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1.
In Vivo ; 36(6): 2986-2992, 2022.
Article in English | MEDLINE | ID: covidwho-2100684

ABSTRACT

BACKGROUND/AIM: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection. PATIENTS AND METHODS: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an "incomplete data" and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model. RESULTS: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up. CONCLUSION: The CoDMI algorithm leads to "unbiased" probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi.


Subject(s)
COVID-19 , Radiation Oncology , Humans , Kaplan-Meier Estimate , COVID-19/epidemiology , Survival Analysis , Algorithms
2.
EBioMedicine ; 76: 103856, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1894987

ABSTRACT

BACKGROUND: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. METHODS: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis. FINDINGS: Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 - 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43-18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55-95% CI 0.31-0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry. INTERPRETATION: In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events. FUNDING: DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Benzamidines/therapeutic use , COVID-19/drug therapy , Guanidines/therapeutic use , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Benzamidines/adverse effects , Benzamidines/pharmacokinetics , Biomarkers/blood , Biomarkers/metabolism , COVID-19/mortality , COVID-19/virology , Drug Administration Schedule , Female , Guanidines/adverse effects , Guanidines/pharmacokinetics , Half-Life , Humans , Immunophenotyping , Kaplan-Meier Estimate , Male , Middle Aged , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Treatment Outcome , Viral Load
3.
Surgery ; 171(5): 1422-1426, 2022 05.
Article in English | MEDLINE | ID: covidwho-1829571

ABSTRACT

BACKGROUND: To determine the impact of COVID-19 infection in patients with chronic limb-threatening ischemia, mainly the limb salvage estimates rate and the overall survival. METHODS: This was a retrospective, consecutive cohort study of chronic limb-threatening ischemia in patients with COVID-19 infection. RESULTS: Overall, 35 patients with chronic limb-threatening ischemia and COVID-19 infection were evaluated. The mean age of the patients was 72.51 years, and most of them were male (60%), with arterial hypertension (85.7%), followed by diabetes mellitus (80%) and tobacco user (71.4%). There was a higher prevalence of wound, ischemia and foot infection (WIfI) classification 4 with 58.8% and Rutherford grade 5 (74.3%). The factors related to overall mortality rate were: D-dimer >1,000 mg/dL (hazard ratio = 22.7, P < .001, confidence interval = 10.49-26.52), respiratory symptoms (hazard ratio = 16.6, P < .001, confidence interval = 9.87-20.90), chest computed tomography compromising higher than 50% of the pulmonary tract (hazard ratio = 16,0, P < .001, confidence interval = 10.41-20.55), acute kidney failure (hazard ratio = 21.58, P < .001, confidence interval = 16.5-30.5), chronic kidney disease (hazard ratio = 4.4, P = .036, confidence interval = 1.45-10.1), therapeutic anticoagulation (hazard ratio = 8.37, P = .004, confidence interval = 1.35-8.45), and WIfI classification (hazard ratio = 5.28, P = .022, confidence interval = 1.34-10.01). The following were related to limb loss: D-dimer >1,000 mg/mL (hazard ratio = 5.47, P = .02, confidence interval = 1.94-10.52), respiratory symptoms (hazard ratio = 5.42, P = .02, confidence interval = 1.87-10.90), and WIfI classification (hazard ratio = 4.44, P = .035, confidence interval = 1.34-8.01). CONCLUSION: This study concluded that COVID-19 has a catastrophic impact among patients with chronic limb-threatening ischemia. The main factors related to overall mortality were D-dimer >1,000 mg/dL, respiratory symptoms, chest computed tomography compromising higher than 50% of the pulmonary tract, acute kidney failure, chronic kidney disease, therapeutic anticoagulation, and WIfI classification. The factors related to limb loss were WIfI classification, D-dimer >1,000 mg/mL and respiratory symptoms.


