Physical and mental health disability associated with long-COVID: Baseline results from a US nationwide cohort. (preprint)

Importance: Persistent symptoms after SARS-COV-2 infection, or long-COVID, may occur in anywhere from 10-55% of those who have had COVID-19, but the extent of impact on daily functioning and disability remains unquantified. Objective: To characterize physical and mental disability associated with long-COVID Design: Cross-sectional analysis of baseline data from a cohort study Setting: Online US nationwide survey Participants: Adults 18 years of age and older who live in the US who either report a history of COVID-19 illness (n=8,874) or report never having had COVID-19 (n=633) Main Outcome and Measures: Self-reported mobility disability (difficulty walking a quarter of a mile and/or up 10 stairs, instrumental activities of daily living [IADL] disability (difficulty doing light or heavy housework), and mental fatigue as measured by the Wood Mental Fatigue Inventory (WMFI). Results: Of 7,926 participants with long-COVID, the median age was 45 years, 84% were female, 89% self-reported white race, and 7.4% self-reported Hispanic/Latino ethnicity. Sixty-five percent of long-COVID participants were classified as having at least one disability, compared to 6% of those with resolved-COVID (n=948) and 14% of those with no-COVID (n=633). Of long-COVID participants, about 1% and 5% were classified as critically physically disabled or mentally fatigued, respectively. Age, prior comorbidity, increased BMI, female gender, hospitalization for COVID-19, non-white race, and multi-race were all associated with significantly higher disability burden. Dizziness at the time of infection (33% non-hospitalized, 39% hospitalized) was associated with all five disability components in both hospitalized and non-hospitalized groups. Heavy limbs, dyspnea, and tremors were associated with four of the five components of disability in the non-hospitalized group, and heavy limbs was associated with four of the five components in the hospitalized group. Vaccination was protective against development of disability. Conclusion and Relevance: We observed a high burden of physical and mental disability associated with long-COVID which has serious implications for individual and societal health that may be partially mitigated by vaccination. Longitudinal characterization and evaluation of COVID-19 patients is necessary to identify patterns of recovery and treatment options.

What does it mean to be "representative"? (preprint)

Medical and population health science researchers frequently make ambiguous statements about whether they believe their study sample or results are "representative" of some (implicit or explicit) target population. Here, we provide a comprehensive definition of representativeness, with the goal of capturing the different ways in which a study can be representative of a target population. We propose that a study is representative if the estimate obtained in the study sample is generalizable to the target population (either due to representative sampling, estimation of stratum specific effects, or quantitative methods to generalize or transport estimates) or the interpretation of the results is generalizable to the target population (based on fundamental scientific premises and substantive background knowledge). We explore this definition in the context of four COVID-19 studies, ranging from laboratory science to descriptive epidemiology. All statements regarding representativeness should make clear the way in which the study results generalize, the target population the results are being generalized to, and the assumptions that must hold for that generalization to be scientifically or statistically justifiable.

Fine scale human mobility changes in 26 US cities in 2020 in response to the COVID-19 pandemic were associated with distance and income (preprint)

Human mobility patterns changed greatly due to the COVID-19 pandemic. Despite many analyses investigating general mobility trends, there has been less work characterising changes in mobility on a fine spatial scale and developing frameworks to model these changes. We analyse zip code-level mobility data from 26 US cities between February 2 - August 31, 2020. We use Bayesian models to characterise the initial decrease in mobility and mobility patterns between June - August at this fine spatial scale. There were similar temporal trends across cities but large variations in the magnitude of mobility reductions. Long-distance routes and higher-income subscribers, but not age, were associated with greater mobility reductions. At the city level, mobility rates around early April, when mobility was lowest, and over summer showed little association with non-pharmaceutical interventions or case rates. Changes in mobility patterns lasted until the end of the study period, despite overall numbers of trips recovering to near baseline levels in many cities.

Post-acute sequelae of SARS-CoV-2 (PASC) impact quality of life at 6, 12 and 18 months post-infection (preprint)

Little data exist on long COVID outcomes beyond one year. In a cohort enrolled with mild-moderate acute COVID-19, a wide range of symptoms manifest at 6, 12, and 18 months. Endorsing over 3 symptoms associates with poorer quality of life in 5 domains: physical, social, fatigue, pain, and general health.

