Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 79
Filter
Add filters

Document Type
Year range
3.
Respir Res ; 22(1): 317, 2021 Dec 22.
Article in English | MEDLINE | ID: covidwho-1582067

ABSTRACT

BACKGROUND: Data on the safety and efficacy profile of tocilizumab in patients with severe COVID-19 needs to be enriched. METHODS: In this open label, prospective study, we evaluated clinical outcomes in consecutive patients with COVID-19 and PaO2/FiO2 < 200 receiving tocilizumab plus usual care versus usual care alone. Tocilizumab was administered at the time point that PaO2/FiO2 < 200 was observed. The primary outcome was 28-day mortality. Secondary outcomes included time to discharge, change in PaO2/FiO2 at day 5 and change in WHO progression scale at day 10. FINDINGS: Overall, 114 patients were included in the analysis (tocilizumab plus usual care: 56, usual care: 58). Allocation to usual care was associated with significant increase in 28-day mortality compared to tocilizumab plus usual care [Cox proportional-hazards model: HR: 3.34, (95% CI: 1.21-9.30), (p = 0.02)]. There was not a statistically significant difference with regards to hospital discharge over the 28 day period for patients receiving tocilizumab compared to usual care [11.0 days (95% CI: 9.0 to 16.0) vs 14.0 days (95% CI: 10.0-24.0), HR: 1.32 (95% CI: 0.84-2.08), p = 0.21]. ΔPaO2/FiO2 at day 5 was significantly higher in the tocilizumab group compared to the usual care group [42.0 (95% CI: 23.0-84.7) vs 15.8 (95% CI: - 19.4-50.3), p = 0.03]. ΔWHO scale at day 10 was significantly lower in the tocilizumab group compared to the usual care group (-0.5 ± 2.1 vs 0.6 ± 2.6, p = 0.005). CONCLUSION: Administration of tocilizumab, at the time point that PaO2/FiO2 < 200 was observed, improved survival and other clinical outcomes in hospitalized patients with severe COVID-19 irrespective of systemic inflammatory markers levels.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , COVID-19/mortality , Hospitalization/trends , Patient Acuity , Administration, Intravenous , Aged , COVID-19/diagnosis , Female , Humans , Male , Middle Aged , Prospective Studies , Survival Rate/trends
4.
J Exp Med ; 219(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1565893

ABSTRACT

In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (BCG) has been reported to confer nonspecific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 (SCV2) and results in reduced viral loads in non-transgenic animals infected with an α variant. The observed increase in host resistance was associated with reductions in SCV2-induced tissue pathology, inflammatory cell recruitment, and cytokine production that multivariate analysis revealed as only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and ensuing immunopathology. While intravenous BCG vaccination is not a clinically acceptable practice, our findings provide an experimental model for identifying mechanisms by which nonspecific stimulation of the pulmonary immune response promotes host resistance to SCV2 lethality.


Subject(s)
BCG Vaccine/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Administration, Intravenous , Angiotensin-Converting Enzyme 2/metabolism , Animals , Chemokines/metabolism , Humans , Inflammation/pathology , Mice, Inbred C57BL , Mice, Transgenic , Viral Load
5.
BMC Pulm Med ; 21(1): 354, 2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1505545

ABSTRACT

BACKGROUND: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established. METHODS: We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis. RESULTS: Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98-6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group. CONCLUSION: IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.


Subject(s)
COVID-19/drug therapy , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Respiratory Distress Syndrome/drug therapy , Administration, Intravenous , Adult , Aged , COVID-19/complications , COVID-19/mortality , Female , Humans , Male , Middle Aged , Propensity Score , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/virology , Retrospective Studies , Severity of Illness Index , Survival Analysis , Treatment Outcome
6.
Ann Med ; 53(1): 1863-1874, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1483235

