SARS-CoV-2 infection elucidates unique features of pregnancy-specific immunity (preprint)

Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls). We found that SARS-CoV-2 infection was associated with altered T cell responses in pregnant compared to non-pregnant women. Differences included a lower percentage of memory T cells, a distinct clonal expansion of CD4-expressing CD8+ T cells, and the enhanced expression of T cell exhaustion markers, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin domain-3 (Tim-3), in pregnant women. We identified additional evidence of immune dysfunction in severely and critically ill pregnant women, including a lack of expected elevation in regulatory T cell (Treg) levels, diminished interferon responses, and profound suppression of monocyte function. Consistent with earlier data, we found maternal obesity was also associated with altered immune responses to SARS-CoV-2 infection, including enhanced production of inflammatory cytokines by T cells. Certain gut bacterial species were altered in pregnancy and upon SARS-CoV-2 infection in pregnant individuals compared to non-pregnant women. Shifts in cytokine and chemokine levels were also identified in the sera of pregnant individuals, most notably a robust increase of interleukin-27 (IL-27), a cytokine known to drive T cell exhaustion, in the pregnant uninfected control group compared to all non-pregnant groups. IL-27 levels were also significantly higher in uninfected pregnant controls compared to pregnant SARS-CoV-2-infected individuals. Using two different preclinical mouse models of inflammation-induced fetal demise and respiratory influenza viral infection, we found that enhanced IL-27 protects developing fetuses from maternal inflammation but renders adult female mice vulnerable to viral infection. These combined findings from human and murine studies reveal nuanced pregnancy-associated immune responses, suggesting mechanisms underlying the increased susceptibility of pregnant individuals to viral respiratory infections.

Offspring cardiometabolic outcomes and postnatal growth trajectories after exposure to maternal SARS-CoV-2 infection (preprint)

Context. Prior birth cohorts have suggested an association between maternal infection in pregnancy and offspring risk for childhood obesity. Whether maternal SARS-CoV-2 infection is similarly associated with increased cardiometabolic risk for offspring is not known. Objective. To determine whether in utero exposure to SARS-CoV-2 is associated with increased risk for cardiometabolic diagnoses by 18 months after birth, compared with unexposed offspring born during the COVID-19 pandemic. Design. This retrospective cohort study included the live offspring of all individuals who delivered during the COVID-19 pandemic (April 1, 2020 - December 31, 2021) at 8 hospitals within 2 health systems in Massachusetts. Exposure. SARS-CoV-2 positivity on polymerase chain reaction (PCR) test during pregnancy. Main Outcome Measures. Electronic health record documentation of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes corresponding to cardiometabolic disorders. Offspring weight-for-age, length-for-age, and body mass index (BMI)-for-age z-scores at birth, 6 months, 12 months, and 18 months of age. Results. The full study cohort includes 29,510 live born offspring (1,599 exposed and 27,911 unexposed offspring). 6.7% of exposed and 4.4% of unexposed offspring had received a cardiometabolic diagnosis by 18 months of age (crude OR 1.47 [95% CI: 1.10-1.94], p=0.007; adjusted OR 1.37 [1.01-1.83]; p=0.04). These diagnoses were preceded by significantly greater mean BMI-for-age z-scores in exposed versus unexposed offspring at 6 months (mean z-score difference 0.19, 95% CI: 0.10, 0.29, p<0.001), and a greater proportion of offspring at risk of, or meeting criteria for, overweight/obesity (16.5% vs. 12.2%, p=0.006). Conclusions. Exposure to maternal SARS-CoV-2 infection was associated with an increased risk of receiving a cardiometabolic diagnosis by 18 months and greater BMI-for-age at 6 months.

Correlates of symptomatic remission among individuals with post-COVID-19 condition (preprint)

