Treatment with anti-SARS-CoV-2 monoclonal antibodies in pregnant and postpartum women: first experiences in Florence, Italy.

PURPOSE: Pregnant and postpartum women are at increased risk of developing severe COVID-19. Monoclonal antibodies (mAbs) are now widely used in high-income countries to treat mild to moderate COVID-19 outpatients at risk for developing severe disease. Very few data are available on the use of mAbs in special populations, including pregnant and postpartum women. Here we present our early experience with mAbs in these two populations. METHODS: Electronic records of pregnant and postpartum women treated with mAbs at Careggi University Hospital, Florence, were retrieved. Relevant data were extracted (age, presence of risk factors for COVID-19, oxygen support, mAb type, gestational age, and pregnancy status). When available, outcomes at 28 days after administration were also included. RESULTS: From March 1st to September 30th 2021, eight pregnant and two postpartum women have been treated with mAbs at our center. The median age was 31 years (IQR 30-33.5, range 29-38), median gestational age was 24 weeks. Seven patients had additional risk factors. According to the Italian disposition, all patients received casirivimab/imdevimab, with five receiving a 2.4 mg dose and five receiving a 8 g dose. Eight patients improved. One developed myocarditis, considered a COVID-19 complication. Another required a transient increase of low flow oxygen support before improving and being discharged. At a 28 days follow-up, all patients were clinically recovered. We did not observe mAbs related adverse events. CONCLUSION: Although preliminary data should be interpreted with caution, it is remarkable how mAbs were well tolerated by pregnant women with COVID-19. Further data on mAbs in this special population should be collected but the use of mAbs in pregnant and postpartum patients should be considered. Even thus oral antivirals are becoming available, they are not recommended in pregnant and postpartum women. This population may specifically benefit from treatment with last generation mAbs.

Parenchymal Cavitations in Pulmonary Tuberculosis: Comparison between Lung Ultrasound, Chest X-ray and Computed Tomography.

This article aims to detect lung cavitations using lung ultrasound (LUS) in a cohort of patients with pulmonary tuberculosis (TB) and correlate the findings with chest computed tomography (CT) and chest X-ray (CXR) to obtain LUS diagnostic sensitivity. Patients with suspected TB were enrolled after being evaluated with CXR and chest CT. A blinded radiologist performed LUS within 3 days after admission at the Infectious Diseases Department. Finally, 82 patients were enrolled in this study. Bronchoalveolar lavage (BAL) confirmed TB in 58/82 (71%). Chest CT showed pulmonary cavitations in 38/82 (43.6%; 32 TB patients and 6 non-TB ones), LUS in 15/82 (18.3%; 11 TB patients and 4 non-TB ones) and CXR in 27/82 (33%; 23 TB patients and 4 non-TB ones). Twelve patients with multiple cavitations were detected with CT and only one with LUS. LUS sensitivity was 39.5%, specificity 100%, PPV 100% and NPV 65.7%. CXR sensitivity was 68.4% and specificity 97.8%. No false positive cases were found. LUS sensitivity was rather low, as many cavitated consolidations did not reach the pleural surface. Aerated cavitations could be detected with LUS with relative confidence, highlighting a thin air crescent sign towards the pleural surface within a hypoechoic area of consolidation, easily distinguishable from a dynamic or static air bronchogram.

Prevention, diagnosis and pharmacological treatment of infections in pregnancy: The mobile app GAIA! for healthcare providers and patients.

