Modelling the direct virus exposure risk associated with respiratory events

The outbreak of the COVID-19 pandemic highlighted the importance of accurately modelling the pathogen transmission via droplets and aerosols emitted while speaking, coughing and sneezing. In this work, we present an effective model for assessing the direct contagion risk associated with these pathogen-laden droplets. In particular, using the most recent studies on multi-phase flow physics, we develop an effective yet simple framework capable of predicting the infection risk associated with different respiratory activities in different ambient conditions. We start by describing the mathematical framework and benchmarking the model predictions against well-assessed literature results. Then, we provide a systematic assessment of the effects of physical distancing and face coverings on the direct infection risk. The present results indicate that the risk of infection is vastly impacted by the ambient conditions and the type of respiratory activity, suggesting the non-existence of a universal safe distance. Meanwhile, wearing face masks provides excellent protection, effectively limiting the transmission of pathogens even at short physical distances, i.e. 1 m.

Harnessing the power of telemedicine to accomplish international pediatric outcome research during the COVID-19 pandemic

The COVID-19 pandemic occurred during planned neurodevelopmental follow-up of Colombian children with antenatal Zika-virus exposure. The objective of the study was to leverage the institution's telemedicine infrastructure to support international clinical child outcome research. In a prospective cohort study of child neurodevelopment (NCT04398901), we used synchronous telemedicine to remotely train a research team and perform live observational assessments of children in Sabanalarga, Colombia. An observational motor and conceptional standardized tool kit was mailed to Colombia; other materials were translated and emailed; team training was done virtually. Children were recruited by team on the ground. Synchronous activities were video-recorded directly to two laptops, each with a telehealth Zoom link to allow simultaneous evaluation of “table” and “standing” activities, and backup recordings were captured directly on the device in Colombia. The U.S. team attended live over Zoom from four states and five distinct locations, made observational notes, and provided real-time feedback. Fifty-seven, 3–4-year-old children with Zika-virus exposure and 70 non-exposed controls were studied during 10 daytrips. Direct laptop recording ensured complete record of child activities due to internet outages. Telemedicine can be used to successfully perform international neurodevelopmental outcome research in children during the COVID-19 pandemic. Telemedicine can benefit global health studies.

Serum anti-Spike antibody titers before and after heterologous booster with mRNA-1273 SARS-CoV-2 vaccine following two doses of inactivated whole-virus CoronaVac vaccine

Background: The inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. Methods: In a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (median 190 days, IQR165-232), we measured anti-Spike IgG titers on paired serum samples taken before and 28 days after a 100μg mRNA-1273 (Moderna) booster. We performed correlations and multivariable ordinal regressions. Findings: Among 304 participants, the median age was 31 years (range 21-59), 235 (77.3%) were women, 197 (64.8%) had one or more previous SARS-CoV-2 infections (including 155 [51.0%] who had a post-CoronaVac breakthrough infection. Pre-boost IgG titers correlated negatively with the time since the latest documented virus exposure (either by the second CoronaVac or SARS-CoV-2-infection whichever most recent). Previous SARS-CoV-2 infection and a longer time interval between second vaccine and mRNA-1273 boost were associated with a higher pre-boost IgG titer. Post-booster, the median IgG titer increased 9.3-fold, from 250 (IQR32-1389) to 2313 (IQR1226-4324) binding antibody units (BAU/mL) (p<0.001). All participants, including seven whose pre-boost IgG was below assay detection limits, became seropositive and all reached a substantial post-boost titer (≥364 BAU/mL). Post-boost IgG was not associated with pre-boost titer or previous SARS-CoV-2 infection. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living (ADL). Interpretation: A heterologous, high-dose mRNA-1273 booster after two-dose CoronaVac was highly immunogenic and safe, including in those most in need of improved immunity. Funding: Wellcome Trust, UK Keywords SARS-CoV-2; COVID-19; inactivated vaccine; CoronaVac; mRNA-1273; antibodies