ABSTRACT

OBJECTIVE: To compare the performance of the Risk-stratification of Emergency Department suspected Sepsis (REDS) score to the SIRS criteria, NEWS2, CURB65, SOFA, MEDS and PIRO scores, to risk-stratify Emergency Department (ED) suspected sepsis patients for mortality. METHOD: A retrospective observational cohort study of prospectively collected data. Adult patients admitted from the ED after receiving intravenous antibiotics for suspected sepsis in the year 2020, were studied. Patients with COVID-19 were excluded. The scores stated above were calculated for each patient. Receiver operator characteristics (ROC) curves were constructed for each score for the primary outcome measure, all-cause in-hospital mortality. The area under the ROC (AUROC) curves and cut-off points were identified by the statistical software. Scores above the cut-off point were deemed high-risk. The test characteristics of the high-risk groups were calculated. Comparisons were based on the AUROC curve and sensitivity for mortality of the high-risk groups. Previously published cut-off points were also studied. Calibration was also studied. RESULTS: Of the 2594 patients studied, 332 (12.8%) died. The AUROC curve for the REDS score 0.73 (95% confidence interval [CI] 0.72-0.75) was significantly greater than the AUROC curve for the SIRS criteria 0.51 (95% CI 0.49-0.53), p < .0001 and the NEWS2 score 0.69 (95% CI 0.67-0.70), p = .005, and similar to all other scores studied. Sensitivity for mortality at the respective cut-off points identified (REDS ≥3, NEWS2 ≥ 8, CURB65 ≥ 3, SOFA ≥3, MEDS ≥10 and PIRO ≥10) was greatest for the REDS score at 80.1% (95% CI 75.4-84.3) and significantly greater than the other scores. The sensitivity for mortality for an increase of two points from baseline in the SOFA score was 63% (95% CI 57.5-68.2). CONCLUSIONS: In this single centre study, the REDS score had either a greater AUROC curve or sensitivity for mortality compared to the comparator scores, at the respective cut-off points identified.KEY MESSAGESThe REDS score is a simple and objective scoring system to risk-stratify for mortality in emergency department (MED) patients with suspected sepsis.The REDS score is better or equivalent to existing scoring systems in its discrimination for mortality.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Emergency Service, Hospital/statistics & numerical data , Intensive Care Units/statistics & numerical data , Sepsis/mortality , Severity of Illness Index , Administration, Intravenous , Aged , Aged, 80 and over , Female , Hospital Mortality , Humans , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Retrospective Studies , Risk Assessment/methods , Sepsis/diagnosis , Sepsis/drug therapy
7.
J Clin Invest ; 131(19)2021 10 01.
Article in English | MEDLINE | ID: covidwho-1448085

ABSTRACT

BACKGROUNDClinical data to support the use of bamlanivimab for the treatment of outpatients with mild to moderate coronavirus disease-19 (COVID-19) are needed.METHODS2335 Patients who received single-dose bamlanivimab infusion between November 12, 2020, and February 17, 2021, were compared with a propensity-matched control of 2335 untreated patients with mild to moderate COVID-19 at Mayo Clinic facilities across 4 states. The primary outcome was the rate of hospitalization at days 14, 21, and 28.RESULTSThe median age of the population was 63 years; 47.3% of the bamlanivimab-treated cohort were 65 years or more; 49.3% were female and 50.7% were male. High-risk characteristics included hypertension (54.2%), BMI greater than or equal to 35 (32.4%), diabetes mellitus (26.5%), chronic lung disease (25.1%), malignancy (16.6%), and renal disease (14.5%). Patients who received bamlanivimab had lower all-cause hospitalization rates at days 14 (1.5% vs. 3.5%; risk ratio [RR], 0.41), 21 (1.9% vs. 3.9%; RR, 0.49), and 28 (2.5% vs. 3.9%; RR, 0.63). Secondary exploratory outcomes included lower intensive care unit (ICU) admission rates at days 14 (0.14% vs. 1%; RR, 0.14), 21 (0.25% vs.1%; RR, 0.25), and 28 (0.56% vs.1.1%; RR. 0.51) and lower all-cause mortality at days 14 (0% vs. 0.33%), 21 (0.05% vs. 0.4%; RR,0.13), and 28 (0.11% vs. 0.44%; RR, 0.26). Adverse events were uncommon with bamlanivimab, occurring in 19 of 2355 patients, and were most commonly fever (n = 6), nausea (n = 5), and lightheadedness (n = 3).CONCLUSIONSAmong high-risk patients with mild to moderate COVID-19, treatment with bamlanivimab was associated with a statistically significant lower rate of hospitalization, ICU admission, and mortality compared with usual care.FUNDINGMayo Clinic.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19 , Hospitalization , SARS-CoV-2/metabolism , Administration, Intravenous , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/mortality , Disease-Free Survival , Female , Humans , Intensive Care Units , Male , Middle Aged , Risk Factors , Survival Rate
8.
Sci Rep ; 11(1): 19458, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1447326

