Successful treatment of persistent SARS-CoV-2 infection with nirmatrelvir/ritonavir plus sotrovimab in four immunocompromised patients.

Immunocompromised patients with leukemia/lymphoma often have a suboptimal response to vaccination against SARS-CoV-2 and, if infected, can develop a persistent infection.SARS-CoV-2 PCR was performed on nasopharingeal swabs and serum IgG anti-SARS-CoV-2 trimeric spike glycoprotein antibodies were measured during persistence of infection. Treatment with a combination of nirmatrelvir/ritonavir plus sotrovimab led to viral clearance in three patients with leukaemia or lymphoma with persistent SARS-CoV-2 and negative SARS-CoV-2 antibody tests. No standardized treatments for persistent infection with SARS-CoV-2 infection are available. We have reported the viral clearance in two immunocompromised patients treated with antiviral drug nirmatrelvir/ritonavir and monoclonal antibody sotrovimab. We suggest that this strategy should be tested in clinical trials to find the right strategy for a clinical problem with public health implications to SARS-CoV-2 evolution and immune escape in these sub-set of patients.

A Community Study of SARS-CoV-2 Detection by RT-PCR in Saliva: A Reliable and Effective Method.

Efficient, wide-scale testing for SARS-CoV-2 is crucial for monitoring the incidence of the infection in the community. The gold standard for COVID-19 diagnosis is the molecular analysis of epithelial secretions from the upper respiratory system captured by nasopharyngeal (NP) or oropharyngeal swabs. Given the ease of collection, saliva has been proposed as a possible substitute to support testing at the population level. Here, we used a novel saliva collection device designed to favour the safe and correct acquisition of the sample, as well as the processivity of the downstream molecular analysis. We tested 1003 nasopharyngeal swabs and paired saliva samples self-collected by individuals recruited at a public drive-through testing facility. An overall moderate concordance (68%) between the two tests was found, with evidence that neither system can diagnose the infection in 100% of the cases. While the two methods performed equally well in symptomatic individuals, their discordance was mainly restricted to samples from convalescent subjects. The saliva test was at least as effective as NP swabs in asymptomatic individuals recruited for contact tracing. Our study describes a testing strategy of self-collected saliva samples, which is reliable for wide-scale COVID-19 screening in the community and is particularly effective for contact tracing.

Management of Recurrent Cystitis in Women: When Prompt Identification of Risk Factors Might Make a Difference.

BACKGROUND: Management of recurrent urinary tract infection (rUTI) is still challenging. A better understanding of the natural history of rUTI could help us reduce antibiotic use and improve antibiotic stewardship. OBJECTIVE: To describe the effect of risk identification, stratification, and counseling on the natural course of the disease in women with rUTI. DESIGN, SETTING, AND PARTICIPANTS: A total of 373 women affected by recurrent cystitis were enrolled in this longitudinal cohort study between December 2014 and December 2019. A systematic and standardized identification of risk factors was performed. INTERVENTION: As intervention, risk factors were treated or removed where possible. Patients with nonremovable risk factors were included in the control group. All patients were scheduled for follow-up visits every 6 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome measures were the rate of symptomatic recurrences and improvement in questionnaire results from baseline to the end of the follow-up period. Reduction of antibiotic usage was regarded as a secondary outcome measure. RESULTS AND LIMITATIONS: Finally, 353 women were analyzed: 196 in the study group and 157 in the control group. At the end of the follow-up period, a statistically significant reduction in the symptomatic recurrence rate was found between the two groups (0.9 ± 0.2 and 2.6 ± 0.5; p < 0.001), as well as in quality of life and anxiety according to mean questionnaire results: quality of life (0.88 ± 0.06 and 0.63 ± 0.09; p < 0.001) and Spielberger State-Trait Anxiety Inventory-Form Y (32.7 ± 9.3 and 47.5 ± 14.3; p < 0.001). The use of antibiotics was significantly lower in the study group: 4410 versus 9821 (p < 0.001). A limitation to consider is the lack of a randomized design for the active approach in the high-risk group. CONCLUSIONS: Identification, counseling, and removal of risk factors, where possible, are able to change the natural history of rUTI, by reducing the number of symptomatic episodes and antibiotic use and improving quality of life. PATIENT SUMMARY: In this report, we analyzed a large cohort of women affected by recurrent urinary tract infections and followed for a long time period. We found that risk factor identification and counseling may change the natural history of recurrent urinary tract infections, concluding that this approach is able to reduce the number of symptomatic episodes, reduce antibiotic usage, and improve patients' quality of life.

Toxoplasma gondii infection during pregnancy: a ten-year observation in the province of Trento, Italy.

