Design and analysis of outcomes following SARS-CoV-2 infection in veterans.

BACKGROUND: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs' (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. METHODS: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts within each month utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. RESULTS: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 39 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). CONCLUSION: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.

Changes in fall rates from before to during the COVID-19 pandemic: Findings from the prospective AMBROSIA study.

BACKGROUND: COVID-19 social distancing policies resulted in reductions in community movement, however fall rates during this time have not been described. METHODS: This prospective study included adults ≥65 years old participating in the Ambulatory Blood Pressure in Older Adults (AMBROSIA) cohort and who completed ≥1 monthly falls calendar (August 2019-March 2021; n=250). Months were grouped to correspond to the fall 2020 phased re-opening (August-October) and the shelter-in-place policy during the winter 2020 surge (November-January) in Los Angeles, California and compared to the same months, one year earlier (i.e., before the pandemic). RESULTS: Participants had a mean (SD) age of 75.2 (6.1) years, 49.6% were White, and 53.2% were women. We obtained 2,795 falls calendars during follow-up. Overall, 110 (44.0%) participants reported a total of 421 falls (rate 15.1 per 100 calendar months). The highest monthly fall rate during the pandemic was 22.9 (95% CI 16.4-31.1) per 100 calendar-months in August 2020. The lowest fall rate during the pandemic was 8.6 (95% CI 3.5-17.8) per 100 calendar-months in February 2021. During the pandemic, fall rates in August, September, and October 2020 were higher than the previous year (rate ratio 1.8 [95% CI 1.1-2.9]) and fall rates in November and December 2020 and January 2021 were lower than the previous year (rate ratio 0.5 [95% CI 0.4-0.8]). CONCLUSIONS: As the pandemic continues and older adults resume community mobility after a shelter-in-place period, providers should pay attention to the risk of falls.

Rates of and Factors Associated With Primary and Booster COVID-19 Vaccine Receipt by US Veterans, December 2020 to June 2022.

Importance: COVID-19 vaccination rates remain suboptimal in the US. Identifying factors associated with vaccination can highlight existing gaps and guide targeted interventions to improve vaccination access and uptake. Objective: To describe incidence and patient characteristics associated with primary, first booster, and second booster COVID-19 vaccination in the Veterans Health Administration (VHA). Design, Setting, and Participants: This retrospective cohort study assessed US veterans receiving care in VHA medical centers and outpatient clinics as of December 1, 2020. All VHA enrollees with an inpatient, outpatient, or telehealth encounter in VHA as well as a primary care physician appointment in the preceding 24 months were included. Exposures: Demographic characteristics, place of residence, prior SARS-CoV-2 infection, and underlying medical conditions. Main Outcomes and Measures: Cumulative incidence of primary, first booster, and second booster COVID-19 vaccination through June 2022. Cox proportional hazards regression was used to identify factors independently associated with COVID-19 vaccination. Results: Among 5 632 413 veterans included in the study, 5 094 392 (90.4%) were male, the median (IQR) age was 66 (51-74) years, 1 032 334 (18.3%) were Black, 448 714 (8.0%) were Hispanic, and 4 202 173 (74.6%) were White. Through June 2022, cumulative incidences were 69.0% for primary vaccination, 42.9% for first booster, and 9.3% for second booster. Cumulative incidence for primary vaccination increased with increasing age, from 46.9% (95% CI, 46.8%-47.0%) among veterans aged 18 to 49 years to 82.9% (95% CI, 82.8%-83.0%) among veterans aged 80 to 84 years. More Black veterans completed primary vaccination (71.7%; 95% CI, 71.6%-71.8%) compared with White veterans (68.9%; 95% CI, 68.9%-69.0%), and more urban-dwelling veterans completed primary vaccination (70.9%; 95% CI, 70.9%-71.0%) compared with highly rural-dwelling veterans (63.8%; 95% CI, 63.4%-64.1%). Factors independently associated with higher likelihood of both primary and booster vaccination included older age, female sex, Asian or Black race, Hispanic ethnicity, urban residence, and lack of prior SARS-CoV-2 infection. Conclusions and Relevance: In this cohort study of US veterans, COVID-19 vaccination coverage through June 2022 was suboptimal. Primary vaccination can be improved among younger, rural-dwelling veterans. Greater uptake of booster vaccination among all veterans is needed.