ABSTRACT

Efficacious therapeutics for Ebola virus disease are in great demand. Ebola virus infections mediated by mucosal exposure, and aerosolization in particular, present a novel challenge due to nontypical massive early infection of respiratory lymphoid tissues. We performed a randomized and blinded study to compare outcomes from vehicle-treated and remdesivir-treated rhesus monkeys in a lethal model of infection resulting from aerosolized Ebola virus exposure. Remdesivir treatment initiated 4 days after exposure was associated with a significant survival benefit, significant reduction in serum viral titer, and improvements in clinical pathology biomarker levels and lung histology compared to vehicle treatment. These observations indicate that remdesivir may have value in countering aerosol-induced Ebola virus disease.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Ebolavirus/drug effects , Hemorrhagic Fever, Ebola/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/pharmacology , Administration, Intravenous , Aerosols , Alanine/administration & dosage , Alanine/pharmacology , Animals , Antiviral Agents/administration & dosage , Disease Models, Animal , Female , Hemorrhagic Fever, Ebola/blood , Kaplan-Meier Estimate , Liver/drug effects , Liver/virology , Lung/pathology , Lung/virology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/virology , Macaca mulatta , Male , Random Allocation , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/virology , Viral Load/drug effects , Viremia/drug therapy
9.
Clin Pharmacol Ther ; 110(6): 1467-1477, 2021 12.
Article in English | MEDLINE | ID: covidwho-1372711

ABSTRACT

Therapeutics for patients hospitalized with coronavirus disease 2019 (COVID-19) are urgently needed during the pandemic. Bamlanivimab is a potent neutralizing monoclonal antibody that blocks severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) attachment and entry into human cells, which could potentially lead to therapeutic benefit. J2W-MC-PYAA was a randomized, double-blind, sponsor unblinded, placebo-controlled, single ascending dose first-in-human trial (NCT04411628) in hospitalized patients with COVID-19. A total of 24 patients received either placebo or a single dose of bamlanivimab (700 mg, 2,800 mg, or 7,000 mg). The primary objective was assessment of safety and tolerability, including adverse events and serious adverse events, with secondary objectives of pharmacokinetic (PK) and pharmacodynamic analyses. Treatment-emergent adverse event (TEAE) rates were identical in the placebo and pooled bamlanivimab groups (66.7%). There were no apparent dose-related increases in the number or severity of TEAEs. There were no serious adverse events or deaths during the study, and no discontinuations due to adverse events. PKs of bamlanivimab is linear and exposure increased proportionally with dose following single i.v. administration. The half-life was ~ 17 days. These results demonstrate the favorable safety profile of bamlanivimab, and provided the initial critical evaluation of safety, tolerability, and PKs in support of the development of bamlanivimab in several ongoing clinical trials.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antiviral Agents/administration & dosage , COVID-19/diagnosis , COVID-19/drug therapy , Hospitalization/trends , Administration, Intravenous , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/adverse effects , COVID-19/immunology , Dose-Response Relationship, Drug , Double-Blind Method , Fatigue/chemically induced , Female , Headache/chemically induced , Humans , Male , Middle Aged
10.
Commun Biol ; 4(1): 956, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1354120

ABSTRACT

Lipid Nanoparticles (LNPs) are used to deliver siRNA and COVID-19 mRNA vaccines. The main factor known to determine their delivery efficiency is the pKa of the LNP containing an ionizable lipid. Herein, we report a method that can predict the LNP pKa from the structure of the ionizable lipid. We used theoretical, NMR, fluorescent-dye binding, and electrophoretic mobility methods to comprehensively measure protonation of both the ionizable lipid and the formulated LNP. The pKa of the ionizable lipid was 2-3 units higher than the pKa of the LNP primarily due to proton solvation energy differences between the LNP and aqueous medium. We exploited these results to explain a wide range of delivery efficiencies in vitro and in vivo for intramuscular (IM) and intravascular (IV) administration of different ionizable lipids at escalating ionizable lipid-to-mRNA ratios in the LNP. In addition, we determined that more negatively charged LNPs exhibit higher off-target systemic expression of mRNA in the liver following IM administration. This undesirable systemic off-target expression of mRNA-LNP vaccines could be minimized through appropriate design of the ionizable lipid and LNP.


