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1.
AME case reports ; 6, 2022.
Article in English | EuropePMC | ID: covidwho-1801432

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a novel emerging disease and a major risk factor for postoperative complications, especially in thoracic surgery. However, it is unclear how previous COVID-19 infection may affect perioperative management of lung resection patients. A 70-year-old woman visited her primary doctor complaining of chest pain. Chest computed tomography (CT) revealed three abnormal nodules in the right upper and middle lung lobes and synchronous triple primary cancer was suspected. Before we could assess the patient for surgery, she developed a persistent fever. A second chest CT scan revealed newly emerged subpleural ground-glass opacities (GGO) in the right lung. The patient was diagnosed with COVID-19 pneumonia and hospitalized. She was treated for COVID-19 (Clinical Trial: jRCTs031200196) and discharged in a satisfactory condition 10 days later. A right upper and middle bilobectomy was performed 60 days after the patient’s initial COVID-19 diagnosis without any complications. Histopathological examination of the nodules identified synchronous triple primary lung cancer. The subpleural right upper and middle lung lobe tissue showed peribronchial lymphocyte infiltration and interstitial thickening. However, immunohistochemical staining for the SARS-CoV-2 antigen and PCR testing for SARS-CoV-2 were both negative. In this case, bilobectomy for triple primary lung cancer was performed safely after COVID-19 pneumonia. Further studies are needed to establish a safe and appropriate perioperative management system for thoracic surgery in patients recovering from COVID-19 pneumonia.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332338

ABSTRACT

ABSTRACT Background In vitro drug-screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). Methods This was a phase 3, multicentre, double-blind, randomised, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were administered camostat mesilate (600 mg qid;four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. Findings One-hundred and fifty-five patients were randomised to receive camostat mesilate (n=78) or placebo (n=77). The median time to the first test was 11 days in both groups, and conversion to negative status was observed in 60·8% and 63·5% of patients in the camostat mesilate and placebo groups, respectively. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. Interpretation Camostat mesilate is no more effective, based on upper airway viral clearance, than placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. Funding Ono Pharmaceutical Co., Ltd. RESEARCH IN CONTEXT PANEL Evidence before this study SARS-CoV-2 infection (COVID-19), as a significant global health threat, is characterised by broad symptoms and varying disease severity. At the time of planning this study, there were no specific treatments for COVID-19 beyond the use of antiviral drugs, steroids and, in severe cases, ventilation with oxygen. Pre-clinical screening studies revealed the spike (S) protein of SARS-CoV-2 bind to angiotensin converting enzyme II (ACE2) on the host cell membrane. The S protein is then cleaved by a type II transmembrane serine protease (TMPRSS2) as an essential enzyme for the viral entry into host cells. In vitro drug-screening studies have shown that drugs that block binding of the S protein to ACE2 can prevent viral entry into a cell line derived from human airway epithelium. The studies identified 4-(4-guanidinobenzoyloxy)phenylacetic acid, the active metabolite of a serine protease inhibitor (camostat mesilate, FOY-305), as a candidate inhibitor of SARS-CoV-2 entry into humans. A retrospective study of critically ill COVID-19 patients with organ failure revealed a decline in disease activity within 8 days of admission among patients treated with camostat mesilate. In consideration of the preclinical and early clinical evidence, it was hypothesised that camostat mesilate is an effective treatment for patients with COVID-19. Therefore, we planned and executed a phase 3, randomised, double-blind, placebo-controlled study to investigate the efficacy and safety of camostat mesilate for the treatment of patients with mild to moderate COVID-19 infection with or without symptoms. The primary endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. No controlled clinical studies of camostat mesilate had been conducted at the time of planning this study. Added value of this study The results of this randomised controlled trial revealed that camostat mesilate, administered at a dose of 600 mg qid for up to 14 days, was no more effective than placebo, based on upper airway viral clearance in patients with mild to moderate SARS-CoV-2 infection with or without symptoms. Furthermore, there were no differences between the study groups in terms of other efficacy endpoints. This study used a dose that was four to eight tim s higher than the clinical doses of camostat mesilate used in Japan for the acute symptoms of chronic pancreatitis and postoperative reflux oesophagitis. The study identified no additional safety concerns beyond those already known for camostat mesilate. Implications of all available evidence After starting this study, another randomised, placebo-controlled study reported the efficacy and safety of camostat mesilate for the treatment of patients with COVID-19, albeit at a lower dose of 200 mg three times daily. That study also found no difference between camostat mesilate and placebo for the primary endpoint (the time to discharge or a clinical improvement in clinical severity of at least two points on a seven-point ordinal scale). Along with this evidence, our study did not support the use of camostat mesilate as a treatment option for COVID-19. However, since the administration of camostat mesilate was started after the onset of symptoms and presumably the peak viral load, we cannot exclude the possibility that camostat mesilate may be effective if administration is started earlier in the course of infection, or perhaps as prophylactic use in close contacts.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312933

ABSTRACT

Background: Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score–matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. Methods: : This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January–April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Results: : Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611;95% confidence interval [CI], 0.388–0.962;p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758;95% CI, 1.323–2.337;p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466;95% CI, 0.841–2.554;p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831;95% CI, 1.347–5.950;p = 0.006). Conclusions: : Corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation. Trial registration : This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).

