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1.
N Engl J Med ; 387(8): 679-691, 2022 08 25.
Article in English | MEDLINE | ID: covidwho-2016969

ABSTRACT

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.


Subject(s)
Global Health , Monkeypox , Adult , Exanthema/etiology , Female , Fever/etiology , Global Health/statistics & numerical data , Humans , Male , Monkeypox/epidemiology , Monkeypox/therapy , Monkeypox virus
2.
Comput Methods Programs Biomed ; 221: 106873, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1930819

ABSTRACT

BACKGROUND AND OBJECTIVE: COVID-19 severity spans an entire clinical spectrum from asymptomatic to fatal. Most patients who require in-hospital care are admitted to non-intensive wards, but their clinical conditions can deteriorate suddenly and some eventually die. Clinical data from patients' case series have identified pre-hospital and in-hospital risk factors for adverse COVID-19 outcomes. However, most prior studies used static variables or dynamic changes of a few selected variables of interest. In this study, we aimed at integrating the analysis of time-varying multidimensional clinical-laboratory data to describe the pathways leading to COVID-19 outcomes among patients initially hospitalised in a non-intensive care setting. METHODS: We collected the longitudinal retrospective data of 394 patients admitted to non-intensive care units at the University Hospital of Padova (Padova, Italy) due to COVID-19. We trained a dynamic Bayesian network (DBN) to encode the conditional probability relationships over time between death and all available demographics, pre-existing conditions, and clinical laboratory variables. We applied resampling, dynamic time warping, and prototyping to describe the typical trajectories of patients who died vs. those who survived. RESULTS: The DBN revealed that the trajectory linking demographics and pre-existing clinical conditions to death passed directly through kidney dysfunction or, more indirectly, through cardiac damage. As expected, admittance to the intensive care unit was linked to markers of respiratory function. Notably, death was linked to elevation in procalcitonin and D-dimer levels. Death was associated with persistently high levels of procalcitonin from admission and throughout the hospital stay, likely reflecting bacterial superinfection. A sudden raise in D-dimer levels 3-6 days after admission was also associated with subsequent death, possibly reflecting a worsening thrombotic microangiopathy. CONCLUSIONS: This innovative application of DBNs and prototyping to integrated data analysis enables visualising the patient's trajectories to COVID-19 outcomes and may instruct timely and appropriate clinical decisions.


Subject(s)
COVID-19 , Bayes Theorem , Humans , Intensive Care Units , Procalcitonin , Retrospective Studies , SARS-CoV-2
3.
PLoS One ; 17(2): e0264172, 2022.
Article in English | MEDLINE | ID: covidwho-1910541

ABSTRACT

During the SARS-CoV-2 pandemic, chest X-Ray (CXR) scores are essential to rapidly assess patients' prognoses. This study evaluates a published CXR score in a different national healthcare system. In our study, this CXR score maintains a prognostic role in predicting length of hospital stay, but not disease severity. However, our results show that the predictive role of CXR score could be influenced by socioeconomic status and healthcare system.


Subject(s)
COVID-19/pathology , Thorax/diagnostic imaging , Adult , Body Mass Index , COVID-19/virology , Comorbidity , Female , Humans , Length of Stay , Male , Middle Aged , Prognosis , Radiography, Thoracic , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Smoking
4.
Lab Med ; 53(6): 609-613, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-1901209

ABSTRACT

OBJECTIVE: To identify the potential prognostic value of lymphocyte subsets in COVID-19 patients, where lymphopenia is a common finding. METHODS: In 353 COVID-19 inpatients and 40 controls T cell subsets with markers of senescence and exhaustion were studied by flow cytometry. RESULTS: In severe illness, total lymphocytes B, NK, and all T subsets were dampened. Senescent CD4+, but mainly CD8+ T cells, increased in patients with respect to controls. The most significant index predicting fatal outcome was neutrophils/CD3+ T ratio. CONCLUSION: In conclusion, an altered T cell pattern underlies COVID-19 severity and is involved in predicting the outcome.


