Efficacy and Safety of Anticoagulant Therapy in COVID-19-Related Pulmonary Embolism with Different Extension.

Pulmonary embolism (PE) has been associated with SARS-CoV-2 infection, and its incidence is highly variable. The aim of our study was to describe the radiological and clinical presentations, as well as the therapeutic management, of PEs that occurred during SARS-CoV-2 infection in a cohort of hospitalized patients. In this observational study, we enrolled patients with moderate COVID-19 who developed PE during hospitalization. Clinical, laboratory, and radiological features were recorded. PE was diagnosed on clinical suspicion and/or CT angiography. According to CT angiography results, two groups of patients were further distinguished: those with proximal or central pulmonary embolism (cPE) and those with distal or micro-pulmonary embolism (mPE). A total of 56 patients with a mean age of 78 ± 15 years were included. Overall, PE occurred after a median of 2 days from hospitalization (range 0-47 days) and, interestingly, the majority of them (89%) within the first 10 days of hospitalization, without differences between the groups. Patients with cPE were younger (p = 0.02), with a lower creatinine clearance (p = 0.04), and tended to have a higher body weight (p = 0.059) and higher D-Dimer values (p = 0.059) than patients with mPE. In all patients, low-weight molecular heparin (LWMH) at anticoagulant dosage was promptly started as soon as PE was diagnosed. After a mean of 16 ± 9 days, 94% of patients with cPE were switched to oral anticoagulant (OAC) therapy, which was a direct oral anticoagulant (DOAC) in 86% of cases. In contrast, only in 68% of patients with mPE, the prosecution with OAC was indicated. The duration of treatment was at least 3 months from PE diagnosis in all patients who started OAC. At the 3-month follow-up, no persistence or recurrence of PE as well as no clinically relevant bleedings were found in both groups. In conclusion, pulmonary embolism in patients with SARS-CoV-2 may have different extensions. Used with clinical judgment, oral anticoagulant therapy with DOAC was effective and safe.

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

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

Evolution of SARS-CoV-2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID-19 in an Italian reference hospital: Impact on clinical outcomes.

Despite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant.

Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study).

Background: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19. Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76). Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths. Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results. Funding: This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and reemerging infections, funded by Italian Ministry of Health.

What is the impact of post-COVID-19 syndrome on health-related quality of life and associated factors: a cross-sectional analysis.

BACKGROUND: After the acute phase, symptoms or sequelae related to post-COVID-19 syndrome may persist for months. In a population of patients, previously hospitalized and not, followed up to 12 months after the acute infection, we aim to assess whether and to what extent post-COVID-19 syndrome may have an impact on health-related quality of life (HRQoL) and to investigate influencing factors. METHODS: We present the cross-sectional analysis of a prospective study, including patients referred to the post-COVID-19 service. Questionnaires and scales administered at 3, 6, 12 months were: Short-Form 36-item questionnaire (SF-36); Visual Analogue Scale of the EQ5D (EQ-VAS); in a subgroup, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II) and Pittsburgh Sleep Quality Index (PSQI). Linear regression models were fitted to identify factors associated with HRQoL. RESULTS: We considered the first assessment of each participant (n = 572). The mean scores in SF-36 and in EQ-VAS were significantly lower than the Italian normative values and remained stable over time, except the mental components score (MCS) of the SF-36 and EQ-VAS which resulted in lower ratings at the last observations. Female gender, presence of comorbidities, and corticosteroids treatment during acute COVID-19, were associated with lower scores in SF-36 and EQ-VAS; patients previously hospitalized (54%) reported higher MCS. Alterations in BAI, BDI-II, and PSQI (n = 265)were associated with lower ratings in SF-36 and EQ-VAS. CONCLUSIONS: This study provides evidence of a significantly bad perception of health status among persons with post-COVID-19 syndrome, associated with female gender and, indirectly, with disease severity. In case of anxious-depressive symptoms and sleep disorders, a worse HRQoL was also reported. A systematic monitoring of these aspects is recommended to properly manage the post-COVID-19 period.

Comparison of SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples from Patients Infected with Omicron Variant.

