Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection.

BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.

Insufficient measles antibody protection in 6-month-old Malawian infants: Reconsider vaccination schedule?

Measles vaccination is currently recommended at 9 months, since maternal antibodies are supposed to protect infants until that age. In this study of 6-month-old Malawian infants 98.3% (58/59) had non-protective IgG levels against measles, irrespective of HIV exposure. Anticipating the first dose at 6 months could be considered.

Micronutrient and Nutritional Status of HIV-Exposed and HIV-Unexposed Malawian Infants in the First Year of Life: Assessment of Ferritin, Vitamin A, and D Status and Its Association with Growth.

Breastfed Malawian infants from Human Immunodeficiency Virus (HIV)-uninfected and HIV-infected women who received antiretroviral therapy were followed until 12 months of age, allowing us to evaluate plasma levels of ferritin, vitamin A (as retinol-binding protein, RBP), and vitamin D (25(OH)D) at six months, as well as nutritional status and growth between six and 12 months. Ferritin and RBP levels were adjusted for inflammation. The study included 88 infants, 63 of whom were part of a recent cohort (2019-2021) that included 49 HIV-exposed but uninfected (HEU) and 14 HIV-unexposed and uninfected (HUU) infants, as well as 25 infants (all HEU) from an earlier cohort (2008-2011). No differences were observed between HEU and HUU infants regarding micronutrient levels, anthropometric indexes, growth, and rates of stunting, being underweight, or wasting. HEU infants from the earlier cohort, when compared to more recent HEU infants, had significantly worse anthropometric measures at six months and inferior growth between six and twelve months. Overall, ferritin deficiency involved 68.6% of infants, while vitamin A and vitamin D deficiency involved 8% and 1.2% of infants, respectively. Micronutrient deficiencies were not associated with HIV exposure, cohort, stunting, being underweight, or wasting. At six months, stunting, being underweight, and wasting involved 25.0%, 2.7% and 2.8% of infants, respectively, with no differences related to HIV exposure. Ferritin deficiency at six months was associated with inferior subsequent growth. In this small observational study conducted in Malawian infants, no major nutritional gap was observed between HIV-exposed and HIV-unexposed infants, though the study highlighted specific nutritional deficiencies that deserve attention. High rates of stunting and ferritin deficiency were observed in the first year of life in Malawian infants, irrespective of maternal HIV status; a significant association between ferritin deficiency and worse subsequent growth was found. Vitamin A and vitamin D deficiencies were much less frequent. Based on the data observed, nutritional interventions should give priority to the correction of ferritin deficiency and chronic undernutrition.

Rates of Seroprotection against Vaccine-Preventable Infectious Diseases in HIV-Exposed and -Unexposed Malawian Infants.

BACKGROUND: The evaluation of seroprotection rates against vaccine-preventable infectious diseases allows for the identification of risk populations. HIV-exposed infants, even if not infected with HIV, have higher morbidity and mortality in comparison to unexposed counterparts. The aim of this study was to compare the specific IgG levels against Haemophilus influenzae type-B (HiB), Hepatitis-B (HBV), and Streptococcus pneumoniae (Spn) in two groups of infants (HIV-exposed and HIV-unexposed) living in Malawi. METHODS: Blood samples from 62 infants, 49 HIV-exposed, uninfected (HEU), and born to women living with HIV and 13 HIV-unexposed and uninfected (HUU), were collected at 6 months, and specific IgG levels were determined using ELISA tests. RESULTS: The antibody levels against HiB, HBV, and Spn were similar in the two groups. At six months, all HUU infants and 81.6% of HEU infants showed seroprotective levels against HiB, while a percentage of protection varying from 80.6 to 84.6% was observed for HBV and Spn regardless of HIV exposure. Only 59.2% of HEU and 69.2% of HUU infants showed antibody protection against all three pathogens. CONCLUSIONS: These results indicate similar rates of seroprotection among HEU and HUU infants but also suggest that a consistent fraction of infants received incomplete vaccinations. Strategies to enforce participation in immunization programs in Malawi should be a health priority.

Cytomegalovirus viremia in HIV-exposed and HIV-unexposed infants in Malawi.