Subject(s)
Gene Expression , Ions/chemistry , Lipids/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , RNA, Messenger/genetics , Administration, Intravenous , Animals , Drug Compounding , Humans , Hydrogen-Ion Concentration , Injections, Intramuscular , Mice , Molecular Structure , Nanoparticles/ultrastructure , RNA, Messenger/administration & dosage , RNA, Messenger/pharmacokinetics , Spectrum Analysis , Tissue Distribution , Transfection
11.
Viruses ; 13(8)2021 07 30.
Article in English | MEDLINE | ID: covidwho-1335232

ABSTRACT

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the susceptibility of animals and their potential to act as reservoirs or intermediate hosts for the virus has been of significant interest. Pigs are susceptible to multiple coronaviruses and have been used as an animal model for other human infectious diseases. Research groups have experimentally challenged swine with human SARS-CoV-2 isolates with results suggesting limited to no viral replication. For this study, a SARS-CoV-2 isolate obtained from a tiger which is identical to human SARS-CoV-2 isolates detected in New York City and contains the D614G S mutation was utilized for inoculation. Pigs were challenged via intravenous, intratracheal, or intranasal routes of inoculation (n = 4/route). No pigs developed clinical signs, but at least one pig in each group had one or more PCR positive nasal/oral swabs or rectal swabs after inoculation. All pigs in the intravenous group developed a transient neutralizing antibody titer, but only three other challenged pigs developed titers greater than 1:8. No gross or histologic changes were observed in tissue samples collected at necropsy. In addition, no PCR positive samples were positive by virus isolation. Inoculated animals were unable to transmit virus to naïve contact animals. The data from this experiment as well as from other laboratories supports that swine are not likely to play a role in the epidemiology and spread of SARS-CoV-2.


Subject(s)
COVID-19/virology , SARS-CoV-2/physiology , Administration, Intranasal , Administration, Intravenous , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Disease Models, Animal , Humans , Mouth/virology , Nose/virology , SARS-CoV-2/genetics , Swine , Trachea/virology , Virus Replication
12.
Life Sci Alliance ; 4(9)2021 09.
Article in English | MEDLINE | ID: covidwho-1332524

ABSTRACT

The use of high-dose of intravenous immunoglobulins (IVIGs) as immunomodulators for the treatment of COVID-19-affected individuals has shown promising results. IVIG reduced inflammation in these patients, who progressively restored respiratory function. However, little is known about how they may modulate immune responses in COVID-19 individuals. Here, we have analyzed the levels of 41 inflammatory biomarkers in plasma samples obtained at day 0 (pretreatment initiation), 3, 7, and 14 from five hospitalized COVID-19 patients treated with a 5-d course of 400 mg/kg/d of IVIG. The plasmatic levels of several cytokines (Tumor Necrosis Factor, IL-10, IL-5, and IL-7), chemokines (macrophage inflammatory protein-1α), growth/tissue repairing factors (hepatic growth factor), complement activation (C5a), and intestinal damage such as Fatty acid-binding protein 2 and LPS-binding protein showed a progressive decreasing trend during the next 2 wk after treatment initiation. This trend was not observed in IVIG-untreated COVID-19 patients. Thus, the administration of high-dose IVIG to hospitalized COVID-19 patients may improve their clinical evolution by modulating their hyperinflammatory and immunosuppressive status.


Subject(s)
COVID-19/therapy , Immunoglobulins, Intravenous/therapeutic use , Administration, Intravenous , Adult , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , Chemokines/blood , Cytokines/blood , Female , Humans , Immunity/immunology , Immunoglobulins/immunology , Immunoglobulins/therapeutic use , Immunoglobulins, Intravenous/immunology , Inflammation/blood , Inflammation/therapy , Inflammation/virology , Male , Middle Aged , SARS-CoV-2/isolation & purification
13.
BMC Infect Dis ; 21(1): 616, 2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1285992

