Employment of a high-throughput functional assay to define the critical factors that influence vaccine-induced, cross-variant neutralizing antibodies for SARS-CoV-2. (preprint)

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19.

Defining factors that influence vaccine-induced, cross-variant neutralizing antibodies for SARS-CoV-2 in Asians (preprint)

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced neutralizing antibody responses for key variants in an Asian volunteer cohort. We demonstrate a reduction in neutralizing antibody titres across all groups six months post-vaccination and show a marked reduction in the serological binding and neutralizing response targeting Omicron compared to other viral variants. We also highlight the increase in cross-protective neutralizing antibody responses against Omicron induced by a third dose (booster) of vaccine. These data illustrate how key virological factors such as immune escape mutation combined with host factors such as age and sex of the vaccinated individuals influence the strength and duration of cross-protective serological immunity for COVID-19.

Durable T cell responses contrast with faster antibody waning in BNT162b2-vaccinated elderly at 6 month (preprint)

Efficient COVID-19 vaccines have been developed in record time. Here, we present findings from a comprehensive and integrated analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 mRNA vaccine. Two vaccine doses induced high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of delta variant was less efficient than that of the Wuhan strain. Age stratified analyses identified a group of low antibody responders where individuals ≥ 60 years were overrepresented. Waning of the antibody and cellular responses was observed in 30% of the vaccinees after six months. However, age did not influence the waning of these responses. Taken together, while individuals ≥ 60 years old took longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at six months post-vaccination. However, the higher proportion of older individuals in the group of antibody low responders and the lower antibody reactivity the Delta variant call for a booster immunization to increase immune responses and protection.

Anosmia in SARS-CoV-2 Patients: a Retrospective Study (preprint)

BackgroundPost viral anosmia has been reported in human coronavirus infections. In this current pandemic, olfactory dysfunction (OD) has emerged as a common key presenting symptom of COVID-19 infection. In this study, we describe OD assessment in the inpatient setting of patients both suspected of and with confirmed COVID-19 infection via University of Pennsylvania Smell Identification Test (UPSIT) objective assessment and a simple self-reported 3-item questionnaire.MethodsThirty patients admitted to the isolation wards of the National University Hospital, Singapore for either suspected or confirmed COVID-19 infection from April to May 2020 were recruited to this study. 10 patients who tested negative for SARS-CoV-2 were recruited as control subjects. The 20 patients with COVID-19 infection were divided into two groups (10 had olfactory testing performed during the first week of illness, 10 in the second week of illness). A simple 3-question survey was administered to each participant - to rank the severity, state the onset and duration of their hyposmia. Olfactory testing was performed using an English version of the UPSIT.ResultsLoss of smell was reported in 2 participants from the control group, 6 participants from the in the first week of illness and 5 participants from the second week of illness. Two COVID-19 patients have anosmia on the UPSIT. COVID-19 patients were more likely to have severe hyposmia or anosmia by objective assessment, a difference that was statistically significant (P = 0.0485). The differences in degree of OD among COVID-19 patients in their first and second week of illness were not statistically significant (P= 0.6563).ConclusionSelf-reported anosmia was higher among COVID-19 patients compared to controls who were admitted to isolation wards for respiratory symptoms but were tested negative for SARS-CoV-2 infection. On objective assessment by the UPSIT, COVID-19 patients were found to have higher rates of severe hyposmia or anosmia, a difference that was statistically significant (P = 0.0485). A limitation of this study is the odorants used in UPSIT which may be less familiar to the primarily Asian participants in this study, owing to cultural differences. 

Epidemiological and Clinical Characteristics of Non-Severe and Severe Pediatric and Adult COVID-19 Patients Across Different Geographical Regions: A Systematic Review and Meta-Analysis of Observational Studies (preprint)

Background: An understanding of key differences in epidemiological and clinical characteristics between geographical regions and populations is limited. This systematic review and meta-analysis aims to compare clinical presentation, outcomes, and care management of different COVID-19 patient groups globally. Methods: The search strategy involved peer-reviewed studies published between 1st January and 9th April 2020 in Pubmed, Google scholar, and Chinese Medical Journal database. Pooled prevalence and means with 95% confidence intervals were computed using a random effects model. Subgroup analyses were performed between different geographies, clinical severities, and age groups. Results: A total of 77 publications were identified after full-text screening. Subsequently, data from 40 non-overlapping studies, comprising 4,884 patients from seven countries, were summarized. Wuhan patients were older (mean age: 54·3) and had higher rates of dyspnea (39·5%), compared to patients in other cities of China (mean age: 43·6; dyspnea: 9·7%) and outside of China (mean age: 50·5; dyspnea: 13·4%). Myalgia, fatigue, acute respiratory distress syndrome (ARDS) and fatalities were also significantly more prevalent amongst Wuhan patients compared to other geographical subgroups (p<0·01). There was a significant dose-response increase in prevalence of diabetes, D-dimer, white blood cells, neutrophil levels and ARDS from non-severe to severe and fatal outcomes (p<0·01). A higher proportion of asymptomatic cases in children (20%) as compared to adults (2.4%) was observed in Chinese hospitals. Interpretation: COVID-19 patients had more severe clinical disease in Wuhan compared to patients outside of Wuhan and beyond China. Pediatric cases had less severe disease compared to adults. Biomarkers at admission may be useful for prognosis among COVID-19 patients.Funding Statement: Ministry of Defence, SingaporeDeclaration of Interests: The authors declare no competing interests.