Detection of Antibody Responses Against SARS-CoV-2 in Plasma and Saliva From Vaccinated and Infected Individuals

Antibodies (Abs) are essential for the host immune response against SARS-CoV-2, and all the vaccines developed so far have been designed to induce Abs targeting the SARS-CoV-2 spike. Many studies have examined Ab responses in the blood from vaccinated and infected individuals. However, since SARS-CoV-2 is a respiratory virus, it is also critical to understand the mucosal Ab responses at the sites of initial virus exposure. Here, we examined plasma versus saliva Ab responses in vaccinated and convalescent patients. Although saliva levels were significantly lower, a strong correlation was observed between plasma and saliva total Ig levels against all SARS-CoV-2 antigens tested. Virus-specific IgG1 responses predominated in both saliva and plasma, while a lower prevalence of IgM and IgA1 Abs was observed in saliva. Antiviral activities of plasma Abs were also studied. Neutralization titers against the initial WA1 (D614G), B.1.1.7 (alpha) and B.1.617.2 (delta) strains were similar but lower against the B.1.351 (beta) strain. Spike-specific antibody-dependent cellular phagocytosis (ADCP) activities were also detected and the levels correlated with spike-binding Ig titers. Interestingly, while neutralization and ADCP potencies of vaccinated and convalescent groups were comparable, enhanced complement deposition to spike-specific Abs was noted in vaccinated versus convalescent groups and corresponded with higher levels of IgG1 plus IgG3 among the vaccinated individuals. Altogether, this study demonstrates the detection of Ab responses after vaccination or infection in plasma and saliva that correlate significantly, although Ig isotypic differences were noted. The induced plasma Abs displayed Fab-mediated and Fc-dependent functions with comparable neutralization and ADCP potencies, but a greater capacity to activate complement was elicited upon vaccination.

Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk

Exposure to infection in utero predisposes towards psychiatric diseases such as autism, depression and schizophrenia in later life. The mechanisms involved are typically studied by administering mimetics of double-stranded (ds) virus or bacterial infection to pregnant rats or mice. The effect of single-stranded (ss) virus mimetics has been largely ignored, despite evidence linking prenatal ss virus exposure with psychiatric disease. Understanding the effects of gestational ss virus exposure has become even more important with recent events. In this study, in pregnant mice, we compare directly the effects, on the maternal blood, placenta and the embryonic brain, of maternal administration of ds-virus mimetic poly I:C (to activate Toll-like receptor 3, TLR3) and ss-virus mimetic resiquimod (to activate TLR7/8). We find that, 4 h after the administration, both poly I:C and resiquimod elevated the levels of IL-6, TNFα, and chemokines including CCL2 and CCL5, in maternal plasma. Both agents also increased placental mRNA levels of IL-6 and IL-10, but only resiquimod increased placental TNFα mRNA. In foetal brain, poly I:C produced no detectable immune-response-related increases, whereas pronounced increases in cytokine (e.g. Il-6, Tnfα) and chemokine (e.g. Ccl2, Ccl5) expression were observed with maternal resiquimod administration. The data show substantial differences between the effect of maternal exposure to a TLR7/8 activator as compared to a TLR3 activator. There are significant implications for future modelling of diseases where maternal ss virus exposure contributes to environmental disease risk in offspring.

Impacts of the Pandemic on Older Adults’ Social Isolation

The risk of COVID-19 exposure and likelihood of severe illness have been critical concerns among older adults during the pandemic. Meanwhile, social distancing has worsened social isolation, with severe impacts on connectedness among seniors. Effects of the pandemic may lead to an extended crisis, with impacts on health outcomes. Our primary purpose was to summarize emerging research describing impacts of the pandemic on social isolation and related health outcomes among older adults. A streamlined search was conducted to fit the scope of this review, with key terms determined to identify relevant publications. Common research databases and mainstream resources were utilized. We focused on research published or released since the start of 2020, primarily rapidly reviewed studies, to align with the timing of the pandemic. Early research suggests that the pandemic has worsened social isolation among older adults. Social isolation is now more urgent, as many seniors lost their usual connections due to social distancing. While these measures help to prevent virus exposure, this approach must be balanced with maintaining social connectedness. Thus, a “COVID-19 paradox” has emerged: safety protocols protect older adults but concurrently place them at risk of social isolation. Adapted approaches are urgently needed to safely address the consequences of a potential long-term social recession.

