Objectives
Evidences from either small series or spontaneous reporting are accumulating that SARS-CoV-2 involves the Nervous Systems. The aim of this study is to provide an extensive overview on the ...major neurological complications in a large cohort of COVID-19 patients.
Methods
Retrospective, observational analysis on all COVID-19 patients admitted from February 23rd to April 30th, 2020 to ASST Papa Giovanni XXIII, Bergamo, Italy for whom a neurological consultation/neurophysiological assessment/neuroradiologic investigation was requested. Each identified neurologic complication was then classified into main neurologic categories.
Results
Of 1760 COVID-19 patients, 137 presented neurologic manifestations that manifested after COVID-19 symptoms in 98 pts and was the presenting symptom in 39. Neurological manifestations were classified as: (a) cerebrovascular disease 53 pts (38.7%) including 37 ischemic and 11 haemorrhagic strokes, 4 transient ischemic attacks, 1 cerebral venous thrombosis; (b) peripheral nervous system diseases 31 (22.6%) including 17 Guillain–Barrè syndromes; (c) altered mental status 49 (35.8%) including one necrotizing encephalitis and 2 cases with RT-PCR detection of SARS-Cov-2 RNA in CSF; (d) miscellaneous disorders, among whom 2 patients with myelopathy associated with Ab anti-SARS-CoV-2 in CSF. Patients with peripheral nervous system involvement had more frequently severe ARDS compared to patients with cerebrovascular disease (87.1% vs 42%; difference = 45.1% 95% CI 42.0–48.2;
χ
2
= 14.306;
p
< 0.0002) and with altered mental status (87.1% vs 55.6%; difference = 31.5% 95% CI 27.5–37.5%;
χ
2
= 7.055;
p
< 0.01).
Conclusion
This study confirms that involvement of nervous system is common in SARS-CoV-2 infection and offers clinicians useful information for prevention and prompt identification in order to set the adequate therapeutic strategies.
The use of DTG-containing two-drug regimens is one of the most promising solutions to the need to ease the management of HIV treatment without harming its efficacy and safety. We report long- term ...results in patients switched, while virologically suppressed, to the combination of dolutegravir (DTG) plus lamivudine (3TC). This is a prospective, clinical, uncontrolled cohort enrolling ART-experienced people living with HIV (PLWH) with HIV-RNA < 50 copies/ml for 6 months or longer, negative hepatitis B virus surface antigen, and without known M184V/I mutations. Kaplan-Meiers curves are used to describe persistency of virological suppression on therapy and a Cox regression model to evaluate baseline characteristics and the risk of stopping therapy. 218 individuals switched their regimen since 2015. The mean estimated follow-up was of 64.3 months (95% CI 61.3-67.3) for approximately 1000 patient/years. After 5 years of follow-up, 77.1% were still on the DTG-3TC combination. No virologic failure was detected throughout the whole study period, and only 15 subjects presented single isolated viral blips above 50 copies/ml. Most patients stopped therapy because of reasons unrelated to study drugs (lost to follow-up; patients' decision; moved to other Centers), but due to the unselected nature of the casuistry; 11 subjects died in the 5 years of follow-up mostly because of pre-existing co-morbidities (6 neoplastic diseases and 2 end-stage liver disease). The median baseline CD4 count was 669 cells/mcl (IQR 483-927). After 5 years it raised to 899 cells/mcl (IQR 646-1160) (P < 0.001) without a significant change of CD8 counts that lowered from 767 cells/mcl (IQR 532-1034) to 683 cells/mcl (IQR 538-988). Consequently, the CD4/CD8 ratio varied from 0.93 (IQR 0.60-1.30) to 1.15 (IQR 0.77-1.45) (P < 0.0001). A non-significant (P = 0.320) increment of mean creatinine, 0.06 mg/dl in magnitude, was observed over the whole follow-up. These long-term results over 5 years reinforce the durability and good tolerability of DTG-3TC. Our results continue to support the recommended switch use of this 2DR as a well-accepted treatment option for ART-experienced PLWH.