Consensus elements for observational research on COVID-19-related long-term outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its long-term outcomes may be jointly caused by a wide range of clinical, social, and economic characteristics. Studies aiming to identify mechanisms for SARS-CoV-2 morbidity and mortality must measure and account for these characteristics to arrive at unbiased, accurate conclusions. We sought to inform the design, measurement, and analysis of longitudinal studies of long-term outcomes among people infected with SARS-CoV-2. We fielded a survey to an interprofessional group of clinicians and scientists to identify factors associated with SARS-CoV-2 infection and subsequent outcomes. Using an iterative process, we refined the resulting list of factors into a consensus causal diagram relating infection and 12-month mortality. Finally, we operationalized concepts from the causal diagram into minimally sufficient adjustment sets using common medical record data elements. Total 31 investigators identified 49 potential risk factors for and 72 potential consequences of SARS-CoV-2 infection. Risk factors for infection with SARS-CoV-2 were grouped into five domains: demographics, physical health, mental health, personal social, and economic factors, and external social and economic factors. Consequences of coronavirus disease 2019 (COVID-19) were grouped into clinical consequences, social consequences, and economic consequences. Risk factors for SARS-CoV-2 infection were developed into a consensus directed acyclic graph for mortality that included two minimally sufficient adjustment sets. We present a collectively developed and iteratively refined list of data elements for observational research in SARS-CoV-2 infection and disease. By accounting for these elements, studies aimed at identifying causal pathways for long-term outcomes of SARS-CoV-2 infection can be made more informative.

Effectiveness of mRNA COVID-19 Vaccine Boosters Against Infection, Hospitalization, and Death: A Target Trial Emulation in the Omicron (B.1.1.529) Variant Era.

BACKGROUND: The effectiveness of a third mRNA COVID-19 vaccine dose (booster dose) against the Omicron (B.1.1.529) variant is uncertain, especially in older, high-risk populations. OBJECTIVE: To determine mRNA booster vaccine effectiveness (VE) against SARS-CoV-2 infection, hospitalization, and death in the Omicron era by booster type, primary vaccine type, time since primary vaccination, age, and comorbidity burden. DESIGN: Retrospective matched cohort study designed to emulate a target trial of booster vaccination versus no booster, conducted from 1 December 2021 to 31 March 2022. SETTING: U.S. Department of Veterans Affairs health care system. PARTICIPANTS: Persons who had received 2 mRNA COVID-19 vaccine doses at least 5 months earlier. INTERVENTION: Booster monovalent mRNA vaccination (Pfizer-BioNTech's BNT162b2 or Moderna's mRNA-1273) versus no booster. MEASUREMENTS: Booster VE. RESULTS: Each group included 490 838 well-matched persons, who were predominantly male (88%), had a mean age of 63.0 years (SD, 14.0), and were followed for up to 121 days (mean, 79.8 days). Booster VE more than 10 days after a booster dose was 42.3% (95% CI, 40.6% to 43.9%) against SARS-CoV-2 infection, 53.3% (CI, 48.1% to 58.0%) against SARS-CoV-2-related hospitalization, and 79.1% (CI, 71.2% to 84.9%) against SARS-CoV-2-related death. Booster VE was similar for different booster types (BNT162b2 or mRNA-1273), age groups, and primary vaccination regimens but was significantly higher with longer time since primary vaccination and higher comorbidity burden. LIMITATION: Predominantly male population. CONCLUSION: Booster mRNA vaccination was highly effective in preventing death and moderately effective in preventing infection and hospitalization for up to 4 months after administration in the Omicron era. Increased uptake of booster vaccination, which is currently suboptimal, should be pursued to limit the morbidity and mortality of SARS-CoV-2 infection, especially in persons with high comorbidity burden. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

Complexity and Challenges of the Clinical Diagnosis and Management of Long COVID.