The study analysed the trend of toxoplasmosis infection in pregnancy by using antenatal serological screening and the incidence of the congenital condition in newborns in the province of Trento, Italy. Data from pregnant women who gave birth at local maternity units between 2009 and 2018 were obtained. The serological test results were collected from birth attendance certificates (BACs), the main - and mandatory - source of information used to monitor pregnancies, births and neonatal health in Italy. The BAC used in the province of Trento acquires the results of serological tests for a vast range of infections in pregnancy. The data collected from the BACs were integrated with those provided by the Hospital Information System (HIS), which was also used to collect data on the trimester in which the seroconversion occurred. A total of 45,492 pregnant women were analysed, of whom 24% were foreigners. The average coverage of serological screening in pregnancy was 99.7%. Mean overall prevalence of Toxoplasma gondii infection was 21.7% (95% CI: 21.3-22.1): in Italians the prevalence was 17.9% (95% CI: 17.5-18.30) and in foreign nationals 32.7% (95% CI: 32.26-33.13). The mean annual seroconversion rate was 0.35% (95% CI: 3.0-4.2) of susceptible women and 0.27% (95% CI: 2.2-3.4) of all pregnant women who were screened. The seroconversion rate was higher amongst foreign women (0.32%, 95% CI: 3.0-3.6) than Italian women (0.24%, 95% CI: 2.1-2.8). In all, 91.0% of seroconverted women were treated during pregnancy in accordance with the anti-toxoplasma protocol. Five cases of congenital infection were identified (2 amongst Italians and 3 amongst foreign women), amounting to an overall transmission rate of 4.0% (2.3% in Italians and 8.8% in foreigners). Transmission risk ranged from 0.0% in the first trimester to 19% in the third. The incidence of congenital toxoplasmosis, over the entire study period, was 0.012% live births (0.011% in Italians and 0.016% in foreigners). Data collection on infections in pregnancy through BAC allows area-based assessment. Although the quality of the data recorded in the BAC can be considered satisfactory, it was also necessary to access other information sources. The screening coverage was very high. The prevalence of toxoplasmosis infection was found to be higher in foreign mothers than in Italians, as well as seroconversion. The extent of serological screening and the high treatment rate helped to keep the risk of infection transmission to the foetus low and to achieve a very low rate of congenital infection.

Coverage and outcomes of antenatal tests for infections: a population based survey in the Province of Trento, Italy.

BACKGROUND: Rubella, syphilis, toxoplasmosis, cytomegalovirus (CMV), hepatitis B (HBV) and C (HCV), HIV, and Group B Streptococcus (GBS) infections may have very severe outcomes during pregnancy, and for this reason, monitoring of infections in pregnant women is a requirement of prenatal assistance. AIMS: To describe coverage and outcome of the screening for rubella, syphilis, toxoplasmosis, CMV, HBV, HCV, HIV, and Group B Streptococcus in pregnancy in the Autonomous Province of Trento, Northern Italy (538,600 inhabitants). METHODS: We analysed the coverage and outcome of the above-mentioned screenings among women who delivered in the hospitals of the Province of Trento between 2007 and 2014 (N = 38,712). Screenings were grouped according to characteristics such as recommendation by national and local guidelines, scheduling of the tests, operating methods, and charge. We also estimated odds ratios (ORs) for missing screening for selected infections through multiple logistic regression. RESULTS: Estimated uptake of antenatal screening was 99.7% for rubella, 99.3% for syphilis, 99.7% for toxoplasmosis, 98.1% for HIV infection, 99.0% for HBV, 98.9% for HCV, 94.0% for GBS infection, and 75.4% for CMV infection. The overall prevalence of immunity was 94.1% for rubella, 24.2% for toxoplasmosis, and 64.2% for CMV. The rate of seroconversion in pregnant women was 0.02% for rubella, 0.29% for toxoplasmosis, and 0.75% for CMV. The overall prevalence of infection was 0.94% for HBV, 0.53% for HCV, 22.3% for GBS, 0.29% for syphilis, and 0.13% for HIV. We found a significant positive association for all screening tests, between lack of testing and late first medical examination in pregnancy (ORs ranging from 1.20 to 1.66 for the first medical visit in the second trimester and ORs ranging from 1.60 to 5.88 for the first medical visit in third trimester, compared to early medical visit in the first trimester). Compared to Italian citizenship, foreign citizenship of the mother was also positively associated with absence of screening (ORs ranging from 1.30 to 1.53). A significant inverse association was observed for calendar year of delivery (ORs ranging from 0.71 to 0.97, for 1 year increment). Less educated mothers and pluriparae were also at higher risks of not being tested. Analysis of the association with mother age showed different heterogeneous effects. CONCLUSIONS: Our study indicates that the attention to screening and detecting infected cases is growing over the time. In addition, care delivered during pregnancy has a leading role in determining coverage of the examinations. Immigrant, pluriparous and less educated women need particular attention.