Subject(s)
COVID-19 , Peripheral Arterial Disease , Wound Infection , Aged , Amputation , Anticoagulants , COVID-19/complications , Chronic Limb-Threatening Ischemia , Cohort Studies , Female , Humans , Ischemia/surgery , Kaplan-Meier Estimate , Limb Salvage , Male , Peripheral Arterial Disease/surgery , Predictive Value of Tests , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Wound Healing , Wound Infection/diagnosis , Wound Infection/surgery
4.
PLoS One ; 17(4): e0267235, 2022.
Article in English | MEDLINE | ID: covidwho-1808573

ABSTRACT

BACKGROUND: Chromogranin A (CgA) and its fragment vasostatin I (VS-I) are secreted in the blood by endocrine/neuroendocrine cells and regulate stress responses. Their involvement in Coronavirus 2019 disease (COVID-19) has not been investigated. METHODS: CgA and VS-I plasma concentrations were measured at hospital admission from March to May 2020 in 190 patients. 40 age- and sex-matched healthy volunteers served as controls. CgA and VS-I levels relationship with demographics, comorbidities and disease severity was assessed through Mann Whitney U test or Spearman correlation test. Cox regression analysis and Kaplan Meier survival curves were performed to investigate the impact of the CgA and VS-I levels on in-hospital mortality. RESULTS: Median CgA and VS-I levels were higher in patients than in healthy controls (CgA: 0.558 nM [interquartile range, IQR 0.358-1.046] vs 0.368 nM [IQR 0.288-0.490] respectively, p = 0.0017; VS-I: 0.357 nM [IQR 0.196-0.465] vs 0.144 nM [0.144-0.156] respectively, p<0.0001). Concentration of CgA, but not of VS-I, significantly increased in patients who died (n = 47) than in survivors (n = 143) (median 0.948 nM [IQR 0.514-1.754] vs 0.507 nM [IQR 0.343-0.785], p = 0.00026). Levels of CgA were independent predictors of in-hospital mortality (hazard ratio 1.28 [95% confidence interval 1.077-1.522], p = 0.005) when adjusted for age, number of comorbidities, respiratory insufficiency degree, C-reactive protein levels and time from symptom onset to sampling. Kaplan Meier curves revealed a significantly increased mortality rate in patients with CgA levels above 0.558 nM (median value, log rank test, p = 0.001). CONCLUSION: Plasma CgA levels increase in COVID-19 patients and represent an early independent predictor of mortality.


Subject(s)
COVID-19 , Chromogranin A , Humans , Kaplan-Meier Estimate , Prognosis , Proportional Hazards Models
5.
Proc Natl Acad Sci U S A ; 119(12): e2200065119, 2022 03 22.
Article in English | MEDLINE | ID: covidwho-1740535

ABSTRACT

SignificanceConcern has increased about the pandemic potential of Nipah virus (NiV). Similar to SARS-CoV-2, NiV is an RNA virus that is transmitted by respiratory droplets. There are currently no NiV vaccines licensed for human use. While several preventive vaccines have shown promise in protecting animals against lethal NiV disease, most studies have assessed protection 1 mo after vaccination. However, in order to contain and control outbreaks, vaccines that can rapidly confer protection in days rather than months are needed. Here, we show that a recombinant vesicular stomatitis virus vector expressing the NiV glycoprotein can completely protect monkeys vaccinated 7 d prior to NiV exposure and 67% of animals vaccinated 3 d before NiV challenge.


Subject(s)
Henipavirus Infections/veterinary , Nipah Virus/immunology , Primate Diseases/prevention & control , Vaccines, Synthetic/immunology , Viral Vaccines/immunology , Animals , Antibodies, Neutralizing , Antibodies, Viral/immunology , Biomarkers , Genetic Vectors , Kaplan-Meier Estimate , Neutralization Tests , Outcome Assessment, Health Care , Primate Diseases/diagnosis , Primate Diseases/mortality , Primate Diseases/virology , Vaccination , Viral Load
6.
PLoS One ; 17(3): e0264178, 2022.
Article in English | MEDLINE | ID: covidwho-1731596

ABSTRACT

Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91-0·98) and increased survival alone by 6% (HR 0·95; CI 0·90-0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.


