Post-COVID-19 health-care utilization: one year after the 2020 first wave in Brunei Darussalam.

Objective: Patients who recover from coronavirus disease (COVID-19) infection are at risk of long-term health disorders and may require prolonged health care. This retrospective observational study assesses the number of health-care visits before and after COVID-19 infection in Brunei Darussalam. Methods: COVID-19 cases from the first wave with 12 months of follow-up were included. Health-care utilization was defined as health-care visits for consultations or investigations. Post-COVID condition was defined using the World Health Organization definition. Results: There were 132 cases; 59.1% were male and the mean age was 37.1 years. The mean number of health-care visits 12 months after recovery from COVID-19 (123 cases, 93.2%; mean 5.0 ± 5.2) was significantly higher than the prior 12 months (87 cases, 65.9%, P < 0.001; mean 3.2 ± 5.7, P < 0.001). There was no significant difference when scheduled COVID-19 visits were excluded (3.6 ± 4.9, P = 0.149). All 22 cases with moderate to critical disease recovered without additional health-care visits apart from planned post-COVID-19 visits. Six patients had symptoms of post-COVID condition, but none met the criteria for diagnosis or had alternative diagnoses. Discussion: There were significantly more health-care visits following recovery from COVID-19. However, this was due to scheduled post-COVID-19 visits as per the national management protocol. This protocol was amended before the second wave to omit post-COVID-19 follow-up, except for complicated cases or cases with no documented radiological resolution of COVID-19 pneumonia. This will reduce unnecessary health-care visits and conserve precious resources that were stretched to the limit during the pandemic.

Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY).

Background: Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes. Methods: COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups. Results: A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51-66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34-49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6-11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99-220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample. Conclusion: We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.

Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY)

Background Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations;Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes. Methods COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups. Results A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51–66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34–49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6–11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99–220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%);with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample. Conclusion We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.

COVID-19 symptom duration: associations with age, severity and vaccination status in Brunei Darussalam, 2021.

Objective: This retrospective, cross-sectional, observational study assessed the duration of coronavirus disease 2019 (COVID-19) symptoms during the second wave in Brunei Darussalam. Methods: Data from COVID-19 cases admitted to the National Isolation Centre during 7-30 August 2021 were included in the study. Symptom onset and daily symptom assessments were entered into a database during hospitalization and disease was categorized by severity. The time between symptom onset and hospital admission, the duration of symptoms and length of hospitalization were assessed separately by age group, disease severity and vaccination status using one-way analysis of variance with Bonferroni post hoc corrections. Results: Data from 548 cases were included in the study: 55.7% (305) of cases were male, and cases had a mean age of 33.7 years. Overall, 81.3% (446) reported symptoms at admission (mean number of symptoms and standard deviation: 2.8 ± 1.6), with cough (59.1%; 324), fever (38.9%; 213) and sore throat (18.4%; 101) being the most common. Being older, having more severe disease and being unvaccinated were significantly associated with the time between symptom onset and hospital admission, symptom duration and length of hospitalization. Discussion: Knowing which factors predict the duration of COVID-19 symptoms can help in planning management strategies, such as the duration of isolation, predict the length of hospitalization and treatment, and provide more accurate counselling to patients regarding their illness.

Primary pilocytic astrocytoma of the cerebellopontine angle in pediatric patient with neurofibromatosis type 1: a case report.

Background: Cerebellopontine angle tumor (CPA) in pediatrics is rare as compared to adults. We describe a case of pediatric pilocytic astrocytoma presented as a right CPA mass with a concurrent clinical diagnosis of neurofibromatosis type 1 (NF1). Case presentation: A 14-year-old boy with a newly diagnosed hypertension presented with a short history of headache and blurring vision. Neurological examination revealed bilateral papilloedema, partial right third nerve palsy and mild sensorineuronal hearing deficits. Skin examination identified multiple café au lait spots with cutaneous neurofibromas. Preoperative neuroimaging suggested the diagnosis of an extraaxial CPA mass consistent with meningioma, with obstructive hydrocephalus. A left ventriculoperitoneal shunt was inserted and the child was subjected for a suboccipital retrosigmoid approach for tumor resection. The histopathological features, however, were typical for pilocytic astrocytoma. Conclusions: A careful evaluation of the clinical presentation and radiological images of CPA lesions is necessary prior to surgical embarkment. To the best of our knowledge, this case is the first report of pilocytic astrocytoma in the CPA in pediatric with NF1.

Challenges during the second wave of COVID-19 in Brunei Darussalam: National Isolation Centre to National COVID-19 Hospital.

