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4.
PLoS One ; 16(12): e0261707, 2021.
Article in English | MEDLINE | ID: covidwho-1581734

ABSTRACT

The objective of this retrospective cohort study was to describe pre-treatment characteristics, treatment patterns, health resource use, and clinical outcomes among adults hospitalized with COVID-19 in the United States (US) who initiated common treatments for COVID-19. The Optum® COVID-19 electronic health records database was used to identify patients >18 years, diagnosed with COVID-19, who were admitted to an inpatient setting and received treatments of interest for COVID-19 between September 2020 and January 2021. Patients were stratified into cohorts based on index treatment use. Patient demographics, medical history, care setting, medical procedures, subsequent treatment use, patient disposition, clinical improvement, and outcomes were summarized descriptively. Among a total of 26,192 patients identified, the most prevalent treatments initiated were dexamethasone (35.4%) and dexamethasone + remdesivir (14.9%), and dexamethasone was the most common subsequent treatment. At day 14 post-index, <10% of patients received any treatments of interest. Mean (standard deviation [SD]) patient age was 65.6 (15.6) years, and the most prevalent comorbidities included hypertension (44.8%), obesity (35.4%), and diabetes (25.7%). At the end of follow-up, patients had a mean (SD) 8.1 (6.6) inpatient days and 1.4 (4.1) days with ICU care. Oxygen supplementation, non-invasive, or invasive ventilation was required by 4.5%, 3.0%, and 3.1% of patients, respectively. At the end of follow-up, 84.2% of patients had evidence of clinical improvement, 3.1% remained hospitalized, 83.8% were discharged, 4% died in hospital, and 9.1% died after discharge. Although the majority of patients were discharged alive, no treatments appeared to alleviate the inpatient morbidity and mortality associated with COVID-19. This highlights an unmet need for effective treatment options for patients hospitalized with COVID-19.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Hypertension/epidemiology , Obesity/epidemiology , Patient Discharge , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Adenosine Monophosphate/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Alanine/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Comorbidity , Drug Therapy, Combination/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , RNA, Viral/genetics , Retrospective Studies , Treatment Outcome , United States/epidemiology , Young Adult
5.
Ann Intern Med ; 174(9): 1261-1269, 2021 09.
Article in English | MEDLINE | ID: covidwho-1547664

ABSTRACT

BACKGROUND: New treatment modalities are urgently needed for patients with COVID-19. The World Health Organization (WHO) Solidarity trial showed no effect of remdesivir or hydroxychloroquine (HCQ) on mortality, but the antiviral effects of these drugs are not known. OBJECTIVE: To evaluate the effects of remdesivir and HCQ on all-cause, in-hospital mortality; the degree of respiratory failure and inflammation; and viral clearance in the oropharynx. DESIGN: NOR-Solidarity is an independent, add-on, randomized controlled trial to the WHO Solidarity trial that included biobanking and 3 months of clinical follow-up (ClinicalTrials.gov: NCT04321616). SETTING: 23 hospitals in Norway. PATIENTS: Eligible patients were adults hospitalized with confirmed SARS-CoV-2 infection. INTERVENTION: Between 28 March and 4 October 2020, a total of 185 patients were randomly assigned and 181 were included in the full analysis set. Patients received remdesivir (n = 42), HCQ (n = 52), or standard of care (SoC) (n = 87). MEASUREMENTS: In addition to the primary end point of WHO Solidarity, study-specific outcomes were viral clearance in oropharyngeal specimens, the degree of respiratory failure, and inflammatory variables. RESULTS: No significant differences were seen between treatment groups in mortality during hospitalization. There was a marked decrease in SARS-CoV-2 load in the oropharynx during the first week overall, with similar decreases and 10-day viral loads among the remdesivir, HCQ, and SoC groups. Remdesivir and HCQ did not affect the degree of respiratory failure or inflammatory variables in plasma or serum. The lack of antiviral effect was not associated with symptom duration, level of viral load, degree of inflammation, or presence of antibodies against SARS-CoV-2 at hospital admittance. LIMITATION: The trial had no placebo group. CONCLUSION: Neither remdesivir nor HCQ affected viral clearance in hospitalized patients with COVID-19. PRIMARY FUNDING SOURCE: National Clinical Therapy Research in the Specialist Health Services, Norway.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Hydroxychloroquine/therapeutic use , Viral Load/drug effects , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Antibodies, Viral/blood , Biomarkers/blood , COVID-19/complications , COVID-19/mortality , Cause of Death , Female , Hospital Mortality , Humans , Inflammation/virology , Male , Middle Aged , Norway/epidemiology , Oropharynx/virology , Respiratory Insufficiency/virology , SARS-CoV-2/immunology , Severity of Illness Index , Standard of Care , Treatment Outcome
6.
J Med Virol ; 93(12): 6732-6736, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544326