OBJECTIVE: To develop and assess the GAIA! app, designed to assist pregnant women and healthcare professionals in managing infectious diseases during pregnancy, and to bridge the information gap between health professionals and expectant mothers. STUDY DESIGN: This collaborative initiative in Italy involved partnerships with the University of Florence, Careggi University Hospital, and other institutions. The app, built on the Ionic framework, is available on both Apple and Google App Stores. It offers two distinct modes: "healthcare providers" and "patients." Content for the app was derived from extensive literature reviews and clinical guidelines. RESULTS: Since its August 2022 launch, the GAIA! app has garnered over 2,500 downloads, indicating its effectiveness and acceptance within the community. The app differentiates itself from others, such as the Sanford Guide, by focusing specifically on the needs of pregnant women. It ensures cross-platform compatibility, a user-friendly interface, and offline functionality. CONCLUSIONS: The GAIA! app has successfully addressed a niche in infectious disease management for pregnant women, gaining significant traction within the community. While it has seen substantial success, challenges like continuous updates and potential language expansion remain. Future endeavors will address these challenges and further evaluate the app's impact on maternal and child health.

Orbital Infiltration in a Patient with Waldenström Macroglobulinemia: Need for Multidisciplinary Approach and Comparison with the Literature.

The use of specific inhibitory drugs of intracellular signalling pathways (such as Bruton-Kinase inhibitors) for the treatment of Waldenström's macroglobulinaemia (WM) is a recognised risk factor for Aspergillus spp. infections. The overlapping clinical manifestations of the two diseases may require the involvement of different medical specialities. We describe the clinical course of a patient with pulmonary and encephalic aspergillosis, with concomitant orbital infiltration, which represented a difficult diagnosis: the case required a multidisciplinary approach to define the ocular lesions and an in-depth study of the literature.

Asymptomatic CMV infection at birth following maternal primary infection despite valacyclovir treatment and a subsequent negative amniocentesis. Case report.

Valacyclovir is currently the only pharmacological intervention demonstrated to reduce the risk of vertical CMV congenital infection within a randomized clinical trial in case of primary infection during pregnancy. So far, no data are available on the prognosis of children with congenital CMV infection diagnosed at birth after a negative amniocentesis whose mother were treated with valacyclovir during pregnancy, therefore it is essential to carry out a rigorous neurocognitive follow-up in these children in order to investigate the potential clinical consequence.

Lung ultrasound (LUS) in pulmonary tuberculosis: correlation with chest CT and X-ray findings.

AIMS: The aim is to describe lung ultrasound (LUS) findings in a cohort of patients with suspected pulmonary tuberculosis (PTB) and compare them with computed tomography (CT) and chest x-ray (CXR) findings in order to evaluate the potentiality of LUS in TB diagnosis. METHODS: In this prospective study, 82 subjects with suspected TB were enrolled after being evaluated with CXR and chest CT. LUS was performed by blinded radiologists within 3 days after admission. A semiquantitative index was used: score 1 (lesions that extend for about 1-15% of the affected zone), score 2 (15-40%) and score 3 (40-100%). RESULTS: Microbiological analysis confirmed TB diagnosis in 58/82 (70.7%). CT was positive in all patients, LUS in 79/82 (96.3%) CXR in 78/82 (95.1%) and adding LUS and CXR in 100%. In PTB patients we found a great number of lungs zones with micronodules and with total findings than non-TPB patients (p < 0.05). Overall LUS sensitivity was 80%, greater for micronodules (82%) and nodules (95%), lower for consolidation with air bronchogram (72%) and cavitations (33%). We reported 5 complicated pleural effusion at LUS, only 1 in CT. CXR overall sensitivity was 81%. Adding CXR and LUS findings we reported a sensitivity of 90%. CONCLUSIONS: LUS could be considered a valid, non-invasive and cost-effective diagnostic tool especially in world regions where CT were not available, also in addiction with CXR. TRIAL REGISTRATION: This study was approved by the Ethics Committee of our University Hospital (rif. CEAVC 14,816).

Infection with SARS-CoV-2 Variants Is Associated with Different Long COVID Phenotypes.

