Occurrence of Central Nervous System Complications of Respiratory Syncytial Virus Infections: A Systematic Review with Meta-Analysis.

An increasing base of evidence suggests that respiratory syncytial virus (RSV) infections may be associated with neurological complications. In accord with the PRISMA statement, we performed a systematic review and meta-analysis on the occurrence of encephalitis and encephalopathy associated with documented RSV infections. PubMed, Embase, and Scopus databases were searched for eligible observational studies published up to 10 April 2024. Raw data included the occurrence of RSV infections among cases of encephalitis and/or encephalopathy and cases of encephalitis and/or encephalopathy among series of RSV infections. Data were pooled in a random effects model. Case reports were also collected, and their data pooled as a cumulative series. Heterogeneity was assessed using the I2 measure, while reporting bias was assessed by means of funnel plots and regression analysis. A total of 15 studies for a total of 7719 RSV infections and 1631 cases of encephalitis were analyzed. Moreover, 27 case reports and case series were retrieved, for a total of 84 individual cases of encephalitis/encephalopathy occurring during a documented RSV infection. A pooled prevalence of 2.20 cases of encephalitis/encephalopathy per 100 RSV cases (I2 = 99%) was calculated, while a prevalence of RSV infections among cases of encephalitis/encephalopathy was estimated to 3.53 per 100 cases for studies on respiratory specimens (I2 = 48%) and 0.37 per cases on central nervous system (CNS) specimens (I2 = 0%). Detection of RSV within the CNS was relatively rare (17.86% of pooled case reports), being associated with male gender (adjusted odds ratio [aOR] 5.021, 95% confidence interval [95%CI] 1.104 to 22.831) and recovery with long-term sequelae (aOR 5.699, 95%CI 1.152; 28.183). Case fatality ratio was estimated to be 0.43 per 100 cases on observational studies and 10.71% in case reports, a difference likely due to publication bias. In summary, RSV represented a not frequent but notable cause of encephalitis/encephalopathy in adults and children. The paucity of available studies not only recommends a cautious appraisal of our results but stresses the clinical significance of future studies on incident cases of encephalitis and/or encephalopathy.

Impact of Nirsevimab Immunization on Pediatric Hospitalization Rates: A Systematic Review and Meta-Analysis (2024).

A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I2 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman's r = -0.546, p = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting (ß = 0.001, 95% CI -0.001 to 0.002; p = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions.

RSV Infection in Refugees and Asylum Seekers: A Systematic Review and Meta-Analysis.

Respiratory diseases, including respiratory syncytial virus (RSV) infections, are common reasons for seeking healthcare among refugees and asylum seekers. A systematic review with meta-analysis was designed to appraise all the available evidence on RSV infections among individuals in refugee camps. Three medical databases (PubMed, Embase, and Scopus) as well as the preprint repository medRxiv.org were searched for eligible observational studies, and the collected cases were pooled in a random-effects meta-analysis model. Heterogeneity was assessed using the I2 statistics. Funnel plots and a regression analysis were calculated for analyzing reporting bias. Eventually, six studies were retrieved from three areas (Bangladesh, Thailand, and Kenya), with pooled estimates of 129.704 cases per 1000 samples (95% CI 66.393 to 237.986) for RSV compared to 110.287 per 1000 people for influenza A (95% CI 73.186 to 162.889), 136.398 cases per 1000 people (95% CI 84.510 to 212.741) for human adenovirus (HAdV), 69.553 per 1000 people (95% CI 49.802 to 96.343) for parainfluenzavirus (PIFV), and 60.338 per 1000 people (95% CI 31.933 to 111.109) for human metapneumovirus (hMPV). Using influenza A as a reference group, the risk for a positive specimen was greater for RSV (relative risk [RR] 1.514, 95% CI 1.396 to 1.641) and HAdV (RR 1.984, 95% CI 1.834 to 2.146) and lower for influenza B (RR 0.276, 95% CI: 0.239 to 0.319), PIFV (RR: 0.889, 95% CI 0.806 to 0.981), and hMPV (RR 0.594, 95% CI 0.534 to 0.662). In summary, high rates of RSV infections were documented among individuals sheltered in refugee camps, stressing the importance of specifically designed preventive strategies.

Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A systematic review and meta-analysis was designed in order to ascertain the effectiveness of respiratory syncytial virus (RSV) vaccination in preventing lower respiratory tract diseases (LRTD) in older adults (age ≥ 60 years). Studies reporting on randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) and the preprint repository medRxiv until 31 March 2024. A total of nine studies were eventually included, two of which were conference proceedings. Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). The meta-analysis documented a pooled vaccine efficacy of 81.38% (95% confidence interval (95% CI) 70.94 to 88.06) for prevention of LRTD with three or more signs/symptoms during the first RSV season after the delivery of the vaccine. Follow-up data were available for RSVPreF3 (2 RSV seasons), RSVpreF (mid-term estimates of second RSV season), and mRNA-1345 (12 months after the delivery of the primer), with a pooled VE of 61.15% (95% CI 45.29 to 72.40). After the first season, the overall risk for developing RSV-related LRTD was therefore substantially increased (risk ratio (RR) 4.326, 95% CI 2.415; 7.748). However, all estimates were affected by substantial heterogeneity, as suggested by the 95% CI of I2 statistics, which could be explained by inconsistencies in the design of the parent studies, particularly when dealing with case definition. In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions.

Infectious risk profile and strategies for prevention and control of outbreaks in refugee, asylum seekers and migrant populations in EU/EEA countries: a systematic narrative review of evidence.

Introduction: The recent surge in migration to and within the European Union and European Economic Area has brought the development of migration policy, including health policy, to the forefront of regional priorities. While migrants, in general, do not pose a health threat to the host population, specific subgroups of migrants, including refugees, asylum seekers, and irregular migrants, are particularly vulnerable to infectious diseases. To support public health policies in this area, the Emergency Preparedness and Management' working group of the Italian Society of Hygiene, Preventive Medicine and Public Health has conducted a systematic narrative review with the aim to comprehensively analyze the infectious disease risk within the refugee and asylum seeker populations in EU, EEA, and EU-applicant countries. Methods: Forty-two studies were systematically selected from scientific articles in the MEDLINE/PubMed database from January 1, 2008, to June 1, 2023. The infectious risk associated with each infectious disease among refugees and asylum seekers, as well as the strategies to prevent and control outbreaks, was collected from all available studies. Results: The congregate living conditions in refugee camps, transit centers, and temporary housing facilities make this population particularly vulnerable to infectious diseases. As such, implementing stringent hygiene and preventive measures is critical to safeguarding the health of refugees and reducing the risk of outbreaks that may affect both the refugee population and the host communities. Conclusion: Effective vaccination and preventive strategies for migrants, refugees, and asylum seekers are vital for public health and the well-being of these populations. They should be delivered as part of universal health care. By addressing barriers and implementing tailored programs, we can ensure equitable access to vaccines and protect the health of these vulnerable individuals.

SARS-CoV-2 before and after Omicron: two different viruses and two different diseases?

For the first time in the history of medicine, it has been possible to describe-after a spillover-the evolution of a new human virus spreading in a non-immune population. This allowed not only to observe the subsequent emersion of variants endowed with features providing the virus with an evolutionary advantage, but also the shift of the pathways of virus replication and the acquisition of immunoevasive features. These characteristics had a remarkable influence on the diffusion of the SARS-CoV-2 and on the clinical presentation and prognosis of COVID-19, aspects that are described and commented in this review.

Risks and Protective Factors Associated With Mental Health Symptoms During COVID-19 Home Confinement in Italian Children and Adolescents: The #Understandingkids Study.