4.
J Clin Med ; 11(1)2021 Dec 27.
Article in English | MEDLINE | ID: covidwho-1580642

ABSTRACT

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.

5.
Pulm Pharmacol Ther ; 72: 102108, 2022 02.
Article in English | MEDLINE | ID: covidwho-1586767

ABSTRACT

BACKGROUND: The RECOVERY clinical trial reported that 6 mg of dexamethasone once daily for up to 10 days reduces the 28-day mortality in patients with coronavirus disease 2019 (COVID-19) receiving respiratory support. In our clinical setting, a fixed dose of dexamethasone has prompted the question of whether inflammatory modulation effects sufficiently reduce lung injury. Therefore, preliminary verification on the possibility of predicted body weight (PBW)-based dexamethasone therapy was conducted in patients with COVID-19 pneumonia. METHODS: This single-center retrospective study was conducted in a Japanese University Hospital to compare the treatment strategies/management in different periods. Consecutive patients (n = 90) with COVID-19 pneumonia requiring oxygen therapy and were treated with dexamethasone between June 2020 and May 2021 were analyzed. Initially, 60 patients administered a fixed dexamethasone dose of 6.6 mg/day were defined as the conventional group, and then, 30 patients were changed to PBW-based therapy. The 30-day discharged alive rate and duration of oxygen therapy were analyzed using the Kaplan-Meier method and compared using the log-rank test. The multivariable Cox regression was used to evaluate the effects of PBW-based dexamethasone therapy on high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), or mechanical ventilation (MV). RESULTS: In the PBW-based group, 9, 13, and 8 patients were administered 6.6, 9.9, and 13.2 mg/day of dexamethasone, respectively. Additional respiratory support including HFNC, NIV, or MV was significantly less frequently used in the PBW-based group (P = 0.0046), with significantly greater cumulative incidence of being discharged alive and shorter oxygen demand within 30 days (92 vs. 89%, log-rank P = 0.0094, 90 vs. 92%, log-rank P = 0.0002, respectively). Patients treated with PBW-based therapy significantly decreased the use of additional respiratory support after adjusting for baseline imbalances (adjusted odds ratio, 0.224; 95% confidence interval, 0.062-0.813, P = 0.023). Infection occurred in 13 (21%) and 2 (7%) patients in the conventional and PBW-based groups, respectively (P = 0.082). CONCLUSIONS: In patients with COVID-19 pneumonia requiring oxygen therapy, PBW-based dexamethasone therapy may potentially shorten the length of hospital stay and duration of oxygen therapy and risk of using HFNC, NPPV, or MV without increasing serious adverse events or 30-day mortality.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Body Weight , COVID-19/drug therapy , Dexamethasone , Humans , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
6.
Respir Investig ; 60(1): 146-153, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1487946

ABSTRACT

BACKGROUND: Although high-flow nasal cannula (HFNC) oxygen treatment has been frequently used in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure after the 3rd wave of the pandemic in Japan, the usefulness of the indicators of ventilator avoidance, including respiratory rate-oxygenation (ROX) index and other parameters, namely oxygen saturation/fraction of inspired oxygen ratio and respiratory rate (RR), remain unclear. METHODS: Between January and May 2021, our institution treated 189 COVID-19 patients with respiratory failure requiring oxygen, among which 39 patients requiring HFNC treatment were retrospectively analyzed. The group that switched from HFNC treatment to conventional oxygen therapy (COT) was defined as the HFNC success group, and the group that switched from HFNC treatment to a ventilator was defined as the HFNC failure group. We followed the patients' oxygenation parameters for a maximum of 30 days. RESULTS: HFNC treatment success occurred in 24 of 39 patients (62%) treated with HFNC therapy. Compared with the HFNC failure group, the HFNC success group had a significantly higher degree of RR improvement in the univariate analysis. Logistic regression analysis of HFNC treatment success adjusting for age, respiratory improvement, and a ROX index ≥5.55 demonstrated that an improved RR was associated with HFNC treatment success. The total COT duration was significantly shorter in the HFNC success group than in the HFNC failure group. CONCLUSIONS: HFNC treatment can be useful for ventilator avoidance and allow the quick withdrawal of oxygen administration. RR improvement may be a convenient, useful, and simple indicator of HFNC treatment success.


Subject(s)
COVID-19 , Noninvasive Ventilation , Pneumonia , Respiratory Insufficiency , Cannula , Humans , Oxygen , Oxygen Inhalation Therapy , Pneumonia/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Respiratory Rate , Retrospective Studies , SARS-CoV-2
7.
Infect Dis Ther ; 10(4): 2489-2509, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1375855

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. METHODS: COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. RESULTS: A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. CONCLUSIONS: The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION: Clinicaltrials.jp number: JapicCTI-205238.