In sub-Saharan Africa the great majority of infants acquire Cytomegalovirus (CMV) infection within the first year of life. Maternal long-term antiretroviral therapy (ART) has been suggested to reduce the rate of CMV acquisition in HIV-exposed infants. In the present study serum samples collected at 6 months of age from HIV-exposed and HIV-unexposed infants were analyzed for the presence of CMV DNA (with CMV positivity defined by levels of CMV DNA > 1000 UI/ml). Twenty out of 58 (34.5%) infants had CMV DNA > 1000 UI/ml. There was no difference in the prevalence of CMV viremia between HIV-exposed and -unexposed infants [33.3% (15/45) vs 38.5% (5/13), respectively, P = 0.488]. In the HIV-exposed group, mothers of CMV-negative infants had received a longer antiretroviral treatment before delivery in comparison to mothers of CMV-positive infants (28 vs 3 months, P = 0.187). No differences in weights and lengths at birth, and at 1, 6 and 12 months were observed between CMV-positive and CMV-negative infants. In this study, the prevalence of CMV viremia at six months of age was high in infants born to HIV-positive mothers receiving long-term ART, similar to that of HIV-unexposed infants. Considering the possible relevant impact of CMV on infant health, strategies for containment of the infection should be explored.

Italian good practice recommendations on management of persons with Long-COVID.

A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient's needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients.

Diagnostic yield of urine lipoarabinomannan and sputum tuberculosis tests in people living with HIV: a systematic review and meta-analysis of individual participant data.

BACKGROUND: Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests. METHODS: In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337. FINDINGS: We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies. INTERPRETATION: AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples. FUNDING: FIND, the Global Alliance for Diagnostics.

A 12-month Prospective Study of HIV-infected and HIV-uninfected Women and Their Infants in Malawi: Comparative Analysis of Clinical Events and Infant Growth.

Few studies have compared clinical outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) infants in the current scenario of universal and lifelong maternal antiretroviral therapy (ART). HIV-uninfected and HIV-infected Malawian women receiving ART and their breastfed infants were followed for 12 months postpartum, analyzing the rates of infectious and noninfectious events and assessing infant growth at 6 weeks, 6 months, and 12 months. The cohorts included 227 mothers (70 HIV-negative, 157 HIV-positive) and 235 infants (72 HUU, 163 HEU). No maternal or infant deaths occurred during follow-up. HIV-negative women were less likely to complete follow-up (48.6% versus 91.1%). Mothers with and without HIV had similar rates of both infectious and noninfectious events per person-month. Infants who were HEU, compared with HUU, had higher rates of events of any type, lower respiratory tract infections (LRTI), and noninfectious events. HEU had lower body mass index (BMI) at 6 weeks but did not differ from HUU in all anthropometric measures at 6 and 12 months; in growth between 6 weeks and 12 months; and in occurrence of stunting, underweight, and wasting at 6 weeks, 6 months, and 12 months. During the first year of life, infants who were HEU, compared with HUU, showed a transiently lower BMI and an increased risk of LRTI.

Maternal retention and early infant HIV diagnosis in a prospective cohort study of HIV-positive women and their children in Malawi.

BACKGROUND: Post-partum loss to follow-up and lack of early HIV infant diagnosis (EID) can significantly affect the efficiency of programs for the prevention of mother-to-child transmission. METHODS: In a prospective observational study 167 women were enrolled at week 36 of gestation and followed with their infants up to one year after delivery. Retention was defined as the proportion of women who attended the 12 months visit and EID as an HIV PCR test performed within 2 months. Determinants for retention and EID were assessed in univariate analyses and in multivariable logistic regression models. RESULTS: Women lost to follow-up (24/167 or 14.4%) had a shorter duration of antiretroviral therapy (ART) at enrolment in comparison to women retained in care (p = 0.025). Lack of EID (occurring in 18.9% of the cases) was directly correlated, although not significantly, with a history of child death (p = 0.071), a higher educational level (p = 0.083), and female infant gender (p = 0.064). CONCLUSIONS: Longer duration of ART at enrolment significantly predicted a better post-partum retention, suggesting that specific counselling interventions should be targeted to recent ART initiators. A low proportion of infants did not receive an EID, but predictive factors were difficult to identify.

Hospital-acquired bloodstream infections in patients deceased with COVID-19 in Italy (2020-2021).

