Hybrid Immunity and the Incidence of SARS-CoV-2 Reinfections during the Omicron Era in Frontline Healthcare Workers.

During the coronavirus disease (COVID-19) pandemic healthcare workers (HCWs) acquired immunity by vaccination or exposure to multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our study is a comparative analysis between subgroups of HCWs constructed based on the number of SARS-CoV-2 infections, vaccination, and the dominant variant of SARS-CoV-2 in the population. We collected and analyzed data using the χ2 test and density incidence of reinfections in Microsoft Excel for Mac, Version 16.84, and MedCalc®, 22.026. Of the 829 HCWs, 70.1% (581) had only one SARS-CoV-2 infection and 29.9% (248) had two infections. Of the subjects with two infections, 77.4% (192) worked in high-risk departments and 93.2% (231) of the second infections were registered during Omicron dominance. The density incidence of reinfections was higher in HCWs vaccinated with the primary schedule than those vaccinated with the first booster, and the incidence ratio was 2.8 (95% CI: 1.2; 6.7). The probability of reinfection was five times lower (95% CI: 2.9; 9.2) in HCWs vaccinated with the primary schedule if the first infection was acquired during Omicron dominance. The subjects vaccinated with the first booster had a density incidence of reinfection three times lower (95% CI: 1.9; 5.8) if the first infection was during Omicron. The incidence ratio in subgroups constructed based on characteristics such as gender, age group, job category, and department also registered significant differences in density incidence. The history of SARS-CoV-2 infection by variant is important when interpreting and understanding public health data and the results of studies related to vaccine efficacy for hybrid immunity subgroup populations.

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.

Clinical Features and Outcomes of the Association of Co-Infections in Children with Laboratory-Confirmed Influenza during the 2022-2023 Season: A Romanian Perspective.

The 2022-2023 influenza season in Romania was characterized by high pediatric hospitalization rates, predominated due to influenza A subtypes (H1N1) pdm09 and H3N2. The lowered population immunity to influenza after the SARS-CoV-2 pandemic and the subsequent stoppage of influenza circulation, particularly in children who had limited pre-pandemic exposures, influenced hospitalization among immunosuppressed children and patients with concurrent medical conditions who are at an increased risk for developing severe forms of influenza. This study focused on the characteristics of influenza issues among pediatric patients, as well as the relationship between different influenza virus types/subtypes and viral and bacterial co-infections, as well as illness severity in the 2022-2023 season after the SARS-CoV-2 pandemic. We conducted a retrospective clinical analysis on 301 cases of influenza in pediatric inpatients (age ≤ 18 years) who were hospitalized at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" IX Pediatric Infectious Diseases Clinical Section between October 2022 and February 2023. The study group's median age was 4.7 years, and the 1-4 year age group had the highest representation (57.8%). Moderate clinical forms were found in 61.7% of cases, whereas severe versions represented 18.2% of cases. Most of the complications were respiratory (acute interstitial pneumonia, 76.1%), hematological (72.1%, represented by intra-infectious and deficiency anemia, leukopenia, and thrombocytopenia), and 33.6% were digestive, such as diarrheal disease, liver cytolysis syndrome, and the acute dehydration syndrome associated with an electrolyte imbalance (71.4%). Severe complications were associated with a risk of unfavorable evolution: acute respiratory failure and neurological complications (convulsions, encephalitis). No deaths were reported. We noticed that the flu season of 2022-2023 was characterized by the association of co-infections (viral, bacterial, fungal, and parasitic), which evolved more severely, with prolonged hospitalization and more complications (p < 0.05), and the time of use of oxygen therapy was statistically significant (p < 0.05); the number of influenza vaccinations in this group was zero. In conclusion, co-infections with respiratory viruses increase the disease severity of the pediatric population to influenza, especially among young children who are more vulnerable to developing a serious illness. We recommend that all people above the age of six months should receive vaccinations against influenza to prevent the illness and its severe complications.

Remdesivir Efficacy and Tolerability in Children with COVID-19-Associated Allergic Comorbidities such as Asthma, Allergic Rhinitis, and Atopic Dermatitis.

