The asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in households: A systematic review (preprint)

Background Understanding the clinical spectrum of SARS-CoV-2 infection, including the asymptomatic fraction, is important as asymptomatic individuals are still able to infect other individuals and contribute to ongoing transmission. The WHO Unity Household transmission investigation (HHTI) protocol provides a platform for the prospective and systematic collection of high-quality clinical, epidemiological, serological, and virological data from SARS-CoV-2 confirmed cases and their household contacts. These data can be used to understand key severity and transmissibility parameters - including the asymptomatic proportion - in relation to local epidemic context and help inform public health response. Methods We aimed to estimate the asymptomatic proportion of SARS-CoV-2 Omicron-variant infections in Unity-aligned HHTIs. We conducted a systematic review and meta-analysis in alignment with the PRISMA 2020 guidelines and registered our systematic review on PROSPERO (CRD42022378648). We searched EMBASE, Web of Science, MEDLINE, and bioRxiv and medRxiv from 1 November 2021 to 22 August 2023. Results We identified 8,368 records, of which 98 underwent full text review. We identified only three studies for data extraction, with substantial variation in study design and corresponding estimates of the asymptomatic proportion. As a result, we did not generate a pooled estimate or I2 metric. Conclusions The limited number of quality studies that we identified highlights the need for improved preparedness and response capabilities to facilitate robust HHTI implementation, analysis and reporting, to better inform national, regional and global risk assessments and policy making.

Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes (preprint)

Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be clearly defined. In this cross-sectional study, blood samples were obtained from three different sites in Australia from individuals with i) a resolved SARS-CoV-2 infection (and no persistent symptoms i.e. Recovered), ii) individuals with prolonged PASC-CVS and iii) SARS-CoV-2 negative individuals. Individuals with PASC-CVS, relative to Recovered individuals, had a blood transcriptomic signature associated with inflammation. This was accompanied by elevated levels of pro-inflammatory cytokines (IL-12, IL-1beta;, MCP-1 and IL-6) at approximately 18 months post-infection. These cytokines were present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of pluripotent stem cell derived cardiomyocytes in vitro. This effect was not observed in the presence of dexamethasone. Plasma proteomics demonstrated further differences between PASC-CVS and Recovered patients at approximately 18 months post-infection including enrichment of complement and coagulation associated proteins in those with prolonged cardiovascular symptoms. Together, these data provide a new insight into the role of chronic inflammation in PASC-CVS and present nanotechnology as a possible novel diagnostic approach for the condition.

Application of a High-Resolution Melt Assay for Monitoring SARS-CoV-2 Variants in Burkina Faso and Kenya (preprint)

The rapid emergence and global dissemination of SARS-CoV-2 highlighted a need for robust, adaptable surveillance systems. However, financial and infrastructure requirements for whole genome sequencing (WGS) mean most surveillance data have come from higher-resource geographies, despite unprecedented investment in sequencing in low-middle income countries (LMICs) throughout the SARS-CoV-2 pandemic. Consequently, the molecular epidemiology of SARS-CoV-2 in some LMICs is limited, and there is a need for more cost-accessible technologies to help close data gaps for surveillance of SARS-CoV-2 variants. To address this, we have developed two high-resolution melt curve (HRM) assays that target key variant-defining mutations in the SARS-CoV-2 genome, which give unique signature profiles that define different SARS-CoV-2 variants of concern (VOCs). Extracted RNA from SARS-CoV-2 positive samples collected from 205 participants (112 in Burkina Faso, 93 in Kenya) on the day of enrolment in the MALCOV study (Malaria as a Risk Factor for COVID-19) between February 2021 and February 2022 were analysed using our optimised HRM assays and compared to Next Generation Sequencing (NGS) on Oxford Nanopore MinION . With NGS as a reference, two HRM assays, HRM-VOC-1 and HRM-VOC-2, demonstrated sensitivity/specificity of 100%/99.29% and 92.86/99.39%, respectively, for detecting Alpha, 90.08%/100% and 92.31%/100% for Delta and 93.75%/100% and 100%/99.38% for Omicron. The assays described here provide a lower-cost approach (<$1 per sample) to conducting molecular epidemiology, capable of high-throughput testing. We successfully scaled up the HRM-VOC-2 assay to screen a total of 506 samples from which we were able to show the replacement of Alpha with the introduction of Delta and the replacement of Delta by the Omicron variant in this community in Kisumu, Kenya. These assays are readily adaptable and can focus on local epidemiological surveillance questions or be updated quickly to accommodate the emergence of a novel variant or adapt to novel and emerging pathogens.

