Influenza-like illness surveillance may underestimate the incidence of respiratory syncytial virus in adult outpatients.

OBJECTIVES: Although respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs), it is unclear which of the case definitions that prompt swab collection predicts RSV best. We aimed to profile RSV-positive adults and to identify possible RSV case definitions. METHODS: This individual-based pooled analysis was based on influenza-like illness (ILI) surveillance conducted among Italian outpatient adults. All samples were tested for influenza, RSV and other respiratory viruses. RESULTS: RSV was detected in 5.2% of the 1240 ILI adults tested. The prevalence of fever/feverishness was significantly lower (83.3%) in individuals positive for RSV and those negative for both viruses (79.4%) than in influenza-positive subjects (96.2%). Conversely, 98.3% of RSV-positive adults reported cough. Compared with subjects who tested negative, the adjusted relative risk ratio of cough in RSV-positive subjects was much higher than in influenza-positive subjects (6.89 vs 2.79). Using ARI with cough as the RSV case definition increased specificity. CONCLUSION: As fever/feverishness is more common among influenza than RSV cases, ILI-based surveillance may underestimate RSV incidence in adult outpatients. While broad ARI definitions are useful for routine RSV surveillance, their low specificity may hamper vaccine effectiveness studies. The use of further ARI qualifiers like cough increases specificity.

Adenovirus infection in adult patients undergoing allogeneic hematopoietic stem cell transplant: Incidence, clinical management, and outcome.

BACKGROUND: Adenovirus infection (ADVi) is an emergent complication in adult patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with poor outcome. Available data on risk factors and optimal management of ADVi in adult allo-HSCT recipients are limited, and recommendations on monitoring and pre-emptive therapy are mainly based on pediatric data. METHODS: In this single-center, retrospective study, we reported all cases of positive ADV-DNA from adult patients undergoing allo-HSCT in the period 2014-2019. The study aimed to describe the incidence of ADVi at day +180 post-transplant. Secondly to describe timing, clinical presentation, risk factors, and outcome of ADVi and to analyze the application of a screening strategy in our cohort. RESULTS: In 445 allo-HSCT recipients, the day +180 incidence was: 9% (39/445) for ADVi, 5% (24/445) for ADV viremia (ADVv), and 3% (15/445) for localized ADVi. The median time to ADVi was 65 (IQR 19; 94) days after HSCT. ADVv-related mortality was 13% (3/24), all cases occurring with blood max-ADV-DNA > 10^3 cp/mL. Independent risk factors for ADVi were diagnosis of lymphoproliferative disease (p = .011) and acute graft-versus-host-disease (p = .021). CONCLUSIONS: In our cohort, ADVi and ADVv were more frequent than previously reported. ADVv with max-ADV-DNA > 10^3 cp/mL was associated with ADV-related mortality, thus careful monitoring and early initiation of treatment are advisable.

Neutralizing monoclonal antibodies for the prevention of severe COVID-19: a retrospective study during Omicron BA.1 variant surge.

Among treatment options for Coronavirus disease 2019 (COVID-19), monoclonal antibodies (mAbs) showed to be effective in preventing disease progression, but real-world data during the Omicron variant surge are still lacking. Multicentre retrospective study evaluating the effectiveness of sotrovimab and casirivimab-imdevimab in fragile patients with mild SARS-CoV-2 infection between November 2021 and March 2022. Unfavourable outcome was defined as increased need for oxygen supplementation and/or death. Of 268 study-participants, 12 (4.48%) previously needed supplemental oxygen, while 6 (2.24%) had active solid neoplasia (2.24%); 186 (69%) have previously received SARS-CoV-2 vaccination. Overall, 22 (8%) had unfavourable outcomes (42% versus 6% of patients with and without previous oxygen need and 50% versus 7% of patients with and without active solid neoplasia). Both supplemental oxygen therapy before SARS-CoV-2 infection and solid malignant tumour have shown to be risk factors for treatment failure. Log-rank test did not identify differences between sotrovimab and casirivimab-imdevimab treatment. Despite diffusion of Omicron variant, the rate of unfavourable outcome was higher than expected. The presence of underlying risk factors, including solid cancer and previous oxygen therapy are independently associated with risk of COVID-19 progression, suggesting the need for antiviral treatments not limited to mAbs and implementation of vaccine campaign.

Genomic epidemiology of the main SARS-CoV-2 variants in Italy between summer 2020 and winter 2021.