Importance: Post-COVID-19 condition (PCC), or long COVID, has become prevalent. The course of this syndrome, and likelihood of remission, has not been characterized. Objective: To quantify the rates of remission of PCC, and the sociodemographic features associated with remission. Design: 16 waves of a 50-state U.S. non-probability internet survey conducted between August 2020 and November 2022 Setting: Population-based Participants: Survey respondents age 18 and older Main Outcome and Measure: PCC remission, defined as reporting full recovery from COVID-19 symptoms among individuals who on a prior survey wave reported experiencing continued COVID-19 symptoms beyond 2 months after the initial month of symptoms. Results: Among 423 survey respondents reporting continued symptoms more than 2 months after acute test-confirmed COVID-19 illness, who then completed at least 1 subsequent survey, mean age was 53.7 (SD 13.6) years; 293 (69%) identified as women, and 130 (31%) as men; 9 (2%) identified as Asian, 29 (7%) as Black, 13 (3%) as Hispanic, 15 (4%) as another category including Native American or Pacific Islander, and the remaining 357 (84%) as White. Overall, 131/423 (31%) of those who completed a subsequent survey reported no longer being symptomatic. In Cox regression models, male gender, younger age, lesser impact of PCC symptoms at initial visit, and infection when the Omicron strain predominated were all statistically significantly associated with greater likelihood of remission; presence of brain fog or shortness of breath were associated with lesser likelihood of remission. Conclusions and Relevance: A minority of individuals reported remission of PCC symptoms, highlighting the importance of efforts to identify treatments for this syndrome or means of preventing it.

Sex-specific neurodevelopmental outcomes in offspring of mothers with SARS-CoV-2 in pregnancy: an electronic health records cohort (preprint)

Importance: Prior studies using large registries suggested a modest increase in risk for neurodevelopmental diagnoses among children of mothers with immune activation during pregnancy, and such risk may be sex-specific. Objective: To determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with sex-specific risk for neurodevelopmental disorders up to 18 months after birth, compared to unexposed offspring born during or prior to the pandemic period. Design: Retrospective cohort. Participants: Live offspring of all mothers who delivered between March 2018 and May 2021 at any of eight hospitals across two health systems in Massachusetts. Exposure: PCR evidence of maternal SARS-CoV-2 infection during pregnancy. Main Outcome and Measures: Electronic health record documentation of ICD-10 diagnostic codes corresponding to neurodevelopmental disorders. Results: The pandemic cohort included 18,323 live births, including 877 (4.8%) to individuals with SARS-CoV-2 positivity during pregnancy. The cohort included 1806 (9.9%) Asian individuals, 1634 (8.9%) Black individuals, 1711 (9.3%) individuals of another race, and 12,694 (69%) White individuals; 2614 (14%) were of Hispanic ethnicity. Mean maternal age was 33.0 years (IQR 30.0-36.0). In adjusted regression models accounting for race, ethnicity, insurance status, hospital type (academic center vs. community), maternal age, and preterm status, SARS-CoV-2 positivity was associated with statistically significant elevation in risk for neurodevelopmental diagnoses among male offspring (adjusted OR 1.99, 95% CI 1.19-3.34; p=0.009) but not female offspring (adjusted OR 0.90, 95% CI 0.43-1.88; p=0.8). Similar effects were identified using matched analyses in lieu of regression. Conclusion and Relevance: SARS-CoV-2 exposure in utero was associated with greater magnitude of risk for neurodevelopmental diagnoses among male offspring in the 12 months following birth. As with prior studies of maternal infection, substantially larger cohorts and longer follow-up will be required to reliably estimate or refute risk.

Association between long COVID symptoms and employment status (preprint)

Background: Symptoms of Coronavirus-19 (COVID-19) infection persist beyond 2 months in a subset of individuals, a phenomenon referred to as long COVID, but little is known about its functional correlates and in particular the relevance of neurocognitive symptoms. Method: We analyzed a previously-reported cohort derived from 8 waves of a nonprobability-sample internet survey called the COVID States Project, conducted every 4-8 weeks between February 2021 and July 2022. Primary analyses examined associations between long COVID and lack of full employment or unemployment, adjusted for age, sex, race and ethnicity, education, urbanicity, and region, using multiple logistic regression with interlocking survey weights. Results: The cohort included 15,307 survey respondents ages 18-69 with test-confirmed COVID-19 at least 2 months prior, of whom 2,236 (14.6%) reported long COVID symptoms, including 1,027/2,236 (45.9%) reporting either 'brain fog' or impaired memory. Overall, 1,418/15,307 (9.3%) reported being unemployed, including 276/2,236 (12.3%) of those with long COVID and 1,142/13,071 (8.7%) of those without; 8,228 (53.8%) worked full-time, including 1,017 (45.5%) of those with long COVID and 7,211 (55.2%) without. In survey-weighted regression models, presence of long COVID was associated with being unemployed (crude OR 1.44, 95% CI 1.20-1.72; adjusted OR 1.23, 95% CI 1.02-1.48), and with lower likelihood of working full-time (crude OR 0.73, 95% CI 0.64-0.82; adjusted OR 0.79, 95% CI 0.70 -0.90). Among individuals with long COVID, the presence of cognitive symptoms -- either brain fog or impaired memory -- was associated with lower likelihood of working full time (crude OR 0.71, 95% CI 0.57-0.89, adjusted OR 0.77, 95% CI 0.61-0.97). Conclusion: Long COVID was associated with a greater likelihood of unemployment and lesser likelihood of working full time in adjusted models. Presence of cognitive symptoms was associated with diminished likelihood of working full time. These results underscore the importance of developing strategies to respond to long COVID, and particularly the associated neurocognitive symptoms.