Objective: To identify risk and protective factors for mental health symptoms associated with lifestyle changes caused by home confinement in pediatric subjects and in children and adolescents with a neuropsychiatric disorder. Study design: This was a prospective, cross-sectional study conducted from May 10 to May 31, 2020. Two online anonymous surveys were developed: population-based and clinical-based (children with neuropsychiatric disorders). Outcomes included emotional and behavioral symptoms, as assessed by psychometric scales (BPSC, PPSC, PSC, CES-DC and SCARED, respectively), and lifestyle changes during home confinement (i.e., physical activity, screen time, home schooling, reading). Results: The sample included 9,688 pediatric subjects, and 289 children and adolescents with a neuropsychiatric disorder. The presence of siblings was a protective factor in all ages. In pre- and school children: male sex, a diagnosis of autism, residency in highly affected areas, high parental educational level or job loss, and screen time (>2 h/day) were risk factors. Physical activity, home-schooling, reading, talking with other people were protective factors. Residency in highly affected areas, a diagnosis of mood disorder, parental job loss, and screen time, were associated with a worsening of the depressive symptoms, whereas physical activity, talking with other people, playing with parents were protective activities. Screen time was also a risk factor for anxiety symptoms, while physical activity, reading and talking with other people were protective factors. Conclusions: This study identified risk and protective factors for mental health symptoms associated with lifestyle changes caused by COVID-19 home confinement to promote mental well-being in pediatrics during pandemic times.

Transitional care: A new model of care from young age to adulthood.

INTRODUCTION: Transition of care represents the transfer from child to adult care. An effective transition maintains continuity of care and presents better clinical outcomes. This process has assumed growing relevance, thanks to improved survivorship of chronic paediatric patients. Actually, there is no a one-size model fitting for all transitions, but each Service organizes its own clinical pathway. AIM: The study proposes an organizational model for transition, differentiated according to patient complexity. METHODS: The working group discussed, through regular meetings, the appropriate transitional model for our Hospital. The working group defined a common scheme of transition and elaborated a synthetic document for patients. Then, the common model is adapted, through clinicians' contribution, for different diseases. The complexity assessment includes clinical data, nursing and social information. RESULTS: The working group defined a common model identifying the main information to be included and detailed in each transition report. The team defined two pathways based on patient's complexity. In case of good compensation and autonomous management, the adolescent is addressed towards standard transition process, a smoother transition from paediatric to adult care with direct connection among healthcare professionals. In case of complex clinical and/or social conditions, an Interdisciplinary Transition Group (ITG) is activated. The group preventively evaluates each patient in periodic meetings and provides a personalized planning of care. In order to define the complexity of a patient, clinical and social determinants are considered. Some diseases are considered complex by default, while others require ITG involvement in case of multiple comorbidities, severe clinical situation, concomitant social criticality and/or cognitive impairment. DISCUSSION: Transition of care represents an important phase in chronic diseases management. The proposed model assures a multidisciplinary approach, involving all specialists of both paediatric and adult teams. A key determinant of transition is information transmission. Then, the model proposes a common transition report format. Finally, a further perspective study is already in program, in order to assess clinical effectiveness.

Cost-effectiveness estimates of vaccination against rotavirus in Piedmont, Italy.

BACKGROUND: Rotavirus-induced gastroenteritis (RVGE) represents the most frequent form of severe gastroenteritis in children. In such a scenario, the availability of an efficient anti-Rotavirus (anti-RV) vaccine represents an effective prevention tool able to prevent those complications mainly linked to the moderate-severe forms of this disease, which require hospital care. The aim of the present study is to estimate the cost effectiveness of universal routine infant RV vaccination program and its budget impact on the Regional Health Service (RHS) of Piedmont, Italy, in order to evaluate the opportunity of the implementation of a national anti-Rotavirus vaccination programme. METHODS: The researchers performed a cost-effectiveness analysis comparing costs and benefits of a Rotarix two-dose vaccination versus non vaccination and a budget impact analysis (BIA), complementary to the cost-effectiveness analysis. RESULTS: Our results show that the mass implementation of an anti-RV vaccination in Piedmont, in addition to the expected public health benefits, also allows the RHS to save a considerable amount of money within a short period of time, due to the remarkable reduction of direct health costs associated with RVGE management. In fact, as the analysis shows, a universal vaccination against RV results in money-saving for the RHS already from the 2nd year (with a vaccination coverage of 50%). During the five year period, the active and free offer of the anti-RV vaccination would determine a total saving for RHS of about € 503.000. The cost-effectiveness analysis results showed a cost-saving ICER (incremental cost-effectiveness ratio) relevant to the RHS and equal to - €12.197/QALY. CONCLUSION: In conclusion the adoption of a universal preventive strategy for all the infants in the Piedmont Region may contribute significantly towards the control of RVGE incidence, thus allowing a noteworthy saving of economic and social resources for both the RHS and the general public.