Since the beginning of the pandemic, SARS-CoV-2 has shown a great genomic variability, resulting in the continuous emergence of new variants that has made their global monitoring and study a priority. This work aimed to study the genomic heterogeneity, the temporal origin, the rate of viral evolution and the population dynamics of the main circulating variants (20E.EU1, Alpha and Delta) in Italy, in August 2020-January 2022 period. For phylogenetic analyses, three datasets were set up, each for a different main lineage/variant circulating in Italy in that time including other Italian and International sequences of the same lineage/variant, available in GISAID sampled in the same times. The international dataset showed 26 (23% Italians, 23% singleton, 54% mixed), 40 (60% mixed, 37.5% Italians, 1 singleton) and 42 (85.7% mixed, 9.5% singleton, 4.8% Italians) clusters with at least one Italian sequence, in 20E.EU1  clade, Alpha and Delta variants, respectively. The estimation of tMRCAs in the Italian clusters (including >70% of genomes from Italy) showed that in all the lineage/variant, the earliest clusters were the largest in size and the most persistent in time and frequently mixed. Isolates from the major Italian Islands tended to segregate in clusters more frequently than those from other part of Italy. The study of infection dynamics showed a positive correlation between the trend in the effective number of infections estimated by BSP model and the Re curves estimated by birth-death skyline plot. The present work highlighted different evolutionary dynamics of studied lineages with high concordance between epidemiological parameters estimation and phylodynamic trends suggesting that the mechanism of replacement of the SARS-CoV-2 variants must be related to a complex of factors involving the transmissibility, as well as the implementation of control measures, and the level of cross-immunization within the population.

Long follow-up of BNT162b2 mRNA vaccine in healthcare workers (2020-2022): A retrospective longitudinal SARS-CoV-2 serological surveillance.

SARS-CoV-2 anti-spike IgG production and protection from severe respiratory illness should be explored in greater depth after COVID-19 booster vaccination. This longitudinal observational retrospective study investigated the anti-spike IgG response elicited by the first, second and booster doses of BNT162b2 mRNA vaccine in healthcare workers (HCW) at San Martino IRCCS Policlinico Hospital (Genoa) up to the 12th month. Sequential blood sampling was performed at T0 (prior to vaccination), T1 (21 days after the 1st dose of vaccine), T2, T3, T4, T5, T6 (7 days and 1, 3, 6 and 9 months after the 2nd dose, respectively), T7 and T8 (1 and 3 months after a booster dose). A SARS-CoV-2 IgG panel (Bio-Rad, Marnes-la-Coquette, France) was used to determine levels of receptor-binding domain (RBD), spike-1 (S1), spike-2 and nucleocapsid structural proteins of SARS-CoV-2. In the 51 HCWs evaluated, seroprevalence was 96% (49/51) at T1 and 100% (51/51) from T2 to T5 for RBD and S1. At T6, only one HCW was negative. T2 [RBD = 2945 (IQR:1693-5364); S1 = 1574 (IQR:833-3256) U/mL], and T7 [RBD = 8204 (IQR:4129-11,912); S1 = 4124 (IQR:2124-6326) U/mL] were characterized by the highest antibody values. Significant humoral increases in RBD and S1 were documented at T7 and T8 compared to T2 and T4, respectively (p-value < .001). Following vaccination with BNT162b2 and a booster dose in the 9th month, naïve and healthy subjects show high antibody titers up to 12 months and a protective humoral response against COVID-19 disease lasting up to 20 months after the last booster.

Effect of SARS-CoV-2 vaccination in a vulnerable COVID-19 cohort: a real-life experience in an Italian Hospital.

Clinical trials demonstrated that SARS-CoV-2 vaccines reduce COVID-19-related mortality and morbidity. We describe the effect of vaccination on COVID-19-patients admitted at our hospital. Retrospective, single-center study conducted in Genoa, Italy, including patients ≥18years hospitalized for COVID-19 from May to December 2021. Demographical and clinical data were collected, vaccinated (group-A) and not-vaccinated (group-B) patients were compared. Impact of vaccination on mortality, ICU admission, and oxygen need was studied using Cox proportional hazards and logistic regression models after adjusting for propensity scores. Overall, 395 patients SARS-CoV-2 infected were included, of which 150 (38%) were vaccinated and 245 (62%) were not vaccinated. Patients in group-A were older, more disable, and with higher morbidity. Overall, 64 patients (16%) died within 30 days from admission, 34 in Group A (23%), and 30 in group B (12%). However, no statistically significant differences were observed (group-A versus group-B: HR 0.83, 95% CI 0.49-1.40, p = 0.483). On the other hand, vaccination was protective in terms of ICU admission (OR = 0.23, p = 0.046) and oxygen need (OR = 0.33, p = 0.008). Our study confirms that SARS-CoV-2 vaccination reduces morbidity among patients hospitalized for COVID-19. The still high mortality in our cohort of vaccinated individuals could be partially due to vulnerable conditions of our patients.

