Precision Phenotyping for Curating Research Cohorts of Patients with Post-Acute Sequelae of COVID-19 (PASC) as a Diagnosis of Exclusion (preprint)

Scalable identification of patients with the post-acute sequelae of COVID-19 (PASC) is challenging due to a lack of reproducible precision phenotyping algorithms and the suboptimal accuracy, demographic biases, and underestimation of the PASC diagnosis code (ICD-10 U09.9). In a retrospective case-control study, we developed a precision phenotyping algorithm for identifying research cohorts of PASC patients, defined as a diagnosis of exclusion. We used longitudinal electronic health records (EHR) data from over 295 thousand patients from 14 hospitals and 20 community health centers in Massachusetts. The algorithm employs an attention mechanism to exclude sequelae that prior conditions can explain. We performed independent chart reviews to tune and validate our precision phenotyping algorithm. Our PASC phenotyping algorithm improves precision and prevalence estimation and reduces bias in identifying Long COVID patients compared to the U09.9 diagnosis code. Our algorithm identified a PASC research cohort of over 24 thousand patients (compared to about 6 thousand when using the U09.9 diagnosis code), with a 79.9 percent precision (compared to 77.8 percent from the U09.9 diagnosis code). Our estimated prevalence of PASC was 22.8 percent, which is close to the national estimates for the region. We also provide an in-depth analysis outlining the clinical attributes, encompassing identified lingering effects by organ, comorbidity profiles, and temporal differences in the risk of PASC. The PASC phenotyping method presented in this study boasts superior precision, accurately gauges the prevalence of PASC without underestimating it, and exhibits less bias in pinpointing Long COVID patients. The PASC cohort derived from our algorithm will serve as a springboard for delving into Long COVID's genetic, metabolomic, and clinical intricacies, surmounting the constraints of recent PASC cohort studies, which were hampered by their limited size and available outcome data.

Residential substance use treatment outcomes for pregnant and postpartum women: Distinct patterns for women enrolled before versus during the COVID-19 pandemic.

INTRODUCTION: Substance use among pregnant and postpartum women (PPW) is a serious public health concern. The COVID-19 pandemic has exacerbated substance use among the general population including pregnant women, and disrupted operations for substance use treatment centers. Little is known about the outcomes of substance use treatment for PPW before and during the COVID-19 pandemic. METHOD: Data from a longitudinal program evaluation were analyzed to examine outcomes among 136 PPW participating in a residential SUD treatment program, and to explore differences in treatment outcomes for women who enrolled in services before versus during the COVID-19 pandemic. Analyses were used to test the significance of change from treatment intake to 6-month post-intake on assessments of substance use, mental health symptoms, and functioning collected to evaluate the Healthy Families Program (HFP), a comprehensive program for PPW located within a gender-specific SUD treatment facility in the United States. RESULTS: Results indicated that from treatment intake to follow-up assessment, clients self-reported statistically significant improvements in family functioning and daily functioning as well as reduced days of substance use. Notably, the rate of treatment intakes declined during the COVID-19 pandemic. In separate analyses by subgroup, mental health indicators showed improvements only for clients engaged in treatment before the COVID-19 pandemic and not for clients served during the COVID-19 pandemic, but substance use decreased significantly for both pre-pandemic and pandemic enrollees. CONCLUSION: Specialized treatment considerations and implications for PPW are discussed, including a need for added emphasis on co-occurring mental health symptoms and family system stress during a pandemic, and the role of nurses in identifying and addressing these concerns. Additionally, potential relapse prevention efforts during COVID-19 for PPW with substance use disorders are examined. CLINICAL RELEVANCE: The present research continues to highlight the importance of specialized treatment programming for PPW with SUDs as well as the potential need for additional recovery support mechanisms to be utilized during the COVID-19 pandemic.

Stakeholder perceptions of the use of a rapidly deployed modified ECHO to train and prepare healthcare providers for COVID-19.