Introduction: In hospitalized patients with COVID-19, bloodstream infections (BSI) are associated with high mortality and high antibiotic resistance rates. The aim of this study was to describe BSI etiology, antimicrobial resistance profile and risk factors in a sample of patients deceased with COVID-19 from the Italian National COVID-19 surveillance. Methods: Hospital charts of patients who developed BSI during hospitalization were reviewed to describe the causative microorganisms and their antimicrobial susceptibility profiles. Risk factors were analyzed in univariate and multivariate analyses. Results: The study included 73 patients (71.2% male, median age 70): 40 of them (54.8%) received antibiotics and 30 (41.1%) systemic steroids within 48 h after admission; 53 (72.6%) were admitted to intensive care unit. Early steroid use was associated with a significantly shorter interval between admission and BSI occurrence. Among 107 isolated microorganisms, the most frequent were Enterococcus spp., Candida spp., Acinetobacter baumannii, and Klebsiella pneumoniae. Median time from admission to BSI was shorter for Staphylococcus aureus compared to all other bacteria (8 vs. 24 days, p = 0.003), and longer for Enterococcus spp., compared to all other bacteria (26 vs. 18 days, p = 0.009). Susceptibility tests showed a high rate of resistance, with 37.6% of the bacterial isolates resistant to key antibiotics. Resistance was associated with geographical area [adjusted odds ratio (AOR) for Central/South Italy compared to North Italy: 6.775, p = 0.002], and with early use of systemic steroids (AOR 6.971, p = 0.018). Conclusions: In patients deceased with COVID-19, a large proportion of BSI are caused by antibiotic-resistant bacteria. Early steroid use may facilitate this occurrence.

Characteristics of Long-COVID care centers in Italy. A national survey of 124 clinical sites.

Background: Despite the growing clinical relevance of Long-COVID, there is minimal information available on the organizational response of health services to this condition. Methods: A national online survey of centers providing assistance for Long-COVID was implemented. Information collected included date of start of activity, target population, mode of assistance and of referral, type and number of specialists available, diagnostic and instrumental tests, use of telemedicine and of specific questionnaires. Results: Between February and May 2022, 124 centers completed the survey. Half of them were situated in northern Italy. Most (88.9%) provided assistance through either outpatient visits or day hospital services. Eleven (8.9%) assisted pediatric patients. Access to centers included scheduled visits for previously hospitalized patients (67.7%), referral from primary care (62.1%), from other specialists (46.8%), and, less commonly, from other services. Almost half of the centers (46.3%) started their activity early in the pandemics (March-September 2020). Almost all (93.5%) communicated with primary care physicians, and 21.8% used telemedicine tools. The mean number of patients followed was 40 per month (median 20, IQR 10-40). In most cases, the center coordinator was a specialist in respiratory diseases (30.6%), infectious diseases (28.2%), or internal medicine (25.0%). At least half of the centers had specialistic support in cardiology, respiratory diseases, radiology, infectious diseases, neurology and psychology, but roughly one quarter of centers had just only one (14.5%) or two (9.7%) specialists available. The clinical assessment was usually supported by a wide range of laboratory and instrumental diagnostics and by multidimensional evaluations. Conclusions: Most of the centers had an articulate and multidisciplinary approach to diagnosis and care of Long-COVID. However, a minority of centers provided only single or dual specialistic support. These findings may be of help in defining common standards, interventions and guidelines that can reduce gaps and heterogeneity in assistance to patients with Long-COVID.

Dynamics of SARS-CoV-2 exposure in Malawian infants between February 2020 and May 2021.

Background: Very limited information is available on SARS-CoV-2 seroprevalence in infants in sub-Saharan countries. Objective: In this study, we aimed to determine the rate and the temporal evolution of SARS CoV-2 seropositivity in breastfed Malawian infants. Study design: Blood samples (n = 250) from 158 infants, born to HIV-negative women and women living with HIV, collected from February 2020 to May 2021, were first tested using an Anti-IgG/A/M SARS CoV 2 ELISA assay against trimeric spike protein, and then, if positive, confirmed using a second ELISA assay detecting IgG against Receptor Binding Domain. Results: The confirmed prevalence of anti-SARS CoV-2 antibodies was 31.0% (95% CI: 23.7%-38.3%) with no significant difference between HIV-exposed and HIV-unexposed infants (29.3% and 37.1% respectively, P = 0.410). The presence of anti-SARS-CoV-2 IgG was not associated with maternal socioeconomic or demographic indices. Conclusions: Our data underline the wide spread of the SARS-CoV-2 infection in the pediatric population in sub-Saharan Africa. Design of more specific serological tests for African samples and improvements in serosurveillance programs are needed for more rigorous monitoring of the dynamics of SARS-CoV-2 infection in Africa.