Pneumocystis jirovecii pneumonia in intensive care units: a multicenter study by ESGCIP and EFISG.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. MATERIALS AND METHODS: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. RESULTS: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13-9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23-11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07-33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76-10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01-4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42-1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. CONCLUSION: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Real-world performance of SARS-CoV-2 rapid antigen testing through the Alpha-, Delta- and Omicron-dominant waves of the COVID-19 pandemic.

OBJECTIVES: Compared with reverse transcription polymerase chain reaction (RT-PCR), rapid antigen detection tests (RADTs) for SARS-CoV-2 diagnostics are faster, less expensive, but also less accurate. Performance of RADTs is context-specific and depends on disease prevalence. In this real-world study, we assessed impact of RADTs in an inpatient setting through the entire COVID-19 emergency phase. METHODS: In this matched retrospective study, data on RT-PCR and RADT laboratory diagnoses of SARS-CoV-2 made between February 2020 and May 2023 in a large hospital were analyzed. To be included in the study, samples used for both RT-PCR and RADT had to be collected on the same day. RESULTS: Of 278,867 RT-PCR tests available, 13,321 same-day RADTs could be matched to RT-PCR. Over the entire period, RADT sensitivity and specificity were 76.4% and 99.4%, respectively. With the observed positivity rate of 9.4%, positive and negative predictive values were 92.7% and 97.6%, respectively. Compared with the periods dominated by the Alpha and Delta variants of concern, RADT accuracy was slightly lower during the Omicron phase. CONCLUSION: This real-world experience demonstrates that despite suboptimal sensitivity and some variation by predominant variants of concern and positivity prevalence, the use of RADTs is useful in hospital settings. Public health implications were discussed.

Influenza vaccine effectiveness in preventing hospital encounters for laboratory-confirmed infection among Italian adults, 2022/23 season.

The effectiveness of seasonal influenza vaccination (SIV) varies from year to year. Interim estimates of vaccine effectiveness (VE) in outpatient settings have suggested that the 2022/23 northern hemisphere SIV was 54 % effective. The main goal of this study was to measure the 2022/23 SIV VE among Italian adults in a hospital setting. The study adopted a retrospective test-negative case-control design and was conducted in a large tertiary hospital (Genoa, Italy) between October 2022 and April 2023. Adult (≥18 years) patients accessing the hospital's Emergency Department for symptoms ascribable to an acute respiratory infection, for which a reverse-transcription real-time polymerase chain reaction test for the detection of influenza virus was prescribed, were potentially eligible. Of 33,692 referrals assessed, 487 patients were included in the study. A total of 13 % of patients were positive for influenza, most of which (63 %) belonged to the A(H3N2) subtype. SIV VE was 57 % (95 % CI: 11-81 %), 53 % (95 % CI: 2-80 %) and 38 % (95 % CI: -34-74 %) against any influenza, influenza A and A(H3N2), respectively. Although no cases caused by A(H1N1)pdm09 and B strains were observed among vaccinated individuals, VE estimates against the latter were imprecise, owing to their low detection rates. In conclusion, the 2022/23 SIV was moderately effective against hospital encounters for laboratory-confirmed influenza.

PRESTIGIO RING: "A 59-year-old HIV-1 positive, highly treatment-experienced woman failing darunavir/ ritonavir plus raltegravir".

Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing.

External validation of unsupervised COVID-19 clinical phenotypes and their prognostic impact.