Importance: There is increasing recognition of the long-term health effects of SARS-CoV-2 infection (sometimes called long COVID). However, little is yet known about the clinical diagnosis and management of long COVID within health systems. Objective: To describe dominant themes pertaining to the clinical diagnosis and management of long COVID in the electronic health records (EHRs) of patients with a diagnostic code for this condition (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code U09.9). Design, Setting, and Participants: This qualitative analysis used data from EHRs of a national random sample of 200 patients receiving care in the Department of Veterans Affairs (VA) with documentation of a positive result on a polymerase chain reaction (PCR) test for SARS-CoV-2 between February 27, 2020, and December 31, 2021, and an ICD-10 diagnostic code for long COVID between October 1, 2021, when the code was implemented, and March 1, 2022. Data were analyzed from February 5 to May 31, 2022. Main Outcomes and Measures: A text word search and qualitative analysis of patients' VA-wide EHRs was performed to identify dominant themes pertaining to the clinical diagnosis and management of long COVID. Results: In this qualitative analysis of documentation in the VA-wide EHR, the mean (SD) age of the 200 sampled patients at the time of their first positive PCR test result for SARS-CoV-2 in VA records was 60 (14.5) years. The sample included 173 (86.5%) men; 45 individuals (22.5%) were identified as Black and 136 individuals (68.0%) were identified as White. In qualitative analysis of documentation pertaining to long COVID in patients' EHRs 2 dominant themes were identified: (1) clinical uncertainty, in that it was often unclear whether particular symptoms could be attributed to long COVID, given the medical complexity and functional limitations of many patients and absence of specific markers for this condition, which could lead to ongoing monitoring, diagnostic testing, and specialist referral; and (2) care fragmentation, describing how post-COVID-19 care processes were often siloed from and poorly coordinated with other aspects of care and could be burdensome to patients. Conclusions and Relevance: This qualitative study of documentation in the VA EHR highlights the complexity of diagnosing long COVID in clinical settings and the challenges of caring for patients who have or are suspected of having this condition.

Rates and Factors Associated With Documentation of Diagnostic Codes for Long COVID in the National Veterans Affairs Health Care System.

Importance: Some persons infected with SARS-CoV-2 experience symptoms or impairments many months after acute infection. Objectives: To determine the rates, clinical setting, and factors associated with documented receipt of COVID-19-related care 3 or more months after acute infection. Design, Setting, and Participants: This retrospective cohort study used data from the US Department of Veterans Affairs health care system. Participants included persons with a positive SARS-CoV-2 test between February 1, 2020, and April 30, 2021, who were still alive 3 months after infection and did not have evidence of reinfection. Data analysis was performed from February 2020 to December 2021. Exposures: Positive SARS-CoV-2 test. Main Outcomes and Measures: Rates and factors associated with documentation of COVID-19-related International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes (U07.1, Z86.16, U09.9, and J12.82) 3 or more months after acute infection (hereafter, long-COVID care), with follow-up extending to December 31, 2021. Results: Among 198 601 SARS-CoV-2-positive persons included in the study, the mean (SD) age was 60.4 (17.7) years, 176 942 individuals (89.1%) were male, 133 924 (67.4%) were White, 44 733 (22.5%) were Black, and 19 735 (9.9%) were Hispanic. During a mean (SD) follow-up of 13.5 (3.6) months, long-COVID care was documented in a wide variety of clinics, most commonly primary care and general internal medicine (18 634 of 56 310 encounters [33.1%]), pulmonary (7360 of 56 310 encounters [13.1%]), and geriatrics (5454 of 56 310 encounters [9.7%]). Long-COVID care was documented in 26 745 cohort members (13.5%), with great variability across geographical regions (range, 10.8%-18.1%) and medical centers (range, 3.0%-41.0%). Factors significantly associated with documented long-COVID care included older age, Black or American Indian/Alaska Native race, Hispanic ethnicity, geographical region, high Charlson Comorbidity Index score, having documented symptoms at the time of acute infection (adjusted odds ratio [AOR], 1.71; 95% CI, 1.65-1.78) and requiring hospitalization (AOR, 2.60; 95% CI, 2.51-2.69) or mechanical ventilation (AOR, 2.46; 95% CI, 2.26-2.69). Patients who were fully vaccinated at the time of infection were less likely to receive long-COVID care (AOR, 0.78; 95% CI, 0.68-0.90). Conclusions and Relevance: Long-COVID care was documented in a variety of clinical settings, with great variability across regions and medical centers and was documented more commonly in older persons, those with higher comorbidity burden, those with more severe acute COVID-19 presentation and those who were unvaccinated at the time of infection. These findings provide support and guidance for health care systems to develop systematic approaches to the evaluation and management of patients who may be experiencing long COVID.

