Efficacy and safety of therapies for COVID-19 in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Clinical evidence suggests that pregnant women are more vulnerable to COVID-19, since they are at increased risk for disease progression and for obstetric complications, such as premature labor, miscarriage, preeclampsia, cesarean delivery, fetal growth restriction and perinatal death. Despite this evidence, pregnant women are often excluded from clinical trials, resulting in limited knowledge on COVID-19 management. The aim of this systematic review and meta-analysis is to provide better evidence on the efficacy and safety of available COVID-19 treatment in pregnant women. METHODS: Four authors searched major electronic databases from inception until 1 st November-2022 for controlled trials/observational studies, investigating outcomes after the administration of anti-SARS-CoV-2 treatments in pregnant women affected by COVID-19. The analyses investigated the cumulative incidence of delivery and maternal outcomes in pregnant women, comparing those taking active medication vs standard care. Risk ratios (RRs) with 95% confidence intervals were calculated. Statistical significance was assessed using the random effects model and inverse-variance method. This systematic review and meta-analysis was conducted in accordance with the updated 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol has been registered in Prospero (number registration: CRD42023397445). RESULTS: From initially 937 non duplicate records, we assessed the full texts of 40 articles, finally including ten studies. In six studies, including 1627 patients, the use of casirivimab/imdevimab (CAS/IMD), remdesivir, and IFN-alpha 2b significantly decreased the need of cesarean section ((RR = 0.665; 95%CI: 0.491-0.899; p = 0.008; I 2 = 19.5%;) (Table 1, (Fig. 1). Treatments did not decrease the risk of preterm delivery, admission to neonatal ICU, or stillbirth/perinatal loss (p-values > 0.50 for all these outcomes) and did not prevent the progression of disease towards severe degrees (k = 8; 2,374 pregnant women; RR = 0.778; 95%CI: 0.550-1.099; p = 0.15; I 2 = 0%). Moreover, the use of medications during pregnancy did not modify the incidence of maternal death in two studies (Table 2). CONCLUSIONS: To our analysis, CAS/IMD, remdesivir, and IFN alpha 2b reduced the number of cesarean sections but demonstrated no effect on disease progression and other obstetric and COVID-19 related outcomes. The inability to evaluate the influence of viral load on illness development in pregnant women was attributed to lack of data. In our systematic review, no major side effects were reported. Though, it is essential for the medical community to focus more on clinical trials and less on episodic case reports and case series, with standardization of fetal and maternal outcomes.

Treatment with valacyclovir during pregnancy for prevention of congenital cytomegalovirus infection: a real-life multicenter Italian observational study.

BACKGROUND: Valacyclovir is the only treatment demonstrated to be effective for the prevention of vertical transmission of cytomegalovirus within a clinical randomized, placebo-controlled trial and has been reimbursed by the Italian National Health System since December 2020. OBJECTIVE: This study reported the results of a real-life Italian multicenter observational study on cytomegalovirus infection in pregnancy evaluating the effect of the introduction of valacyclovir in the clinical practice for the prevention of vertical transmission of cytomegalovirus. STUDY DESIGN: The outcomes of women who received valacyclovir treatment and their fetuses or newborns were compared with those of a retrospective cohort observed between 2010 and 2020 who did not receive the antiviral treatment. The inclusion criterion was the diagnosis of cytomegalovirus primary infection occurring in the periconceptional period or up to 24 weeks of gestation. The primary outcome was the transmission by the time of amniocentesis. The secondary outcomes were termination of pregnancy, transmission at birth, symptomatic infection at birth, and a composite outcome (termination of pregnancy or transmission at birth). RESULTS: A total of 447 pregnant women from 10 centers were enrolled, 205 women treated with valacyclovir (called the valacyclovir group, including 1 twin pregnancy) and 242 women not treated with valacyclovir (called the no-valacyclovir group, including 2 twin pregnancies). Valacyclovir treatment was significantly associated with a reduction of the diagnosis of congenital cytomegalovirus infection by the time of amniocentesis (weighted odds ratio, 0.39; 90% confidence interval, 0.22-0.68; P=.005; relative reduction of 61%), termination of pregnancy (weighted odds ratio, 0.36; 90% confidence interval, 0.17-0.75; P=.0021; relative reduction of 64%), symptomatic congenital cytomegalovirus infection at birth (weighted odds ratio, 0.17; 90% confidence interval, 0.06-0.49; P=.006; relative reduction of 83%). The treatment had no significant effect on the rate of diagnosis of congenital cytomegalovirus infection at birth (weighted odds ratio, 0.85; 90% confidence interval, 0.57-1.26; P=.500), but the composite outcome (termination of pregnancy or diagnosis of congenital cytomegalovirus infection at birth) occurred more frequently in the no-valacyclovir group (weighted odds ratio, 0.62; 90% confidence interval, 0.44-0.88; P=.024). Of note, the only symptomatic newborns with congenital cytomegalovirus infection in the valacyclovir group (n=3) were among those with positive amniocentesis. Moreover, 19 women (9.3%) reported an adverse reaction to valacyclovir treatment, classified as mild in 17 cases and moderate in 2 cases. Lastly, 4 women (1.9%) presented renal toxicity with a slight increase in creatinine level, which was reversible after treatment suspension. CONCLUSION: Our real-life data confirm that valacyclovir significantly reduces the rate of congenital cytomegalovirus diagnosis at the time of amniocentesis with a good tolerability profile and show that the treatment is associated with a reduction of termination of pregnancy and symptomatic congenital cytomegalovirus infection at birth.