Subject(s)
COVID-19 , Humans , Lymphocyte Subsets , T-Lymphocyte Subsets , CD8-Positive T-Lymphocytes , Cellular Senescence
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337042

ABSTRACT

The spread of SARS-CoV-2 has fueled the COVID-19 pandemic with its enduring medical and socioeconomic challenges due to subsequent waves and long-term consequences of great concern. Here we charted the molecular basis of COVID-19 pathogenesis, by analysing patients' immune response at single-cell resolution across disease course and severity. This approach uncovered cell subpopulation-specific dysregulation in COVID-19 across disease course and severity and identified a severity-associated activation of the receptor for advanced glycation endproduct (RAGE) pathway in monocytes. In vitro experiments confirmed that monocytes bind the SARS-CoV-2 S1-RBD via RAGE and that RAGE-Spike interactions drive monocyte infection. Our results demonstrate that RAGE is a novel functional receptor of SARS-CoV-2 contributing to COVID-19 severity.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-336832

ABSTRACT

Background Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting SARS-CoV-2 varies according to the Variant of Concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with early COVID-19. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was COVID-19 progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results Overall, 319 patients were included. Among 141 patients infected with Delta, no disease progression was recorded and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.895). Among 170 patients infected with Omicron (80.6% BA.1, 19.4% BA.1.1), two disease progressions were recorded in the bamlanivimab/etesevimab group and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared to bamlanivimab/etesevimab and casirivimab/imdevimab (HR 0.526 and HR 0.451, 95% CI 0.359 - 0.77 and 95% CI 0.303 - 0.669, p 0.001 and 0.0001, respectively). Conclusions These results confirm the in-vitro data of superiority of sotrovimab versus casirivimab/imdevimab and bamlanivimab/etesivamab in reducing the time to recovery in patients infected with Omicron BA.1 and BA.1.1, while no difference was detected in Delta infections. Casirivimab/imdevimab seems to maintain a role in preventing severe COVID-19 in the Omicron population. Adaptive clinical trials comparing mAbs by VOC should be pursued to promptly inform clinical recommendations. Funding This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101016167. Clinical trial number NCT05205759

7.
Clin Chem Lab Med ; 60(7): 1110-1115, 2022 Jun 27.
Article in English | MEDLINE | ID: covidwho-1817523

ABSTRACT

OBJECTIVES: The waning of humoral immunity after COVID-19 vaccine booster (third dose) has not yet been fully evaluated. This study updates data on anti-SARS-CoV-2 spike protein receptor binding domain (S-RBD) binding antibodies (bAb) and neutralizing antibodies (NAb) levels in individuals with homologous vaccination 3-4 months after receiving the booster dose. METHODS: Fifty-five healthcare workers (HCW) from Padova University-Hospital were asked to collect serum samples for determining antibodies (Ab) at 12 (t12) and 28 (t28) days, at 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation, and 3-4 months after receiving the 3rd homologous booster dose. HCW were monitored weekly for SARS-CoV-2 infection. Ab titers were measured by two chemiluminescent immunoassays, one targeting the S-RBD immunoglobulin G (IgG), and one surrogate viral neutralization test (sVNT), measuring NAb. RESULTS: Twenty of the HCW had natural COVID-19 infection (COVID+) at different times, before either the first or the second vaccination. Median S-RBD IgG and NAb levels and their interquartile ranges 3-4 months after the 3rd dose were 1,076 (529-3,409) kBAU/L and 15.8 (11.3-38.3) mg/L, respectively, for COVID-, and 1,373 (700-1,373) kBAU/L and 21 (12.8-53.9) mg/L, respectively, for COVID+. At multivariate regression analyses, with age and gender included as covariates, S-RBD IgG bAb and sVNT NAb levels were closely associated with the time interval between serological determination and the 3rd vaccine dose (log10 ßcoeff=-0.013, p=0.012 and log10 ßcoeff=-0.010, p=0.025) for COVID+, whereas no such association was found in COVID- individuals. CONCLUSIONS: The third booster dose increases anti-SARS-CoV-2 Ab levels, elevated levels persisting for up to 3-4 months. Waning of Ab levels appears to be less pronounced for COVID+ individuals.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Cohort Studies , Health Personnel , Humans , Immunization, Secondary , Immunoglobulin G
8.
Mayo Clin Proc Innov Qual Outcomes ; 2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1804780