COVID-19 has been associated with a broad range of long-term sequelae, commonly referred to as "long-COVID" or "post-COVID-19" syndrome. Despite an increasing body of literature, long COVID remains poorly characterized. We retrospectively analysed data from electronic medical records of patients admitted to the post-COVID-19 outpatient service of the Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy, between June 2020 and June 2021, 4-12 weeks after hospital discharge. A total of 428 patients, 41% women, median age 64 years, underwent a follow-up visit a median 53 days after hospital discharge. Overall, 76% patients reported at least one persistent symptom, including dyspnoea (37%), chronic fatigue (36%), insomnia (16%), visual disorders (13%) and brain fog (13%). Increasing oxygen support (OR 1.4, 95% CI 1.1-1.8), use of immunosuppressants (OR 6.4, 95% CI 1.5-28) and female sex (OR 1.8, 95% CI 1.1-2.9) were associated with a higher risk of long COVID symptoms. Comparison between symptomatic patients infected in the period March-December 2020 (prevalent circulation of wild-type SARS-CoV-2) with those infected in the period January-April 2021 (prevalent circulation of B.1.1.7 Alpha variant) showed a significant modification in the pattern of symptoms belonging to the neurological and cognitive/emotional categories. Our findings confirmed shortness of breath and chronic fatigue as the most frequent long COVID manifestations, while female sex and severe COVID-19 course were the main risk factors for developing lingering symptoms. SARS-CoV-2 variants may induce different long COVID phenotypes, possibly due to changes in cell tropism and differences in viral-host interaction.

Emerging Infectious Diseases in Pregnant Women in a Non-Endemic Area: Almost One Out of Four Is at Risk.

We report the results of a targeted testing strategy for five emerging infectious diseases (Chagas disease, human T-lymphotropic virus 1 infection, malaria, schistosomiasis, and Zika virus infection) in pregnant women accessing an Italian referral centre for infectious diseases in pregnancy for unrelated reasons. The strategy is based on a quick five-question questionnaire which allows the identification of pregnant women at risk who should be tested for a specific disease. One hundred and three (24%) out of 429 pregnant women evaluated in a 20 month period were at risk for at least one emerging infectious disease. Three (2.9%, all from sub-Saharan Africa) out of 103 at-risk women resulted in being affected (one case of Plasmodium falciparum malaria, two cases of schistosomiasis) and were appropriately managed. Prevalence of emerging infectious disease was particularly high in pregnant women from Africa (three out of 25 pregnant women tested, 12%). The proposed strategy could be used by health care professionals managing pregnant women in non-endemic setting, to identify those at risk for one of the five infection which could benefit for a targeted test and treatment.

Should obstetricians working in non-endemic countries care about emerging tropical diseases?

Due to migration and international travels, obstetricians are increasingly faced with a globalized obstetric setting and should adapt their daily clinical and diagnostic approach to the modifications of tropical and subtropical infections epidemiology. This paper is focused on five emerging infectious diseases, namely Chagas disease, HTLV-1 infection, malaria, schistosomiasis and Zika virus infection, having a high prevalence in migrant populations and which can affect international travelers. These diseases frequently pass unrecognized since they are characterized by few or no symptoms during pregnancy, however they may cause a relevant maternal, fetal and neonatal impact. Specific and reliable diagnostic and treatment options are available but are rarely used during routine obstetrical practice.

Primary toxoplasmosis acquired during early pregnancy: Is it currently overestimated?

OBJECTIVE: Toxoplasmosis acquired in early pregnancy is a potentially severe complication for the fetus. Evaluating the risk of transplacental infection in pregnant women accessing the Tuscany Reference Center for Infectious Diseases in Pregnancy during the last 20 years with suspected or confirmed toxoplasmosis acquired in early pregnancy was the aim of the study. STUDY DESIGN: We retrospectively enrolled all pregnant women undergoing amniocentesis for toxoplasmosis acquired in the first 16 gestational weeks in the period 1999-2019, comparing patients with certain acute infection (seroconversion occurred in pregnancy, CAIP) with those with suspected acute infection (IgG positive with low/intermediate IgG avidity index, SAIP). RESULTS: 237 patients were enrolled, 187 (78.9%) with SAIP and 50 (21.1%) with CAIP. Specific IgM was detected in 47.5% and 76.7% (p-value 0.001), and the mean IgG avidity index was 22.7% and 7.1% (p-value < 0.001) in the SAIP and in the CAIP group, respectively. The mean delay from diagnosis to antibiotic initiation was 14.6 in SAIP and 11 days in CAIP group. Toxoplasma DNA was detected in the amniotic fluid in one case in a patient with CAIP. Excluding 24 newborns with not available data, prevalence of congenital infection was 0.47% [1/213 (95% CI 0.08%-2.61%)], 0% [0/178 (95% CI 0%-2.11%)] in SAIP and 2.8% [1/35 (95% CI 0.51%-14.53%)] in CAIP group. CONCLUSIONS: Toxoplasmosis acquired in early pregnancy has a low risk of fetal infection. Actively discussing case-by-case amniocentesis indication with patients, especially when a recent toxoplasmosis is not properly confirmed, is desirable.