Background: Innovative approaches to deliver timely information to rural healthcare providers are necessary with the COVID-19 pandemic. Project Extension for Community Healthcare Outcomes (ECHO) is a telementoring program designed to provide practitioners in rural communities with opportunities to engage in specialty training. We examined participant perceptions of a rapidly deployed, single continuing education session to improve healthcare provider preparedness for COVID-19 in Idaho. Methods: A modified Project ECHO session was developed to inform providers about emergency preparedness, treatment, testing, and resources for COVID-19. A post-session survey examined session impact and barriers on clinical practice. Results: Respondents believed the modified ECHO session increased COVID-19 knowledge and would improve their clinical practice and preparedness. Respondents were satisfied with the session and identified content, interdisciplinary collaboration, and format as beneficial; perceived barriers for utilizing session information included a lack of relevance of content and clinical applicability, and time constraints. Conclusions: A rapidly deployed modified Project ECHO session was perceived as an effective mechanism to foster collaboration and relay information to promote best practices at the start of the COVID-19 pandemic. An established Project ECHO network may be useful to rapidly exchange knowledge and information during a health emergency.

Identification of promising high-affinity inhibitors of SARS-CoV-2 main protease from African Natural Products Databases by Virtual Screening (preprint)

With the rapid spread of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen agent of COVID-19 pandemic created a serious threat to global public health, requiring the most urgent research for potential therapeutic agents. The availability of genomic data of SARS-CoV-2 and efforts to determine the protein structure of the virus facilitated the identification of potent inhibitors by using structure-based approach and bioinformatics tools. Many pharmaceuticals have been proposed for the treatment of COVID-19, although their effectiveness has not been assessed yet. However, it is important to find out new-targeted drugs to overcome the resistance concern. Several viral proteins such as proteases, polymerases or structural proteins have been considered as potential therapeutic targets. But the virus target must be essential for host invasion match some drugability criterion. In this Work, we selected the highly validated pharmacological target main protease Mpro and we performed high throughput virtual screening of African Natural Products Databases such as NANPDB, EANPDB, AfroDb, and SANCDB to identify the most potent inhibitors with the best pharmacological properties. In total, 8753 natural compounds were virtually screened by AutoDock vina against the main protease of SARS-CoV-2. Two hundred and five (205) compounds showed high-affinity scores (less than − 10.0 Kcal/mol), while fifty-eight (58) filtered through Lipinski’s rules showed better affinity than known Mpro inhibitors (i.e., ABBV-744, Onalespib, Daunorubicin, Alpha-ketoamide, Perampanel, Carprefen, Celecoxib, Alprazolam, Trovafloxacin, Sarafloxacin, Ethyl biscoumacetate…). Those promising compounds could be considered for further investigations toward the developpement of SARS-CoV-2 drug development.

A concerted mechanism involving ACAT and SREBPs by which oxysterols deplete accessible cholesterol to restrict microbial infection.

Most of the cholesterol in the plasma membranes (PMs) of animal cells is sequestered through interactions with phospholipids and transmembrane domains of proteins. However, as cholesterol concentration rises above the PM's sequestration capacity, a new pool of cholesterol, called accessible cholesterol, emerges. The transport of accessible cholesterol between the PM and the endoplasmic reticulum (ER) is critical to maintain cholesterol homeostasis. This pathway has also been implicated in the suppression of both bacterial and viral pathogens by immunomodulatory oxysterols. Here, we describe a mechanism of depletion of accessible cholesterol from PMs by the oxysterol 25-hydroxycholesterol (25HC). We show that 25HC-mediated activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) in the ER creates an imbalance in the equilibrium distribution of accessible cholesterol between the ER and PM. This imbalance triggers the rapid internalization of accessible cholesterol from the PM, and this depletion is sustained for long periods of time through 25HC-mediated suppression of SREBPs and continued activation of ACAT. In support of a physiological role for this mechanism, 25HC failed to suppress Zika virus and human coronavirus infection in ACAT-deficient cells, and Listeria monocytogenes infection in ACAT-deficient cells and mice. We propose that selective depletion of accessible PM cholesterol triggered by ACAT activation and sustained through SREBP suppression underpins the immunological activities of 25HC and a functionally related class of oxysterols.

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

PURPOSE: In young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population. METHODS: A retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS. RESULTS: Among the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%). CONCLUSION: Trough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor.

Common and rare variant associations with clonal haematopoiesis phenotypes.