Subject(s)
COVID-19/pathology , Monoamine Oxidase/blood , Adult , Aged , COVID-19/mortality , COVID-19/virology , Endothelium/metabolism , Endothelium/pathology , Female , Hospitalization , Humans , Intensive Care Units , Interleukin-6/blood , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index
7.
N Engl J Med ; 386(9): 837-846, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721750

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain. METHODS: We randomly assigned, in a 2:1 ratio, infants who had been born at a gestational age of at least 35 weeks to receive a single intramuscular injection of nirsevimab or placebo before the start of an RSV season. The primary efficacy end point was medically attended RSV-associated lower respiratory tract infection through 150 days after the injection. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after the injection. RESULTS: A total of 1490 infants underwent randomization: 994 were assigned to the nirsevimab group and 496 to the placebo group. Medically attended RSV-associated lower respiratory tract infection occurred in 12 infants (1.2%) in the nirsevimab group and in 25 infants (5.0%) in the placebo group; these findings correspond to an efficacy of 74.5% (95% confidence interval [CI], 49.6 to 87.1; P<0.001) for nirsevimab. Hospitalization for RSV-associated lower respiratory tract infection occurred in 6 infants (0.6%) in the nirsevimab group and in 8 infants (1.6%) in the placebo group (efficacy, 62.1%; 95% CI, -8.6 to 86.8; P = 0.07). Among infants with data available to day 361, antidrug antibodies after baseline were detected in 58 of 951 (6.1%) in the nirsevimab group and in 5 of 473 (1.1%) in the placebo group. Serious adverse events were reported in 67 of 987 infants (6.8%) who received nirsevimab and in 36 of 491 infants (7.3%) who received placebo. CONCLUSIONS: A single injection of nirsevimab administered before the RSV season protected healthy late-preterm and term infants from medically attended RSV-associated lower respiratory tract infection. (Funded by MedImmune/AstraZeneca and Sanofi; MELODY ClinicalTrials.gov number, NCT03979313.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , Infant, Premature, Diseases/prevention & control , Infant, Premature , Respiratory Syncytial Virus Infections/prevention & control , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Drug Administration Schedule , Female , Humans , Infant , Infant, Newborn , Injections, Intramuscular , Kaplan-Meier Estimate , Male
8.
PLoS One ; 17(2): e0264301, 2022.
Article in English | MEDLINE | ID: covidwho-1703889

ABSTRACT

Remdesivir (RDV) reduces time to clinical improvement in hospitalized COVID -19 patients requiring supplemental oxygen. Dexamethasone improves survival in those requiring oxygen support. Data is lacking on the efficacy of combination therapy in patients on mechanical ventilation. We analyzed for comparative outcomes between Corticosteroid (CS) therapy with combined Corticosteroid and Remdesivir (CS-RDV) therapy. We conducted an observational cohort study of patients aged 18 to 90 with COVID-19 requiring ventilatory support using TriNetX (COVID-19 Research Network) between January 20, 2020, and February 9, 2021. We compared patients who received at least 48 hours of CS-RDV combination therapy to CS monotherapy. The primary outcome was 28-day all-cause mortality rates in propensity-matched (PSM) cohorts. Secondary outcomes were Length of Stay (LOS), Secondary Bacterial Infections (SBI), and MRSA (Methicillin-Resistant Staphylococcus aureus), and Pseudomonas infections. We used univariate and multivariate Cox proportional hazards models and stratified log-rank tests. Of 388 patients included, 91 (23.5%) received CS-RDV therapy, and 297 (76.5%) received CS monotherapy. After propensity score matching, with 74 patients in each cohort, all-cause mortality was 36.4% and 29.7% in the CS-RDV and CS therapy, respectively (P = 0.38). We used a Kaplan-Meier with a log-rank test on follow up period (P = 0.23), and a Hazards Ratio model (P = 0.26). SBI incidence was higher in the CS group (13.5% vs. 35.1%, P = 0.02) with a similar LOS (13.4 days vs. 13.4 days, P = 1.00) and similar incidence of MRSA/Pseudomonas infections (13.5% vs. 13.5%, P = 1.00) in both the groups. Therefore, CS-RDV therapy is non-inferior to CS therapy in reducing 28-day all-cause in-hospital mortality but associated with a significant decrease in the incidence of SBI in critically ill COVID-19 patients.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Adrenal Cortex Hormones/therapeutic use , Alanine/analogs & derivatives , COVID-19/drug therapy , Adenosine Monophosphate/therapeutic use , Aged , Alanine/therapeutic use , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Cohort Studies , Drug Therapy, Combination , Female , Hospital Mortality , Humans , Incidence , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Proportional Hazards Models , Pseudomonas Infections/diagnosis , Pseudomonas Infections/epidemiology , Pseudomonas Infections/etiology , Respiration, Artificial , SARS-CoV-2/isolation & purification , Staphylococcal Infections/diagnosis , Staphylococcal Infections/epidemiology , Staphylococcal Infections/etiology , Treatment Outcome
9.
Sci Rep ; 12(1): 2552, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1692551

