Darius Beh

Coronavirus disease 2019 (COVID-19) has been associated with various neurologic manifestations, including anosmia, acute ischemic stroke, Guillain-Barré syndrome, and encephalopathy.c During the COVID-19 pandemic, physicians seeing patients with these neurologic manifestations should consider COVID-19 as a differential diagnosis to prevent diagnostic delays and further transmission of disease.c Cranial nerve involvement could potentially be associated with COVID-19. Oy-sters cWhen a patient presents with isolated facial nerve palsy, a careful neurologic examination is required to rule out concomitant cranial nerve involvement (such as trigeminal nerve or vestibulocochlear nerve palsies) that would suggest alternative localization sites.c Facial nerve palsy is commonly due to, or associated with, a viral infection and should not be assumed to be idiopathic.c Investigations such as CSF analysis and MRI can be helpful in evaluating for CNS infection, inflammation, and other secondary causes.In early March 2020, a previously healthy 27-year-old man was admitted directly to the isolation ward of a tertiary health care center in Singapore with symptoms of myalgia, cough, and fever for 4 days.His symptoms started the day after he returned from Spain.He also complained of a new left-sided throbbing headache with no associated photophobia or neck stiffness.On examination, he had mild bilateral conjunctival injection and respiratory examination was unremarkable.He did not have any focal neurologic deficits.Chest radiography did not show any infiltrates and a nasopharyngeal swab returned positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on real-time reverse transcription PCR (RT-PCR) assay.On the third day of hospitalization (day 6 of illness), the patient developed left facial weakness, which was preceded by left retro-auricular pain and dysgeusia.Neurologic examination revealed involvement of the left frontalis, orbicularis oculi, buccinator, and orbicularis oris, consistent with a left lower motor neuron type facial nerve palsy.Corneal reflex was present, and there was no hyperacusis.The rest of the neurologic examination was unremarkable and his reflexes were normal.Kernig and Brudzinski signs were negative.There were no associated vesicles in the outer ear nor was there any parotid swelling.HIV screen was negative.CSF analysis did not show any pleocytosis, and glucose and protein levels were normal.CSF PCR for herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus, and cytomegalovirus and RT-PCR for SARS-CoV-2 were negative.MRI of the brain showed enhancement of the left facial nerve (figure, A).He was started on prednisone and valacyclovir for treatment of Bell palsy.

Objectives: The vast majority of COVID-19 cases in Singapore have occurred amongst migrant workers. This paper examined trends in the hospitalised cases and tested the assumption that the low severity of disease was related to the relatively young affected population. Methods: All patients with PCR-positive SARS-CoV-2 admitted from February to April 2020 were divided into: (i) imported cases, (ii) locally-transmitted cases outside migrant worker dormitories and (iii) migrant worker dormitory cases. They were examined for underlying comorbidities, clinical progress and outcomes. Results: Imported cases (n = 29) peaked in mid-March 2020, followed by local cases (n = 100) in mid-April 2020; migrant worker cases (n = 425) continued to increase in late April 2020. Migrant worker cases were younger, had few medical comorbidities and less severe disease. As the migrant worker cases increased, the proportion of patients with pneumonia decreased, whilst patients presenting earlier in their illness and asymptomatic disease became more common. Conclusion: Singapore experienced a substantial shift in the population at risk of severe COVID-19. Successful control in the community protected an aging population. Large migrant worker dormitory outbreaks occurred, but the disease incurred was less severe, resulting in Singapore having one of the lowest case fatality rates in the world.

Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state-the transition state-that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/μl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples.

Accessible and adaptable nucleic acid diagnostics remains a critical challenge in managing the evolving COVID-19 pandemic. Here, an integrated molecular nanotechnology that enables direct and programmable detection of SARS-CoV-2 RNA targets in native patient specimens is reported. Termed synergistic coupling of responsive equilibrium in enzymatic network (SCREEN), the technology leverages tunable, catalytic molecular nanostructures to establish an interconnected, collaborative architecture. SCREEN mimics the extraordinary organization and functionality of cellular signaling cascades. Through programmable enzyme-DNA nanostructures, SCREEN activates upon interaction with different RNA targets to initiate multi-enzyme catalysis; through system-wide favorable equilibrium shifting, SCREEN directly transduces a single target binding into an amplified electrical signal. To establish collaborative equilibrium coupling in the architecture, a computational model that simulates all reactions to predict overall performance and optimize assay configuration is developed. The developed platform achieves direct and sensitive RNA detection (approaching single-copy detection), fast response (assay reaction is completed within 30 min at room temperature), and robust programmability (across different genetic loci of SARS-CoV-2). When clinically evaluated, the technology demonstrates robust and direct detection in clinical swab lysates to accurately diagnose COVID-19 patients.

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.