A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions ...involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.
The aim of this study is the characterization and genomic tracing by phylogenetic analyses of 59 new SARS-CoV-2 Italian isolates obtained from patients attending clinical centres in North and Central ...Italy until the end of April 2020. All but one of the newly-characterized genomes belonged to the lineage B.1, the most frequently identified in European countries, including Italy. Only a single sequence was found to belong to lineage B. A mean of 6 nucleotide substitutions per viral genome was observed, without significant differences between synonymous and non-synonymous mutations, indicating genetic drift as a major source for virus evolution. tMRCA estimation confirmed the probable origin of the epidemic between the end of January and the beginning of February with a rapid increase in the number of infections between the end of February and mid-March. Since early February, an effective reproduction number (R
) greater than 1 was estimated, which then increased reaching the peak of 2.3 in early March, confirming the circulation of the virus before the first COVID-19 cases were documented. Continuous use of state-of-the-art methods for molecular surveillance is warranted to trace virus circulation and evolution and inform effective prevention and containment of future SARS-CoV-2 outbreaks.
Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients.
Observational ...study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization.
431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO
/FiO
was similar between men and women (228 IQR, 134-273 vs 238 mmHg 150-281, p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687).
Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.
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.
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.
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;
= 0.016), and with DTG-based regimens with pre-treatment DRMs to the backbone (aHR 17.27;
= 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;
= 0.011), C (aHR 8.10;
= 0.005), CRF02-AG (aHR 5.59;
= 0.006) and G (aHR 13.90;
< 0.001); DTG also demonstrated a reduced efficacy in subtypes C (versus B, aHR 10.24;
= 0.035) and CRF01-AE (versus B; aHR 10.65;
= 0.035). Higher baseline HIV-RNA and a longer time since HIV diagnosis also predicted VF.
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.
Severe COVID-19 outcomes have been reported in people living with HIV (PLWH), yet the underlying pathogenetic factors are largely unknown. We therefore aimed to assess SARS-CoV-2 RNAemia and plasma ...cytokines in PLWH hospitalized for COVID-19 pneumonia, exploring associations with magnitude and functionality of SARS-CoV-2-specific immune responses.
Eighteen unvaccinated PLWH (16/18 on cART; median CD4 T cell count 361.5/μL; HIV-RNA<50 cp/mL in 15/18) and 18 age/sex-matched people without HIV were consecutively recruited at a median time of 10 days from symptoms onset. PLWH showed greater SARS-CoV-2 RNAemia, a distinct plasma cytokine profile, and worse respiratory function (lower PaO2/FiO2nadir), all correlating with skewed T cell responses (higher perforin production by cytotoxic T cells as well as fewer and less polyfunctional SARS-CoV-2-specific T cells), despite preserved humoral immunity.
In conclusion, these data suggest a link between HIV-related T cell dysfunction and poor control over SARS-CoV-2 replication/dissemination that may in turn influence COVID-19 severity in PLWH.
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•PLWH hospitalized for COVID-19 pneumonia feature higher SARS-CoV-2 RNAemia•PLWH are also characterized by a distinct plasma cytokine pattern•Unlike humoral immunity, SARS-CoV-2-specific T cell responses are skewed in PLWH•Skewed T cell responses associate with higher RNAemia, inflammation, and severity
Biological sciences; Immunology; Immune response; Microbiology; Virology
Our work concerns the actual problem of spread of SARS- CoV-2 outbreak which requires fast and correct as possible answer. In current scenario, the need of rapid answer put away the imperative of ...proper methodology. We focus on the serogical immunoassay for diagnosis of Covid-19 as an important weapon not only for diagnostic purpose, but also for epidemiologic one. The right equilibrium between high speed, low cost and accuracy is obtained with easy-to-use decentralized point-of-care test as the colloidal gold-based immunochromatographic strip assay which detects IgM and IgG antibodies directed against SARS-CoV-2. As our aim is to evaluate the efficacy of Covid-19 rapid tests and of serological assays in real-life settings, we designed a research protocol aimed to establish how to use correctly these diagnostics, taking into account the different possible clinical and epidemiological scenarios.