Neurodevelopmental outcomes at one year in offspring of mothers who test positive for SARS-CoV-2 during pregnancy (preprint)

Importance: Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring. Objective: To determine whether in utero exposure to the novel coronavirus SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth. Design: Retrospective cohort Participants: Live offspring of all mothers who delivered between March and September 2020 at one of six Massachusetts hospitals across two health systems. Exposure: SARS-CoV-2 infection confirmed by PCR during pregnancy Main Outcome and Measures: Neurodevelopmental disorders determined from ICD-10 diagnostic codes over 12 months; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record. Results: The cohort included 7,772 live births (7,466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean maternal age of 32.9 years; offspring were 9.9% Asian, 8.4% Black, and 69.0% white; 15.1% were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers (14% versus 8.7%; p=.003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses (crude OR 2.17 [95% CI 1.24-3.79, p=0.006]) as well as models adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR 1.86 [95% CI 1.03-3.36, p=0.04]). Third-trimester infection was associated with effects of larger magnitude (adjusted OR 2.31, 95% CI 1.16-4.21, p=0.01) Conclusion and Relevance: Our results provide preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these effects.

Persistence of neuropsychiatric symptoms associated with SARS-CoV-2 positivity among a cohort of children and adolescents (preprint)

BackgroundPost-acute sequelae of COVID-19 are common among adults. The prevalence of such syndromes among community samples of children and adolescents remains less well characterized. MethodWe identified all individuals age 5-18 across 2 New England health systems who had a positive SARS-CoV-2 PCR test between 3/12/2020 and 4/18/2021 and at least 90 days of follow-up visits documented in electronic health records. We identified neuropsychiatric symptoms in intervals prior to, and following, this testing using a previously-derived set of ICD-10 codes and natural language processing terms. Primary analysis examined sociodemographic features associated with presence of at least one incident (i.e., new-onset) neuropsychiatric symptom between 90 and 150 days after an initial positive test for COVID-19. ResultsAmong 5058 children (50% female, 2.9% Asian, 6.3% Black, and 63% White; 30% Hispanic; mean age was 12.4 (IQR 8.9-15.6), 366 (7.2%) exhibited at least one new-onset neuropsychiatric symptom between 90 and 150 days following initial SARS-CoV-2 test positivity. The most common incident symptoms at 90-150 days were headache (2.4%), mood and anxiety symptoms (2.4%), cognitive symptoms (2.3%), and fatigue (1.1%). In regression models, older children, girls, those with Hispanic ethnicity, those with public versus private insurance, and those with greater overall burden of medical comorbidity were more likely to exhibit subsequent symptoms. ConclusionThe prevalence of neuropsychiatric symptoms between 3- and 5-months following SARS-CoV-2 test positivity is similar to that observed in the period prior to infection. Prospective controlled studies will be needed to further refine these estimates.