Single-Cell Immunogenomic Approach Identified SARS-CoV-2 Protective Immune Signatures in Asymptomatic Direct Contacts of COVID-19 Cases

The response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely impacted by the level of virus exposure and status of the host immunity. The nature of protection shown by direct asymptomatic contacts of coronavirus disease 2019 (COVID-19)-positive patients is quite intriguing. In this study, we have characterized the antibody titer, SARS-CoV-2 surrogate virus neutralization, cytokine levels, single-cell T-cell receptor (TCR), and B-cell receptor (BCR) profiling in asymptomatic direct contacts, infected cases, and controls. We observed significant increase in antibodies with neutralizing amplitude in asymptomatic contacts along with cytokines such as Eotaxin, granulocyte-colony stimulating factor (G-CSF), interleukin 7 (IL-7), migration inhibitory factor (MIF), and macrophage inflammatory protein-1α (MIP-1α). Upon single-cell RNA (scRNA) sequencing, we explored the dynamics of the adaptive immune response in few representative asymptomatic close contacts and COVID-19-infected patients. We reported direct asymptomatic contacts to have decreased CD4+ naive T cells with concomitant increase in CD4+ memory and CD8+ Temra cells along with expanded clonotypes compared to infected patients. Noticeable proportions of class switched memory B cells were also observed in them. Overall, these findings gave an insight into the nature of protection in asymptomatic contacts.

Barriers and Facilitators to Resuming In-Person Psychotherapy with Perinatal Patients amid the COVID-19 Pandemic: A Multistakeholder Perspective

During the COVID-19 pandemic, outpatient psychotherapy transitioned to telemedicine. This study aimed to examine barriers and facilitators to resuming in-person psychotherapy with perinatal patients as the pandemic abates. We conducted focus group and individual interviews with a sample of perinatal participants (n = 23), psychotherapy providers (n = 28), and stakeholders (n = 18) from Canada and the U.S. involved in the SUMMIT trial, which is aimed at improving access to mental healthcare for perinatal patients with depression and anxiety. Content analysis was used to examine perceived barriers and facilitators. Reported barriers included concerns about virus exposure in a hospital setting (77.8% stakeholders, 73.9% perinatal participants, 71.4% providers) or on public transportation (50.0% stakeholders, 26.1% perinatal participants, 25.0% providers), wearing a mask during sessions (50.0% stakeholders, 25.0% providers, 13.0% participants), lack of childcare (66.7% stakeholders, 46.4% providers, 43.5% perinatal participants), general transportation barriers (50.0% stakeholders, 47.8% perinatal participants, 25.0% providers), and the burden of planning and making time for in-person sessions (35.7% providers, 34.8% perinatal participants, 27.8% stakeholders). Reported facilitators included implementing and communicating safety protocols (72.2% stakeholders, 47.8% perinatal participants, 39.3% providers), conducting sessions at alternative or larger locations (44.4% stakeholders, 32.1% providers, 17.4% perinatal participants), providing incentives (34.8% perinatal participants, 21.4% providers, 11.1% stakeholders), and childcare and flexible scheduling options (31.1% perinatal participants, 16.7% stakeholders). This study identified a number of potential barriers and illustrated that COVID-19 has fostered and amplified barriers. Future interventions to facilitate resuming in-person sessions should focus on patient-centered strategies based on empathy regarding ongoing risk-aversion among perinatal patients despite existing safety protocols, and holistic thinking to make access to in-person psychotherapy easier and more accessible for perinatal patients.