The role of Lung Ultrasound in the diagnosis of SARS-COV-2 disease in pregnant women.

AIM: To evaluate the role of lung ultrasound (LUS) in recognizing lung abnormalities in pregnant women affected by COVID-19 pneumonia. MATERIALS AND METHODS: An observational study analyzing LUS patterns in 60 consecutively enrolled pregnant women affected by COVID-19 infection was performed. LUS was performed by using a standardized protocol by Soldati et al. The scoring system of LUS findings ranged from 0 to 3 in increasing alteration severity. The highest score obtained from each landmark was reported and the sum of the 12 zones examined was calculated. RESULTS: Patients were divided into two groups: 26 (43.3%) patients with respiratory symptoms and 32 (53.3%) patients without respiratory symptoms; 2 patients were asymptomatic (3.3%). Among the patients with respiratory symptoms 3 (12.5%) had dyspnea that required a mild Oxygen therapy. A significant correlation was found between respiratory symptoms and LUS score (p < 0.001) and between gestational weeks and respiratory symptoms (p = 0.023). Regression analysis showed that age and respiratory symptoms were risk factors for highest LUS score (p < 0.005). DISCUSSION: LUS can affect the clinical decision course and can help in stratifying patients according to its findings. The lack of ionizing radiation and its repeatability makes it a reliable diagnostic tool in the management of pregnant women.

Evidence of Maternal Antibodies Elicited by COVID-19 Vaccination in Amniotic Fluid: Report of Two Cases in Italy.

With SARS-CoV-2 infection, pregnant women may be at a high risk of severe disease and adverse perinatal outcomes. A COVID-19 vaccination campaign represents the key strategy to combat the pandemic; however, public acceptance of maternal immunization has to be improved, which may be achieved by highlighting the promising mechanism of passive immunity as a strategy for protecting newborns against SARS-CoV-2 infection. We tested the anti-SARS-CoV-2 antibody response following COVID-19 full-dose vaccination in the serum and amniotic fluid of two pregnant women who presented between April and June 2021, at the Center for the Treatment and Prevention of Infections in Pregnancy of the National Institute for Infectious Diseases "L. Spallanzani", for antenatal consultancy. Anti-SARS-CoV-2 IgG was found in residual samples of amniotic fluid collected from both women at the 18th week of gestation (63 and 131 days after the second dose's administration). Titers in amniotic fluid mirrored the levels detected in serum and were inversely linked to the time from vaccination. Our results suggest that antibodies elicited by COVID-19 vaccination can cross the placenta and reach the fetus; therefore, they may offer passive immunity at birth. It is critical to fully understand the kinetics of the maternal response to vaccination, the efficiency of IgG transfer, and the persistence of antibodies in infants to optimize maternal immunization regimens.

T helper profile in pregnant women recovered from COVID-19.

T helper (Th) cell subsets play distinct and important roles during pregnancy. This work was focused on investigating the Th and cytokine profile in pregnant women recovered from COVID-19. To this aim, the frequency of Th1, Th2, Th17 subsets and the level of associated cytokines were analysed in pregnant women recovered from COVID-19 and in matched non-pregnant women. Principal component analysis highlighted a significant impact of pregnancy on Th profile with an increase of ex-Th17 subset and a parallel decrease of Th1 population. These modulations may participate in both preserving the pregnancy and reducing the risk of severe infection.

Association of COVID-19 case fatality rate with disease burden: an ecological analysis in Italy during the first wave.