ABSTRACT

OBJECTIVE: To conduct a comprehensive evaluation of coagulation profiles - via traditional and whole blood thromboelastometry tests - in COVID-19 positive vs. COVID-19 negative patients admitted to medical wards for acute pneumonia. PATIENTS AND METHODS: We enrolled all consecutive patients admitted to Internal Medicine wards of Padova University Hospital between 7 March and 30 April 2020 for COVID-19-related pneumonia (cases) vs. non-COVID-19 pneumonia (controls). A group of healthy subjects acted as baseline for thromboelastometry parameters. RESULTS: Fifty-six cases (mean age 64±15 yrs, M/F 37/19) and 56 controls (mean age 76±11 yrs, M/F 35/21) were enrolled. Cases and controls showed markedly hypercoagulable thromboelastometry profiles vs. healthy subjects, mainly characterized by a significantly shorter propagation phase of coagulation (Clot Formation Time, CFT) and significantly increased maximum clot firmness (MCF) (p <0.001 in all comparisons). COVID-19 patients with pneumonia had significantly shorter CFT and higher MCF (p <0.01 and <0.05, respectively in all comparisons) vs. controls. CONCLUSION: Patients admitted to internal medicine wards for COVID-19 pneumonia presented a markedly prothrombotic state, which seems peculiar to COVID-19 rather than pneumonia itself.

9.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331841

ABSTRACT

Population testing remains central to COVID-19 control and surveillance, with countries increasingly using antigen tests rather than molecular tests. Here we describe a SARS-CoV-2 variant that escapes N antigen tests due to multiple disruptive amino-acid substitutions in the N protein. By fitting a multistrain compartmental model to genomic and epidemiological data, we show that widespread antigen testing in the Italian region of Veneto favored the undetected spread of the antigen-escape variant compared to the rest of Italy. We highlight novel limitations of widespread antigen testing in the absence of molecular testing for diagnostic or confirmatory purposes. Critically, in the presence of a variant that escapes antigen testing, following up a proportion of negative antigen tests with a molecular test is the optimal testing strategy. Together, these findings highlight the importance of retaining molecular testing for surveillance purposes, also in contexts where the use of antigen tests is widespread.

10.
Viruses ; 14(3)2022 03 09.
Article in English | MEDLINE | ID: covidwho-1732255

ABSTRACT

Vaccination with an mRNA COVID-19 vaccine determines not only a consistent reduction in the risk of SARS-CoV-2 infection but also contributes to disease attenuation in infected people. Of note, hyperinflammation and damage-associated molecular patterns (DAMPs) have been clearly associated with severe illness and poor prognosis in COVID-19 patients. In this report, we revealed a significant reduction in the levels of IL-1ß and DAMPs molecules, as S100A8 and High Mobility Group Protein B1 (HMGB1), in vaccinated patients as compared to non-vaccinated ones. COVID-19 vaccination indeed prevents severe clinical manifestations in patients and limits the release of systemic danger signals in SARS-CoV-2 infected people.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
11.
Front Med (Lausanne) ; 8: 823600, 2021.
Article in English | MEDLINE | ID: covidwho-1707730

ABSTRACT

BACKGROUND: Few is known about the long-term pulmonary sequelae after COVID-19 infection. Hence, the aim of this study is to characterize patients with persisting pulmonary sequelae at follow-up after hospitalization. We also aimed to explore clinical and radiological predictors of pulmonary fibrosis following COVID-19. METHODS: Two hundred and 20 consecutive patients were evaluated at 3-6 months after discharge with high-resolution computed tomography (HRCT) and categorized as recovered (REC) or not recovered (NOT-REC). Both HRCTs at hospitalization (HRCT0), when available, and HRCT1 during follow-up were analyzed semiquantitatively as follows: ground-glass opacities (alveolar score, AS), consolidations (CONS), and reticulations (interstitial score, IS). RESULTS: A total of 175/220 (80%) patients showed disease resolution at their initial radiological evaluation following discharge. NOT-REC patients (45/220; 20%) were mostly older men [66 (35-85) years vs. 56 (19-87); p = 0.03] with a longer in-hospital stay [16 (0-75) vs. 8 (1-52) days; p < 0.0001], and lower P/F at admission [233 (40-424) vs. 318 (33-543); p = 0.04]. Moreover, NOT-REC patients presented, at hospital admission, higher ALV [14 (0.0-62.0) vs. 4.4 (0.0-44.0); p = 0.0005], CONS [1.9 (0.0-26.0) vs. 0.4 (0.0-18.0); p = 0.0064], and IS [11.5 (0.0- 29.0) vs. 0.0 (0.0-22.0); p < 0.0001] compared to REC patients. On multivariate analysis, the presence of CONS and IS at HRCT0 was independent predictors of radiological sequelae at follow-up [OR 14.87 (95% CI: 1.25-175.8; p = 0.03) and 28.9 (95% CI: 2.17-386.6; p = 0.01, respectively)]. CONCLUSIONS: In our population, only twenty percent of patients showed persistent lung abnormalities at 6 months after hospitalization for COVID-19 pneumonia. These patients are predominantly older men with longer hospital stay. The presence of reticulations and consolidation on HRCT at hospital admission predicts the persistence of radiological abnormalities during follow-up.