A simplified screening tool to identify seriously ill patients in the Emergency Department for referral to a palliative care team.

BACKGROUND: The aims of this study were to evaluate the feasibility of an Emergency Department (ED)-initiated screening to identify seriously ill patients in need of palliative care (PC) and to develop a simplified screening tool (SST). METHODS: Eligible patients with known diagnosis of chronic heart, lung, liver, and kidney failures, progressive neurological diseases or advanced cancer, awaiting to be hospitalized after an ED visit, were assessed with the screening tool from the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI). RESULTS: Out of 1497 patients with an ED visit, 485 were hospitalized, and 257 of them met the inclusion criteria. Of 257 enrolled patients, 91 (35%) were identified as in need of PC. Comparing patients with 4 positive criteria to those with <4, the general clinical indicators more frequently positive were: ≥1 admission within the last 12 months (P<0.001); hospital admission from or awaiting admission to health care services (HCS)/Hospice (P<0.001); cachexia (P<0.012); home oxygen use (P<0.001); dialysis (P<0.008). A SST was developed to identify patients in need of PC when a Palliative Performance Scale score <50 was present with at least one of the following indicators: ≥1 admission within the last 12 months; hospital admission from HCS; awaiting admission to HCS/Hospice; dialysis; home oxygen use; non-invasive ventilation. This SST showed a good agreement with the SIAARTI one as sensitivity (97.8%), specificity (92.8%), and accuracy (94.5%). CONCLUSIONS: Our study estimated that over one-third of the people with chronic diseases awaiting to be hospitalized after an ED visit were in need of PC and can be identified with this easy-to-use, non-disease-specific SST.

Knowledge and attitudes towards the use of antibiotics in the paediatric age group: a multicenter survey in Italy.

Background: : The misuse of antibiotics is one of the leading causes of antibiotic resistance. Paediatric patients are highly involved in this issue, as they are those who receive the largest amount of prescriptions of these drugs. Therefore, this study aimed to investigate the general knowledge regarding the use of antibiotics, as well as the attitudes related to the administration of these drugs to children, amongst parents of children in the paediatric age-group. : In 2014, a multicentre cross-sectional study was conducted amongst parents of children aged 0-14. A questionnaire made up of 33 items was administered in waiting rooms of outpatient departments. Multivariable logistic regression models were performed, in order to assess the potential predictors of a better knowledge about antibiotics. : A total of 1247 parents took part to the survey. Around 33% of the samples declared that antibiotics are useful for viral infections, 20.6% that antibiotics are useful for every kind of pain and inflammation, while 14% of the parents stated that they stop giving antibiotics to their children when they start feeling better. Multivariable models showed that males, unemployed and those with lower levels of education are less prone to answer correctly to the questions about antibiotics. : The present study demonstrates that parents have a lack of knowledge regarding the use of antibiotics, which results in bad habits and inappropriate attitudes when it comes to giving antibiotics to their children. Attention should be particularly focused on disadvantaged parents.

Adherence to European Society for Cataract and Refractive Surgery recommendations among Italian cataract surgeons: a survey.