In children, coronavirus disease 2019 (COVID-19) starts as a minor illness compared to adults, but during the ongoing COVID-19 pandemic, distinct SARS-CoV-2 variants and subvariants have changed options for therapies in both adults and children, especially for those with comorbidities such as allergies. On 25 April 2022, Remdesivir (RDV), a viral RNA-dependent RNA polymerase inhibitor, was approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 28 days and older, weighing ≥3 kg, hospitalized or non-hospitalized, who are at high risk of progression to severe forms of COVID-19. While RDV has been shown to have favorable effects in numerous types of research conducted on adults, such as shortening hospital stays, and has shown it has antiviral effects on various RNA viruses, there is a lack of findings regarding safety, tolerability, and efficacy of RDV in allergic pediatric patients since its initial FDA approval. This study aims to assess RDV's efficacy and tolerability in treating pediatric patients with mild and severe forms of COVID-19-associated allergies such as asthma, allergic rhinitis, and atopic dermatitis and how RDV affects the duration of hospitalization, especially for these comorbidities. The most recent pandemic wave among children rose due to the high transmissibility of the Omicron variant, and this study analyzed changes between July 2020 and September 2022 at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș", Bucharest, Romania. Our retrospective study included 250 children <18 years old, 42 (16.8%) had allergies, 132 were males (52.8%), age group 0-5 years old (80%), with a positive viral test for SARS-CoV-2. Severity was categorized as mild (43.6%), moderate (53.2%), and severe (1.6%) COVID-19, and treatment with RDV was administered in 50.4% (126/250) of children included in the study. The presence of comorbidities, asthma (7.2%), allergic rhinitis (4.4%), and atopic dermatitis (4.4%), was associated with an increased risk of developing severe COVID-19 infection in children, p < 0.05. We did not register deaths and severe complications; all cases evolved favorably under the instituted treatment. Laboratory abnormalities in transaminase levels 53.97% (ALT) and 61.9% (AST) were grades 1 or 2 and did not require discontinuation of the antiviral treatment, p < 0.05. RDV in children reduced the duration and evolution of COVID-19 and decreased the length of hospitalization in group-associated allergies; p < 0.05. This article summarizes RDV's efficacy among children with COVID-19 and allergies when the clinical result was improved and reports positive effects on tolerability and reduced duration of hospitalization, especially in children with asthma, atopic dermatitis, and allergic rhinitis. More studies are needed to confirm our findings.

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.

Liver fibrosis progression in a cohort of young HIV and HIV/ HBV co-infected patients: A longitudinal study using non-invasive APRI and Fib-4 scores.

Background: The risk of liver fibrosis increases over time in HIV and HIV-HBV individuals even under antiretroviral treatment (ART), warranting a rigorous and periodic monitorization. Given the lower availability of transient elastography, we aimed to assess the longitudinal variation of two non-invasive liver fibrosis scores, APRI and Fib-4, in cases with HIV monoinfection, HIV-HBV co-infection and individuals with HBsAg-seroclearance. Methods: We performed an observational retrospective study between 2013 and 2019 on 212 HIV patients including 111 individuals with HIV mono-infection, 62 individuals with HIV-HBV co-infection and positive HBsAg and 39 cases with HIV-HBV infection and HBsAg-loss. The groups were followed at 36, 48, and 60 months. Liver fibrosis was indicated by an APRI >0.5 or Fib-4≥1.45 score and advanced fibrosis by an APRI score >1.5 or Fib-4 >3.25. Logistic regression with generalized estimating equations (GEE) was used to assess the predictors for the presence of liver fibrosis over time. Results: During a median follow-up of 58.5 months the prevalence of liver fibrosis in all patients increased with 0.5% reaching 11.3% using an APRI score and with 0.9% reaching 10.8% using the Fib-4 score. At the visit corresponding to 60 months the prevalence of liver fibrosis was higher in all HIV-HBV patients compared with individuals with HIV mono-infection, namely: 16.1% on APRI and 12.9% on the Fib-4 score in HIV-HBV/HBsAg-positive individuals, 12.8% on both APRI and Fib-4 scores in HIV-HBV/HBsAg-negative individuals vs. 8.1 and 9%, respectively in HIV mono-infection. The presence of liver fibrosis over the study period was independently associated with plasma HIV RNA, CD4+T cell counts, HIV-HBV co-infection (for APRI >0.5) and ART non-adherence (for Fib-4 >1.45). At the final visit, non-adherence to ART and CD4+T cell counts remained associated with liver fibrosis. Conclusions: The study found a slow progression of APRI and Fib-4 scores over time in young PLWH with extensive ART. Liver fibrosis scores continued to increase in patients with HIV mono-infection yet remained lower than in HIV-HBV patients irrespective on the presence of HBsAg. The periodic follow-up using non-invasive scores on the long-term could help improve the surveillance in low-income settings and high scores should be followed by additional diagnostic methods.