Clonal haematopoiesis involves the expansion of certain blood cell lineages and has been associated with ageing and adverse health outcomes1-5. Here we use exome sequence data on 628,388 individuals to identify 40,208 carriers of clonal haematopoiesis of indeterminate potential (CHIP). Using genome-wide and exome-wide association analyses, we identify 24 loci (21 of which are novel) where germline genetic variation influences predisposition to CHIP, including missense variants in the lymphocytic antigen coding gene LY75, which are associated with reduced incidence of CHIP. We also identify novel rare variant associations with clonal haematopoiesis and telomere length. Analysis of 5,041 health traits from the UK Biobank (UKB) found relationships between CHIP and severe COVID-19 outcomes, cardiovascular disease, haematologic traits, malignancy, smoking, obesity, infection and all-cause mortality. Longitudinal and Mendelian randomization analyses revealed that CHIP is associated with solid cancers, including non-melanoma skin cancer and lung cancer, and that CHIP linked to DNMT3A is associated with the subsequent development of myeloid but not lymphoid leukaemias. Additionally, contrary to previous findings from the initial 50,000 UKB exomes6, our results in the full sample do not support a role for IL-6 inhibition in reducing the risk of cardiovascular disease among CHIP carriers. Our findings demonstrate that CHIP represents a complex set of heterogeneous phenotypes with shared and unique germline genetic causes and varied clinical implications.

Factors Associated with Mortality in Patients with COVID-19 Receiving Prolonged Ventilatory Support.

Background: Since its emergence in early 2020, coronavirus disease 2019 (COVID-19)-associated pneumonia has caused a global strain on intensive care unit (ICU) resources with many intubated patients requiring prolonged ventilatory support. Outcomes for patients with COVID-19 who receive prolonged intubation (>21 days) and possible predictors of mortality in this group are not well established. Patients and Methods: Data were prospectively collected from adult patients with COVID-19 requiring mechanical ventilation from March 2020 through December 2021 across a system of 11 hospitals. The primary end point was in-hospital mortality. Factors associated with mortality were evaluated using univariable and multivariable logistic regression analyses. Results: Six hundred six patients were placed on mechanical ventilation for COVID-19 pneumonia during the study period, with in-hospital mortality of 40.3% (n = 244). Increased age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.03-1.09), increased creatinine (OR, 1.40; 95% CI, 1.08-1.82), and receiving corticosteroids (OR, 2.68; 95% CI, 1.20-5.98) were associated with mortality. Intubations lasting longer than 21 days (n = 140) had a lower in-hospital mortality of 25.7% (n = 36; p < 0.001). Increasing Elixhauser comorbidity index (OR, 1.12; 95% CI, 1.04-1.19) and receiving corticosteroids (OR, 1.92; 95% CI, 1.06-3.47) were associated with need for prolonged ventilation. In this group, increased age (OR, 1.06; 95% CI, 1.01-1.08) and non-English speaking (OR, 3.74; 95% CI, 1.13-12.3) were associated with mortality. Conclusions: In-hospital mortality in mechanically ventilated patients with COVID-19 pneumonia occurs primarily in the first 21 days after intubation, possibly related to the early active inflammatory process. In patients on prolonged mechanical ventilation, increased age and being non-English speaking were associated with mortality.

A Community-Based COVID-19 Vaccine Education Initiative.

Coronavirus disease 2019 (COVID-19) has had a disparate impact on Black and Latinx communities. Even before the COVID-19 pandemic, inaccessibility and distrust of the medical community rooted in historical oppression led to hesitancy about medical interventions. In Boston, COVID-19 vaccination rates of Black and Latinx adolescents lagged behind their white and Asian peers. In response, Boston Medical Center created community vaccine clinic sites across Suffolk County. Pediatric resident physicians subsequently partnered with Boston Medical Center to establish an accompanying education program entitled "Ask-a-Doc" to help improve health literacy and address vaccine hesitancy that focused on Black and Latinx adolescents. In partnership with multidisciplinary stakeholders, including Boston Public School leaders, Ask-a-Doc pediatric resident physicians staffed 46 community vaccine events in 15 zip codes. At these events, 1521 vaccine doses were administered, with most administered to Black and Latinx community members. As of January 1, 2022, 67% of 51 first-year pediatric resident physicians had participated. Ask-A-Doc is an example of a community-based intervention that directly targets health inequities and misinformation and demonstrates that pediatric resident physicians can meaningfully engage in community outreach with sufficient protected time, resources, and institutional support. The resulting connections may lead to greater trust and credibility within systematically oppressed communities.