A mixture model to estimate SARS-CoV-2 seroprevalence in Chennai, India (preprint)

Serological assays used to estimate SARS-CoV-2 seroprevalence rely on manufacturer cut-offs established based on more severe early cases who tended to be older. We conducted a household-based serosurvey of 4,677 individuals from 2,619 households in Chennai, India from January to May, 2021. Samples were tested for SARS-CoV-2 IgG antibodies to the spike (S) and nucelocapsid (N) proteins. We calculated seroprevalence using manufacturer cut-offs and using a mixture model in which individuals were assigned a probability of being seropositive based on their measured IgG, accounting for heterogeneous antibody response across individuals. The SARS-CoV-2 seroprevalence to anti-S and anti-N IgG was 62.0% (95% confidence interval [CI], 60.6 to 63.4) and 13.5% (95% CI, 12.6 to 14.5), respectively applying the manufacturer's cut-offs, with low inter-assay agreement (Cohen's kappa 0.15). With the mixture model, estimated anti-S IgG and anti-N IgG seroprevalence was 64.9% (95% Credible Interval [CrI], 63.8 to 66.0) and 51.5% (95% CrI, 50.2 to 52.9) respectively, with high inter-assay agreement (Cohen's kappa 0.66). Age and socioeconomic factors showed inconsistent relationships with anti-S IgG and anti-N IgG seropositivity using manufacturer's cut-offs, but the mixture model reconciled these differences. In the mixture model, age was not associated with seropositivity, and improved household ventilation was associated with lower seropositivity odds. With global vaccine scale-up, the utility of the more stable anti-S IgG assay may be limited due to the inclusion of the S protein in several vaccines. SARS-CoV-2 seroprevalence estimates using alternative targets must consider heterogeneity in seroresponse to ensure seroprevalence is not underestimated and correlates not misinterpreted.

A Targeted Geospatial Approach to COVID-19 Vaccine Delivery: Findings from the Johns Hopkins Hospital Emergency Department (preprint)

While COVID-19 vaccines have been shown to significantly decrease morbidity and mortality, there is still much debate about optimal strategies of vaccine rollout. We tested identity-unlinked stored remnant blood specimens of patients at least 18 years presenting to the Johns Hopkins Hospital emergency department (ED) between May to November 2020 for IgG to SARS-CoV-2. Data on SARS-CoV-2 RT PCR were available for patients who were tested due to suspected infection. SARS-CoV-2 infections was defined as either a positive IgG and/or RT-PCR. SARS-CoV-2 infection clustering by zipcode was analyzed by spatial analysis using the Bernoulli model (SaTScan software, Version 9.7). Median age of the 7,461 unique patients visiting the ED was 47 years and 50.8% were female; overall, 740 (9.9%) unique patients had evidence of SARS-CoV-2 infection. Prevalence of infection in ED patients by ZIP code ranged from 4.1% to 22.3%. The observed number of cases in ZIP code C was nearly double the expected (observed/expected ratio = 1.99; 95% CI: 1.62, 2.42). These data suggest a targeted geospatial approach to COVID vaccination should be considered to maximize vaccine rollout efficiency and include high-risk populations that may otherwise be subjected to delays, or missed.

Delayed rise of oral fluid antibodies, elevated BMI, and absence of early fever correlate with longer time to SARS-CoV-2 RNA clearance in an longitudinally sampled cohort of COVID-19 outpatients (preprint)

BackgroundSustained molecular detection of SARS-CoV-2 RNA in the upper respiratory tract (URT) in mild to moderate COVID-19 is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection. MethodsNinety-five outpatients self-collected mid-turbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models. ResultsViral RNA clearance, as measured by SARS-CoV-2 RT-PCR, in 507 URT samples occurred a median (IQR) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR positive samples tested. All participants but one with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (aHR 0.96, 95% CI 0.92-0.99, p=0.020) and BMI [≥] 25kg/m2 (aHR 0.37, 95% CI 0.18-0.78, p=0.009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as one of first three COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR 2.06, 95% CI 1.02-4.18, p=0.044). ConclusionsWe demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance.