ABSTRACT

There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.


Subject(s)
COVID-19/therapy , Adult , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Double-Blind Method , Female , HIV Infections/complications , Hospitals, Public , Humans , Immunization, Passive , Kaplan-Meier Estimate , Male , Middle Aged , Placebo Effect , SARS-CoV-2/isolation & purification , Severity of Illness Index , South Africa , Treatment Outcome
10.
N Engl J Med ; 386(9): 847-860, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1684178

ABSTRACT

BACKGROUND: The Ad26.COV2.S vaccine was highly effective against severe-critical coronavirus disease 2019 (Covid-19), hospitalization, and death in the primary phase 3 efficacy analysis. METHODS: We conducted the final analysis in the double-blind phase of our multinational, randomized, placebo-controlled trial, in which adults were assigned in a 1:1 ratio to receive single-dose Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe-critical Covid-19 with onset at least 14 days after administration and at least 28 days after administration in the per-protocol population. Safety and key secondary and exploratory end points were also assessed. RESULTS: Median follow-up in this analysis was 4 months; 8940 participants had at least 6 months of follow-up. In the per-protocol population (39,185 participants), vaccine efficacy against moderate to severe-critical Covid-19 at least 14 days after administration was 56.3% (95% confidence interval [CI], 51.3 to 60.8; 484 cases in the vaccine group vs. 1067 in the placebo group); at least 28 days after administration, vaccine efficacy was 52.9% (95% CI, 47.1 to 58.1; 433 cases in the vaccine group vs. 883 in the placebo group). Efficacy in the United States, primarily against the reference strain (B.1.D614G) and the B.1.1.7 (alpha) variant, was 69.7% (95% CI, 60.7 to 76.9); efficacy was reduced elsewhere against the P.1 (gamma), C.37 (lambda), and B.1.621 (mu) variants. Efficacy was 74.6% (95% CI, 64.7 to 82.1) against severe-critical Covid-19 (with only 4 severe-critical cases caused by the B.1.617.2 [delta] variant), 75.6% (95% CI, 54.3 to 88.0) against Covid-19 leading to medical intervention (including hospitalization), and 82.8% (95% CI, 40.5 to 96.8) against Covid-19-related death, with protection lasting 6 months or longer. Efficacy against any severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was 41.7% (95% CI, 36.3 to 46.7). Ad26.COV2.S was associated with mainly mild-to-moderate adverse events, and no new safety concerns were identified. CONCLUSIONS: A single dose of Ad26.COV2.S provided 52.9% protection against moderate to severe-critical Covid-19. Protection varied according to variant; higher protection was observed against severe Covid-19, medical intervention, and death than against other end points and lasted for 6 months or longer. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).