12.
Frontiers in medicine ; 8, 2021.
Article in English | EuropePMC | ID: covidwho-1678732

ABSTRACT

Background Few is known about the long-term pulmonary sequelae after COVID-19 infection. Hence, the aim of this study is to characterize patients with persisting pulmonary sequelae at follow-up after hospitalization. We also aimed to explore clinical and radiological predictors of pulmonary fibrosis following COVID-19. Methods Two hundred and 20 consecutive patients were evaluated at 3–6 months after discharge with high-resolution computed tomography (HRCT) and categorized as recovered (REC) or not recovered (NOT-REC). Both HRCTs at hospitalization (HRCT0), when available, and HRCT1 during follow-up were analyzed semiquantitatively as follows: ground-glass opacities (alveolar score, AS), consolidations (CONS), and reticulations (interstitial score, IS). Results A total of 175/220 (80%) patients showed disease resolution at their initial radiological evaluation following discharge. NOT-REC patients (45/220;20%) were mostly older men [66 (35–85) years vs. 56 (19–87);p = 0.03] with a longer in-hospital stay [16 (0–75) vs. 8 (1–52) days;p < 0.0001], and lower P/F at admission [233 (40–424) vs. 318 (33–543);p = 0.04]. Moreover, NOT-REC patients presented, at hospital admission, higher ALV [14 (0.0–62.0) vs. 4.4 (0.0–44.0);p = 0.0005], CONS [1.9 (0.0–26.0) vs. 0.4 (0.0–18.0);p = 0.0064], and IS [11.5 (0.0– 29.0) vs. 0.0 (0.0–22.0);p < 0.0001] compared to REC patients. On multivariate analysis, the presence of CONS and IS at HRCT0 was independent predictors of radiological sequelae at follow-up [OR 14.87 (95% CI: 1.25–175.8;p = 0.03) and 28.9 (95% CI: 2.17–386.6;p = 0.01, respectively)]. Conclusions In our population, only twenty percent of patients showed persistent lung abnormalities at 6 months after hospitalization for COVID-19 pneumonia. These patients are predominantly older men with longer hospital stay. The presence of reticulations and consolidation on HRCT at hospital admission predicts the persistence of radiological abnormalities during follow-up.

13.
Diabetes ; 71(4): 788-794, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1643401

ABSTRACT

Admission hyperglycemia has emerged worldwide as a predictor of poor coronavirus disease 2019 (COVID-19) outcome. Hyperglycemia leads to a defect in circulating hematopoietic stem/progenitor cells (HSPCs), which, in turn, predicts diabetic complications. Here, we explored whether reduced HSPCs mediated at least part of the prognostic effect of hyperglycemia on COVID-19 outcome. We found that patients with COVID-19 (n = 100) hospitalized in a nonintensive setting displayed dramatically (50-60%) reduced levels of HSPCs measured by flow cytometry as CD34+, CD34+CD45dim, or CD34+CD133+ cells, compared with control subjects (n = 595). This finding was highly significant (all P < 10-10) after multivariable adjustment, or manual 1:1 patient match, or propensity score matching. Admission hyperglycemia (≥7.0 mmol/L) was present in 45% of patients, was associated with a significant further ∼30% HSPCs reduction, and predicted a 2.6-fold increased risk of the primary outcome of adverse COVID-19 course (admittance to the intensive care unit or death). Low HSPCs were also associated with advanced age, higher peak C-reactive protein, and neutrophil-to-lymphocyte ratio. Independently from confounders, 1 SD lower CD34+ HSPCs was associated with a more than threefold higher risk of adverse outcome. Upon formal analysis, reduction of HSPCs was a significant mediator of the admission hyperglycemia on COVID-19 outcome, being responsible for 28% of its prognostic effect.