SARS-CoV-2 Testing in Florida, Illinois, and Maryland: Access and Barriers (preprint)

Objective: To characterize the SARS-CoV-2 testing cascade and associated barriers in three US states. Methods: We recruited participants from Florida, Illinois, and Maryland (~1000/state) for an online survey September 16 - October 15, 2020. The survey covered demographics, COVID-19 symptoms, and experiences around SARS-CoV-2 PCR testing in the prior 2 weeks. Logistic regression was used to analyze associations with outcomes of interest. Results: Overall, 316 (10%) of 3,058 respondents wanted/needed a test in the two weeks prior to the survey. Of these, 166 (53%) were able to get tested and 156 (94%) received results; 53% waited 8 or more days to get results from when they wanted/needed a test. There were no significant differences by state. Among those wanting/needing a test, getting tested was significantly less common among men (aOR: 0.46) and those reporting black race (aOR: 0.53) and more common in those reporting recent travel (aOR: 3.35). Conclusions: There is an urgent need for a national communication strategy on who should get tested and where one can get tested. Additionally, measures need to be taken to improve access and reduce turn-around-time.

"There's No Place Like Home for The Holidays:" Travel and SARS-CoV-2 Test Positivity Following Thanksgiving Weekend (preprint)

In the US, public health officials discouraged travel and social gatherings for Thanksgiving. Data suggests that many individuals did travel over the holidays, albeit in smaller numbers than previous years. Using an online panel survey of individuals across ten US states, we found that many individuals reported spending Thanksgiving outside of their home (25.9%) or at home with at least one non-household member (27.3%). Among those who were tested, those who had Thanksgiving outside their home were significantly more likely to self-report a positive PCR test for SARS-CoV-2 infection in the prior two weeks compared to those who had Thanksgiving at home with non-household members or with household members only (41.7% vs. 22.4% and 13.8%, respectively; p<0.001). Persons who had Thanksgiving outside their home and tested positive for SARS-CoV-2 participated in a median 35 (IQR: 21 - 53). non-essential activities compared to those who had Thanksgiving at home and tested positive (median 3 activities, IQR 0-13). Notably, planned travel over the December holidays was most common among those who tested positive for SARS-CoV-2 in the prior 2 weeks (66.5%) compared with 25.4% of those who tested negative in the prior 2 weeks and 11.0% among those who were not tested. While public health authorities should continue promoting messages to dissuade travel and social gatherings over the holidays, as supported by these data, it is equally important to promote messaging on how to get together in a "low-risk" manner for those who travel and plan gatherings. In particular, it is critical that those who do travel or visit with others outside their household do so cautiously and avoid or significantly minimize all other activities where they may potentially acquire and transmit infection in the weeks prior to and after their visit.

Rapid real-time tracking of non-pharmaceutical interventions and their association SARS-CoV-2 positivity: The COVID-19 Pandemic Pulse Study (preprint)

Background: Current mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on population-wide adoption of non-pharmaceutical interventions (NPIs). Collecting demographically and geographically resolved data on NPIs and their association with SARS-CoV-2 infection history can provide critical information related to reopening geographies. Methods: We sampled 1,030 individuals in Maryland from June 17 - June 28, 2020 to capture socio-demographically and geographically resolved information about NPI adoption, access to SARS-CoV-2 testing, and examine associations with self-reported SARS-CoV-2 positivity. Results: Median age of the sample was 43 years and 45% were men; Whites and Blacks/African Americans represented 60% and 23%, respectively. Overall, 96% of the sample reported traveling outside their home for non-employment related services: most commonly cited reasons were essential services (92%) and visiting friends/family (66%). Use of public transport was reported by 18% of respondents. 68% reported always social distancing indoors and 53% always wearing masks indoors; indoor social distancing was significantly less common among younger vs. older individuals, and race/ethnicity and income were significantly associated with mask use (p<0.05 for all). 55 participants (5.3%) self-reported ever testing positive for SARS-CoV-2 with strong dose-response relationships between movement frequency and SARS-CoV-2 positivity that were significantly attenuated by social distancing. In multivariable analysis, history of SARS-CoV-2 infection was negatively associated with the practice of social distancing (adjusted Odd Ratio [aOR]: 0.10; 95% Confidence Interval: 0.03 - 0.33); the only travel associated with higher likelihood of SARS-CoV-2 infection was use of public transport (aOR for 7 or more times vs. never: 4.29) and visiting a place of worship (aOR for 3 or more times vs. never: 16.0) after adjusting for social distancing. Conclusions: Using a rapid cost-efficient approach, we highlight the role of movement and social distancing on SARS-CoV-2 transmission risk. Continued monitoring of NPI uptake, access to testing, and the subsequent impact on SARS-CoV-2 transmission will be critical for pandemic control and decisions about reopening geographies.