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study.

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1-365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53-3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03-4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55-5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14-1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37-0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17-1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20-1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45-1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80-13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10-1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32-1.67) and 365 days (RR 1.54, 95%CI 1.21-1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section.

Impact of COVD-19 on liver transplantation in Australia and New Zealand

Background and Aim: The COVID-19 pandemic has led to significant disruption to the delivery of health care worldwide. The impact of the pandemic on liver transplant (LT) services in Australia and New Zealand has not yet been established. In March 2020, the Transplantation Society of Australia and New Zealand COVID-19 Taskforce raised the minimum eligibility for LT to patients with high short-term mortality (i.e. Model for End-Stage Liver Disease [MELD] score > 20). This directive was later removed, but services continued to be affected by broader government and hospital pandemic responses. This study aimed to examine the impact of the various responses to the pandemic on LT services in Australia and New Zealand. Method(s): We performed a retrospective analysis of all LT activity on the Australia and New Zealand Liver and Intestinal Transplant Registry from 2012 to 2021. The primary outcome was delisting from the LT waitlist (WL) due to disease progression or death. Outcomes were assessed at the end of each year and categorized as transplanted, died, or delisted. Delisted patients were defined as those who were removed and not relisted onto the WL within 180 days. Additional registrations onto the WL for retransplantation in the same patient were considered separate events. Annual trends in LT and WL activity were observed for the entire study period, using interrupted time series analysis. Differences between the pandemic cohort (1 January 2020 to 31 December 2021) and a corresponding pre-pandemic cohort (1 January 2018 to 31 December 2019), were then analyzed using chi2 and Mann-Whitney U tests as appropriate. Additionally, organ donation rates were obtained from the publicly accessible Australia and New Zealand Organ Donation (ANZOD) registry. Result(s): From 2012 to 2021, there were 3219 LTs performed, 3920 WL registrations, and 416 patients who died or were delisted due to disease progression. On interrupted time series analysis, there was a predicted annual increase of 17 LTs from 2012 to 2019 (95% CI, 12-22;P < 0.001);however, in 2020-2021, there was an annual reduction of 43 LTs (95% CI, 38-48;P < 0.001) compared with 2018-2019 (Fig. 1a). Concurrently, there was a predicted annual increase of 12 new WL registrations (95% CI, 7-17;P = 0.001) before the pandemic, which reduced by 18 new registrations annually in 2020-2021 (95% CI, 14-24;P < 0.001) (Fig. 1b). The number of patients remaining on the WL at year's end remained stable. ANZOD donor data found a corresponding predicted annual reduction of 86 actual/intended donors (95% CI, 80-93;P < 0.001) in 2020-2021 compared with before COVID-19 (Fig. 1c). Compared with the pre-pandemic cohort, the pandemic cohort had more severe liver disease at listing (median MELD score, 18 [12-24] vs 17 [11-22];P = 0.020) but no other baseline differences. The Australian pandemic cohort had a higher proportion of death or delisting due to disease progression (8.6% vs 6.0%, P = 0.043) and a corresponding lower proportion transplanted (66.9% vs 72.6%, P = 0.011) compared with the pre-pandemic cohort. In contrast, New Zealand transplant activity and outcomes were unchanged. Overall WL numbers and median days on the WL were unchanged before and after the pandemic in both nations. Conclusion(s): Despite low community rates of COVID-19, the effects on LT in Australia were similar to those seen in nations with high COVID-19 prevalence. Reduced Australian LT activity corresponded with reduced donor numbers and was associated with more severe disease at WL, as well as higher rates of disease progression. In New Zealand, LT activity was less disrupted and outcomes were unchanged.

The impact of COVID-19 on student learning during the transition from remote to in-person learning: using mind mapping to identify and address faculty concerns.

