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1.
Am J Trop Med Hyg ; 102(5): 940-942, 2020 05.
Article in English | MEDLINE | ID: covidwho-2066918

ABSTRACT

This case report underlines the appearance of a "walking pneumonia" in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections , Lung/diagnostic imaging , Pandemics , Pneumonia, Viral , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Female , Humans , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Radiography , SARS-CoV-2
2.
Diagnostics (Basel) ; 12(9)2022 Aug 26.
Article in English | MEDLINE | ID: covidwho-2005961

ABSTRACT

BACKGROUND: Quantitative radiological scores for the extent and severity of pulmonary infiltrates based on chest radiography (CXR) and computed tomography (CT) scan are increasingly used in critically ill invasively ventilated patients. This study aimed to determine and compare the prognostic capacity of the Radiographic Assessment of Lung Edema (RALE) score and the chest CT Severity Score (CTSS) in a cohort of invasively ventilated patients with acute respiratory distress syndrome (ARDS) due to COVID-19. METHODS: Two-center retrospective observational study, including consecutive invasively ventilated COVID-19 patients. Trained scorers calculated the RALE score of first available CXR and the CTSS of the first available CT scan. The primary outcome was ICU mortality; secondary outcomes were duration of ventilation in survivors, length of stay in ICU, and hospital-, 28-, and 90-day mortality. Prognostic accuracy for ICU death was expressed using odds ratios and Area Under the Receiver Operating Characteristic curves (AUROC). RESULTS: A total of 82 patients were enrolled. The median RALE score (22 [15-37] vs. 26 [20-39]; p = 0.34) and the median CTSS (18 [16-21] vs. 21 [18-23]; p = 0.022) were both lower in ICU survivors compared to ICU non-survivors, although only the difference in CTSS reached statistical significance. While no association was observed between ICU mortality and RALE score (OR 1.35 [95%CI 0.64-2.84]; p = 0.417; AUC 0.50 [0.44-0.56], this was noticed with the CTSS (OR, 2.31 [1.22-4.38]; p = 0.010) although with poor prognostic capacity (AUC 0.64 [0.57-0.69]). The correlation between the RALE score and CTSS was weak (r2 = 0.075; p = 0.012). CONCLUSIONS: Despite poor prognostic capacity, only CTSS was associated with ICU mortality in our cohort of COVID-19 patients.

3.
EClinicalMedicine ; 45: 101323, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1828408

ABSTRACT

Background: Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. Methods: This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg, 1 µg+CpG1018 (a toll-like receptor 9 agonist), 3 µg, 3 µg+CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422). Findings: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 international units per mL (IU/mL; 1 µg, 95% confidence interval (CI) 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥ 4-fold increase over baseline. Interpretation: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2. Funding: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).

4.
Infect Dis Ther ; 11(1): 231-248, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1682185

ABSTRACT

INTRODUCTION: Many immunomodulators have been studied in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). However, data identifying the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank immunomodulators in the treatment of COVID-19 according to their efficacy and safety. METHODS: Published and peer-reviewed randomized controlled trials assessing the efficacy of immunomodulators in hospitalized patients with COVID-19 were searched up to June 30, 2021. Direct and network meta-analyses were applied to assess the outcomes. The probability of efficacy and safety was estimated, and the drugs were awarded a numerical ranking. RESULTS: Twenty-six studies were eligible. Compared with standard of care, dexamethasone and tocilizumab had significantly lower mortality rates with pooled risk ratios (RRs) of 0.91 (95% confidence interval [CI] 0.84-0.99) and 0.88 (95% CI 0.82-0.96), respectively. Meanwhile, the most effective corticosteroid, interleukin-6 antagonist, and Janus kinase (JAK) inhibitor were hydrocortisone, sarilumab, and ruxolitinib, respectively. However, when superimposed infection was considered, ruxolitinib was the best treatment followed by baricitinib. Moreover, methylprednisolone had the worst combined efficacy and safety among the examined treatments. CONCLUSIONS: Overall, immunomodulators were more effective than standard of care. Important differences exist among immunomodulators regarding both efficacy and safety in favor of ruxolitinib and baricitinib. Further well-conducted randomized controlled trials should focus on JAK inhibitors. Methylprednisolone use should be discouraged because of its poor efficacy and high risk of superimposed infection. TRIAL REGISTRATION: PROSPERO registration identifier CRD 42021257421.