ABSTRACT

We aimed to investigate the interventions of remdesivir in both diabetic and nondiabetic individuals who were suffering from a severe infection of novel coronavirus disease (COVID-19). In this study, we aimed to explore the relationship between therapeutic effectiveness of remdesivir and complications of diabetes mellitus by observing the recovery period among diabetic and nondiabetic patients associated with COVID-19 infection. A total of 850 COVID-19 patients were recruited for this study, out of which 48% were diabetic and 52% were nondiabetics. The results of this study indicated that nondiabetic individuals administered with remdesivir recovered from COVID-19 within 10 days showing a 95% confidence interval (p < 0.01), while the diabetic individuals recovered in 15 days. Nondiabetic patients administered with remdesivir exhibited higher chances of clinical improvement at 15th day than those who were associated with diabetes. Remdesivir administration improved the levels of various biochemical parameters, such as C-reactive protein, lactate dehydrogenase, d-Dimer, and ferritin both in diabetic and nondiabetic patients. However, a significant improvement (p < 0.01) was seen in the level of biochemical parameters among nondiabetic patients as compared to that of diabetic patients administered with remdesivir treatment. In the end, it was concluded that remdesivir could be considered as a possible therapeutic agent in the treatment of COVID-19 both in diabetic and nondiabetic situations. However, diabetic patients showed a delayed recovery as compared with that of nondiabetic patients, in which the recovery rate was high.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus/virology , Adenosine Monophosphate/therapeutic use , Adolescent , Adult , Alanine/therapeutic use , Female , Hospitalization , Humans , Male , Middle Aged , Pakistan , Prospective Studies , Young Adult
7.
J Med Virol ; 94(1): 161-172, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544335

ABSTRACT

Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Evolution, Molecular , SARS-CoV-2/genetics , Adenosine Monophosphate/therapeutic use , Adolescent , Alanine/therapeutic use , Child , Child, Preschool , Drug Resistance, Viral , Female , Haplotypes , Humans , Infant , Lung/virology , Male , Phylogeny , RNA, Viral/analysis , RNA, Viral/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Viral Load , Virus Replication/drug effects
9.
Ann Intern Med ; 174(10): 1409-1419, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1515633

ABSTRACT

BACKGROUND: The COVID-19 pandemic has caused substantial morbidity and mortality. OBJECTIVE: To describe monthly clinical trends among adults hospitalized with COVID-19. DESIGN: Pooled cross-sectional study. SETTING: 99 counties in 14 states participating in the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET). PATIENTS: U.S. adults (aged ≥18 years) hospitalized with laboratory-confirmed COVID-19 during 1 March to 31 December 2020. MEASUREMENTS: Monthly hospitalizations, intensive care unit (ICU) admissions, and in-hospital death rates per 100 000 persons in the population; monthly trends in weighted percentages of interventions, including ICU admission, mechanical ventilation, and vasopressor use, among an age- and site-stratified random sample of hospitalized case patients. RESULTS: Among 116 743 hospitalized adults with COVID-19, the median age was 62 years, 50.7% were male, and 40.8% were non-Hispanic White. Monthly rates of hospitalization (105.3 per 100 000 persons), ICU admission (20.2 per 100 000 persons), and death (11.7 per 100 000 persons) peaked during December 2020. Rates of all 3 outcomes were highest among adults aged 65 years or older, males, and Hispanic or non-Hispanic Black persons. Among 18 508 sampled hospitalized adults, use of remdesivir and systemic corticosteroids increased from 1.7% and 18.9%, respectively, in March to 53.8% and 74.2%, respectively, in December. Frequency of ICU admission, mechanical ventilation, and vasopressor use decreased from March (37.8%, 27.8%, and 22.7%, respectively) to December (20.5%, 12.3%, and 12.8%, respectively); use of noninvasive respiratory support increased from March to December. LIMITATION: COVID-NET covers approximately 10% of the U.S. population; findings may not be generalizable to the entire country. CONCLUSION: Rates of COVID-19-associated hospitalization, ICU admission, and death were highest in December 2020, corresponding with the third peak of the U.S. pandemic. The frequency of intensive interventions for management of hospitalized patients decreased over time. These data provide a longitudinal assessment of clinical trends among adults hospitalized with COVID-19 before widespread implementation of COVID-19 vaccines. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Subject(s)
COVID-19/therapy , Hospitalization/trends , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Age Distribution , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/ethnology , COVID-19/mortality , Critical Care/trends , Cross-Sectional Studies , Female , Humans , Intensive Care Units/trends , Length of Stay/trends , Male , Middle Aged , Pandemics , Respiration, Artificial/trends , SARS-CoV-2 , United States/epidemiology , Vasoconstrictor Agents/therapeutic use , Young Adult
10.
Mol Med Rep ; 24(6)2021 12.
Article in English | MEDLINE | ID: covidwho-1504040

