Pathogen genomic surveillance status among lower resource settings in Asia.

Asia remains vulnerable to new and emerging infectious diseases. Understanding how to improve next generation sequencing (NGS) use in pathogen surveillance is an urgent priority for regional health security. Here we developed a pathogen genomic surveillance assessment framework to assess capacity in low-resource settings in South and Southeast Asia.

Advancing pathogen genomics in resource-limited settings.

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health and clinical decision making. Although widely available in developed countries, the application of pathogen genomics among low-resource, high-disease burden settings remains at an early stage. In these contexts, tailored approaches for integrating pathogen genomics within infectious disease control programs will be essential to optimize cost efficiency and public health impact.

Early pathogenesis profiles across SARS-CoV-2 variants in K18-hACE2 mice revealed differential triggers of lung damages.

The on-going COVID-19 pandemic has given rise to SARS-CoV-2 clades and variants with differing levels of symptoms and severity. To this end, we aim to systematically elucidate the changes in the pathogenesis as SARS-CoV-2 evolved from ancestral to the recent Omicron VOC, on their mechanisms (e.g.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Pediatric Age on Delta Variant Household Transmission.

Background: In Singapore, quarantine of all close contacts with entry and exit polymerase chain reaction testing enabled evaluation of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and pediatric age on transmission of the Delta variant.

Methods: This retrospective cohort study included all household close contacts between 1 March 2021 and 31 August 2021.

Results: Among 8470 Delta variant-exposed contacts linked to 2583 indices, full-vaccination of the index with BNT162b2 or mRNA-1273 was associated with reduction in acquisition by contacts (adjusted odds ratio [aOR], 0.

Epidemiological, Clinical, and Phylogenetic Characteristics of the First SARS-CoV-2 Transmission in a Nursing Home of Singapore: A Prospective Observational Investigation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has resulted in a significant burden among nursing home facilities globally. This prospective observational cohort study aims to define the potential sources of introduction and characteristics of SARS-CoV-2 transmission of the first nursing home facility in Singapore. An epidemiological serial point-prevalence survey of SARS-CoV-2 was conducted among 108 residents and 56 healthcare staff (HCS).

Clinical and Virological Features of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern: A Retrospective Cohort Study Comparing B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.2 (Delta).

Background: The impact of SARS-CoV-2 variants of concern (VOCs) on disease severity is unclear. In this retrospective study, we compared the outcomes of patients infected with B.1.

Viral Load of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Respiratory Aerosols Emitted by Patients With Coronavirus Disease 2019 (COVID-19) While Breathing, Talking, and Singing.

Background: Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading events suggest that aerosols play an important role in driving the coronavirus disease 2019 (COVID-19) pandemic. To better understand how airborne SARS-CoV-2 transmission occurs, we sought to determine viral loads within coarse (>5 μm) and fine (≤5 μm) respiratory aerosols produced when breathing, talking, and singing.

Methods: Using a G-II exhaled breath collector, we measured viral RNA in coarse and fine respiratory aerosols emitted by COVID-19 patients during 30 minutes of breathing, 15 minutes of talking, and 15 minutes of singing.

Factors influencing SARS-CoV-2 transmission and outbreak control measures in densely populated settings.

Starting with a handful of SARS-CoV-2 infections in dormitory residents in late March 2020, rapid transmission in their dense living environments ensued and by October 2020, more than 50,000 acute infections were identified across various dormitories in Singapore. The aim of the study is to identify combination of factors facilitating SARS-CoV-2 transmission and the impact of control measures in a dormitory through extensive epidemiological, serological and phylogenetic investigations, supported by simulation models. Our findings showed that asymptomatic cases and symptomatic cases who did not seek medical attention were major drivers of the outbreak.

Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study.

Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available.

Methods: We conducted an observational cohort study at seven public hospitals in Singapore.

Human neutralising antibodies elicited by SARS-CoV-2 non-D614G variants offer cross-protection against the SARS-CoV-2 D614G variant.

Objectives: The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralise against the G614 variant.

Methods: Antibody profiling against the SARS-CoV-2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS-CoV-2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID-19 patients with known D614G status ( = 44 infected with D614,  = 6 infected with G614,  = 7 containing all other clades: O, S, L, V, G, GH or GR).

Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity.

Background: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

Methods: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81).

Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection.

Methods: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore.

Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2.

To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.

Burden and Cost of Hospitalization for Respiratory Syncytial Virus in Young Children, Singapore.

Respiratory syncytial virus (RSV) is the most common cause of pediatric acute lower respiratory tract infection worldwide. Detailed data on the health and economic burden of RSV disease are lacking from tropical settings with year-round RSV transmission. We developed a statistical and economic model to estimate the annual incidence and healthcare cost of medically attended RSV disease among young children in Singapore, using Monte Carlo simulation to account for uncertainty in model parameters.

Imported Monkeypox, Singapore.

In May 2019, we investigated monkeypox in a traveler from Nigeria to Singapore. The public health response included rapid identification of contacts, use of quarantine, and postexposure smallpox vaccination. No secondary cases were identified.

Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has spread globally with sustained human-to-human transmission outside China.

Objective: To report the initial experience in Singapore with the epidemiologic investigation of this outbreak, clinical features, and management.

Design, Setting, And Participants: Descriptive case series of the first 18 patients diagnosed with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection at 4 hospitals in Singapore from January 23 to February 3, 2020; final follow-up date was February 25, 2020.