5.
Front Med (Lausanne) ; 8: 772056, 2021.
Article in English | MEDLINE | ID: covidwho-1650404

ABSTRACT

Background: The radiographic assessment for lung edema (RALE) score has an association with mortality in patients with acute respiratory distress syndrome (ARDS). It is uncertain whether the RALE scores at the start of invasive ventilation or changes thereof in the next days have prognostic capacities in patients with COVID-19 ARDS. Aims and Objectives: To determine the prognostic capacity of the RALE score for mortality and duration of invasive ventilation in patients with COVID-19 ARDS. Methods: An international multicenter observational study included consecutive patients from 6 ICUs. Trained observers scored the first available chest X-ray (CXR) obtained within 48 h after the start of invasive ventilation ("baseline CXR") and each CXRs thereafter up to day 14 ("follow-up CXR"). The primary endpoint was mortality at day 90. The secondary endpoint was the number of days free from the ventilator and alive at day 28 (VFD-28). Results: A total of 350 CXRs were scored in 139 patients with COVID-19 ARDS. The RALE score of the baseline CXR was high and was not different between survivors and non-survivors (33 [24-38] vs. 30 [25-38], P = 0.602). The RALE score of the baseline CXR had no association with mortality (hazard ratio [HR], 1.24 [95% CI 0.88-1.76]; P = 0.222; area under the receiver operating characteristic curve (AUROC) 0.50 [0.40-0.60]). A change in the RALE score over the first 14 days of invasive ventilation, however, had an independent association with mortality (HR, 1.03 [95% CI 1.01-1.05]; P < 0.001). When the event of death was considered, there was no significant association between the RALE score of the baseline CXR and the probability of being liberated from the ventilator (HR 1.02 [95% CI 0.99-1.04]; P = 0.08). Conclusion: In this cohort of patients with COVID-19 ARDS, with high RALE scores of the baseline CXR, the RALE score of the baseline CXR had no prognostic capacity, but an increase in the RALE score in the next days had an association with higher mortality.

6.
Am J Trop Med Hyg ; 105(1): 73-80, 2021 05 03.
Article in English | MEDLINE | ID: covidwho-1212055

ABSTRACT

Exuberant inflammation manifesting as a "cytokine storm" has been suggested as a central feature in the pathogenesis of severe coronavirus disease 2019 (COVID-19). This study investigated two prognostic biomarkers, the high mobility group box 1 (HMGB1) and interleukin-6 (IL-6), in patients with severe COVID-19 at the time of admission in the intensive care unit (ICU). Of 60 ICU patients with COVID-19 enrolled and analyzed in this prospective cohort study, 48 patients (80%) were alive at ICU discharge. HMGB1 and IL-6 plasma levels at ICU admission were elevated compared with a healthy control, both in ICU nonsurvivors and ICU survivors. HMGB1 and IL-6 plasma levels were higher in patients with a higher Sequential Organ Failure Assessment (SOFA) score (> 10), and the presence of septic shock or acute kidney injury. HMGB1 and IL-6 plasma levels were also higher in patients with a poor oxygenation status (PaO2/FiO2 < 150 mm Hg) and a longer duration of ventilation (> 7 days). Plasma HMGB1 and IL-6 levels at ICU admission also correlated with other prognostic markers, including the maximum neutrophil/lymphocyte ratio, D-dimer levels, and C-reactive protein levels. Plasma HMGB1 and IL-6 levels at ICU admission predicted ICU mortality with comparable accuracy to the SOFA score and the COVID-GRAM risk score. Higher HMGB1 and IL-6 were not independently associated with ICU mortality after adjustment for age, gender, and comorbidities in multivariate analysis models. In conclusion, plasma HMGB1 and IL6 at ICU admission may serve as prognostic biomarkers in critically ill COVID-19 patients.


Subject(s)
COVID-19/metabolism , COVID-19/pathology , Critical Illness , HMGB1 Protein/metabolism , Interleukin-6/metabolism , SARS-CoV-2 , Biomarkers/blood , Gene Expression Regulation/immunology , HMGB1 Protein/genetics , Humans , Intensive Care Units , Interleukin-6/genetics
7.
Am J Trop Med Hyg ; 104(5): 1676-1686, 2021 Mar 11.
Article in English | MEDLINE | ID: covidwho-1128113

ABSTRACT

Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6-12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.


Subject(s)
COVID-19/complications , Hypoxia/therapy , Prone Position/physiology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Acute Disease , Continuous Positive Airway Pressure , Health Personnel , Humans , Wakefulness
8.
Am J Trop Med Hyg ; 103(1): 48-54, 2020 07.
Article in English | MEDLINE | ID: covidwho-339930

ABSTRACT

Since late December 2019, the world has been challenged with an outbreak of COVID-19. In Thailand, an upper middle-income country with a limited healthcare infrastructure and restricted human resources, nearly 3,000 confirmed COVID-19 cases have been reported as of early May 2020. Public health policies aimed at preventing new COVID-19 cases were very effective in halting the pandemic in Thailand. Case fatality in Thailand has been low (1.7%), at least in part due to early stratification according to risk of disease severity and timely initiation of supportive care with affordable measures. We present our initial experience with COVID-19 in Thailand, focusing on several aspects that may have played a crucial role in curtailment of the pandemic, and elements of care for severely ill COVID-19 patients, including stratification, isolation, and affordable diagnostic approaches and supportive care measures. We also discuss local considerations concerning some proposed experimental treatments.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Critical Care/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , Adult , Aged , Airway Management , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Female , Health Resources/supply & distribution , Humans , Immunomodulation , Infection Control , Intensive Care Units/organization & administration , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Patient Isolation , SARS-CoV-2 , Thailand/epidemiology
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