Subject(s)
COVID-19 , Hyperglycemia , Antigens, CD34/metabolism , Flow Cytometry , Hematopoietic Stem Cells/metabolism , Humans , Hyperglycemia/metabolism
14.
Front Immunol ; 12: 781352, 2021.
Article in English | MEDLINE | ID: covidwho-1613552

ABSTRACT

After the outburst of the SARS-CoV-2 pandemic, a worldwide research effort has led to the uncovering of many aspects of the COVID-19, among which we can count the outstanding role played by inflammatory cytokine milieu in the disease progression. Despite that, molecular mechanisms that regulate SARS-CoV-2 pathogenesis are still almost unidentified. In this study, we investigated whether the pro-inflammatory milieu of the host affects the susceptibility of SARS-CoV-2 infection by modulating ACE2 and TMPRSS2 expression. Our results indicated that the host inflammatory milieu favors SARS-CoV-2 infection by directly increasing TMPRSS2 expression. We unveiled the molecular mechanism that regulates this process and that can be therapeutically advantageously targeted.


Subject(s)
GATA2 Transcription Factor/metabolism , Interleukin-1beta/metabolism , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Virus Internalization , A549 Cells , COVID-19 , Humans , p38 Mitogen-Activated Protein Kinases/metabolism
15.
Clin Chem Lab Med ; 60(3): 456-463, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1575220

ABSTRACT

OBJECTIVES: mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. METHODS: A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). RESULTS: The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1-92.8%) for S-RBD IgG, 82% (58.6-89.3%) for trimeric-S, 70.4% (34.5-86.4%) for VNT-Nab, 75% (50-87.5%) for PRNT50 and 75% (50-93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). CONCLUSIONS: After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19 , SARS-CoV-2 , Adult , Aged , COVID-19/prevention & control , Female , Humans , Immunoassay , Immunoglobulin G/blood , Kinetics , Male , Middle Aged , Vaccination , Young Adult
16.
Clin Chim Acta ; 523: 446-453, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544839

ABSTRACT

BACKGROUND: Studies evaluating neutralizing antibody (NAb) after BNT162b2 vaccine are scarce. We therefore compared NAb using the plaque reduction neutralization test (PRNT) in vaccinated subjects, with those from five chemiluminescent (CLIA) assays, two targeting ACE and S-RBD interaction. METHODS: Sera from 174 completely Comirnaty/BNT162b2 vaccinated healthcare workers (HCW) were evaluated at t12 and t28. NAb titers at low (PRNT50) or high (PRNT90) stringency were compared with: Liaison SARS-CoV-2 Trimeric-S IgG, Elecsys S-RBD Ab, Maglumi SARS-CoV-2 S-RBD IgG and SARS-CoV-2 Nab; iFlash 2019-nCoV NAb. RESULTS: Neither PRNT50 nor PRNT90 correlated with age (range, 24-65 years); no significant differences were found for gender. PRNT50 and PRNT90 seropositive titers (≥1:20) were 43 (24.7%) and 15 (8.6%) at t12 and 167 (95.9%) and 149 (85.6%) at t28. CLIA results at t28 were uncorrelated with age, apart from Elecsys S-RBD Ab (r = -0.164, p = 0.046). Gender differences were found for Maglumi SARS-CoV-2 S-RBD IgG (p = 0.037) and Maglumi NAb (p = 0.046). Considering PRNT50 at thresholds of 1:20 (or 1:40) and 1:160 (or 1:320), corresponding to different immune protective levels, CLIA cut-offs have been identified. CONCLUSIONS: Comirnaty/BNT162b2 elicits strong NAb production, especially 28 days after first inoculum. Differences in correlation between Nab titers and circulating antibodies measured by 5 immunoassays have been found, being stronger the correlation for Maglumi Nab.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Aged , Antibodies, Neutralizing , Humans , Kinetics , Luminescent Measurements , Middle Aged , Young Adult
17.
Front Psychiatry ; 12: 711461, 2021.
Article in English | MEDLINE | ID: covidwho-1450842