The COVID-19 pandemic led to the suspension of in-person learning at many higher education institutions (HEIs) in March 2020. In response, HEIs transitioned most courses to online formats immediately and continued this mode of instruction through the 2020-2021 academic year. In fall 2021, numerous HEIs resumed in-person courses and some hybrid courses, and faculty began noting academic-related behavior deficiencies not previously observed in students. Focus groups of teaching faculty (n = 8) from one university department were conducted to gather information on changes in student academic-related behaviors attributed to the disruption of teaching and learning due to COVID-19 and to compare observed deficiencies with the university's undergraduate learning goals. Mind mapping software was utilized to capture themes and subthemes. Identified themes were related to problem-solving skills, grades, time management, attendance, and interpersonal communication, both in terms of student-to-student and student-to-faculty communication. For these identified areas, outcomes during the return to in-person learning were mostly undesirable. Based on these identified issues, suggested modifications that HEIs could use to modify course content and delivery to offset skill gaps and improve interpersonal communication were identified. Furthermore, observations may indicate that fully remote learning inhibited student learning and skill development during the 2020-2021 academic year. Future work should examine the effectiveness of the proposed modifications on student success.NEW & NOTEWORTHY This article contains information gathered from mind map-driven faculty focus group observations of student academic-related deficiencies resulting from transitioning from remote to in-person learning and how said deficiencies compare to university undergraduate learning goals.

Persistence of surrogates for high consequence viral and bacterial pathogens in a pilot-scale activated sludge treatment system.

The persistence of high consequence public health pathogens in a wastewater treatment system can significantly impact worker safety, as well as the public and downstream water bodies, particularly if the system is forced to shut down the treatment processes. This study utilizes organism viability to compare the persistence of three pathogen surrogates in wastewater using a pilot-scale activated sludge treatment (AST) system, operated to mimic treatment processes of large-scale plants. Bacillus globigii spores, surrogate for Bacillus anthracis, persisted in the AST system for at least a 50-day observation period leading to a possible steady condition far beyond the solid retention time for sludge particles. MS2 bacteriophage, surrogate for Poliovirus and other non-enveloped enteric viruses, was observed for up to 35 days after introduction, which largely and expectedly correlated to the measured solid retention time. Phi-6 bacteriophage, a surrogate for Ebola virus and other enveloped viruses, was detected for no more than 4 days after introduction, even though the AST system was operated to provide three times slower solids removal than for the other surrogates. This suggests Phi-6 is subject to inactivation under AST conditions rather than physical removal. These results may suggest similar persistence for the surrogated pathogens, leading to appropriate consequence management actions.

Stakeholder perceptions of the use of a rapidly deployed modified ECHO to train and prepare healthcare providers for COVID-19

Background: Innovative approaches to deliver timely information to rural healthcare providers are necessary with the COVID-19 pandemic. Project Extension for Community Healthcare Outcomes (ECHO) is a telementoring program designed to provide practitioners in rural communities with opportunities to engage in specialty training. We examined participant perceptions of a rapidly deployed, single continuing education session to improve healthcare provider preparedness for COVID-19 in Idaho. Methods: A modified Project ECHO session was developed to inform providers about emergency preparedness, treatment, testing, and resources for COVID-19. A post-session survey examined session impact and barriers on clinical practice. Results: Respondents believed the modified ECHO session increased COVID-19 knowledge and would improve their clinical practice and preparedness. Respondents were satisfied with the session and identified content, interdisciplinary collaboration, and format as beneficial;perceived barriers for utilizing session information included a lack of relevance of content and clinical applicability, and time constraints. Conclusions: A rapidly deployed modified Project ECHO session was perceived as an effective mechanism to foster collaboration and relay information to promote best practices at the start of the COVID-19 pandemic. An established Project ECHO network may be useful to rapidly exchange knowledge and information during a health emergency.

Schooling amidst a pandemic in the United States: Parents' perceptions about reopening schools and anticipated challenges during COVID-19.