ABSTRACT

BACKGROUND: Critically ill patients frequently suffer from vitamin C deficiency. Previous studies showed that high doses of vitamin C administration had conflicting results on clinical outcomes in patients with severe sepsis, burns, and trauma. Because of the high incidence and morbidity/mortality with severe pneumonia, we aimed to investigate the effect of administration of high dose vitamin C in critically ill patients with severe pneumonia. METHODS: Eighty critically ill patients with pneumonia were enrolled in this randomized double-blinded clinical trial. Patients with a CURB-65 score > 3, one major criterion, or ≥ 3 minor criteria were considered as severe pneumonia. Patients were randomly assigned to intervention or placebo groups receiving standard treatment plus 60 mg/kg/day vitamin C as a continuous infusion or normal saline in the same volume correspondingly for 96 h. Serum levels of vitamin C were noted at baseline and 48 h after vitamin C administration. Duration of mechanical ventilation, ICU length of stay, PaO2/FiO2, and mortality rate were noted for all patients till the 28th day. Any complications related to the vitamin C administration were recorded. RESULTS: Duration of mechanical ventilation and vasopressor use were significantly lower in the intervention group (p: < 0.001 and 0.003, respectively). Baseline levels of vitamin C in both groups did not have a significant difference but its levels increased in the intervention group and decreased in the control group during the study period. Mortality rate insignificantly decreased in the intervention group (p = 0.17). Three patients showed hypotension and tachycardia during the administration of vitamin C which was self-limited with decreasing the dose of vitamin C. Our results showed that the intravenous administration of a relatively high dose of vitamin C to critically ill patients with severe pneumonia was safe and could decrease the inflammation, duration of mechanical ventilation, and vasopressor use without any significant effect on mortality. TRIAL REGISTRATION: IRCT registration number: IRCT20190312043030N1, Registration date: 2019-08-26, Seied Hadi Saghaleini.


Subject(s)
Ascorbic Acid/administration & dosage , Critical Care/methods , Intensive Care Units , Pneumonia/drug therapy , Pneumonia/mortality , Severity of Illness Index , Vitamins/administration & dosage , Administration, Intravenous , Adult , Aged , Ascorbic Acid/blood , Critical Illness , Double-Blind Method , Female , Humans , Length of Stay , Male , Middle Aged , Pneumonia/blood , Respiration, Artificial/adverse effects , Treatment Outcome
14.
Nutrition ; 91-92: 111405, 2021.
Article in English | MEDLINE | ID: covidwho-1284427

ABSTRACT

OBJECTIVE: High-dose intravenous vitamin C (HIVC) is a major concern when treating patients with coronavirus disease 2019 (COVID-19). The aim of this study was to assess the clinical efficacy of HIVC on hyperinflammation in patients with severe COVID-19. METHODS: This retrospective cohort study included hospitalized patients with severe COVID-19, a subset of whom was treated with HIVC. The medical records were screened for demographic data, laboratory findings, and medications, as well as initial and repeated values of multiple inflammatory markers for analysis. RESULTS: A high percentage of patients presented with hyperinflammation based on inflammatory marker levels above the upper limit of normal (high-sensitivity C-reactive protein, 80.1%; interleukin-6, 91.5%; and tumor necrosis factor-α, 67.4%). Eighty-five (36%) patients received HIVC therapy. After treatment with HIVC, the levels of inflammatory markers displayed a significant decrease compared with those of patients without HIVC. Furthermore, the percentages of reduction in inflammatory marker levels were higher in patients receiving HIVC compared with those in patients treated without HIVC. Stepwise multiple linear regression analysis revealed that HIVC was independently associated with percentages of reduction in levels of inflammatory markers. CONCLUSIONS: HIVC has the potential benefit of attenuating hyperinflammation by reducing inflammatory marker levels in patients with severe COVID-19.


Subject(s)
COVID-19 , Administration, Intravenous , Ascorbic Acid , Humans , Retrospective Studies , SARS-CoV-2
17.
Int Immunopharmacol ; 98: 107891, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267708

ABSTRACT

BACKGROUND: Intravenous immunoglobulins (IVIg) have been used in management of severe Covid-19. Here in this study, we report our single-center experience regarding IVIg treatment in management of severe Covid-19. MATERIALS AND METHOD: Among hospitalized adult Covid-19 patients between April 1 and December 31, 2020, patients with confirmed diagnosis of Covid-19 who had Brescia-COVID respiratory severity scale score ≥ 3, hyperinflammation and received IVIg treatment in addition to standard of care were retrospectively investigated. We grouped IVIg recipients into three according to reasons for IVIg administration: Group 1 patients requiring anti-inflammatory treatment but complicated with secondary infection and/or sepsis , group 2 patients with Covid-19 related complications including progressive disease refractory to other anti-inflammatory agents, myocarditis, adult multisystem inflammatory syndrome, hemophagocytic lymphohystiocytosis like syndrome and group 3 patients with other complications non-specific to Covid-19. Mortality and clinical data was compared among groups. RESULTS: A total of 46 IVIg recipients were enrolled. Group 1 comprised 17 (36.9%), group 2 comprised 18 (39.1%) and group 3 comprised 11 (23.9%) patients. No significant differences in means of age, gender and comorbidities were observed among groups. Mortality was significantly lower in group 3 when compared to group 1 (64.7% vs 18.2%, p = 0.016) and close to significance when compared to group 2 (50% vs 18.2% p = 0.087). CONCLUSIONS: IVIg seemed to be used mostly in severe, refractory and complicated cases in our population. As a rescue agent in severe cases refractory to other anti-inflammatory strategies, 33.7% survival rate was observed with IVIg.