ABSTRACT

Literature about the novel Coronavirus (COVID-19) is currently focusing on the potential cognitive and neuropsychiatric sequelae observed in individuals receiving intensive care unit (ICU) treatments. The aim of the present study is to evaluate the differences in cognitive and psychological sequelae of COVID-19 between younger and older adults, regardless of being admitted to the ICU or not. The study involved 299 recovered individuals (from 18 to 90 years old), who underwent a comprehensive cognitive and psychological assessment. Linear regression models were conducted separately for Montreal Cognitive Assessment (MoCA) test and Post-traumatic Stress Disorder Checklist (PCL) scores to investigate the effect of socio-demographic and clinical characteristics on them. Separate linear regression models were then applied sorting participants by age: younger adults (<65 years) and older adults (≥65 years). In the whole sample, PCL scores were predicted by the intensity of care received, by being intubated, and by the persistence of cough after 1 month after hospitalization. Only age had instead an effect on cognition. In younger adults, PCL scores were predicted by the presence of neurological symptoms, by the intensity of care received, and by being intubated; MoCA scores were only predicted by the intensity of care received. No significant associations were found in older adults. Psychological negative effects of the COVID-19 pandemic particularly affect individuals under 65 years old, who also subjectively report cognitive sequelae associated with the infection. Individuals over 65 years old, instead, seem to be free from psychological and cognitive difficulties due to COVID-19.

18.
Front Med (Lausanne) ; 8: 714221, 2021.
Article in English | MEDLINE | ID: covidwho-1441117

ABSTRACT

Background: The impact of viral burden on severity and prognosis of patients hospitalized for Coronavirus Disease 2019 (COVID-19) is still a matter of debate due to controversial results. Herein, we sought to assess viral load in the nasopharyngeal swab and its association with severity score indexes and prognostic parameters. Methods: We included 127 symptomatic patients and 21 asymptomatic subjects with a diagnosis of SARS-CoV-2 infection obtained by reverse transcription polymerase chain reaction and presence of cycle threshold. According to the level of care needed during hospitalization, the population was categorized as high-intensity (HIMC, n = 76) or low intensity medical care setting (LIMC, n = 51). Results: Viral load did not differ among asymptomatic, LIMC, and HIMC SARS-CoV-2 positive patients [4.4 (2.9-5.3) vs. 4.8 (3.6-6.1) vs. 4.6 (3.9-5.7) log10 copies/ml, respectively; p = 0.31]. Similar results were observed when asymptomatic individuals were compared to hospitalized patients [4.4 (2.9-5.3) vs. 4.68 (3.8-5.9) log10 copies/ml; p = 0.13]. When the study population was divided in High (HVL, n = 64) and Low Viral Load (LVL, n = 63) group no differences were observed in disease severity at diagnosis. Furthermore, LVL and HVL groups did not differ with regard to duration of hospital stay, number of bacterial co-infections, need for high-intensity medical care and number of deaths. The viral load was not an independent risk factor for HIMC in an adjusted multivariate regression model (OR: 1.59; 95% CI: 0.46-5.55, p = 0.46). Conclusions: Viral load at diagnosis is similar in asymptomatic and hospitalized patients and is not associated with either worse outcomes during hospitalization. SARS CoV-2 viral load might not be the right tool to assist clinicians in risk-stratifying hospitalized patients.

19.
Mycoses ; 64(10): 1223-1229, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1280362

ABSTRACT

BACKGROUND: An increasing number of reports have described the COVID-19-associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA. METHODS: We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID-19 laboratory-confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case. RESULTS: Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases. CONCLUSION: We found a high frequency of proven CAPA among patients with severe COVID-19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.


Subject(s)
COVID-19/epidemiology , Invasive Pulmonary Aspergillosis/epidemiology , Respiratory Insufficiency/mortality , Aged , Aged, 80 and over , Aspergillus , COVID-19/mortality , COVID-19/pathology , Comorbidity , Female , Humans , Intensive Care Units , Invasive Pulmonary Aspergillosis/mortality , Invasive Pulmonary Aspergillosis/pathology , Male , Middle Aged , Respiratory Insufficiency/microbiology , Respiratory Insufficiency/pathology , SARS-CoV-2
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