BACKGROUND: Hospitalized patients with coronavirus disease 2019 (COVID-19) can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory features. We aimed to validate in an external cohort of hospitalized COVID-19 patients the prognostic value of a previously described phenotyping system (FEN-COVID-19) and to assess the reproducibility of phenotypes development as a secondary analysis. METHODS: Patients were classified in phenotypes A, B or C according to the severity of oxygenation impairment, inflammatory response, hemodynamic and laboratory tests according to the FEN-COVID-19 method. RESULTS: Overall, 992 patients were included in the study, and 181 (18%), 757 (76%) and 54 (6%) of them were assigned to the FEN-COVID-19 phenotypes A, B, and C, respectively. An association with mortality was observed for phenotype C vs. A (hazard ratio [HR] 3.10, 95% confidence interval [CI] 1.81-5.30, p < 0.001) and for phenotype C vs. B (HR 2.20, 95% CI 1.50-3.23, p < 0.001). A non-statistically significant trend towards higher mortality was also observed for phenotype B vs. A (HR 1.41; 95% CI 0.92-2.15, p = 0.115). By means of cluster analysis, three different phenotypes were also identified in our cohort, with an overall similar gradient in terms of prognostic impact to that observed when patients were assigned to FEN-COVID-19 phenotypes. CONCLUSIONS: The prognostic impact of FEN-COVID-19 phenotypes was confirmed in our external cohort, although with less difference in mortality between phenotypes A and B than in the original study.

Hospitalized patients with COVID-19 can be classified into different clinical phenotypes based on their demographic, clinical, radiology, and laboratory featuresIn this study, we externally confirmed the prognostic impact of clinical phenotypes previously identified by Gutierrez-Gutierrez and colleagues in a Spanish cohort of hospitalized patients with COVID-19, and the usefulness of their simplified probabilistic model for phenotypes assignmentThis could indirectly support the validity of both phenotype's development and their extrapolation to other hospitals and countries for management decisions during other possible future viral pandemics.

Efficacy of Dolutegravir versus Darunavir in Antiretroviral First-Line Regimens According to Resistance Mutations and Viral Subtype.

BACKGROUND: Dolutegravir (DTG)-based first-line regimens have shown superior efficacy versus darunavir (DRV)-based ones in randomized trials. We compared these two strategies in clinical practice, particularly considering the role of pre-treatment drug resistance mutations (DRMs) and of the HIV-1 subtype. MATERIALS AND METHODS: The multicenter Antiretroviral Resistance Cohort Analysis (ARCA) database was queried to identify HIV-1-positive patients starting a first-line therapy with 2NRTIs plus either DTG or DRV between 2013 and 2019. Only adult (≥18 years) patients with a genotypic resistance test (GRT) prior to therapy and with HIV-1 RNA ≥1000 copies/mL were selected. Through multivariable Cox regressions, we compared DTG- versus DRV-based regimens in the time to virological failure (VF) stratifying for pre-treatment DRMs and the viral subtype. RESULTS: A total of 649 patients was enrolled, with 359 (55.3%) and 290 (44.7) starting DRV and DTG, respectively. In 11 months of median follow-up time, there were 41 VFs (8.4 in 100 patient-years follow-up, PYFU) and 15 VFs (5.3 per 100 PYFU) in the DRV and DTG groups, respectively. Compared with a fully active DTG-based regimen, the risk of VF was higher with DRV (aHR 2.33; p = 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27; p = 0.001), after adjusting for age, gender, baseline CD4 count and HIV-RNA, concurrent AIDS-defining event and months since HIV diagnosis. Compared with patients harboring a B viral subtype and treated with a DTG-based regimen, patients on DRV had an increased risk of VF, both in subtype B (aHR 3.35; p = 0.011), C (aHR 8.10; p = 0.005), CRF02-AG (aHR 5.59; p = 0.006) and G (aHR 13.90; p < 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24; p = 0.035) and CRF01-AE (versus B; aHR 10.65; p = 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF. CONCLUSIONS: In line with randomized trials, DTG-based first-line regimens showed an overall superior efficacy compared with DRV-based regimens. GRT may still play a role in identifying patients more at risk of VF and in guiding the choice of an antiretroviral backbone.

Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients.