ABSTRACT

The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID­19). To date, there is no specific therapy established to treat COVID­19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS­CoV­2 in humans. For the present review, >100 publications on therapeutic agents for COVID­19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta­analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS­CoV­2 infection were highlighted. Since the outbreak of COVID­19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID­19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID­19. The molecular mechanisms of these therapeutic agents against SARS­CoV2 have been investigated, including inhibition of viral interactions with angiotensin­converting enzyme 2 receptors in human cells, viral RNA­dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID­19 were acknowledged.


Subject(s)
COVID-19/therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Animals , Antimalarials/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , Chloroquine/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , SARS-CoV-2/isolation & purification
11.
Medicine (Baltimore) ; 100(37): e27228, 2021 Sep 17.
Article in English | MEDLINE | ID: covidwho-1501195

ABSTRACT

ABSTRACT: Remdesivir is the only antiviral approved for lower respiratory tract infection produced by SARS-CoV-2. The main objective of this study was to determine the mortality rate, readmissions, mean hospital stay, need for higher levels of oxygen support, and adverse effect-induced abandonment rate in hospitalized patients diagnosed with COVID-19 and treated with remdesivir (RDSV). The secondary objective was to determine mortality-related risk factors in these patients.The study included a prospective cohort of patients admitted to a third level Spanish hospital between July 5, 2020 and February 3, 2021 for COVID-19 diagnosed by SARS-CoV-2 polymerase chain reaction and/or antigen test and treated with RDSV.Remdesivir was received by 185 patients (69.7% males) with a mean age of 62.5 years, median Charlson index of 3 (interquartile range [IQR]: 1-4), and median ambient air oxygen saturation of 91% (IQR: 90-93); 61.6% of patients had hyper-inflammatory syndrome at admission. Median time with symptoms before RDSV treatment was 5 days (IQR: 3-6) and the median hospital stay was 10 days (IQR: 7-15); 19 patients (10.3%) died after a median stay of 13.5 days (IQR: 9.7-24 days), 58 patients (12.9%) were admitted to ICU, 58 (31.4%) needed higher levels of oxygen support, 0.5% abandoned the treatment due to adverse effects, and there were no readmissions. The only mortality-related factor was the need for higher levels of oxygen support (odds ratio 12.02; 95% confidence interval 2.25-64.2).All studied patients were admitted to hospital with a diagnosis of COVID-19 and in respiratory failure, needing initial low-flow oxygen support, and all received RDSV within 1 week of symptom onset. The percent mortality was lower in these patients than was observed in all patients with severe COVID-19 admitted to our center (10.3% vs 20.3%, respectively). Despite receiving RDSV, 1 in 3 patients needed higher levels of oxygen support, the sole mortality-related factor.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Aged , Alanine/pharmacology , Alanine/therapeutic use , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/mortality , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Retrospective Studies , Spain , Statistics, Nonparametric
12.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
13.
Mol Syst Biol ; 17(11): e10260, 2021 11.
Article in English | MEDLINE | ID: covidwho-1488874