Circulation of influenza A viruses among patients hospitalized for severe acute respiratory infection in a tertiary care hospital in Romania in the 2018/19 season: Results from an observational descriptive epidemiological study.

ABSTRACT: The seasonal circulation of influenza viruses and the impact that this infection has on the population varies from year to year. We have prospectively captured hospital-based surveillance data describing the circulation of influenza viruses and characterizing patients with influenza admitted to a tertiary hospital in Bucharest, Romania in the 2018/19 season.We have conducted an observational descriptive epidemiological study analyzing all consecutive patients hospitalized for influenza like illness or severe acute respiratory infection at the National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Bucharest, Romania, from November 2018 to April 2019. For all patients we actively collected standardized clinical information and performed real-time reverse transcription polymerase chain reaction testing of respiratory samples to identify the presence of influenza viruses and to determine the subtype/lineage.A total of 1128 hospitalized patients were tested in this study, with an influenza positivity rate of 41.2% (n = 465). We identified an exclusive circulation of influenza A viruses (A/H1 - 57.2%, A/H3 - 29.3%, A not subtyped - 13.3%), with only 1 case of influenza B detected at the end of the season (week 18/2019). Children under 5 years of age accounted for the majority of cases (40%, n = 186), and all cases had a favorable evolution. Females were more likely to test positive for influenza (53.3%) compared to males (46.7%), P = .048, and presence of asthma or chronic obstructive pulmonary disease increased the risk of influenza 4.4-fold and 2-fold, respectively (P < .001 and P = .034). Thirteen influenza patients required hospitalization in intensive care and 5 deaths were recorded (1.1%). The vaccination rate for all patients included in the study was low (4.6%). The existence of chronic conditions or age over 65 years prolonged the hospitalization period with 2 days (P < .001 each).In the 2018/19 season, we identified an important circulation of influenza A viruses among patients hospitalized for influenza like illness/severe acute respiratory infection in a tertiary care hospital in Romania, with a higher likelihood of affecting females and patients with pre-existing lung conditions. Monitoring of the clinical and epidemiological characteristics of influenza virus infection is of great interest and should be done carefully each season to better inform on the necessary measures to limit the impact that this infection may have on risk groups.

Transient immune hepatitis as post-coronavirus disease complication: A case report.

BACKGROUND: We report a case of post-coronavirus disease (COVID) immune hepatitis occurring in a young male with no pre-existing comorbidities. CASE SUMMARY: A previously healthy 21-year-old male patient was admitted to our hospital with mild COVID-19. During the course of in-hospital isolation and monitoring, he developed an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase, with the enzymes peaking at day 24 (ALT 15 times the upper normal limit), with preserved liver function. The liver enzyme increase occurred 20 d after the complete clinical remission of COVID-19, and ALT dynamics paralleled the increase in total antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The case was interpreted as post-COVID immune hepatitis, with extensive laboratory investigations excluding other potential causes. The hepatocytolysis remitted 20 d after the peak ALT, without further intervention, with complete recovery, but the total anti-SARS-CoV-2 antibodies continued to increase the next 5 mo following the acute infection. CONCLUSION: Close attention should also be paid to young patients with mild forms of disease, and a high index of suspicion should be maintained for post-COVID complications.