Spatial proteomics identifies a novel CRTC-dependent viral sensing pathway that stimulates production of Interleukin-11 (preprint)

Appropriate cellular recognition of viruses is essential for the generation of effective innate and adaptive antiviral immunity. Viral sensors and their signalling components thus provide a crucial first line of host defence. Many exhibit subcellular relocalisation upon activation, triggering expression of interferon and antiviral genes. To identify novel signalling factors we analysed protein relocalisation on a global scale during viral infection. CREB Regulated Transcription Coactivators-2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon a diversity of viral stimuli, in diverse cell types. This movement was depended on Mitochondrial Antiviral Signalling Protein (MAVS), cyclo-oxygenase proteins and protein kinase A. We identify a key effect of transcription stimulated by CRTC2/3 translocation as production of the pro-fibrogenic cytokine interleukin-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2.

Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation (preprint)

The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Finally, we demonstrate that the N:G215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.

Exploring the Research Interest, Capacity and Culture of NHS Staff in South-East Scotland following the SARS-CoV-2 Pandemic: a Qualitative Study (preprint)

Background Research is a key driver in improving the quality of care in health settings. The UK Government has published its strategy to increase research within the National Health Service (NHS) and to implement lessons learned from the SARS-CoV-2 pandemic. We have investigated the current research interest, culture, and capacity amongst staff in one small, non-teaching regional Health Board in Scotland to determine how research activity may be increased and how attitudes to research may have changed following the recent pandemic.Methods Semi-structured interviews (n = 28) were conducted with staff of all grades exploring the research culture at an organisational, team and individual level. Topics included perceived barriers and facilitators for engaging in research activities and the impact of the SARS-CoV-2 pandemic on changes in attitude to research within the NHS. Interviews were audio recorded, transcribed verbatim, and analysed using thematic analysis.Results Respondents comprised 7 nurses/midwives, 6 doctors/dentists, 3 allied health professionals, 3 other therapeutic and 9 admin/support staff. Some staff had research written into their job descriptions. All respondents identified similar facilitators and barriers to undertaking research, irrespective of their role or experience with research. Four key themes affecting research capacity and capability were time, resources, culture, and communication. Responses varied between staff grades where those who had research embedded as part of their training and professional role expressed more accepting views to undertaking research. Issues identified were the provision of protected time, skills training, practical support from research facilitators, active encouragement by managers of all grades, improved communication, the development of ‘champions’ working in clinical teams and the adoption of a research strategy at Board level. The pandemic had a negative impact on research activity but many respondents expressed an increased awareness of the importance of research as a priority in improving health outcomes during the pandemic.Conclusions The research interest and culture in our Health Board can be improved by addressing the four broad themes identified, thereby increasing research capacity in line with Government aspirations. The findings may have relevance for other small health providers that intend to respond to the call to increase their research profile.

copepodTCR: Identification of Antigen-Specific T Cell Receptors with combinatorial peptide pooling (preprint)

T cell receptor (TCR) repertoire diversity enables the orchestration of antigen-specific immune responses against the vast space of possible pathogens. Identifying TCR/antigen binding pairs from the large TCR repertoire and antigen space is crucial for biomedical research. Here, we introduce copepodTCR, an open-access tool for the design and interpretation of high-throughput experimental assays to determine TCR specificity. copepodTCR implements a combinatorial peptide pooling scheme for efficient experimental testing of T cell responses against large overlapping peptide libraries, useful for "deorphaning" TCRs of unknown specificity. The scheme detects experimental errors and, coupled with a hierarchical Bayesian model for unbiased results interpretation, identifies the response-eliciting peptide for a TCR of interest out of hundreds of peptides tested using a simple experimental set-up. We experimentally validated our approach on a library of 253 overlapping peptides covering the SARS-CoV-2 spike protein. We provide experimental guides for efficient design of larger screens covering thousands of peptides which will be crucial for the identification of antigen-specific T cells and their targets from limited clinical material.

Heterotypic responses against nsp12/nsp13 from prior SARS-CoV-2 infection associates with lower subsequent endemic coronavirus incidence (preprint)

Immune responses from prior SARS-CoV-2 infection and COVID-19 vaccination do not prevent re-infections and may not protect against future novel coronaviruses (CoVs). We examined the incidence of and immune differences against human endemic CoVs (eCoV) as a proxy for response against future emerging CoVs. Assessment was among those with known SARS-CoV-2 infection, COVID-19 vaccination but no documented SARS-CoV-2 infection, or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not COVID-19 vaccination alone, protects against subsequent symptomatic eCoV infection. CD8+ T cell responses to the non-structural eCoV proteins, nsp12 and nsp13, were significantly higher in individuals with previous SARS-CoV-2 infection as compared to the other groups. The three groups had similar cellular responses against the eCoV spike and nucleocapsid, and those with prior spike exposure had lower eCoV-directed neutralizing antibodies. Incorporation of non-structural viral antigens in a future pan-CoV vaccine may improve protection against future heterologous CoV infections.