Subject(s)
Ad26COVS1 , COVID-19/prevention & control , Vaccine Efficacy/statistics & numerical data , Ad26COVS1/adverse effects , Ad26COVS1/immunology , Adolescent , Adult , COVID-19/epidemiology , COVID-19/mortality , Double-Blind Method , Follow-Up Studies , Hospitalization/statistics & numerical data , Humans , Immunogenicity, Vaccine , Kaplan-Meier Estimate , Middle Aged , Patient Acuity , SARS-CoV-2 , Young Adult
11.
Biomolecules ; 12(2)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1674482

ABSTRACT

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , COVID-19/diagnosis , COVID-19/urine , Critical Illness/mortality , Acute Kidney Injury/complications , Acute Kidney Injury/mortality , Adult , Aged , Biomarkers/urine , COVID-19/complications , COVID-19/mortality , Female , Humans , Insulin-Like Growth Factor Binding Proteins/urine , Kaplan-Meier Estimate , Lipocalin-2/urine , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk Factors , Tissue Inhibitor of Metalloproteinase-2/urine
12.
Antimicrob Resist Infect Control ; 11(1): 27, 2022 02 05.
Article in English | MEDLINE | ID: covidwho-1673927

ABSTRACT

BACKGROUND: There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). METHODS: Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. RESULTS: We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6-1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5-1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5-13.5; aOR 5.0, 95% CI 3.9-6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5-0.8; aOR 0.6 for seroconversion, 95% CI 0.4-1.0). CONCLUSIONS: Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients.


Subject(s)
COVID-19/prevention & control , Health Personnel , Masks , Respiratory Protective Devices , Adolescent , Adult , Aerosols , Aged , COVID-19/epidemiology , Female , Humans , Infection Control/methods , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Prospective Studies , Seroconversion , Switzerland , Young Adult
13.
J Cardiothorac Vasc Anesth ; 36(8 Pt B): 2935-2941, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1665734

ABSTRACT

OBJECTIVES: Cardiac injury has been reported in up to 20%-to-30% of patients with COVID-19, and severe disease can lead to cardiopulmonary failure. The role of mechanical circulatory support in these patients remains undetermined. The authors here aimed to determine the characteristics and outcomes of patients with COVID-19 requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) or veno-arterial-venous (VAV) ECMO support. DESIGN AND SETTING: A multicenter, retrospective case series. PARTICIPANTS: The cohort consisted of adult patients (18 years of age and older) with confirmed COVID-19 requiring VA ECMO or VAV ECMO support in the period from March 1, 2020, to April 30, 2021. Outcomes were recorded until July 31, 2021. MEASUREMENTS AND MAIN RESULTS: To show factors related to death during hospitalization, patients were grouped as survivors and nonsurvivors. Kaplan-Meier analysis was used to estimate 90-day in-hospital mortality. Overall, 37 patients from 12 centers comprised the study cohort. The median patient age was 44 years old (interquartile range [IQR], 35-52), and 12 (32%) were female patients. The duration of ECMO support ranged from 2-to-132 days. At the end of the follow-up period, 13 patients (35%) were discharged or transferred alive, and 24 patients (65%) died during the hospitalization. The cumulative in-hospital mortality at 90 days was 64% (95% confidence interval: 47-81). During the time from intubation to VA ECMO or VAV ECMO initiation (1 day [IQR 0-7.5] v 6 days [IQR 2.5-14], p = 0.0383), body mass index (32 [IQR 26-36] v 37 [IQR 33-40], p = 0.009), and baseline C-reactive protein (7.15 v 38.9 mg/dL, p = 0.009) were higher in those who expired. CONCLUSION: Only one-third of the patients with COVID-19 requiring VA ECMO or VAV ECMO survived to discharge. Close monitoring of at-risk patients with early initiation of ECMO with circulatory support may further improve outcomes.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Adolescent , Adult , COVID-19/therapy , Female , Hospital Mortality , Humans , Kaplan-Meier Estimate , Male , Retrospective Studies
14.
J Korean Med Sci ; 37(4): e29, 2022 Jan 24.
Article in English | MEDLINE | ID: covidwho-1648601