PURPOSE: To survey the surgical routines with regards to prophylactic strategies in a sample of Italian hospitals and compare these with European Society for Cataract and Refractive Surgery (ESCRS) guidelines. METHODS: Six private and 18 public hospitals were included in this clinical-based retrospective study. The overall volume of cataract operations in the 24 centers in 2013 was 43,553. Main outcome measure was incidence of endophthalmitis per 1,000. An incidence of less than 0.13% was considered acceptable. RESULTS: Our study provides the first Italian data on the use of intracameral antibiotics in cataract surgery as recommended by the ESCRS. Thirteen centers (54%) used intracameral cefuroxime at the end of surgery. Of the 13 centers that used cefuroxime, 8 (62%) had an incidence of endophthalmitis less than 0.13%. Of the 7 (29%) centers that did not use intracameral cefuroxime, all had an endophthalmitis rate of greater than 0.13%. This difference was statistically significant (p<0.05). Among the 4 centers not included, 2 used vancomycin in the infusion bottle, 1 a fluoroquinolone, and the last a combination of antibiotics. The majority of surgeons (71%) used preoperative antibiotic eyedrops, but this measure was not shown to be significantly protective. CONCLUSIONS: Slightly more than half of the centers surveyed in this study adhered to the recommendations of the ESCRS and routinely employed prophylactic intracameral cefuroxime. An incidence of endophthalmitis greater than 0.13% was encountered significantly more frequently among centers that did not employ intracameral cefuroxime.

Job satisfaction among radiology assistants: a multicentre cross-sectional study in Italy.

OBJECTIVES: Job satisfaction among physicians is an important occupational health issue since it is related to different factors such as work motivation or career decisions. The aim of this study was to investigate  job satisfaction among radiology assistants for the first time in Italy. METHODS: In 2012, a cross-sectional survey was conducted among a convenience sample of radiology assistants drawn from all Italian regions who submitted an electronic or paper-based self-administered questionnaire. The data collected were analysed using logistic regressions in order to assess the role of socio-demographic variables. RESULTS: Overall, 574 radiology assistants were interviewed. More than half of the subjects were males and  were younger than 40 years old. Around 76% of the sample was not satisfied  as regards salary. Moreover, the majority of the participants (66.1%) was not satisfied  with the professional refresher courses. Compared with males, females were more satisfied in terms of professional enrichment (OR=1.79, 95% CI: 1.23-2.62) but less satisfied with their relationships with superiors (OR=0.57, 95% CI: 0.38-0.85). CONCLUSIONS: Since radiology assistants and, in general, healthcare workers assist medical doctors, thus playing a  significant role  in safeguarding patients' health , it would be  desirable to give  due importance to the issue of job satisfaction,  from all points of view.

[The "Ice Bucket Challenge": wondering about the impact of social networks to promote public health interventions]. / Il caso Ice Bucket Challenge: analisi e riflessioni sulle potenzialità dell'uso dei social network per promuovere interventi di Sanità Pubblica.

The "Ice Bucket Challenge" was an activity launched to promote awareness of amyotrophic lateral sclerosis (ALS) and encourage donations to research for this disease. The campaign went viral on social media during July to August 2014. It consisted in nominating people and challenging them to donate 100 dollars to the ALS Association or pour a bucket of ice water over their head and post the video on the web. Participants in turn then had to challenge others to do the same. The initiative was hugely successful, involved millions of people and, just in the US, collected 35 times more money than in the same time period in 2013. We analyzed possible factors that determined the success of this initiative, to identify strengths and weaknesses of the activity and evaluate the possibility of applying the same model to promote public health interventions. Several features of the challenge were identified as strengths: the involvement of wellknown people from different contexts, the "public platform" which triggers a positive combination of competitiveness, social pressure and narcissism, the chain-letter like method of nomination, the ironic and entertaining nature of the performance. Besides these strengths, weaknesses were also identified: information spread via social media can only partially reach potential donors and supporters, due to the digital divide phenomenon which excludes people who do not have web access. Also, it is not possible to predict if the message will be long-lasting or will cease shortly after the end of the campaign. The latter could be acceptable for fund-raising, where the aim is simply to collect as much money as possible, but not for a public health intervention program, whose success requires that the intended message has a long-lasting effect to produce an effective change in people's behavior. Despite the above-mentioned limits, social networks undeniably show great potential to spread messages to the community and to involve a large number of people. Their use as a complementary tool to increase the effectiveness of public health campaigns should therefore be encouraged.

Antibiotic use: a cross-sectional survey assessing the knowledge, attitudes and practices amongst students of a school of medicine in Italy.