Case-control study of neuropsychiatric symptoms following COVID-19 hospitalization in 2 academic health systems (preprint)

Neuropsychiatric symptoms may persist following acute COVID-19 illness, but the extent to which these symptoms are specific to COVID-19 has not been established. We utilized electronic health records across 6 hospitals in Massachusetts to characterize cohorts of individuals discharged following admission for COVID-19 between March 2020 and May 2021, and compared them to individuals hospitalized for other indications during this period. Natural language processing was applied to narrative clinical notes to identify neuropsychiatric symptom domains up to 150 days following hospitalization. Among 6,619 individuals hospitalized for COVID-19 drawn from a total of 42,961 hospital discharges, the most commonly documented symptom domains between 31 and 90 days after initial positive test were fatigue (13.4%), mood and anxiety symptoms (11.2%), and impaired cognition (8.0%). In models adjusted for sociodemographic features and hospital course, none of these were significantly more common among COVID-19 patients; indeed, mood and anxiety symptoms were less frequent (adjusted OR 0.72 95% CI 0.64-0.92). Between 91 and 150 days after positivity, most commonly-detected symptoms were fatigue (10.9%), mood and anxiety symptoms (8.2%), and sleep disruption (6.8%), with impaired cognition in 5.8%. Frequency was again similar among non-COVID-19 post-hospital patients, with mood and anxiety symptoms less common (aOR 0.63, 95% CI 0.52-0.75). Neuropsychiatric symptoms were common up to 150 days after initial hospitalization, but occurred at generally similar rates among individuals hospitalized for other indications during the same period. Post-acute sequelae of COVID-19 thus may benefit from standard if less-specific treatments developed for rehabilitation after hospitalization.

SARS-CoV-2 Neurotropism and Single Cell Responses in Brain Organoids Containing Innately Developing Microglia (preprint)

Neuropsychiatric manifestations are common in both acute and post-acute phase of SARS-CoV-2 infection, but the mechanism of these effects is unknown. Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level. We find evidence of limited tropism to SARS-CoV-2 for all major cell types and observe extensive neuronal cell death that also include non-infected cells. Single cell transcriptome profiling reveals distinct responses in microglia and astrocytes that share features with cellular states observed in neurodegenerative diseases, includes upregulation of genes with relevance for synaptic stripping, and suggests altered blood brain barrier integrity. Across all cell types, we observe a global translational shut-down as well as altered carbohydrate metabolism and cellular respiration. Together, our findings provide insights into cellular responses of the resident brain immune cells to SARS-CoV-2 and pinpoint mechanisms that may be of relevance for the neuropathological changes observed in COVID-19 patients.

Comparison of post-COVID depression and major depressive disorder (preprint)

BackgroundDuring the COVID-19 pandemic rates of depressive symptoms are markedly elevated, particularly among survivors of infection. Understanding whether such symptoms are distinct among those with prior SARS-CoV-2 infection, or simply a nonspecific reflection of elevated stress, could help target interventions. MethodWe analyzed data from multiple waves of a 50-state survey that included questions about COVID-19 infection as well as the Patient Health Questionnaire examining depressive and anxious symptoms. We utilized multiple logistic regression to examine whether sociodemographic features associated with depression liability differed for those with or without prior COVID-19, and then whether depressive symptoms differed among those with or without prior COVID-19. ResultsAmong 91,791 respondents, in regression models, age, gender, race, education, and income all exhibited an interaction with prior COVID-19 in risk for moderate or greater depressive symptoms (p<0.0001 in all cases), indicating differential risk in the two subgroups. Among those with such symptoms, levels of motoric symptoms and suicidality were significantly greater among those with prior COVID-19 illness. Depression risk increased with greater interval following acute infection. DiscussionOur results suggest that major depressive symptoms observed among individuals with prior COVID-19 illness may not reflect typical depressive episodes, and merit more focused neurobiological investigation.

Persistence of symptoms up to 10 months following acute COVID-19 illness (preprint)

Importance: COVID-19 symptoms are increasingly recognized to persist among a subset of individual following acute infection, but features associated with this persistence are not well-understood. Objective: We aimed to identify individual features that predicted persistence of symptoms over at least 2 months at the time of survey completion. Design: Non-probability internet survey. Participants were asked to identify features of acute illness as well as persistence of symptoms at time of study completion. We used logistic regression models to examine association between sociodemographic and clinical features and persistence of symptoms at or beyond 2 months. Setting: Ten waves of a fifty-state survey between June 13, 2020 and January 13, 2021. Participants: 6,211 individuals who reported symptomatic COVID-19 illness confirmed by positive test or clinician diagnosis. Exposure: symptomatic COVID-19 illness Results: Among 6,211 survey respondents reporting COVID-19 illness, with a mean age of 37.8 (SD 12.2) years and 45.1% female, 73.9% white, 10.0% Black, 9.9% Hispanic, and 3.1% Asian, a total of 4946 (79.6%) had recovered within less than 2 months, while 491 (7.9%) experienced symptoms for 2 months or more. Of the full cohort, 3.4% were symptomatic for 4 months or more and 2.2% for 6 months or more. In univariate analyses, individuals with persistent symptoms on average reported greater initial severity. In logistic regression models, older age was associated with greater risk of persistence (OR 1.10, 95% CI 1.01-1.19 for each decade beyond 40); otherwise, no significant associations with persistence were identified for gender, race/ethnicity, or income. Presence of headache was significantly associated with greater likelihood of persistence (OR 1.44, 95% CI 1.11-1.86), while fever was associated with diminished likelihood of persistence (OR 0.66, 95% CI 0.53-0.83). Conclusion and Relevance: A subset of individuals experience persistent symptoms from 2 to more than 10 months after acute COVID-19 illness, particularly those who recall headache and absence of fever. In light of this prevalence, strategies for predicting and managing such sequelae are needed. Trial Registration: NA