ABSTRACT

BACKGROUND: Several studies have recently suggested that liver disease and cirrhosis were risk factors for poor outcomes in patients with coronavirus disease 2019 (COVID-19) infections. However, no large data study has reported the clinical course of COVID-19 patients with chronic hepatitis B virus (HBV) infections. This study investigated whether HBV infection had negative impacts on the clinical outcomes of COVID-19 patients. METHODS: We performed a nationwide population-based cohort study with 19,160 COVID-19-infected patients in 2020 from the Korean Health Insurance Review and Assessment database. The clinical outcomes of COVID-19 patients with chronic HBV infections were assessed and compared to those of non-HBV-infected patients. RESULTS: Of the 19,160 patients diagnosed with COVID-19, 675 (3.5%) patients had chronic HBV infections. The HBV-infected patients were older and had more commodities than the non-HBV infected COVID-19 patients. During the observation period, COVID-19-related mortality was seen in 1,524 (8.2%) of the non-HBV-infected 18,485 patients, whereas 91 (13.5%) in HBV-infected 675 patients died of COVID-19 infection. Compared to patients without HBV infections, a higher proportion of patients with chronic HBV infections required intensive care unit (ICU) admission and had organ failures. However, odds ratios for mortality, ICU admission, and organ failure were comparable between the two groups after adjusting for age, sex, and comorbid diseases including liver cirrhosis and hepatocellular carcinoma. CONCLUSION: COVID-19-infected patients with HBV infections showed worse clinical courses than non-HBV-infected COVID-19 patients. However, after adjustment, chronic HBV infection itself does not seem to affect the clinical outcomes in COVID-19 patients.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/mortality , Antiviral Agents/therapeutic use , COVID-19/therapy , Cell Line, Tumor , Comorbidity , Female , Hepatitis B virus , Hepatitis B, Chronic/therapy , Humans , Kaplan-Meier Estimate , Length of Stay/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , SARS-CoV-2 , Treatment Outcome
15.
PLoS One ; 17(1): e0262811, 2022.
Article in English | MEDLINE | ID: covidwho-1633309

ABSTRACT

INTRODUCTION: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. MATERIALS AND METHODS: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. RESULTS: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. CONCLUSIONS: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/pathology , Thrombosis/drug therapy , Acute Kidney Injury/complications , Acute Kidney Injury/diagnosis , Age Factors , Aged , Anticoagulants/adverse effects , COVID-19/drug therapy , COVID-19/mortality , COVID-19/virology , Cardiovascular Diseases/complications , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification , Sex Factors , Thrombosis/complications
16.
J Clin Invest ; 131(20)2021 10 15.
Article in English | MEDLINE | ID: covidwho-1626086

ABSTRACT

BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5-7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19-1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III.


Subject(s)
COVID-19/therapy , SARS-CoV-2 , Aged , COVID-19/mortality , COVID-19/physiopathology , Combined Modality Therapy , Disease Progression , Female , Hospitalization , Humans , Immunization, Passive/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Odds Ratio , Pandemics , Spain/epidemiology , Treatment Outcome
17.
Clin Lung Cancer ; 22(3): 225-233.e7, 2021 05.
Article in English | MEDLINE | ID: covidwho-1592247

ABSTRACT

BACKGROUND: To examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities. RESULTS: Median follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n = 131) and HR (n = 84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P = .08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P > .2 for all). Field size was not associated with OS, PFS, or LRR (P > .40 for all). LRR rates were 20% for HR and 26% for WM groups (P = .30). There was no significant difference in patterns of initial site of LRR between groups (P > .1). WM fields (OR 3.73, P = .001) and concurrent chemotherapy (odds ratio 3.62, P = .001) were associated with grade ≥2 toxicity. CONCLUSIONS: Locoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of HR PORT fields.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Radiotherapy, Conformal/methods , Aged , COVID-19/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Middle Aged , Progression-Free Survival , Radiotherapy, Adjuvant/methods , Retrospective Studies , Survival Rate
18.
J Leukoc Biol ; 111(1): 269-281, 2022 01.
Article in English | MEDLINE | ID: covidwho-1591653

ABSTRACT

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID-19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID-19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID-19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL-6 and IL-10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL-6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927-1.000, P < 0.0001). In addition, the preoperative IL-6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL-6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/µl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.