Using a function-first "scout fragment"-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes (preprint)

Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity. As a result, helicases are important targets for chemical probes and therapeutics. However, it has been very challenging to develop selective chemical inhibitors for helicases, enzymes with highly dynamic conformations. We envisioned that electrophilic "scout fragments", which have been used for chemical proteomic based profiling, could be leveraged to develop covalent inhibitors of helicases. We adopted a function-first approach, combining enzymatic assays with enantiomeric probe pairs and mass spectrometry, to develop a covalent inhibitor that selectively targets an allosteric site in SARS-CoV-2 nsp13, a superfamily-1 helicase. Further, we demonstrate that scout fragments inhibit the activity of two human superfamily-2 helicases, BLM and WRN, involved in genome maintenance. Together, our findings suggest a covalent inhibitor discovery approach to target helicases and potentially other conformationally dynamic mechanoenzymes.

Understanding the impact of numerical solvers on inference for differential equation models (preprint)

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers which seem sufficiently accurate for the forward problem, i.e., for obtaining an accurate simulation, may not be sufficiently accurate for the inverse problem, i.e., for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which may become jagged, causing inference algorithms to get stuck in local "phantom" optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyze an ODE changepoint model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall-runoff model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.

Long-term outcomes of hospitalized SARS-CoV-2/COVID-19 patients with and without neurological involvement: 3-year follow-up assessment (preprint)

Background and ObjectivesAcute neurological manifestations are a common complication of acute COVID-19 disease. This study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. MethodsPatients infected by SARS-CoV-2 between March 1 and April 16, 2020 and hospitalized in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to January 23, 2023 (3 years post COVID-19). This cohort consisted of 414 COVID-19 patients with significant neurological manifestations and 1199 propensity-matched COVID- 19 patients without neurological manifestations. Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were clinical neuroimaging findings (hemorrhage, active stroke, prior stroke, mass effect, and microhemorrhage, white-matter changes, microvascular disease, and volume loss). Predictive models were used to identify risk factors of mortality post-discharge. ResultsMore patients in the neurological cohort were discharged to acute rehabilitation (10.54% vs 3.68%, p<0.0001), skilled nursing facilities (30.67% vs 20.78%, p=0.0002) and fewer to home (55.27% vs 70.21%, p<0.0001) compared to the matched controls. Incidence of readmission for any medical reason (65.70% vs 60.72%, p=0.036), stroke (6.28% vs 2.34%, p<0.0001), and MACE (20.53% vs 16.51%, p=0.032) was higher in the neurological cohort post-discharge. Neurological patients were more likely to die post-discharge (58 (14.01%) vs 94 (7.84%), p=0.0001) compared to controls (HR=2.346, 95% CI=(1.586, 3.470), p<0.0001). The major causes of death post-discharge were heart disease (14.47%), sepsis (13.82%), influenza and pneumonia (11.18%), COVID-19 (8.55%) and acute respiratory distress syndrome (7.89%). Factors associated with mortality after leaving the hospital were belonging to the neurological cohort (OR=1.802 (1.237, 2.608), p=0.002), discharge disposition (OR=1.508, 95% CI=(1.276, 1.775), p<0.0001), congestive heart failure (OR=2.281 (1.429, 3.593), p=0.0004), higher COVID-19 severity score (OR=1.177 (1.062, 1.304), p=0.002), and older age (OR=1.027 (1.010, 1.044), p=0.002). There were no group differences in gross radiological findings, except the neurological cohort showed significantly more age-adjusted brain volume loss (p<0.05) compared to controls. DiscussionCOVID-19 patients with neurological manifestations have worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for COVID-19 patients with neurological manifestations.

Needing Space During Lockdown: A Test of Relational Turbulence Theory in the Context of Conversations About Physical and Emotional Space During the COVID-19 Pandemic

The COVID-19 pandemic upended home life for couples across the globe. Many couples faced increased relational uncertainty and interference from a partner as a result of stay at home and lockdown orders. This study uses relational turbulence theory to examine how (a) relational uncertainty and (b) partner interdependence are associated with cognitions and emotions about needing space conversations with a partner. We examine links between perceptions of needing space conversations and relational turbulence. In the first months of the COVID-19 pandemic, 609 adults in a romantic relationship from 29 countries completed an online survey. Relationship uncertainty was negatively associated with relational cognitions (i.e., solidarity and intimacy), and interference from a partner was associated with more intense hopeful feelings about needing space conversations. Relational cognitions were associated with reduced relational turbulence, and hope was associated with higher relational turbulence. Theoretical implications for relational turbulence theory and practical implications for couples are discussed.