Clinical and Laboratory Follow-up After Hospitalization for COVID-19 at an Italian Tertiary Care Center.

We evaluated 100 postacute coronavirus disease 2019 (COVID-19) patients a median (interquartile range) of 60 (48-67) days after discharge from the Careggi University Hospital, Italy. Eighty-four (84%) had at least 1 persistent symptom, irrespective of COVID-19 severity. A considerable number of hospital readmissions (10%) and/or infectious diseases (14%) during the postdischarge period were reported.

Valacyclovir for prevention and treatment of fetal CMV infection: inclusion in the Law 648/96 list and launch of the Italian multicentre observational prospective study "MEGAL-ITALI".

Not available.

Continuum of care among HIV-1 positive patients in a single center in Italy (2007-2017).

AIM: This study aimed to determine rates of retention in care, viral suppression, and use of antiretroviral therapy (ART) and identify risk factors for loss to follow-up (FU) in an adult cohort from a tertiary teaching hospital in Florence, Italy. METHODS: We included all newly diagnosed HIV-infected patients aged >18 years who were linked to our clinic from July 2007 to December 2015. On July 31, 2017, we evaluated the proportion of patients retained in care, on ART, and having HIV RNA <50 copies/mL. We assessed predictors of loss to FU through univariate and multivariate analyses. RESULTS: We included 423 patients. By July 2017, 23 (5.5%) patients died, 25 (5.9%) moved to a different center, and 64 (15.1%) were lost to follow-up. Among the remaining 311 patients (73.5%), 96.5% were on ART and 95% had HIV RNA <50 copies/mL. After adjustment for sex, age at diagnosis, origin, and risk of transmission, our results showed a lower retention rate in those not on ART at the end of the follow-up (adjusted HR [aHR]: 10.33, 95% CI 5.80-18.40, P<0.001), non-Italians (aHR: 1.69, 95% CI: 0.99-2.89, P=0.054) and <35 years old (aHR: 1.85; 95% CI 1.04-3.30, P=0.037). CONCLUSION: In our hospital in Florence, we found a gap in retention in care among foreigners, people <35 years old, and those who were not in treatment at the end of the follow-up. The results of this study may help to identify opportunities for appropriate future interventions.

Seroprevalence of Hepatitis A Virus, Hepatitis E Virus, and Helicobacter pylori in Rural Communities of the Bolivian Chaco, 2013.

In the Bolivian Chaco, south-east of Bolivia, studies conducted over the past three decades reported hepatitis A virus (HAV) and Helicobacter pylori seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV) prevalence was previously found to be 6-7% but is probably an underestimate because of the poor sensitivity of the assays used. In November 2013, we conducted a cross-sectional study of 263 healthy volunteers from two rural communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori seroprevalence 10-20 years following the previous surveys. Hepatitis A virus seroprevalence was 95%, with universal exposure after the first decade of life; HEV seroprevalence was considerably higher (31-35%) than that previously reported; H. pylori seroprevalence was 59%, with an age-dependent distribution. The high prevalence of these infections suggests that major efforts are still needed to reduce fecal-oral transmission and to improve human health in the Bolivian Chaco.