Subject(s)
COVID-19/blood , COVID-19/mortality , Interleukin-6/blood , Severity of Illness Index , Africa, Northern , Aged , Biomarkers/blood , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Cytokines/metabolism , Female , Humans , Kaplan-Meier Estimate , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Middle Aged , Multivariate Analysis , Prognosis , Treatment Outcome
19.
Biomed Pharmacother ; 146: 112481, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588218

ABSTRACT

INTRODUCTION: Patients over 80 years of age are more prone to develop severe symptoms and die from COVID-19. Antibiotics were massively prescribed in the first days of the pandemic without evidence of super infection. Antibiotics may increase the risk of mortality in cases of viral pneumonia. With age and antibiotic use, the microbiota becomes altered and less protective effect against lethal viral pneumonia. Thus we assessed whether it is safe to prescribe antibiotics for COVID-19 pneumonia to patients over 80 years of age. METHOD: We conducted a retrospective monocentric study in a 1240-bed university hospital. Our inclusion criteria were patients aged ≥ 80 years, hospitalized in a COVID-19 unit, with either a positive SARS-CoV-2 RT-PCR from a nasopharyngeal swab or a CT scan within 72 h after or prior to hospitalization in the unit suggestive of infection. RESULTS: We included 101 patients who received antibiotics and 48 who did not. The demographics in the two groups were similar. Overall mortality was higher for the group that received antibiotics than for the other group (36.6% vs 14.6%,). According to univariate COX analysis, the risk of mortality was higher (HR = 1.98 [0.926; 4.23]) but non-significantly for the antibiotic group. In multivariate analysis, independent risk factors of mortality were an increased leukocyte count and decreased oxygen saturation (HR = 1.097 [1.022; 1.178] and HR = 0.927 [0.891; 0.964], respectively). CONCLUSION: This study raises questions about the interest of antibiotic therapy, its efficacy, and its effect on COVID-19 and encourages further research.


Subject(s)
Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Aged, 80 and over , Female , Hospitalization , Hospitals, University , Humans , Kaplan-Meier Estimate , Male , Mortality , Multivariate Analysis , Retrospective Studies , Risk Assessment , Risk Factors
20.
Mol Med ; 27(1): 151, 2021 12 03.
Article in English | MEDLINE | ID: covidwho-1551198

ABSTRACT

BACKGROUND: We investigated the feasibility of two biomarkers of endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), and their association with inflammation, coagulopathy, and mortality. METHODS: The records of 49 COVID-19 patients who were admitted to an intensive care unit (ICU) in Wuhan, China between February and April 2020 were examined. Demographic, clinical, and laboratory data, and outcomes were compared between survivors and non-survivors COVID-19 patients, and between patients with high and low serum Syndecan-1 levels. The dynamics of serum Syndecan-1 levels were also analyzed. RESULTS: The levels of Syndecan-1 were significantly higher in non-survivor group compared with survivor group (median 1031.4 versus 504.0 ng/mL, P = 0.002), and the levels of thrombomodulin were not significantly different between these two groups (median 4534.0 versus 3780.0 ng/mL, P = 0.070). Kaplan-Meier survival analysis showed that the group with high Syndecan-1 levels had worse overall survival (log-rank test: P = 0.023). Patients with high Syndecan-1 levels also had significantly higher levels of thrombomodulin, interleukin-6, and tumor necrosis factor-α. Data on the dynamics of Syndecan-1 levels indicated much greater variations in non-survivors than survivors. CONCLUSIONS: COVID-19 patients with high levels of Syndecan-1 develop more serious endothelial damage and inflammatory reactions, and have increased mortality. Syndecan-1 has potential for use as a marker for progression or severity of COVID-19. Protecting the glycocalyx from destruction is a potential treatment for COVID-19.


Subject(s)
COVID-19/blood , COVID-19/therapy , Endothelium/metabolism , Glycocalyx/metabolism , Syndecan-1/blood , Aged , Biomarkers/blood , Blood Coagulation , COVID-19/mortality , China/epidemiology , Cytokines/metabolism , Endothelium, Vascular/pathology , Female , Humans , Inflammation , Intensive Care Units , Interleukin-6/blood , Kaplan-Meier Estimate , Male , Middle Aged , Oxygen , ROC Curve , SARS-CoV-2 , Thrombomodulin/blood , Treatment Outcome , Tumor Necrosis Factor-alpha/blood
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