Everyday non-partisan fake news: Sharing behavior, platform specificity, and detection.

Concern over the impact of fake news on major socio-political events is growing. The use of deliberate misinformation is thought to have played a role in the outcome of the UK EU referendum, the 2016 US presidential election, and in the effectiveness of COVID-19 public health messaging. As a result, recent research has tended to focus on hyper-partisan (e.g., US politics; Democrat/Republican), person specific (e.g., Hillary Clinton/Donald Trump) content that incorporates emotive and hyperbolic language. However, in this study, we focus on an alternative form of fake news, across a variety of topics (e.g., Crime, Immigration, and Health), that avoids these characteristics, and which may therefore be more pervasive and difficult to detect. In a three-part study, we examined participants sharing intentions for fake news (including platform preference; Facebook, Twitter, Instagram, and WhatsApp), their ability to explicitly detect fake news, and whether individual differences on psychological measures of critical thinking ability, rational thinking, and emotional stability predict sharing behavior and detection ability. The results show that even our well-informed sample (political science students) were not immune to the effects of fake news, some issues (e.g., health and crime) were more likely to be shared than others (e.g., immigration), and on specific platforms (e.g., Twitter, Facebook). In addition, we show that individual differences in emotional stability appears to be a key factor in sharing behavior, while rational thinking aptitude was key to fake news detection. Taken together, this study provides novel data that can be used to support targeted fake news interventions, suggesting possible news topic, sharing behavior, and platform specific insights. Such interventions, and implications for government policy, education, and social media companies are discussed.

A Systematic Review of the Efficacy of Haemostatic Interventions in Primary Cleft Palate Repair.

OBJECTIVE: To evaluate the effectiveness of adrenaline infiltration, topical adrenaline, systemic tranexamic acid, fibrin tissue sealants and alginate-based topical coagulants at reducing blood loss and post-operative bleeding in primary cleft palate repair. DESIGN: Systematic review according to PRISMA-P guidelines, using Covidence systematic review software to facilitate 3-stage screening and data extraction by two reviewers. SETTING: Academic cleft surgery center. INTERVENTIONS: Any peri-operative intervention to reduce intra-operative and post-operative bleeding. MAIN OUTCOME MEASURES: Estimated blood loss, rate of post-operative bleeding, rate of return to theatre for haemostasis. RESULTS: Sixteen relevant studies were identified, with a total of 1469 study participants. Nine studies examined efficacy of infiltrating vasoconstrictors and all concluded that 1:100,000-1:400,000 adrenaline infiltration reduced intra-operative blood loss, to the range of 12-60 ml. Secondary bleeding and re-operation for haemostasis were uncommon. Tranexamic acid was studied in five randomised controlled trials, two of which demonstrated a significant reduction in blood loss compared to a control group. Use of fibrin and gelatin sponge products was examined in 3 studies, all of which reported no or minimal bleeding, but did not have quantifiable outcome measures. CONCLUSIONS: Infiltration with vasoconstricting agents, administration of systemic tranexamic acid and application of fibrin sealants have a well-studied and favorable safety profile in pediatric cases, and likely contribute to the relatively low incidence of post-operative bleeding and intra-operative blood loss in primary cleft palate repair.

Oligonucleotide mapping via mass spectrometry to enable comprehensive primary structure characterization of an mRNA vaccine against SARS-CoV-2.

Oligonucleotide mapping via liquid chromatography with UV detection coupled to tandem mass spectrometry (LC-UV-MS/MS) was recently developed to support development of Comirnaty, the world's first commercial mRNA vaccine which immunizes against the SARS-CoV-2 virus. Analogous to peptide mapping of therapeutic protein modalities, oligonucleotide mapping described here provides direct primary structure characterization of mRNA, through enzymatic digestion, accurate mass determinations, and optimized collisionally-induced fragmentation. Sample preparation for oligonucleotide mapping is a rapid, one-pot, one-enzyme digestion. The digest is analyzed via LC-MS/MS with an extended gradient and resulting data analysis employs semi-automated software. In a single method, oligonucleotide mapping readouts include a highly reproducible and completely annotated UV chromatogram with 100% maximum sequence coverage, and a microheterogeneity assessment of 5' terminus capping and 3' terminus poly(A)-tail length. Oligonucleotide mapping was pivotal to ensure the quality, safety, and efficacy of mRNA vaccines by providing: confirmation of construct identity and primary structure and assessment of product comparability following manufacturing process changes. More broadly, this technique may be used to directly interrogate the primary structure of RNA molecules in general.