BACKGROUND: Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. METHODS: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. RESULTS: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction). CONCLUSIONS: Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

Epidemiology and molecular characteristics of respiratory syncytial virus (RSV) among italian community-dwelling adults, 2021/22 season.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections worldwide. While historically RSV research has been focused on children, data on RSV infection in adults are limited. The goal of this study was to establish the prevalence of RSV in community-dwelling Italian adults and analyze its genetic variability during the 2021/22 winter season. METHODS: In this cross-sectional study, a random sample of naso-/oropharyngeal specimens from symptomatic adults seeking for SARS-CoV-2 molecular testing between December 2021 and March 2022 were tested for RSV and other respiratory pathogens by means of reverse-transcription polymerase chain reaction. RSV-positive samples were further molecularly characterized by sequence analysis. RESULTS: Of 1,213 samples tested, 1.6% (95% CI: 0.9-2.4%) were positive for RSV and subgroups A (44.4%) and B (55.6%) were identified in similar proportions. The epidemic peak occurred in December 2021, when the RSV prevalence was as high as 4.6% (95% CI: 2.2-8.3%). The prevalence of RSV detection was similar (p = 0.64) to that of influenza virus (1.9%). All RSV A and B strains belonged to the ON1 and BA genotypes, respectively. Most (72.2%) RSV-positive samples were also positive for other pathogens being SARS-CoV-2, Streptococcus pneumoniae and rhinovirus the most frequent. RSV load was significantly higher among mono-detections than co-detections. CONCLUSION: During the 2021/22 winter season, characterized by the predominant circulation of SARS-CoV-2 and some non-pharmaceutical containment measures still in place, a substantial proportion of Italian adults tested positive for genetically diversified strains of both RSV subtypes. In view of the upcoming registration of vaccines, establishment of the National RSV surveillance system is urgently needed.

Rapid differential diagnosis of SARS-CoV-2, influenza A/B and respiratory syncytial viruses: Validation of a novel RT-PCR assay.

BACKGROUND: Influenza and respiratory syncytial (RSV) viruses are expected to co-circulate with SARS-CoV-2 in the upcoming seasons and clinical differential diagnosis between them is difficult. Laboratory-based RT-PCR is a gold standard diagnostic method for influenza, RSV and SARS-CoV-2. The objective of this study was to estimate the diagnostic performance of a novel point-of-care RT-PCR assay STANDARD M10 Flu/RSV/SARS-CoV-2 (SD Biosensor) in a large number of clinical specimens with diversified (co)-infection patterns and viral loads. METHODS: This was a retrospective study, in which all samples were tested in both STANDARD M10 Flu/RSV/SARS-CoV-2 index and Allplex SARS-CoV-2/Respiratory Panel 1 (Seegene) reference kits. Samples with discordant results were further processed in a third resolver test (Resp-4-Plex, Abbott). RESULTS: A total of 1,019 naso-/oropharyngeal samples (50.3% positive for at least one virus) were processed in both STANDARD M10 Flu/RSV/SARS-CoV-2 and Allplex assays and the overall between-assay agreement was as high as 94.6%. Positive percent agreement of the STANDARD M10 Flu/RSV/SARS-CoV-2 was 100%, 96.6%, 97.3% and 99.4% for influenza A, B, RSV and SARS-CoV-2, respectively. The corresponding negative percent agreement was 99.7%. 100%, 100% and 98.4%, respectively. The expected positive and negative predictive values for all viruses were constantly above 96% in a reasonable range of disease prevalence. CONCLUSIONS: STANDARD M10 Flu/RSV/SARS-CoV-2 is a reliable RT-PCR assay able to detect influenza A, influenza B, RSV and SARS-CoV-2 in one hour or less, fostering a rapid differential diagnosis of common respiratory viruses.

Monkeypox outbreak in Genoa, Italy: Clinical, laboratory, histopathologic features, management, and outcome of the infected patients.

Since May 2022, multiple human Monkeypox cases were identified in nonendemic countries, mainly among men who have sex with men. We aimed to report the features, clinical course, management, and outcome of the Monkeypox cases diagnosed in the Dermatology and Infectious Disease Units of the San Martino Hospital, Genoa, Italy. We performed an observational study of the Monkeypox cases diagnosed from July 1 until August 31, 2022, collecting clinical, laboratory, and histological data. We studied 16 Monkeypox-infected men (14 homosexual, 2 bisexual) with a median age of 37 years. Three were HIV-infected. All patients reported multiple sexual partners and/or unprotected sex in the 2 weeks before the diagnosis. Most patients had prodromal signs/symptoms before the appearance of the skin/mucosal eruption, consisting of erythematous papules/vesicles/pustules in the anogenital area, which tended to erode evolving into crusts and ulcers. Lesions were often associated with local and/or systemic symptoms. Histopathology showed overlapping features in all cases: epidermal ulceration and dermal inflammatory infiltrate consisting of lymphocytes and neutrophils with an interstitial and perivascular/peri-adnexal pattern and endothelial swelling. Concomitant sexually transmitted infections (STIs) (gonococcal/nongonococcal proctitis and anal high-risk human papillomavirus [HR-HPV] infection) were frequent. Four patients were hospitalized, and one received specific treatment. The overall outcome was good. At the follow-up visit, three patients presented skin scars. Our series confirms the features of the current Monkeypox outbreak; however, different from other studies, we found a considerable rate of concomitant STIs, such as anal HR-HPV infection, that should be kept in mind because this persistent infection is the main cause of anal cancers.