Measles in Romania - clinical and epidemiological characteristics of hospitalized measles cases during the first three years of the 2016-ongoing epidemic.

A large measles epidemic has been ongoing in Romania and many European countries, since 2016. We report case-based surveillance data for all patients (n = 1371) with laboratory-confirmed and epidemiologically-confirmed measles hospitalized in a major infectious diseases hospital in Bucharest Romania during the first three years of the current measles epidemic (July 2016-July 2019). More than half of the patients (57.6%) had ages below 5 years; 6% (n = 82) had preexisting comorbidities. Only 1.5% of the patients had been fully vaccinated, 5.9% had received only one vaccine dose, while 92.8% had not been vaccinated at all against measles. The rate of measles-related complications was 93.4%; complications occurred more frequently among patients who were not eligible for vaccination due to young age or underlying diseases, and among children, who developed pneumonia and enterocolitis more frequently than adults. The median hospital length-of-stay was 6 days. Eight cases (0.6%) required intensive care and mechanical ventilation, and three deaths (0.2%) were recorded. Measles disproportionately affects patient groups who are not eligible for vaccination. During the current epidemic in Romania, 98.5% of the patients hospitalized for measles had not been vaccinated and among these, 75.7% would have been eligible for vaccination. For the remaining pool of unvaccinated children, supplementary immunization activities are urgently needed.

The 2017-2018 influenza season in Bucharest, Romania: epidemiology and characteristics of hospital admissions for influenza-like illness.

BACKGROUND: Seasonal influenza causes a considerable burden to healthcare services every year. To better measure the impact of severe influenza cases in Romania, we analyzed active surveillance data collected during the 2017-2018 season from patients admitted for influenza-like illness (ILI) at a tertiary care hospital in Bucharest. METHODS: Patients admitted for acute ILI were included if they were resident in the Bucharest-Ilfov region, had been hospitalized for at least 24 h, and had onset of symptoms within 7 days before admission. Patient demographics, healthcare use, vaccination status, and outcome data were collected by questionnaire or by searching clinical records. Respiratory swabs were also obtained from each patient to confirm influenza A (A/H1 and A/H3 subtypes) or influenza B (Yamagata and Victoria lineages) infection by real-time reverse-transcription polymerase chain reaction assay. RESULTS: The study included 502 patients, many (45.2%) of whom were aged < 5 years. Overall, 108 patients (21.5%) had one or more comorbidities. Seventeen adults aged 18-64 years (3.4%) had been vaccinated against influenza. Patients were hospitalized for a median of 5 days and most (90.4%) were prescribed antiviral treatment. More than one-half of the patients (n = 259, 51.6%) were positive for influenza. Most influenza cases were caused by B viruses (172/259, 66.4%), which were mostly of the B/Yamagata lineage (85 of 94 characterized, 90.4%). Most of the subtyped A viruses were A/H1 (59/74, 79.7%). A/H1 viruses were frequently detected in influenza-positive admissions throughout the 2017-2018 season, whereas the predominant B/Yamagata viruses were detected around the middle of the season, with a peak in cases at week 7 of 2018. Eleven patients were admitted to an intensive care unit; of these, one patient with confirmed B/Yamagata infection died. CONCLUSIONS: These results show that seasonal influenza results in considerable hospitalization in Bucharest-Ilfov, Romania and suggest vaccine coverage should be extended, especially to the youngest age groups. The data from this study should help inform and optimize national influenza healthcare policies.

The influenza season 2016/17 in Bucharest, Romania - surveillance data and clinical characteristics of patients with influenza-like illness admitted to a tertiary infectious diseases hospital.

BACKGROUND: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. OBJECTIVES: To describe the influenza cases and viral circulation among hospitalized patients. METHODS: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. RESULTS: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3-13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n=57) and all influenza B were B/Victoria (n=76). Patients who tested positive for influenza presented fewer comorbidities (p=0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p=0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p=0.031). CONCLUSIONS: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.