INTRODUCTION: During the COVID-19 pandemic, numerous states in the United States instituted measures to close schools or shift them to virtual platforms. Understanding parents' preferences for sending their children back to school, and their experiences with distance learning is critical for informing school reopening guidelines. This study characterizes parents' plans to return their children to school, and examines the challenges associated with school closures during the 2020-2021 academic year. METHODS: A national-level cross-sectional online survey was conducted in September 2020. Focusing on a subset of 510 respondents, who were parents of school-aged children, we examined variations in parents' plans for their children to return to school by their demographic and family characteristics, and challenges they anticipated during the school-year using multivariable logistic regressions. RESULTS: Fifty percent of respondents (n = 249) said that they would send their children back to school, 18% (n = 92) stated it would depend on what the district plans for school reopening, and 32% (n = 160) would not send their children back to school. No demographic characteristics were significantly associated with parents plans to not return their children to school. Overall, parents reported high-level of access to digital technology to support their child's learning needs (84%). However, those who reported challenges with distance learning due to a lack of childcare were less likely to not return their children to school (aOR = 0.33, 95% CI: 0.17, 0.64). Parents who reported requiring supervision after school had higher odds of having plans to not return their children to school (aOR = 1.97, 95% CI: 1.03, 3.79). Parents viewed COVID-19 vaccines and face-masks important for resuming in-person classes. DISCUSSION: About one-third of parents objected to their children returning to school despite facing challenges with distance learning. Besides access to vaccines and face-masks, our findings highlight the need to better equip parents to support remote learning, and childcare.

Social connection and gene regulation during the COVID-19 pandemic: Divergent patterns for online and in-person interaction☆

Background Social connection has been linked to reduced disease risk and enhanced antiviral immunity, but it is unclear whether online social connections have similar effects to those previously documented for in-person/offline social relationships, or whether online connections can substitute for in-person social relations when the latter are restricted. We examined this question in the context of the COVID-19 pandemic, focusing specifically on an immune system gene regulation profile known as the conserved transcriptional response to adversity (CTRA), which is characterized by up-regulation of proinflammatory genes and down-regulation of genes linked to innate antiviral responses and antibody production. Methods We analyzed CTRA RNA profiles in blood samples from 142 healthy young adults (69% female, 87% white) during the “social distancing” period of the COVID-19 pandemic. Mixed effect linear models quantified the relation of CTRA gene expression to measures of in-person social connection (number of friends, social eudaimonia, loneliness) and online psychosocial connection (online loneliness, perceived social value in online leisure and educational contexts, and internet use) while controlling for demographic and health factors. Results Multiple indicators of in-person and generalized social connection were associated with lower CTRA gene expression, whereas no measure of online social connection showed any significant association with CTRA gene expression. Conclusion Experiences of in-person social connection are associated with reduced CTRA gene expression during a period of restricted social interaction. In contrast, online social relationships show no such association. Digitally mediated social relations do not appear to substantially offset the absence of in-person/offline social connection in the context of immune cell gene regulation. Graphical

Social connection and gene regulation during the COVID-19 pandemic: Divergent patterns for online and in-person interaction.

BACKGROUND: Social connection has been linked to reduced disease risk and enhanced antiviral immunity, but it is unclear whether online social connections have similar effects to those previously documented for in-person/offline social relationships, or whether online connections can substitute for in-person social relations when the latter are restricted. We examined this question in the context of the COVID-19 pandemic, focusing specifically on an immune system gene regulation profile known as the conserved transcriptional response to adversity (CTRA), which is characterized by up-regulation of proinflammatory genes and down-regulation of genes linked to innate antiviral responses and antibody production. METHODS: We analyzed CTRA RNA profiles in blood samples from 142 healthy young adults (69% female, 87% white) during the "social distancing" period of the COVID-19 pandemic. Mixed effect linear models quantified the relation of CTRA gene expression to measures of in-person social connection (number of friends, social eudaimonia, loneliness) and online psychosocial connection (online loneliness, perceived social value in online leisure and educational contexts, and internet use) while controlling for demographic and health factors. RESULTS: Multiple indicators of in-person and generalized social connection were associated with lower CTRA gene expression, whereas no measure of online social connection showed any significant association with CTRA gene expression. CONCLUSION: Experiences of in-person social connection are associated with reduced CTRA gene expression during a period of restricted social interaction. In contrast, online social relationships show no such association. Digitally mediated social relations do not appear to substantially offset the absence of in-person/offline social connection in the context of immune cell gene regulation.