Association of COVID-19 pandemic-related concern and health routine changes with functioning among individuals with systemic lupus erythematosus.

OBJECTIVE: To examine whether pandemic-related issues were associated with physical functioning, community mobility and cognition among individuals with SLE. METHODS: Participants were recruited (6 October 2020-11 November 2021) for this cross-sectional study from a population-based cohort of individuals with validated SLE in metropolitan Atlanta, as part of an ongoing ancillary study. Pandemic-related issues (concern about the pandemic (very vs somewhat/not at all concerned); changes in physical activity and sleep (less vs more/same); difficulty obtaining food and medications and accessing routine care (any vs none)) were self-reported. Self-reported physical functioning and episodic and working memory performance were reported as t-scores (such that a score of 50=population mean and a 10-point difference=1 SD) and community mobility scores ranged from 0 to 120, with higher scores representing better functioning for all domains. Differences in scores were assessed via t-tests and age-adjusted, sex-adjusted and race-adjusted linear regression. RESULTS: Among 245 participants (mean age, 46 years; 95% female, 77% black), physical functioning t-scores (mean=44) were consistently lower (by 3-5 points) for those who reported concern about the pandemic, less physical activity and sleep, difficulty obtaining food and medications, and accessing routine care. Similarly, community mobility scores (mean=48) were lower (by 10-20 points) for these individuals. There were no substantial differences in episodic memory and working memory t-scores (mean=50 and 47, respectively) by pandemic-related issues. CONCLUSION: We found that physical functioning and community mobility, but not cognition, were lower among those who reported more concern about the pandemic or greater disruptions to health routines. Future studies should explore interventions among these vulnerable individuals with SLE, who already disproportionately suffer from functional impairment, to maintain functioning and prevent adverse outcomes during times of crisis.

Changes in the associations of race and rurality with SARS-CoV-2 infection, mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study.

BACKGROUND: We examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study. METHODS AND FINDINGS: In a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2-related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations. CONCLUSIONS: In this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.

Unintended Consequences of COVID-19 Social Distancing Among Older Adults With Kidney Disease.

BACKGROUND: While social distancing policies protect older adults with advanced chronic kidney disease (CKD) from exposure to COVID-19, reduced social interaction may also have unintended consequences. METHODS: To identify subgroups of patients at risk for unintended health consequences of social distancing, we conducted a cross-sectional analysis of data from a national cohort study of older veterans with advanced CKD (n = 223). Characteristics included activities of daily living (ADLs), instrumental ADLs (IADLs), cognition score, depression score, social support, financial stress, symptom burden, and number of chronic conditions. Unintended consequences of social distancing included restricted Life Space mobility, low willingness for video telehealth, reduced in-person contact with caregivers, and food insecurity. We identified subgroups of patients at risk of unintended consequences using model-based recursive partitioning (MoB). RESULTS: Participants had a mean age of 77.9 years, 64.6% were white, and 96.9% were male. Overall, 22.4% of participants had restricted Life Space, 33.9% reported low willingness for video telehealth, 19.0% reported reduced caregiver contact, and 3.2% reported food insecurity. For Life Space restriction, 4 subgroups partitioned (ie, split) by IADL difficulty, cognition score, and ADL difficulty were identified. The highest rate of restricted Life Space was 54.7% in the subgroup of participants with >3 IADL difficulties. For low willingness for telehealth and reduced caregiver contact, separate models identified 2 subgroups split by cognition score and depression score, respectively. CONCLUSIONS: Measures of function, cognition, and depressive symptoms may identify older adults with advanced CKD who are at higher risk for unintended health consequences of social distancing.