To compare the detection of the SARS-CoV-2 Omicron variant in nasopharyngeal-swab (NPS) and oral saliva samples. 255 samples were obtained from 85 Omicron-infected patients. SARS-CoV-2 load was measured in the NPS and saliva samples by using Simplexa™ COVID-19 direct and Alinity m SARS-CoV-2 AMP assays. Results obtained with the two diagnostic platforms showed very good inter-assay concordance (91.4 and 82.4% for saliva and NPS samples, respectively) and a significant correlation among cycle threshold (Ct) values. Both platforms revealed a highly significant correlation among Ct obtained in the two matrices. Although the median Ct value was lower in NPS than in saliva samples, the Ct drop was comparable in size for both types of samples after 7 days of antiviral treatment of the Omicron-infected patients. Our result demonstrates that the detection of the SARS-CoV-2 Omicron variant is not influenced by the type of sample used for PCR analysis, and that saliva can be used as an alternative specimen for detection and follow-up of Omicron-infected patients.

Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents.

The efficacy on the Omicron variant of the approved early coronavirus disease-2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. We assessed potential decrease from Day 1 to Day 7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect by weighted marginal linear regression models. A total of 521 patients (378 BA.1 [73%], 143 [27%] BA.2) received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day 1 mean VL was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except versus Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission.

Genomic surveillance of SARS-CoV-2 positive passengers on flights from China to Italy, December 2022.

With numbers of COVID-19 cases having substantially increased at the end of 2022 in China, some countries have started or expanded testing and genomic surveillance of travellers. We report screening results in Italy in late December 2022 of 556 flight passengers in provenance from two Chinese provinces. Among these passengers, 126 (22.7%) tested SARS-CoV-2 positive. Whole genome sequencing of 61 passengers' positive samples revealed Omicron variants, notably sub-lineages BA.5.2.48, BF.7.14 and BQ.1.1, in line with data released from China.

Proteomic analysis identifies a signature of disease severity in the plasma of COVID-19 pneumonia patients associated to neutrophil, platelet and complement activation.

Most patients infected with SARS-CoV-2 display mild symptoms with good prognosis, while 20% of patients suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due to severe acute respiratory syndrome, which could be accompanied by multiorgan failure.Plasma proteomics provide valuable and unbiased information about disease progression and therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma of COVID-19 patients that implied significant dysregulation of several aspects of the inflammatory response accompanied by a general metabolic suppression. However, which of these plasma alterations are associated with disease severity remains only partly characterized.A known limitation of proteomic studies of plasma samples is the large difference in the macromolecule abundance, with concentration spanning at least 10 orders of magnitude. To improve the coverage of plasma contents, we performed a deep proteomic analysis of plasma from 10 COVID-19 patients with severe/fatal pneumonia compared to 10 COVID-19 patients with pneumonia who did not require ICU admission (non-ICU). To this aim, plasma samples were first depleted of the most abundant proteins, trypsin digested and peptides subjected to a high pH reversed-phase peptide fractionation before LC-MS analysis.These results highlighted an increase of proteins involved in neutrophil and platelet activity and acute phase response, which is significantly higher in severe/fatal COVID-19 patients when compared to non-ICU ones. Importantly, these changes are associated with a selective induction of complement cascade factors in severe/fatal COVID-19 patients. Data are available via ProteomeXchange with identifier PXD036491. Among these alterations, we confirmed by ELISA that higher levels of the neutrophil granule proteins DEFA3 and LCN2 are present in COVID-19 patients requiring ICU admission when compared to non-ICU and healthy donors.Altogether, our study provided an in-depth view of plasma proteome changes that occur in COVID-19 patients in relation to disease severity, which can be helpful to identify therapeutic strategies to improve the disease outcome.

Safety and immune response kinetics of GRAd-COV2 vaccine: phase 1 clinical trial results.

Despite the successful deployment of efficacious vaccines and therapeutics, the development of novel vaccines for SARS-CoV-2 remains a major goal to increase vaccine doses availability and accessibility for lower income setting. We report here on the kinetics of Spike-specific humoral and T-cell response in young and old volunteers over 6 months follow-up after a single intramuscular administration of GRAd-COV2, a gorilla adenoviral vector-based vaccine candidate currently in phase-2 of clinical development. At all three tested vaccine dosages, Spike binding and neutralizing antibodies were induced and substantially maintained up to 3 months, to then contract at 6 months. Potent T-cell responses were readily induced and sustained throughout the study period, with only minor decline. No major differences in immune response to GRAd-COV2 vaccination were observed in the two age cohorts. In light of its favorable safety and immunogenicity, GRAd-COV2 is a valuable candidate for further clinical development and potential addition to the COVID-19 vaccine toolbox to help fighting SARS-CoV-2 pandemic.

SARS-CoV-2 nasopharyngeal viral load in individuals infected with BA.2, compared to Alpha, Gamma, Delta and BA.1 variants: A single-center comparative analysis.