Frequency and profile of objective cognitive deficits in hospitalized patients recovering from COVID-19 (preprint)

BackgroundCognitive impairment is common following critical illness. A number of case reports and case series have suggested that cognitive deficits occur in patients with COVID-19. This study evaluated the frequency, severity, and profile of cognitive dysfunction in hospitalized patients recovering from COVID-19. MethodsWe obtained and analyzed cross-sectional neuropsychological data from a cohort of N=57 patients participating in inpatient rehabilitation. Our primary outcome measure was the Brief Memory and Executive Test (BMET). We calculated the frequency of impairment based on clinician diagnosis and by the BMET subtests using age-normed classification of impairment. We explored associations with intubation and extubation as markers of illness severity and complications, as well as psychiatric diagnosis. OutcomesOur sample was 75% male, 61% non-white, with a mean age of 64.5 (SD = 13.9) years. Patients were evaluated at a mean of 43.2 days post-admission. 88% had documented hypoxemic respiratory failure and 77% required intubation. 81% of patients had cognitive impairment, ranging from mild to severe. Deficits were most common in working memory (55% of patients impaired), set-shifting (47%), divided attention (46%), and processing speed (40%). Executive dysfunction was not significantly associated with intubation length or the time from extubation to assessment, nor was it associated with the presence of a psychiatric diagnosis. InterpretationMedically stable inpatients recovering from COVID-19 commonly have deficits in attention and executive functions. These deficits were not significantly correlated with length of intubation or time since extubation. Findings provide an early benchmark for studying the evolution of cognitive difficulties after COVID-19 and suggest that easy to disseminate interventions that remediate attention and executive dysfunctions may be important in this population. FundingThe authors have no funding for this study to report.

Umbilical cord blood derived microglia-like cells to model COVID-19 exposure (preprint)

Microglia, the resident brain immune cells, play a critical role in normal brain development, and are impacted by the intrauterine environment, including maternal immune activation and inflammatory exposures. The COVID-19 pandemic presents a potential developmental immune challenge to the fetal brain, in the setting of maternal SARS-CoV-2 infection with its attendant potential for cytokine production and, in severe cases, cytokine storming. There is currently no biomarker or model for in utero microglial priming and function that might aid in identifying the neonates and children most vulnerable to neurodevelopmental morbidity, as microglia remain inaccessible in fetal life and after birth. This study aimed to generate patient-derived microglial-like cell models unique to each neonate from reprogrammed umbilical cord blood mononuclear cells, adapting and extending a novel methodology previously validated for adult peripheral blood mononuclear cells. We demonstrate that umbilical cord blood mononuclear cells can be used to create microglial-like cell models morphologically and functionally similar to microglia observed in vivo. We illustrate the application of this approach by generating microglia from cells exposed and unexposed to maternal SARS-CoV-2 infection. Our ability to create personalized neonatal models of fetal brain immune programming enables non-invasive insights into fetal brain development and potential childhood neurodevelopmental vulnerabilities for a range of maternal exposures, including COVID-19.