The influenza season 2016/17 in Bucharest, Romania - surveillance data and clinical characteristics of patients with influenza-like illness admitted to a tertiary infectious diseases hospital

ABSTRACT Background: Influenza continues to drive seasonal morbidity, particularly in settings with low vaccine coverage. Objectives: To describe the influenza cases and viral circulation among hospitalized patients. Methods: A prospective study based on active surveillance of inpatients with influenza-like illness from a tertiary hospital in Bucharest, Romania, in the season 2016/17. Results: A total of 446 patients were tested, with a balanced gender distribution. Overall, 192 (43%) patients tested positive for influenza, with the highest positivity rate in the age groups 3-13 years and >65 years. Peak activity occurred between weeks 1 and 16/2017, with biphasic distribution: A viruses were replaced by B viruses from week 9/2017; B viruses predominated (66.1%). Among the 133 (69.3%) subtyped samples, all influenza A were subtype H3 (n = 57) and all influenza B were B/Victoria (n = 76). Patients who tested positive for influenza presented fewer comorbidities (p = 0.012), except for the elderly, in whom influenza was more common in patients with comorbidities (p = 0.050). Disease evolution was generally favorable under antiviral treatment. The length of hospital stay was slightly longer in patients with influenza-like illness who tested patients negative for influenza (p = 0.031). Conclusions: Distinctive co-circulation of A/H3 and B/Victoria in Bucharest, Romania in the 2016/17 influenza season was found. While the A/H3 subtype was predominant throughout Europe that season, B/Victoria appears to have circulated specifically in Romania and the Eastern European region, predominantly affecting preschoolers and school children.

Nasopharyngeal carriage of Streptococcus pneumoniae in Romanian children before the introduction of the pneumococcal conjugated vaccination into the national immunization programme: a national, multi-centre, cross-sectional observational study.

OBJECTIVES: We analysed the distribution of vaccine and non-vaccine Streptococcus pneumoniae serotypes and the antimicrobial susceptibility of pneumococcal strains isolated from healthy Romanian children. METHODS: A multi-centre cross-sectional study was performed in four counties to evaluate carried strains of S. pneumoniae isolated from 2000 children aged 0-5 years. RESULTS: S. pneumoniae carriage was detected in 25.25% of the tested children. Carriage increased from 16.7% among infants to 29.4% in 3-5-year-old children (p<0.0001). The proportions of the serotypes included in pneumococcal conjugate vaccines PCV7, PCV10, and PCV13 among our isolates were 39.9%, 40.1%, and 58.7%, respectively. Erythromycin resistance was 72.5%, and it was significantly lower in non-vaccine serotypes compared with PCV13 serotypes: 57.3% versus 83.6% (p<10(-7)). Penicillin minimum inhibitory concentrations (MICs) >0.064mg/l were recorded in 71.6%, but the penicillin MIC was >2mg/l for only 8.4% of tested isolates. CONCLUSIONS: In Romanian children, the majority of carried S. pneumoniae isolates are vaccine serotypes. The isolates with MICs defining macrolide resistance were very frequent, as well as the isolates with MICs defining penicillin resistance in the case of meningitis or penicillin dose-dependent susceptibility for other infections, mainly for the strains belonging to PCV13 serotypes. The implementation of PCV13 within the Romanian national immunization programme could reduce the circulation of these strains with higher macrolide and/or penicillin MICs.

Postinfectious arthritis in pediatric practice.

ABSTRACT: Postinfectious arthritis is a relatively often encountered in pediatric practice. The authors present the most important data concerneing this pathology, with up to date informations exemplifying with case presentations. Clinical cases bring to attention the most common forms of postinfectious arthritis (reactive arthritis, postinfectious arthritis bacterial, viral, spirochete, and so on). Although highly studied and commonly found in current pediatric practice, arthritis occurring after infections remains controversial entities, especially regarding terminology. While, according to some authors, postinfectious arthritis belongs to the large group of reactive arthritis, by other authors, these joint events are independent entities.