Problem: Soon after the start of the second wave of coronavirus disease 2019 (COVID-19) in Brunei Darussalam, which was confirmed to be due to the more infectious Delta strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it became apparent that the National Isolation Centre (NIC) was not coping. Context: The NIC was the only isolation and treatment centre for COVID-19 in Brunei Darussalam. During the first wave and the first 11 days of the second wave, all confirmed cases were admitted to the NIC for isolation and treatment in line with the management strategy to isolate all confirmed cases to control the outbreak. Action: The Ministry of Health opened five community isolation centres and two quarantine centres to divert asymptomatic and mild cases from the NIC. The community isolation centres also functioned as triage centres for the NIC, and the quarantine centres accommodated recovered patients who did not have their own quarantine facilities. Outcome: The community isolation and quarantine centres diverted cases from the NIC and enabled recovered cases to be transferred to these step-down facilities. This reduced the NIC's occupancy to a safe level and enabled the reorganization of the NIC to function as a treatment centre and a national COVID-19 hospital. Discussion: During any disease outbreak, health facilities must be prepared to adapt to changing situations. Strong leadership, stakeholder commitments, teamwork and constant communication are important in this process.

Screening of potent phytochemical inhibitors against SARS-CoV-2 protease and its two Asian mutants.

BACKGROUND: COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. OBJECT: The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. METHODS: Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y7M). The predicted lead compound was further subjected to Molecular Dynamics (MD) simulation to check the stability of the leads compound with the evolution of time. RESULTS: In pharmacophore-based virtual screening, 2,361 compounds were retained out of 30,927. In the structure-based screening, the lead compounds were filtered based on their docking scores. Among the 2,360 compounds, 12 lead compounds were selected based on their docking score. Kazinol T with NPASS ID: NPC474104 showed the highest docking score of -14.355 and passed criteria of Lipinski's drug-like parameters. Monitoring ADMET properties, Kazinol T showed its safety for consumption. Docking of Kazinol T with two Asian mutants (R60C and I152V) showed variations in binding and energy parameters. Normal mode analysis for ligand-bound and unbound form of protease along with its mutants, revealed displacement and correlation parameters for C-alpha atoms. MD simulation results showed that all ligand-protein complexes remained intact and stable in a dynamic environment with negative Gibbs free energy. CONCLUSIONS: The natural product Kazinol T was a predicted lead compound against the main protease of SARS-CoV-2 and will be the possible treatment for COVID-19.

Vaccine Design from the Ensemble of Surface Glycoprotein Epitopes of SARS-CoV-2: An Immunoinformatics Approach.

The present study aimed to work out a peptide-based multi-epitope vaccine against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We predicted different B-cell and T-cell epitopes by using the Immune Epitopes Database (IEDB). Homology modeling of the construct was done using SWISS-MODEL and then docked with different toll-like-receptors (TLR4, TLR7, and TLR8) using PatchDock, HADDOCK, and FireDock, respectively. From the overlapped epitopes, we designed five vaccine constructs C1-C5. Based on antigenicity, allergenicity, solubility, different physiochemical properties, and molecular docking scores, we selected the vaccine construct 1 (C1) for further processing. Docking of C1 with TLR4, TLR7, and TLR8 showed striking interactions with global binding energy of -43.48, -65.88, and -60.24 Kcal/mol, respectively. The docked complex was further simulated, which revealed that both molecules remain stable with minimum RMSF. Activation of TLRs induces downstream pathways to produce pro-inflammatory cytokines against viruses and immune system simulation shows enhanced antibody production after the booster dose. In conclusion, C1 was the best vaccine candidate among all designed constructs to elicit an immune response SARS-CoV-2 and combat the coronavirus disease (COVID-19).

Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused about 2 million infections and is responsible for more than 100,000 deaths worldwide. To date, there is no specific drug registered to combat the disease it causes, named coronavirus disease 2019 (COVID-19). In the current study, we used an in silico approach to screen natural compounds to find potent inhibitors of the host enzyme transmembrane protease serine 2 (TMPRSS2). This enzyme facilitates viral particle entry into host cells, and its inhibition blocks virus fusion with angiotensin-converting enzyme 2 (ACE2). This, in turn, restricts SARS-CoV-2 pathogenesis. A three-dimensional structure of TMPRSS2 was built using SWISS-MODEL and validated by RAMPAGE. The natural compounds library Natural Product Activity and Species Source (NPASS), containing 30,927 compounds, was screened against the target protein. Two techniques were used in the Molecular Operating Environment (MOE) for this purpose, i.e., a ligand-based pharmacophore approach and a molecular docking-based screening. In total, 2140 compounds with pharmacophoric features were retained using the first approach. Using the second approach, 85 compounds with molecular docking comparable to or greater than that of the standard inhibitor (camostat mesylate) were identified. The top 12 compounds with the most favorable structural features were studied for physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties. The low-molecular-weight compound NPC306344 showed significant interaction with the active site residues of TMPRSS2, with a binding energy score of −14.69. Further in vitro and in vivo validation is needed to study and develop an anti-COVID-19 drug based on the structures of the most promising compounds identified in this study.