ABSTRACT

Tremendous progress has been made to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. However, effective therapeutic options are still rare. Drug repurposing and combination represent practical strategies to address this urgent unmet medical need. Viruses, including coronaviruses, are known to hijack host metabolism to facilitate viral proliferation, making targeting host metabolism a promising antiviral approach. Here, we describe an integrated analysis of 12 published in vitro and human patient gene expression datasets on SARS-CoV-2 infection using genome-scale metabolic modeling (GEM), revealing complicated host metabolism reprogramming during SARS-CoV-2 infection. We next applied the GEM-based metabolic transformation algorithm to predict anti-SARS-CoV-2 targets that counteract the virus-induced metabolic changes. We successfully validated these targets using published drug and genetic screen data and by performing an siRNA assay in Caco-2 cells. Further generating and analyzing RNA-sequencing data of remdesivir-treated Vero E6 cell samples, we predicted metabolic targets acting in combination with remdesivir, an approved anti-SARS-CoV-2 drug. Our study provides clinical data-supported candidate anti-SARS-CoV-2 targets for future evaluation, demonstrating host metabolism targeting as a promising antiviral strategy.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/metabolism , Metabolic Networks and Pathways/genetics , Pandemics , SARS-CoV-2/physiology , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Animals , COVID-19/drug therapy , COVID-19/virology , Caco-2 Cells , Chlorocebus aethiops , Datasets as Topic , Drug Development , Drug Repositioning , Host-Pathogen Interactions , Humans , RNA, Small Interfering , Sequence Analysis, RNA , Vero Cells
14.
Ann Intern Med ; 174(10): 1395-1403, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1481181

ABSTRACT

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Hydroxychloroquine/therapeutic use , Practice Patterns, Physicians' , Adenosine Monophosphate/therapeutic use , Adolescent , Adult , Aged , Alanine/therapeutic use , Anti-Inflammatory Agents/therapeutic use , COVID-19/therapy , Female , Humans , Male , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , United States , Young Adult
15.
Int J Mol Sci ; 22(20)2021 Oct 10.
Article in English | MEDLINE | ID: covidwho-1463713

ABSTRACT

We report a lymphoma patient with profound B-cell deficiency after chemotherapy combined with anti-CD20 antibody successfully treated with remdesivir and convalescent plasma for prolonged SARS-CoV-2 infection. Viral clearance was likely attributed to the robust expansion and activation of TCR Vß2 CD8+ cytotoxic T cells and CD16 + CD56- NK cells. This is the first presentation of TCR-specific T cell oligoclonal response in COVID-19. Our study suggests that B-cell depleted patients may effectively respond to anti-SARS-CoV-2 treatment when NK and antigen-specific Tc cell response is induced.


Subject(s)
COVID-19/therapy , Killer Cells, Natural/immunology , T-Lymphocytes, Cytotoxic/immunology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , B-Lymphocytes/metabolism , COVID-19/virology , Humans , Immunization, Passive , SARS-CoV-2/isolation & purification
16.
J Hematol Oncol ; 14(1): 163, 2021 10 11.
Article in English | MEDLINE | ID: covidwho-1463258

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently constitutes the leading and overwhelming health issue worldwide. In comparison with adults, children present milder symptoms, with most having an asymptomatic course. We hypothesized that COVID-19 infection has a negative impact on the continuation of chemotherapy and increases nonrelapse mortality. MATERIAL AND METHODS: This study was performed to assess the course of SARS-CoV-2 among children with hematological or oncological malignancies and its impact on cancer therapy. Records of SARS-CoV-2 infection in 155 children with malignancies from 14 Polish centers for pediatric hematology and oncology were collected and analyzed. RESULTS: SARS-CoV-2 replication was observed in 155 patients. Forty-nine patients were symptomatic, with the following being the most common manifestations: fever (31 patients), gastrointestinal symptoms (10), coryza (13), cough (13) and headache (8). In children who were retested, the median time of a positive PCR result was 16 days (range 1-70 days), but 12.7% of patients were positive beyond day + 20. The length of viral PCR positivity correlated with the absolute neutrophil count at diagnosis. Seventy-six patients did not undergo further SARS-CoV-2 testing and were considered convalescents after completion of isolation. Antibiotic therapy was administered in 15 children, remdesivir in 6, convalescent plasma in 4, oxygen therapy in 3 (1-mechanical ventilation), steroids in 2, intravenous immunoglobulins in 2, and heparin in 4. Eighty patients were treated with chemotherapy within 30 days after SARS-CoV-2 infection diagnosis or were diagnosed with SARS-CoV-2 infection during 30 days of chemotherapy administration. Respiratory symptoms associated with COVID-19 and associated with oxygen therapy were present in 4 patients in the study population, and four deaths were recorded (2 due to COVID-19 and 2 due to progressive malignancy). The probability of 100-day overall survival was 97.3% (95% CI 92.9-99%). Delay in the next chemotherapy cycle occurred in 91 of 156 cases, with a median of 14 days (range 2-105 days). CONCLUSIONS: For the majority of pediatric cancer patients, SARS-CoV-2 infection does not result in a severe, life-threatening course. Our data show that interruptions in therapy are common and can result in suboptimal therapy.