Microbiologically confirmed infections and antibiotic-resistance in a national surveillance study of hospitalised patients who died with COVID-19, Italy 2020-2021.

BACKGROUND: Patients hospitalised for COVID-19 may present with or acquire bacterial or fungal infections that can affect the course of the disease. The aim of this study was to describe the microbiological characteristics of laboratory-confirmed infections in hospitalised patients with severe COVID-19. METHODS: We reviewed the hospital charts of a sample of patients deceased with COVID-19 from the Italian National COVID-19 Surveillance, who had laboratory-confirmed bacterial or fungal bloodstream infections (BSI) or lower respiratory tract infections (LRTI), evaluating the pathogens responsible for the infections and their antimicrobial susceptibility. RESULTS: Among 157 patients with infections hospitalised from February 2020 to April 2021, 28 (17.8%) had co-infections (≤ 48 h from admission) and 138 (87.9%) had secondary infections (> 48 h). Most infections were bacterial; LRTI were more frequent than BSI. The most common co-infection was pneumococcal LRTI. In secondary infections, Enterococci were the most frequently recovered pathogens in BSI (21.7% of patients), followed by Enterobacterales, mainly K. pneumoniae, while LRTI were mostly associated with Gram-negative bacteria, firstly Enterobacterales (27.4% of patients, K. pneumoniae 15.3%), followed by A. baumannii (19.1%). Fungal infections, both BSI and LRTI, were mostly due to C. albicans. Antibiotic resistance rates were extremely high in Gram-negative bacteria, with almost all A. baumannii isolates resistant to carbapenems (95.5%), and K. pneumoniae and P. aeruginosa showing carbapenem resistance rates of 59.5% and 34.6%, respectively. CONCLUSIONS: In hospitalised patients with severe COVID-19, secondary infections are considerably more common than co-infections, and are mostly due to Gram-negative bacterial pathogens showing a very high rate of antibiotic resistance.

Immunoglobulin G passive transfer from mothers to infants: total IgG, IgG subclasses and specific antipneumococcal IgG in 6-week Malawian infants exposed or unexposed to HIV.

BACKGROUND: The impaired transplacental passage of IgG from mothers living with HIV to their infants could be one of the causes of the high vulnerability to infections of HIV-exposed uninfected (HEU) infants, but controversial results have been obtained in different settings. The aim of this study was to assess in 6-week old HEU and HIV-unexposed, uninfected (HUU) Malawian infants the total IgG levels, the subclasses profile and the concentrations of global anti-pneumococcal capsular polysaccharide (anti-PCP) IgG and IgG2. METHODS: Dried blood spots were collected from 80 infants (40 HEU, 40 HUU) and antibodies concentrations determined by nephelometric method (total IgG and subclasses), or using ELISA (anti-PCP total IgG and IgG2). Results are expressed as median levels with IQR, while the proportions of each subclass out of the total IgG are used to describe the subclasses profile. RESULTS: At 6 weeks HEU infants had higher median levels of total IgG and IgG1 and a significantly lower level of IgG2 [0.376 (0.344-0.523) g/l vs 0.485 (0.374-0.781) g/l, p = 0.037] compared to the HUU counterparts. The IgG subclasses distribution confirmed the underrepresentation of IgG2 (IgG2 represented 5.82% of total IgG in HEU and 8.87% in HUU). The anti-PCP IgG and IgG2 levels were significantly lower in HEU infants [8.9 (5.4-15.1) mg/l vs 16.2 (9.61-25.8) mg/l in HUU, p < 0.001, and 2.69 (1.90-4.29) mg/l vs 4.47 (2.96-5.71) mg/l in HUU, p = 0.001, respectively]. CONCLUSION: Compared to HUU infants, HEU infants have IgG abnormalities mainly represented by low IgG2 levels, suggesting that despite maternal antiretroviral therapy, the mechanisms of IgG transplacental passage continue to be impaired in women living with HIV. HEU infants also showed a significantly lower level of specific anti-PCP IgG, possibly favouring a high vulnerability to S. pneumoniae infection at an age when protection is mostly depending on maternal IgG.

Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy.

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.

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.

Differences in the clinical characteristics of COVID-19 patients who died in hospital during different phases of the pandemic: national data from Italy.