The number of circulating CD26 expressing cells is decreased in critical COVID-19 illness.

We evaluated the number of CD26 expressing cells in peripheral blood of patients with COVID-19 within 72 h of admission and on day 4 and day 7 after enrollment. The majority of CD26 expressing cells were presented by CD3+ CD4+ lymphocytes. A low number of CD26 expressing cells were found to be associated with critical-severity COVID-19 disease. Conversely, increasing numbers of CD26 expressing T cells over the first week of standard treatment was associated with good outcomes. Clinically, the number of circulating CD26 cells might be a marker of recovery or the therapeutic efficacy of anti-COVID-19 treatment. New therapies aimed at preserving and increasing the level of CD26 expressing T cells may prove useful in the treatment of COVID-19 disease.

The impact of a comprehensive coronavirus disease 2019 (COVID-19) infection prevention bundle on non-COVID-19 hospital-acquired respiratory viral infection (HA-RVI) rates.

After implementing a coronavirus disease 2019 (COVID-19) infection prevention bundle, the incidence rate ratio (IRR) of non-severe acute respiratory coronavirus virus 2 (non-SARS-CoV-2) hospital-acquired respiratory viral infection (HA-RVI) was significantly lower than the IRR from the pre-COVID-19 period (IRR, 0.322; 95% CI, 0.266-0.393; P < .01). However, HA-RVIs incidence rates mirrored community RVI trends, suggesting that hospital interventions alone did not significantly affect HA-RVI incidence.

Creation and impact of containment units with high-risk zones during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) required swift preparation to protect healthcare personnel (HCP) and patients, especially considering shortages of personal protective equipment (PPE). Due to the lack of a pre-existing biocontainment unit, we needed to develop a novel approach to placing patients in isolation cohorts while working with the pre-existing physical space. OBJECTIVES: To prevent disease transmission to non-COVID-19 patients and HCP caring for COVID-19 patients, to optimize PPE usage, and to provide a comfortable and safe working environment. METHODS: An interdisciplinary workgroup developed a combination of approaches to convert existing spaces into COVID-19 containment units with high-risk zones (HRZs). We developed standard workflow and visual management in conjunction with updated staff training and workflows. The infection prevention team created PPE standard practices for ease of use, conservation, and staff safety. RESULTS: The interventions resulted in 1 possible case of patient-to-HCP transmission and zero cases of patient-to-patient transmission. PPE usage decreased with the HRZ model while maintaining a safe environment of care. Staff on the COVID-19 units were extremely satisfied with PPE availability (76.7%) and efforts to protect them from COVID-19 (72.7%). Moreover, 54.8% of HCP working in the COVID-19 unit agreed that PPE monitors played an essential role in staff safety. CONCLUSIONS: The HRZ model of containment unit is an effective method to prevent the spread of COVID-19 with several benefits. It is easily implemented and scaled to accommodate census changes. Our experience suggests that other institutions do not need to modify existing physical structures to create similarly protective spaces.

Age and adult attachment style predict psychological distress in the Singapore general population during COVID-19.

To date, there is increasing evidence to suggest that age and adult attachment styles, such as secure, anxious and avoidant attachment are predictive or protective for psychological distress. The study aimed to investigate the extent to which age and adult attachment style, measured by the Attachment Style Questionnaire, predicted psychological distress, measured by the Kessler 10 Psychological Distress Scale, in the Singapore general population during COVID-19. Ninety-nine residents of Singapore (44 females, 52 males, 3 prefer not to state their gender) aged between 18 and 66 completed an online survey, which collected information on age, adult attachment styles and levels of psychological distress. Multiple regression analysis was performed to study the influence of predictive factors on psychological distress. The study identified 20.2%, 13.1% and 14.1% of participants reporting psychological distress at the mild, moderate and severe levels, respectively. The study also reported that age and psychological distress were negatively correlated, and that psychological distress was negatively correlated with both anxious and avoidant attachment styles. It was concluded that age and adult attachment style significantly predicted psychological distress in the Singapore general population during COVID-19. Further studies exploring other variables and risk factors are required to further consolidate these results. At the global level, these findings may help countries predict residents' reactions to future outbreaks and help them prepare strategies and approaches to address these situations.