Nasal monkeypox virus infection successfully treated with cidofovir in a patient newly diagnosed with HIV.

Monkeypox (MPXV) usually causes a mild and self-limited infection. To date there are no data about cidofovir for the treatment for MPXV in humans. We report a case of a 25 years-old Brazilian man with a concurrent diagnosis of acute HIV (human immunodeficiency virus) infection, primary syphilis and MPXV infection with a nasal lesion successfully treated with intravenous cidofovir.

Intermediate monocytes expansion and homing markers expression in COVID-19 patients associate with kidney dysfunction.

Patients with severe SARS-CoV-2 infection have an overwhelming inflammatory response characterized by remarkable organs monocyte infiltration. We performed an immunophenotypic analysis on circulating monocytes in 19 COVID-19 patients in comparison with 11 naïve HIV-1 patients and 10 healthy subjects. Reduced frequency of classical monocytes and increased frequency of intermediate monocytes characterized COVID-19 patients with respect to both HIV naïve patients and healthy subjects. Intensity of C-C motif chemokine receptor 2 (CCR2) monocyte expression highly correlated with parameters of kidney dysfunction. Our data indicate that highly activated monocytes of COVID-19 patients may be pathogenically associated with the development of renal disease.

Epidemiological and Clinical Features of SARS-CoV-2 Variants Circulating between April-December 2021 in Italy.

SARS-CoV-2 is constantly evolving, leading to new variants. We analysed data from 4400 SARS-CoV-2-positive samples in order to pursue epidemiological variant surveillance and to evaluate their impact on public health in Italy in the period of April-December 2021. The main circulating strain (76.2%) was the Delta variant, followed by the Alpha (13.3%), the Omicron (5.3%), and the Gamma variants (2.9%). The B.1.1 lineages, Eta, Beta, Iota, Mu, and Kappa variants, represented around 1% of cases. There were 48.2% of subjects who had not been vaccinated, and they had a lower median age compared to the vaccinated subjects (47 vs. 61 years). An increasing number of infections in the vaccinated subjects were observed over time, with the highest proportion in November (85.2%). The variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed with the Delta variant, while subjects harbouring the Gamma variant showed the highest proportion of asymptomatic infection (21.6%), albeit also deaths (5.4%). The Omicron variant was only found in the vaccinated subjects, of which 47% had been hospitalised. The diffusivity and pathogenicity associated with the different SARS-CoV-2 variants are likely to have relevant public health implications, both at the national and international levels. Our study provides data on the rapid changes in the epidemiological landscape of the SARS-CoV-2 variants in Italy.

Adverse Reactions after the Third Dose of the BNT162b2 mRNA COVID-19 Vaccine among Medical School Residents in a Regional Reference University Hospital in Italy.

The recent emergence of new variants of concern (VOCs) of SARS-CoV-2 and the uncertain duration of protection provided by the primary immunization cycle have highlighted the need for COVID-19 booster vaccinations. However, only a few studies have assessed the safety and reactogenicity profile of mRNA booster doses. Therefore, we conducted an online survey with the aim of assessing the adverse reaction profile in the 7 days following a third dose of the BNT162b2 vaccine in a population of resident physicians who had already been investigated after the primary vaccination. Among the 512 resident physicians (female = 53.2%, mean age = 29.8 years) invited to participate in the survey, 222 completed the survey (56.5% female, mean age of 29.9 years), with an average time from second to third dose of 8.6 months. The most common adverse reactions were local pain (88.3%), fatigue (58.1%), muscle/joint pain (44.1%), and headache (38.3%), all subsiding in 48-72 h. While the local reaction rate was similar to that following the first two doses, the systemic reactions were considerably less common and milder compared to the second vaccination. Nonetheless, over one third (36.1%) of participants reported interference with their normal activities. These results complement our previous findings and could aid occupational and public health professionals in the counselling of vaccinees.