OBJECTIVES: In Italy, the case fatality rate (CFR) of coronavirus disease 2019 (COVID-19) during the first wave of the pandemic showed significant geographic heterogeneity. The aim of this study was to explore the possible association between the CFR and measures of disease burden in the Italian regions using an ecological approach. METHODS: Cumulated regional data for the period February 24 to May 11, 2020 were analysed to assess the association of the CFR with the cumulative incidence of COVID-19 and the ratio between the maximum number of COVID-19 patients in intensive care units (ICU) and ICU beds available before the pandemic (ICU load), adjusting for median age of the patients at disease onset, number of nasopharyngeal swabs performed per confirmed case, and prevalence of chronic diseases . RESULTS: During the study period, the COVID-19 CFR in the Italian regions ranged between 5.0% and 18.4%. On multivariable regression analysis, the CFR was found to be significantly associated with the cumulative incidence (relative rate (RR) 1.02 per 100 cases/1 million increase), median patient age (RR 1.07 per 1 year increase), and ICU load (RR 1.72, 2.18, and 2.57, for >40-70% vs ≤40%, 70-140% vs ≤40%, and ≥140 vs ≤40%, respectively). CONCLUSIONS: A high burden of COVID-19 may contribute to increased disease fatality, possibly as a result of the increasing demand for care of critically ill patients beyond health system capability.

CD4/CD8 ratio in pregnant women with HIV and its association with pregnancy outcome: data from a national study in Italy.

PURPOSE: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. METHODS: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. RESULTS: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111-0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082-5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690-6.900). CONCLUSION: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection in an Italian patient: Mini-review of the literature.

A case of acute respiratory distress syndrome due to SARS-CoV-2 and Influenza A co-infection and a mini-review of the literature is reported. Even in COVID-19 epidemics, the early identification of concurrent respiratory pathogens is important to improve etiological diagnosis, preventive measures and patients' clinical management and outcome.

Prevalence, Correlates and Outcomes of Smoking in Pregnant Women with HIV: A National Observational Study in Italy.

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001-2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013-2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22-2.34) and FGR (AOR 1.88, 95%CI 1.27-2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

Isolated auditory neuropathy at birth in congenital cytomegalovirus infection.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most frequent non-genetic cause of sensorineural hearing-loss (SNHL) (i.e., hearing loss due to a cochlear and/or auditory nerve damage). It is widely accepted that SNHL at birth, when associated to cCMV symptomatic infection involving the central nervous system, benefits from antiviral therapy started in the neonatal period. Conversely, there is no consensus for antiviral treatment in congenitally infected infants diagnosed with isolated SNHL (i.e., SNHL in an otherwise asymptomatic infant) at birth. Our aim was to assess the frequency and the auditory outcome of isolated SNHL at birth due to auditory neuropathy (AN) (i.e., SNHL in a patient with normal cochlear function and auditory nerve dysfunction) in infants with cCMV infection. METHODS: We retrospectively reviewed the clinical history of 60 infants, born at term, with cCMV asymptomatic infection, without additional risk factors for SNHL, and exhibiting bilateral "pass" otoacustic emissions (OAE). None of them underwent antiviral therapy. Hearing thresholds were assessed by means of Auditory Brainstem Responses (ABR). AN affected children were followed up until possible normalization of the hearing thresholds or definitive diagnosis of AN. Each infant diagnosed with monolateral or bilateral AN was classified according to the worst ear threshold. RESULTS: In our population, the first ABR was performed at a mean age of 5.00 ± 2.79 (SD) months and AN was diagnosed in 16/60 (26.67%) infants; in 4 infants the AN was defined as mild (4/4 monolateral), moderate in 11 (5/11 bilateral), and severe in 1 (bilateral). The mean age at first ABR was 3.69 ± 2.80 (SD) months in the 16 babies with AN and 5.48 ± 2.66 (SD) months in the 44 infants with normal hearing (p = 0.007). All AN cases spontaneously recovered a normal auditory threshold over time. The mean length of the audiological follow-up was 32.44 ± 17.58 (SD) months (range 5-60 months). CONCLUSION: A delayed maturation of the auditory pathways should be considered when a mild/moderate isolated AN at birth is detected in cCMV infected infants. Prospective studies conducted on larger populations, and with a longer audiological follow-up, are needed to confirm our findings.

Weight gain during pregnancy in women with HIV receiving different antiretroviral regimens.

BACKGROUND: No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes. METHODS: Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses. RESULTS: Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+ T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65). CONCLUSIONS: No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

Rescue of Replication-Competent ZIKV Hidden in Placenta-Derived Mesenchymal Cells Long After the Resolution of the Infection.