BACKGROUND: SARS-CoV-2 has evolved, leading to the emergence of new Variants Of Concern (VOCs) with significant impact on transmissibility. Although the transmission process is complex, higher nasopharyngeal viral load (NP-VL) can be considered as a proxy for greater transmissibility. OBJECTIVES: The aim of this analysis was to compare NP-VL across a set of representative VOCs observed in mildly symptomatic patients. STUDY DESIGN: Observational single-center comparative analysis of patients with early mild-to-moderate COVID-19, enrolled within the early treatment access program of Lazzaro Spallanzani Institute (March 2021-March 2022). NP-VL before drug administration was estimated through RT-PCR, based on cycle threshold values (CTs); VOCs were identified by Sanger sequencing. VOCs' average treatment effect (ATE) was estimated on the CTs fitted in the log2 scale, controlling for potential confounders. RESULTS: A total of 707 patients were included. VOCs were: 10% Alpha, 3% Gamma, 34% Delta, 34% BA.1, 19% BA.2. Mean CTs for BA.1 and BA.2 were lower than Delta and BA.1, respectively. After adjusting for calendar time, age, immunodeficiency and vaccination, CTs for Gamma were lower than those seen for Alpha and higher than Delta, for Delta were similar to BA.1, for BA.2 were lower than Delta and BA.1. CONCLUSIONS: Our analysis shows higher NP-VL of BA.2 compared to previously circulating VOCs, even after controlling for factors potentially contributing to the amount of nasopharyngeal viral RNA, included vaccination, supporting the increased transmissibility of BA.2. Further studies are necessary to clarify this mechanism and to provide guidance for public health measures.

Molecular Characterization of Whole-Genome SARS-CoV-2 from the First Suspected Cases of the XE Variant in the Lazio Region, Italy.

We report two cases of SARS-CoV-2 recombinant variant XE detected in nasopharyngeal swabs (NPS) of hospitalized patients with no evident epidemiological link in Lazio, Central Italy. Whole-Genome Sequencing (WGS) performed on an Ion Torrent GSS5 platform according to Italian flash surveys showed genomes corresponding to the PANGOLIN unclassified lineage and the Nextclade XE clade. Further analyses were then carried out to investigate more deeply the genetic characteristics of these XE-like sequences. When phylogenetic trees, by using IQ-TREE, were built splitting the genome into two regions according to the putative XE recombination site, the upstream and downstream regions were seen to be clustered near BA.1 and BA.2 sequences, respectively. However, our XE-like sequences clustered separately, with a significant bootstrap, from the classified European and Italian XE strains, although the recombination site between BA.1 and BA.2 was identified at the nucleotide site 11556 by RDP4 software, consistent with the putative XE breakpoint. These findings show the risk of the introduction of novel recombinant variants of SARS-CoV-2 and the existence of XE-like strains, phylogenetically separated, that could make their exact taxonomy difficult. It follows the need for continued SARS-CoV-2 surveillance by WGS.

The impact of COVID-19 vaccination programme in the Republic of San Marino: Focus on effectiveness of Gam-Covid-Vac.

OBJECTIVE: The adenovirus-based vaccine Gam-COVID-Vac (Sputnik V) showed promising effectiveness in a phase 3 clinical trial; however, data concerning its impact at a population level are scarce. The Republic of San Marino (RSM) conducted a SARS-CoV-2 vaccination programme mainly based (>80%) on Gam-COVID-Vac. Our aims were to investigate the impact of Gam-COVID-Vac vaccination programme and its effectiveness in a retrospective observational study based on the entire RSM population aged ≥12 years. METHODS: We calculated the incidence rate and the vaccine effectiveness (VE) in the entire RSM population not previously infected, against SARS-CoV-2 infection and COVID-19-related hospitalization, from 25 February to 1 October 2021, considering any vaccine and separately according to the vaccine used. Vaccine effectiveness was calculated using a multivariable negative binomial regression model as 1-Incidence Rate Ratio. RESULTS: During the study period, 21 568/28 791 (74.9%) not previously infected subjects received at least one dose of the Gam-COVID-Vac (84%) or BNT162b2, vaccines with 98% completing the vaccination schedule. Overall, 1634 SARS-CoV-2 infections and 166 COVID-19-related hospitalizations were observed with 17 COVID-19-related deaths reported. Incidence rates of SARS-CoV-2 infection and COVID-19-related hospitalization were 7.11 and 0.49/100 000 person-days in the fully vaccinated population, respectively. The adjusted overall VE was 67.6% (95% CI: 61.8-72.5) against SARS-CoV-2 infection and 87.9% (95% CI: 77.4-93.5) against COVID-19-related hospitalizations. Gam-COVID-Vac against SARS-CoV-2 infection VE peaked 91.8% (95% CI: 86.3-95.1) in the first bimester from the second dose, declining to 57.8% (95% CI: 42.2-69.2) at 6 months. Protection against hospitalization with COVID-19 was overall 91.6% (95% CI: 81.5-96.2), with no relevant waning trend over time. DISCUSSION: Our study demonstrated the effectiveness of overall vaccination (Gam-COVID-Vac [84%] and BNT162b2 [16%]) in the prevention SARS-CoV-2 infection (pre-Omicron variant), waning over time but still with sustainable effectiveness against COVID-19-related hospitalization in the Republic of San Marino.