Laboratory findings associated with mechanical ventilation requirement and mortality among hospitalized individuals with Covid-19 in Eastern Massachusetts (preprint)

ImportanceThe coronavirus disease 2019 (COVID-19) pandemic has placed unprecedented stress on health systems across the world, and reliable estimates of risk for adverse hospital outcomes are needed. ObjectiveTo quantify admission laboratory and comorbidity features associated with critical illness and mortality risk across 6 Eastern Massachusetts hospitals. DesignRetrospective cohort study using hospital course, prior diagnoses, and laboratory values. SettingEmergency department and inpatient settings from 2 academic medical centers and 4 community hospitals. ParticipantsAll individuals with hospital admission and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR testing across these 6 hospitals through June 5, 2020. ExposureCoronavirus 2 (SARS-CoV-2). Main Outcome MeasuresSevere illness defined by ICU admission, mechanical ventilation, or death. ResultsAmong 2,511 hospitalized individuals who tested positive for SARS-CoV-2 (of whom 50.9% were male, 53.9% white, and 27.0% Hispanic, with mean age 62.6 years), 215 (8.6%) were admitted to the ICU, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. L1-regression models developed in 3 of these hospitals yielded area under ROC curve (AUC) of 0.807 for severe illness and 0.847 for mortality in the 3 held-out hospitals. In total, 212/292 (78%) of the deaths occurred in the highest-risk mortality quintile. Conclusions and RelevanceIn this cohort, specific admission laboratory studies in concert with sociodemographic features and prior diagnosis facilitated risk stratification among individuals hospitalized for COVID-19. Funding1R56MH115187-01 Trial RegistrationNone Key PointsO_ST_ABSQuestionC_ST_ABSHow well can sociodemographic features, laboratory values, and comorbidities of individuals hospitalized with coronavirus disease 2019 (COVID-19) in Eastern Massachusetts through June 5, 2020 predict severe illness course? FindingsIn this cohort study of 2,511 hospitalized individuals positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR who were admitted to one of six hospitals, 215 (8.6%) were admitted to the ICU, 164 (6.5%) required mechanical ventilation, and 292 (11.6%) died. In a risk prediction model, 212 (78%) deaths occurred in the top mortality-risk quintile. MeaningSimple prediction models may assist in risk stratification among hospitalized COVID-19 patients.

Identifying common pharmacotherapies associated with reduced COVID-19 morbidity using electronic health records (preprint)

Importance: Absent a vaccine or any established treatments for the novel and highly infectious coronavirus-19 (COVID-19), rapid efforts to identify potential therapeutics are required. Objective: To identify commonly-prescribed medications that may be associated with lesser risk of morbidity with COVID-19 across 5 Eastern Massachusetts hospitals. Design: In silico cohort using electronic health records between 7/1/2019 and 4/07/2020. Setting: Outpatient, emergency department and inpatient settings from 2 academic medical centers and 3 community hospitals. Participants: All individuals presenting to a clinical site and undergoing COVID-19 testing. Main Outcome or Measure: Inpatient hospitalization; documented requirement for mechanical ventilation. Results: Among 12,818 individuals with COVID-19 testing results available, 2271 (17.7%) were test-positive, and 707/2271 (31.1%) were hospitalized in one of 5 hospitals. Based on a comparison of ranked electronic prescribing frequencies, medications enriched among test-positive individuals not requiring hospitalization included ibuprofen, valacyclovir, and naproxen. Among individuals who were hospitalized, mechanical ventilation was documented in 213 (30.1%); ibuprofen and naproxen were also more commonly prescribed among individuals not requiring ventilation. Conclusions and Relevance: These preliminary findings suggest that electronic health records may be applied to identify medications associated with lower risk of morbidity with COVID-19, but larger cohorts will be required to address confounding by indication. Larger scale efforts at repositioning may help to identify FDA-approved medications meriting study for prevention of COVID-19 morbidity and mortality.

Impact of COVID-19 on psychiatric assessment in emergency and outpatient settings measured using electronic health records (preprint)

Key PointsO_ST_ABSQuestionC_ST_ABSHow did documentation of psychiatric symptoms in outpatient and emergency room settings change with onset of COVID-19 infection in Eastern Massachusetts? FindingsIn this cohort study spanning 2 academic medical centers and 3 community hospitals, prevalence of narrative notes referencing depression or anxiety decreased 75-81% in outpatient settings following onset of coronavirus in March 2019, and by 44-45% in emergency departments. MeaningThe observation that documentation of psychiatric symptoms declined sharply with increasing coronavirus infection in Massachusetts, even as prevalence of such symptoms is anticipated to increase, suggests additional efforts may be required to address these symptoms in the context of COVID-19.