9.
BMJ Open Respir Res ; 8(1)2021 07.
Article in English | MEDLINE | ID: covidwho-1315812

ABSTRACT

BACKGROUND: Although several studies have reported an association between atherosclerosis-related diseases and COVID-19, the relationship between COVID-19 severity and atherosclerosis progression remains unclear. The aim of this study is to determine the coronary artery calcium score (CACS) prognostic value in patients with COVID-19 using indices such as deterioration in oxygenation and CT images of the chest. METHODS: This was a single-centre retrospective study of 53 consecutive patients with COVID-19 in Narita who were admitted to our hospital between March 2020 and August 2020. CACS was calculated based on non-gated CT scans of the chest performed on admission day. The patients were divided into the following two groups based on CACS: group 1 (CACS ≥180, n=11) and group 2 (CACS <180, n=42). Following univariate analysis of the main variables, multivariate analysis of variables that may be associated with COVID-19 progression was performed. RESULTS: Multivariable logistic regression analysis of age, sex, smoking history, diabetes, hypertension, dyslipidaemia, number of days from symptom onset to hospitalisation and CACS of ≥180 was performed. It revealed that unlike CACS of <180, CACS of ≥180 is associated with exacerbation of oxygenation or CT images of the chest during hospitalisation (OR: 12.879, 95% CI: 1.399 to 380.401). Furthermore, this model of eight variables showed good calibration (Hosmer-Lemeshow p=0.119). CONCLUSION: CACS may be a prognosis marker of COVID-19 severity. Although coronary artery calcification is not typically assessed in pneumonia cases, it may provide a valuable clinical indicator for predicting severe COVID-19 outcomes.


Subject(s)
COVID-19/physiopathology , Coronary Artery Disease/diagnostic imaging , Vascular Calcification/diagnostic imaging , Aged , Aged, 80 and over , COVID-19/epidemiology , Coronary Artery Disease/epidemiology , Diabetes Mellitus/epidemiology , Disease Progression , Dyslipidemias/epidemiology , Female , Hospitalization , Humans , Hypertension/epidemiology , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Sex Factors , Smoking/epidemiology , Time Factors , Tomography, X-Ray Computed , Vascular Calcification/epidemiology
10.
Sci Rep ; 11(1): 10727, 2021 05 21.
Article in English | MEDLINE | ID: covidwho-1238019

ABSTRACT

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).


Subject(s)
Adrenal Cortex Hormones/administration & dosage , COVID-19/therapy , Hospitalization , Respiration, Artificial , SARS-CoV-2 , COVID-19/diagnostic imaging , COVID-19/pathology , Critical Illness , Female , Humans , Male , Middle Aged , Retrospective Studies
11.
JPRN; 11/11/2020; TrialID: JPRN-jRCTs031200196
Clinical Trial Register | ICTRP | ID: ictrp-JPRN-jRCTs031200196

ABSTRACT

Condition:

Coronavirus Disease 2019 (COVID-19)
COVID-19

Intervention:

10 day treatment with the combination usage of favipiravir, camostat mesilate and inhaled ciclesonide

Primary outcome:

Length of hospital stay

Criteria:

Inclusion criteria: 1) Patients who have given written consent to participate in the study
2) age > 20 years old
3) SARS-CoV-2 PCR or LAMP test positive or COVID-19 confirmed by the diagnostic test which is approved by the Ministry of Health, Labor and Welfare
4) Patients with COVID-19 pneumonia on chest CT scan
5) Patients who can admit on the hospital at least 10 days during treatment
6) Patients who can use ciclesonide inhaler
7) Pregnancy test-negative

Exclusion criteria: 1) Patients who had been already treated with ceratain drug for COVID-19
2) Patients diagnosed with relapse or 2nd infection of COVID-19
3) Patiens with obvious other respiratory infection
4) Patients having cardiac dysfunctions such as congestive heart failure
5) Patients having severe liver dysfunction such as Child-Pugh C state
6) Patients having renal dysfunction requiring dialysis
7) Patients having immuno deficiency such as HIV infection
8) Patients having disorders of consciousness such as disorientation
9) Patients using the drug of immuno suppression
10) Patients using steroid inhaler
11) Patients who are pregnant or who may be pregnant
12) Patients who cannot use contraceptive
13) Male patients having a partner who agree with the usage of contraceptive
14) Patients with hereditary xanthineuria
15) Patients with Patients with hypouricemia or xanthine urinary stone
16) Patients with retractable gout or hyperuricemia
17) Patents with allergy of favipiravir, camostat mesilate or inhaled ciclesonide
18) Patients in severe disease state with artificial ventilation, or ECMO in intensive care unit
19) Patients who are considered inappropriate for inclusion in the study by the investigator

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