Common Genetic Variation in Humans Impacts In Vitro Susceptibility to SARS-CoV-2 Infection.

The host response to SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, demonstrates significant interindividual variability. In addition to showing more disease in males, the elderly, and individuals with underlying comorbidities, SARS-CoV-2 can seemingly afflict healthy individuals with profound clinical complications. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants influence vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single-nucleotide polymorphism (rs4702), common in the population and located in the 3' UTR of the protease FURIN, influences alveolar and neuron infection by SARS-CoV-2 in vitro. Thus, we provide a proof-of-principle finding that common genetic variation can have an impact on viral infection and thus contribute to clinical heterogeneity in COVID-19. Ongoing genetic studies will help to identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs.

Psychological distress in the face of a pandemic: An observational study characterizing the impact of COVID-19 on immigrant outpatient mental health.

Undocumented immigrants have disproportionately suffered during the novel coronavirus disease 2019 (COVID-19) pandemic due to factors including limited medical access and financial insecurity, which can exacerbate pandemic-associated distress. Psychological outcomes for immigrant outpatients were assessed after transition to telepsychiatry in March 2020. Mental health was assessed with Patient Health Questionnaire (PHQ-2) and Generalized Anxiety Disorder (GAD-2) inventories, a novel coronavirus-specific survey, and the Kessler Psychological Distress Scale (K10+). Feedback on telepsychiatry sessions and access to non-clinical resources were also gathered, after which multivariable linear regression modeling identified psychosocial factors underlying changes in distress levels. 48.57% and 45.71% of participants reported worsened anxiety and depression levels due to the pandemic, respectively. From March to April, PHQ-2 and GAD-2 scores significantly increased by 0.81 and 0.63 points, respectively. The average total psychological distress score was 23.8, with 60% of scores reflecting serious mental illness. Factors that most influenced K10+ scores included a pre-existing depressive disorder, food insecurity, and comfort during telepsychiatry visits. 93.75% of participants believed access to remote psychiatry helped their mental health during COVID-19. The negative impact of COVID-19 on mental health in vulnerable populations stems from medical and psychosocial factors such as pre-existing psychiatric conditions and unmet essential needs.

Common genetic variation in humans impacts in vitro susceptibility to SARS-CoV-2 infection.

The host response to SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, demonstrates significant inter-individual variability. In addition to showing more disease in males, the elderly, and individuals with underlying co-morbidities, SARS-CoV-2 can seemingly render healthy individuals with profound clinical complications. We hypothesize that, in addition to viral load and host antibody repertoire, host genetic variants also impact vulnerability to infection. Here we apply human induced pluripotent stem cell (hiPSC)-based models and CRISPR-engineering to explore the host genetics of SARS-CoV-2. We demonstrate that a single nucleotide polymorphism (rs4702), common in the population at large, and located in the 3'UTR of the protease FURIN, impacts alveolar and neuron infection by SARS-CoV-2 in vitro . Thus, we provide a proof-of-principle finding that common genetic variation can impact viral infection, and thus contribute to clinical heterogeneity in SARS-CoV-2. Ongoing genetic studies will help to better identify high-risk individuals, predict clinical complications, and facilitate the discovery of drugs that might treat disease.