BACKGROUND: Since antibiotic resistance has become a worldwide public health concern and is in part related to physicians' lack of knowledge, it is essential to focus our attention on healthcare profession students. The present study aims at evaluating the knowledge and attitudes of the School of Medicine's students towards antibiotic usage and antibiotic resistance. METHODS: In December 2013, a cross sectional study was conducted amongst medical, dental, nursing and other health care profession students of the School of Medicine at the University of Torino. Students of all the academic years took part in this study. Questionnaires were submitted during regular lectures (only students who attended courses on one specific day were surveyed) and the data collected was analyzed using StataMP11 statistical software. RESULTS: Overall, 1,050 students were interviewed. The response rate was 100%. Around 20% of the sample stated that antibiotics are appropriate for viral infections and 15% of the students that they stop taking those drugs when symptoms decrease. Results of the multivariate analyses showed that females were more likely than males to take antibiotics only when prescribed (OR 1.43, 95% CI 1.04-1.98). Interestingly, students with a relative working in a health-related field, as well as those who took at least one course of antibiotics in the last year, had a lower probability of taking those drugs only under prescription (OR = 0.69 95% CI: 0.49-0.97 and OR = 0.38 95% CI: 0.27-0.53, respectively). CONCLUSION: The present paper shows how healthcare profession students do not practice what they know. Since those students will be a behavioral model for citizens and patients, it is important to generate more awareness around this issue throughout their studies. It would be advisable to introduce a specific course and training on antibiotics in the core curriculum of the School of Medicine.

General population's knowledge and attitudes about antibiotics: a systematic review and meta-analysis.

PURPOSE: Nowadays, the development of antibiotic resistance represents one of the most important issues of the global public health. The incorrect use of antimicrobial drugs is recognized as one of the leading causes of antibiotic resistance. Therefore, a better understanding of the existing pieces of evidence pertaining knowledge and attitudes about antibiotic and antibiotic resistance in the general population worldwide is advisable. METHODS: A systematic review and proportion meta-analyses were performed through PubMed and Scopus scientific databases. Cross-sectional studies published from January 2000 to November 2013 and investigating knowledge about antibiotic use and antibiotic resistance were included. RESULTS: Overall, 26 studies have been selected for the systematic review, and 24 of these were included in the meta-analyses. A lack of knowledge about antibiotics was detected. In particular, 33.7% (95%CI 25.2-42.8) of the sample did not know that antibiotics can treat bacterial infections, and 53.9% (95%CI 41.6-66.0) of them did not know that antibiotics are not useful against viruses. Besides, although 59.4% (95%CI 45.7-72.4) of the sample was aware of antibiotic resistance, 26.9% (95%CI 16.6-38.7) of them did not know that misuse of antibiotics can lead to this problem. Finally, 47.1% (95%CI 36.1-58.2) of the subjects stop taking antibiotics when they start feeling better. CONCLUSIONS: It would be necessary to strengthen educational initiatives in the community and to push physicians to correctly inform patients in order to make them aware of the importance of a correct behavior concerning antibiotic consumption.

CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN) in two preterm twin neonates.

The diagnosis of congenital CMV is usually guided by a number of specific symptoms and findings. Unusual presentations may occur and diagnosis is challenging due to uncommon or rare features. Here we report the case of two preterm, extremely low birthweight, 28-week gestational age old twin neonates with CMV infection associated with severe lung involvement and persistent pulmonary hypertension of the newborn (PPHN). They were born to a HIV-positive mother, hence they underwent treatment with zidovudine since birth. Both infants featured severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support, with full recovery after 2 months. Treatment with ganciclovir was not feasible due the concomitant treatment with zidovudine and the risk of severe, fatal toxicity. Therefore administration of intravenous hyperimmune anti-CMV immunoglobulin therapy was initiated. Severe lung involvement at birth and subsequent pulmonary hypertension are rarely described in preterm infants as early manifestations of CMV congenital disease. In the two twin siblings here described, the extreme prematurity and the treatment with zidovudine likely worsened immunosuppression and ultimately required a complex management of the CMV-associated lung involvement.