Subject(s)
COVID-19/drug therapy , Immunoglobulins, Intravenous/administration & dosage , Administration, Intravenous , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Immunoglobulins, Intravenous/adverse effects , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Time Factors , Treatment Outcome , Turkey
18.
Pharmacol Rep ; 73(6): 1650-1659, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1265619

ABSTRACT

BACKGROUND: We designed this single-centre clinical trial to assess the potential benefits of N-Acetylcysteine (NAC) in patients with COVID19-associated acute respiratory distress syndrome (ARDS). METHODS: Ninety-two patients with mild-to-moderate COVID19-associated ARDS were allocated to the placebo (45-cases) or NAC groups (47-cases). Besides standard-of-care treatment, the patients received either intravenous NAC at a dose of 40 mg/kg/day or the placebo for three consecutive days. The efficacy outcomes were overall mortality over 28-day, clinical status on day 28, based on the WHO Master Protocol, the proportion of patients requiring mechanical ventilation, changes in ARDS-severity (based on the PaO2/FiO2 ratio), and Sequential Organ Failure Assessment (SOFA) scores 48 and 96 h after intervention, RESULTS: No differences were found in the 28-day mortality rate between the two groups (25.5% vs. 31.1% in the NAC and placebo groups, respectively). Although the distribution of the clinical status at day 28 shifted towards better outcomes in the NAC-treated group, it did not reach a statistical significance level (p value = 0.83). Similar results were achieved in terms of the proportion of patients who required invasive ventilator support (38.3% vs. 44.4%), the number of ventilator-free days (17.4 vs. 16.6), and median time of ICU and hospital stay. Results regarding the change in PaO2/FiO2 ratio and SOFA scores also showed no significant differences between the groups. CONCLUSIONS: Our pilot study did not support the potential benefits of intravenous NAC in treating patients with COVID-19-associated ARDS. More studies are needed to determine which COVID-19 patients benefit from the NAC administration. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (identifier code: IRCT20120215009014N355). Registration date: 2020-05-18.


Subject(s)
Acetylcysteine/therapeutic use , COVID-19/complications , COVID-19/drug therapy , Respiratory Distress Syndrome/drug therapy , Acetylcysteine/administration & dosage , Acetylcysteine/adverse effects , Administration, Intravenous , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Mortality , Pilot Projects , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Treatment Outcome
20.
Expert Rev Endocrinol Metab ; 16(4): 181-189, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1233816

ABSTRACT

Introduction: The COVID-19 pandemic has affected the entire population with the most deleterious effects in elders. Elders, especially those with diabetes, are at the highest risk of COVID-19 related adverse outcomes and mortality. This is usually linked to the comorbidities that accumulate with age, diabetes-related chronic inflammation, and the pandemic's psychosocial effects.Areas covered: We present some approaches to manage these complicated elderly patients with diabetes during the COVID-19 pandemic. In the inpatient setting, we suggest similar (pre-pandemic) glycemic targets and emphasize the importance of using IV insulin and possible use of continuous glucose monitoring to reduce exposure and PPE utilization. Outside the hospital, we recommend optimal glycemic control within the limits imposed by considerations of safety. We also describe the advantages and challenges of using various technological platforms in clinical care.Expert opinion: The COVID-19 pandemic has lifted the veil off serious deficiencies in the infrastructures for care at both the individual level and the population level and also highlighted some of the strengths, all of which affect individuals with diabetes and COVID-19. We anticipate that things will not return to 'normal' after the COVID-19 pandemic has run its course, but rather they will be superseded by 'New Normal.'


Subject(s)
COVID-19/psychology , Diabetes Mellitus/drug therapy , Inflammation/complications , Personal Protective Equipment/ethics , Administration, Intravenous , Aged , Aged, 80 and over , Blood Glucose/analysis , Blood Glucose Self-Monitoring/methods , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/mortality , Chronic Disease , Comorbidity , Diabetes Mellitus/diagnosis , Diabetes Mellitus/epidemiology , Disease Management , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Insulin/administration & dosage , Insulin/therapeutic use , Patient Education as Topic/methods , Personal Protective Equipment/standards , Prevalence , Risk Assessment , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Telemedicine/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...