BACKGROUND: Epidemiological data obtained during the initial wave of the COVID-19 epidemic showed that persons dying with COVID-19 were typically older men with multiple chronic conditions. No studies have assessed if the characteristics of patients dying with COVID-19 have changed in the second phase of the epidemic, when the initial wave subsided. The aim of the present study was to compare characteristics of patients dying with COVID-19 in Italy in the first 'peak' phase of the epidemic and in its second phase. METHODS: Medical charts of patients with COVID-19 who died while in hospital in Italy were reviewed to extract information on pre-existing comorbidities, in-hospital complications, and disease trajectories. The course of the epidemic was classified in two 3-month periods: March-May 2020 and June-August 2020. FINDINGS: Overall, in the Italian population, 34,191 COVID-19 deaths occurred in March-May 2020 and 1,404 in June-August 2020. Patients dying in March-May were significantly younger (80.1 ± 10.6 vs. 82.8 ± 11.1 years, p < 0.001) and less frequently female (41.9% vs. 61.8%, p < 0.001) than those dying in June-August. The medical charts of 3533 patients who died with PCR-confirmed SARS-CoV-2 infection in March-May 2020 (10.3% of all deaths occurring in this period) and 203 patients who died in June-August 2020 (14.5% of all deaths occurring in this period) were analysed. Patients who died in March-May 2020, compared to those who died in June-August 2020, had significantly lower rates of multiple comorbidities (3 or more comorbidities: 61.8% vs 74.5%, p = 0.001) and superinfections (15.2% vs. 52.5%, p < 0.001). Treatment patterns also substantially differed in the two study periods, with patients dying in March-May 2020 being less likely to be treated with steroids (41.7% vs. 69.3%, p < 0.001) and more likely to receive antivirals (59.3% vs. 41.4%, p < 0.001). Survival time also largely differed, with patients dying in March-May 2020 showing a shorter time from symptoms onset to death (mean interval: 15.0 vs. 46.6 days, p < 0.001). The differences observed between the two periods remained significant in a multivariate analysis. INTERPRETATION: The clinical characteristics of patients dying with COVID-19 in Italy, their treatment and symptom-to-death survival time have significantly changed overtime. This is probably due to an improved organization and delivery of care and to a better knowledge of disease treatment.

Clinical characteristics of individuals with Down syndrome deceased with CoVID-19 in Italy-A case series.

BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.

Low mortality rates at two years in HIV-infected individuals undergoing systematic tuberculosis testing with rapid assays at initiation of antiretroviral treatment in Mozambique.

BACKGROUND: Few studies have evaluated the mortality rate in individuals with HIV initiating antiretroviral therapy (ART), undergoing screening with combined or repeated rapid tests for tuberculosis (TB). METHODS: All individuals with HIV starting ART, irrespective of the presence of TB-related symptoms, received two consecutive Xpert tests plus a rapid test for the detection of mycobacterial lipoarabinomannan in urine (LAM). Mortality was evaluated by Kaplan-Meier analysis using the log-rank test in univariate analyses and Cox regression models with time-dependent covariates in multivariate analyses. RESULTS: Among 972 individuals screened with combined tests, 98 (10.1%) tested positive for TB with Xpert, LAM, or both. At the end of the study, 780 (80.2%) had completed 2 years of follow-up, 39 (4.0%) had died, and 153 (15.7%) were lost to follow-up. In the multivariate analyses, the factors significantly associated with mortality were missed ART (hazard ratio (HR) 7.05, 95% confidence interval (CI) 2.33-21.35), symptomatic HIV disease (WHO-HIV stage >1) (HR 3.31, 95% CI 1.28-8.54), and low CD4 count (<200/mm3) (HR 2.72, 95% CI 1.21-6.13), with no significant effect of TB status. In the subgroup of the 98 TB-positive individuals, only missed ART (HR 4.12, 95% CI 1.03-16.46) and missed anti-TB treatment (HR 9.25, 95% CI 2.65-32.28) were significantly associated with mortality. CONCLUSIONS: A low mortality rate was observed among individuals with HIV undergoing systematic testing for TB at initiation of ART. After adjusting for confounders, mortality was significantly associated with missed ART, advanced disease, and missed anti-TB treatment. These findings reinforce the need to promote early diagnosis of HIV and the adoption of screening strategies for TB that prevent presentation with severe disease.