Epidemiology of ventilator-associated pneumonia in ICU COVID-19 patients: an alarming high rate of multidrug-resistant bacteria

Background COVID‑19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator‑associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). Methods Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. Results Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%);of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. Conclusions COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission. Supplementary Information The online version contains supplementary material available at 10.1186/s44158-022-00065-4.

Immunogenicity to COVID-19 mRNA vaccine third dose in people living with HIV.

In order to investigate safety and immunogenicity of SARS-CoV-2 vaccine third dose in people living with HIV (PLWH), we analyze anti-RBD, microneutralization assay and IFN-γ production in 216 PLWH on ART with advanced disease (CD4 count <200 cell/mm3 and/or previous AIDS) receiving the third dose of a mRNA vaccine (BNT162b2 or mRNA-1273) after a median of 142 days from the second dose. Median age is 54 years, median CD4 nadir 45 cell/mm3 (20-122), 93% HIV-RNA < 50 c/mL. In 68% of PLWH at least one side-effect, generally mild, is recorded. Humoral response after the third dose was strong and higher than that achieved with the second dose (>2 log2 difference), especially when a heterologous combination with mRNA-1273 as third shot is used. In contrast, cell-mediated immunity remain stable. Our data support usefulness of third dose in PLWH currently receiving suppressive ART who presented with severe immune dysregulation.

Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital.

Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08-12.09, and 19.95, 95% CI 5.31-74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25-1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

SARS-CoV-2 Omicron Variant Neutralization after Third Dose Vaccination in PLWH.

The aim was to measure neutralizing antibody levels against the SARS-CoV-2 Omicron (BA.1) variant in serum samples obtained from vaccinated PLWH and healthcare workers (HCW) and compare them with those against the Wuhan-D614G (W-D614G) strain, before and after the third dose of a mRNA vaccine. We included 106 PLWH and 28 HCWs, for a total of 134 participants. Before the third dose, the proportion of participants with undetectable nAbsT against BA.1 was 88% in the PLWH low CD4 nadir group, 80% in the high nadir group and 100% in the HCW. Before the third dose, the proportion of participants with detectable nAbsT against BA.1 was 12% in the PLWH low nadir group, 20% in the high nadir group and 0% in HCW, respectively. After 2 weeks from the third dose, 89% of the PLWH in the low nadir group, 100% in the high nadir group and 96% of HCW elicited detectable nAbsT against BA.1. After the third dose, the mean log2 nAbsT against BA.1 in the HCW and PLWH with a high nadir group was lower than that seen against W-D614G (6.1 log2 (±1.8) vs. 7.9 (±1.1) and 6.4 (±1.3) vs. 8.6 (±0.8)), respectively. We found no evidence of a different level of nAbsT neutralization by BA.1 vs. W-D614G between PLWH with a high CD4 nadir and HCW (0.40 (-1.64, 2.43); p = 0.703). Interestingly, in PLWH with a low CD4 nadir, the mean log2 difference between nAbsT against BA.1 and W-D614G was smaller in those with current CD4 counts 201-500 vs. those with CD4 counts < 200 cells/mm3 (-0.80 (-1.52, -0.08); p = 0.029), suggesting that in this target population with a low CD4 nadir, current CD4 count might play a role in diversifying the level of SARS-CoV-2 neutralization.

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

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

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak.

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1ß, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann-Whitney or Kruskal-Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53-62); 76% male; median HIV duration of infection, 18 years (15-29); nadir of CD4, 57/mmc (23-100) current CD4 count, 348/mmc (186-565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.