Subject(s)
COVID-19/complications , COVID-19/therapy , Hematologic Neoplasms/complications , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adolescent , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , Child , Child, Preschool , Disease Management , Female , Hematologic Neoplasms/drug therapy , Humans , Immunization, Passive , Infant , Male , Poland/epidemiology , SARS-CoV-2/isolation & purification
18.
J Microbiol ; 59(11): 1056-1062, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1453895

ABSTRACT

The COVID-19 pandemic has caused unprecedented health, social, and economic crises worldwide. However, to date, there is an only a limited effective treatment for this disease. Human placenta hydrolysate (hPH) has previously been shown to be safe and to improve the health condition in patients with hyperferritinemia and COVID-19. In this study, we aimed to determine the antiviral effects of hPH against SARS-CoV-2 in vitro and in vivo models and compared with Remdesivir, an FDA-approved drug for COVID-19 treatment. To assess whether hPH inhibited SARS-CoV-2 replication, we determined the CC50, EC50, and selective index (SI) in Vero cells by infection with a SARS-CoV-2 at an MOI of 0.01. Further, groups of ferrets infected with 105.8 TCID50/ml of SARS-CoV-2 and treated with hPH at 2, 4, 6 dpi, and compared their clinical manifestation and virus titers in respiratory tracts with PBS control-treated group. The mRNA expression of immune-related cytokines was determined by qRT-PCR. hPH treatment attenuated virus replication in a dose-dependent manner in vitro. In a ferret infection study, treatment with hPH resulted in minimal bodyweight loss and attenuated virus replication in the nasal wash, turbinates, and lungs of infected ferrets. In addition, qRT-PCR results revealed that the hPH treatment remarkably upregulated the gene expression of type I (IFN-α and IFN-ß) and II (IFN-γ) IFNs in SARS-CoV-2 infected ferrets. Our data collectively suggest that hPH has antiviral efficacy against SARS-CoV-2 and might be a promising therapeutic agent for the treatment of SARS-CoV-2 infection.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Placenta/chemistry , Protein Hydrolysates , SARS-CoV-2/drug effects , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/pharmacology , Alanine/therapeutic use , Animals , Chlorocebus aethiops , Female , Ferrets , Humans , Male , Pregnancy , Protein Hydrolysates/pharmacology , Protein Hydrolysates/therapeutic use , Vero Cells , Virus Replication/drug effects
20.
Am J Emerg Med ; 38(7): 1488-1493, 2020 07.
Article in English | MEDLINE | ID: covidwho-1450042

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has been particularly challenging due to a lack of established therapies and treatment guidelines. With the rapid transmission of disease, even the off-label use of available therapies has been impeded by limited availability. Several antivirals, antimalarials, and biologics are being considered for treatment at this time. The purpose of this literature review is to synthesize the available information regarding treatment options for COVID-19 and serve as a resource for health care professionals. OBJECTIVES: This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). PubMed and SCOPUS were queried using a combination of the keywords "COVID 19," "SARS-CoV-2," and "treatment." All types of studies were evaluated including systematic reviews, case-studies, and clinical guidelines. DISCUSSION: There are currently no therapeutic drugs available that are directly active against SARS-CoV-2; however, several antivirals (remdesivir, favipiravir) and antimalarials (chloroquine, hydroxychloroquine) have emerged as potential therapies. Current guidelines recommend combination treatment with hydroxychloroquine/azithromycin or chloroquine, if hydroxychloroquine is unavailable, in patients with moderate disease, although these recommendations are based on limited evidence. Remdesivir and convalescent plasma may be considered in critical patients with respiratory failure; however, access to these therapies may be limited. Interleukin-6 (IL-6) antagonists may be used in patients who develop evidence of cytokine release syndrome (CRS). Corticosteroids should be avoided unless there is evidence of refractory septic shock, acute respiratory distress syndrome (ARDS), or another compelling indication for their use. ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever. CONCLUSION: There are several ongoing clinical trials that are testing the efficacy of single and combination treatments with the drugs mentioned in this review and new agents are under development. Until the results of these trials become available, we must use the best available evidence for the prevention and treatment of COVID-19. Additionally, we can learn from the experiences of healthcare providers around the world to combat this pandemic.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adrenal Cortex Hormones , Alanine/analogs & derivatives , Alanine/therapeutic use , Amides/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Drug Therapy, Combination , Emergency Service, Hospital , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/antagonists & inhibitors , Pandemics , Pyrazines/therapeutic use , Randomized Controlled Trials as Topic , SARS-CoV-2
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