The Zika virus (ZIKV) genome, its negative-strand viral proteins, and virus-like particles were detected in placenta-derived mesenchymal cells (MSCs), indicating that ZIKV persists after virus clearance from maternal blood and can be rescued by in vitro cultivation. We report for the first time the presence of replication-competent ZIKV in MSCs from an asymptomatic woman who acquired infection during pregnancy.

Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.

Case Report: Delayed Diagnosis of Congenital Malaria by Plasmodium vivax in a Newborn of an Eritrean Woman with Varicella Infection.

Congenital malaria (CM) is uncommon in both malaria-endemic and non-endemic countries. It may be caused by any Plasmodium spp., although Plasmodium falciparum and Plasmodium vivax are the more frequent etiologic agents. We report a case of delayed diagnosis of CM by P. vivax in a newborn of an Eritrean primigravida. The mother developed pregnancy-related immunodepression and varicella-zoster viral infection 9 days before natural delivery; therefore, the child was admitted in the neonatal intensive care unit (NICU) to administer specific varicella-zoster immunoglobulin prophylaxis and for clinical monitoring. During the NICU stay, the newborn presented a febrile syndrome with vomiting, anemia, and thrombocytopenia. A P. vivax severe malaria diagnosis was made by detecting trophozoites in the thick and thin blood smears. The infant was successfully treated with intravenous artesunate and clindamycin. Our experience suggests that malaria diagnostic tests need to be included in routine blood analyses in newborns with febrile syndrome from mothers with an epidemiologic link to malaria-endemic areas.

Brief Report: Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women With HIV: Laboratory and Clinical Outcomes in an Observational National Study.

BACKGROUND: Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study. METHODS: Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC. RESULTS: The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P < 0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030). CONCLUSIONS: In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission.

As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.

Clinical management of women with listeriosis risk during pregnancy: a review of national guidelines.

INTRODUCTION: Listeriosis is an uncommon foodborne infection that may cause moderate maternal illness, but can be extremely serious for the fetus and the newborn. Several guidelines have been elaborated in order to help clinicians on the care of pregnant women with known or suspected exposure to Listeria monocytogenes. The aim of this review is to collect, assess and summarize them, in order to provide a comprehensive overlook and to highlight the grey areas in the guidance that could result in failure to detect some infected but asymptomatic women. Areas covered: A literature review was performed to provide an update on listeriosis infections, with a greater focus on diagnosis and management of pregnancy-related cases. Expert commentary: Since pregnancy-associated listeriosis causes potentially fatal consequences, it is important that healthcare providers recognize earlier symptoms, diagnosis methods and treatment of the infection. Listeriosis could be asymptomatic and/or a pregnant woman could not be aware of being exposed to Listeria, therefore a serological test is suggested to detect the presence of anti-listeriolysin O antibodies in blood. Finally, a final flowchart is proposed that could improve the early diagnosis of the infection in pregnant women.

Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child.

BACKGROUND: HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child. CASE PRESENTATION: A perinatally HIV-1 infected infant was treated within 7 weeks of age with zidovudine, lamivudine, nevirapine and lopinavir/ritonavir. At antiretroviral treatment (ART) initiation HIV-1 viral load (VL) and CD4 percentage were >500,000 copies/ml and 35%, respectively. Plasma genotypic resistance test showed a wild-type virus. The child reached VL undetectability after 33 weeks of combination antiretroviral therapy (cART) since he maintained a stable VL <40copies/ml. After 116 weeks on ART we were able to perform amplification and sequencing assay on the plasma virus. At this time VL was <40 copies/ml and CD4 percentage was 40%. Again the genotypic resistance test revealed a wild-type virus. The phylogenetic analysis performed on the HIV-1 pol sequences of the mother and the child revealed that sequences clustered with C subtype reference strains and formed a monophyletic cluster distinct from the other C sequences included in the analysis (bootstrap value >90%). Any major evolutionary divergence was detected. CONCLUSIONS: eART limits the viral evolution avoiding the emergence of new viral variants. This result may have important implications in host immune control and may sustain the challenge search of new personalized immunotherapeutic approaches to achieve a prolonged viral remission.

Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016.

A man in his early 30s reported in January 2016 a history of fever, asthenia and erythematous rash during a stay in Haiti. On his return to Italy, ZIKV RNA was detected in his urine and saliva 91 days after symptom onset, and in his semen on day 188, six months after symptom onset. Our findings support the possibility of sexual transmission of ZIKV and highlight the importance of continuing to investigate non-vector-borne ZIKV infection.