The aim of this study was to evaluate the impact of resistance mutations on efficacy of dolutegravir-based two-drug regimens (2DR).
Virologically suppressed patients with HIV-1 switching to ...dolutegravir + lamivudine or rilpivirine or to a dolutegravir-based three-drug regimen (3DR) with pre-baseline genotype were selected. Virological failure (VF) was defined as one HIV-RNA viral load (VL) >200 cps/mL or two consecutive VL >50 cps/mL; treatment failure (TF) was defined as VF or treatment discontinuation (TD). Resistance was defined as at least low-level resistance to at least one drug of the current regimen. Propensity score matching was used to conduct adjusted analyses within a competing risks framework.
A total of 971 dolutegravir-based regimens were selected: 339 (34.9%) 2DR and 632 (65.1%) 3DR. The adjusted cumulative 48-week incidence of VF was 4.2% (90% CI 3.1%–5.3%) with 2DR and 4.7% (90% CI 3.5%–5.8%) with 3DR. The cumulative 48-week incidence of TF was 15.8% (90% CI 13.9%–17.9%) with 2DR and 24.5% (90% CI 22.2%–27.0%) with 3DR. For VF, the estimated hazard ratio (HR) for 2DR vs. 3DR was 1.02 (90% CI: 0.78–1.34), with evidence of effect modification by low-level resistance (HR 3.96, 90% CI: 2.10–7.46). The estimated HR of TF for 2DR vs. 3DR was 0.54 (90% CI: 0.48–0.60). The 48-week cumulative incidence of TD was 11.7% (8.7%, 14.6%) in 2DR and 19.6% (16.9%, 22.4%) in 3DR.
Dolutegravir-based 2DR showed high virological efficacy and durability; however, past resistance increased the risk of VF, but not of TD or TF.
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic calls for rapid actions, now principally oriented to a world‐wide vaccination campaign. In this study we verified if, in ...individuals with a previous SARS‐CoV‐2 infection, a single dose of messenger RNA (mRNA) vaccine would be immunologically equivalent to a full vaccine schedule in naïve individuals. Health care workers (184) with a previous SARS‐CoV‐2 infection were sampled soon before the second dose of vaccine and between 7 and 10 days after the second dose, the last sampling time was applied to SARS‐CoV‐2 naïve individuals, too. Antibodies against SARS‐CoV‐2 were measured using Elecsys Anti‐SARS‐CoV‐2 S immunoassay. The study was powered for non‐inferiority. We used non parametric tests and Pearson correlation test to perform inferential analysis. After a single vaccine injection, the median titer of specific antibodies in individuals with previous coronavirus disease 2019 was 30.527 U/ml (interquartile range IQR: 19.992–39.288) and in subjects with previous SARS‐CoV‐2 asymptomatic infection was 19.367.5 U/ml (IQR: 14.688–31.353) (p = .032). Both results were far above the median titer in naïve individuals after a full vaccination schedule: 1974.5 U/ml (IQR: 895–3455) (p < .0001). Adverse events after vaccine injection were more frequent after the second dose of vaccine (mean: 0.95; 95% confidence interval CI: 0.75–1.14 vs. mean: 1.91; 95% CI: 1.63–2.19) (p < .0001) and in exposed compared to naïve (mean: 1.63; 95% CI: 1.28–1.98 vs. mean: 2.35; 95% CI: 1.87–2.82) (p = .015). In SARS‐CoV‐2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity. Modifying current dosing schedules would speed‐up vaccination campaigns.
Highlights
1) Individuals COVID 19 positive shows a single dose antibody titers 10 fold higher than naive individuals with full vaccination schedule
2) In SARS‐CoV‐2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity.
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