals, which target host cell factors that are involved in steps of the viral life cycle. We discuss both these types of antivirals, highlighting the agents that have already been approved for treatment of COVID-19, and providing an overview of the main molecules that are currently in drug development. Direct-acting antivirals target viral enzymes that are essential in the viral life cycle. Three direct-acting antivirals are currently in use: two are nucleoside analogs that inhibit the RNA-dependent RNA polymerase of SARS-CoV-2, i.e., remdesivir and molnupiravir, and the third one, nirmatrelvir/ritonavir, is an inhibitor of SARS-CoV-2 main protease. The potential for induction of viral resistance is discussed for each of these antivirals, along with their clinical activity on each of the SARS-CoV-2 variants and sublineages that have been dominant over the course of the pandemic, i.e., Alpha, Delta, as well as Omicron and its sublineages BA.1, BA.2, BA.5, BQ.1 and XBB. Host-directed antivirals are currently in preclinical or clinical development; these agents target host cell enzymes that are involved in facilitating viral entry, replication, or virion release. By blocking these enzymes, viral replication can theoretically be effectively stopped. As no SARS-CoV-2 host-directed antiviral has been approved so far, further research is still needed and we present the host-directed antivirals that are currently in the pipeline. Another specific type of agents that have been used in the treatment of COVID-19 are neutralizing antibodies (NAbs). Their main binding site is the spike protein, and therefore their neutralization activity is influenced by mutations occurring in this region. We discuss the main changes in neutralization activity of NAbs for the most important dominant SARS-CoV-2 variants. Close monitoring of emerging variants and sublineages is still warranted, to better understand the impact of viral mutations on the clinical efficiency of antivirals and neutralizing antibodies developed for the treatment of COVID-19.

Prevalence of undiagnosed hepatitis B virus infection in patients with COVID-19A single center retrospective study.

At its onset, the coronavirus disease 2019 (COVID-19) pandemic brought significant challenges to healthcare systems, changing the focus of medical care on acute illness. Disruptions in medical service provision have impacted the field of viral hepatitis, with screening programs paused throughout much of 2020 and 2021. We performed a retrospective study on consecutive outpatients with COVID-19 during the second and third wave of COVID-19 in Romania, from November 2020 to April 2021, aiming to characterize the prevalence of undiagnosed hepatitis B virus (HBV) infection among patients presenting with acute illness. Overall, 522 patients had available records during the study timespan. Their mean ±â€…standard deviation age was 51 ±â€…13 years; 274 (52.5%) were male. We identified 16 (3.1%) cases of active HBV infection; only six of these patients were aware of their HBV status, and 3 of the newly diagnosed cases were identified as candidates for HBV treatment. A total of 96 patients (18.4%) had serological markers suggestive for prior HBV vaccination. A large proportion of patients (n = 120, 23.0%) had positive HBV core antibodies; among these, 90 (17.2%) had cleared a previous HBV infection (being positive for HBV surface antibodies and HBV core antibodies). We identified the following parameters that were significantly more frequent in patients with a history of HBV infection: older age (P < .001), hypoalbuminemia (P = .015), thrombocytopenia (P < .001), thrombocytopenia followed by thrombocytosis (P = .041), increased blood urea nitrogen (P < .001) and increased creatinine (P = .011). In conclusion, the COVID-19 pandemic has taught us essential lessons about the importance of maintaining access to screening programs and of ensuring active monitoring of patients with chronic infections such as hepatitis B, even during a medical crisis.