Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

COVID-19 vaccination and changes in the menstrual cycle among vaccinated persons.

OBJECTIVE: To describe the characteristics of people who experience changes to their menstrual cycle after COVID-19 vaccination. DESIGN: Longitudinal study. PATIENT(S): We recruited a volunteer sample with and without a history of SARS-CoV-2 infection who enrolled in the Arizona COVID-19 Cohort (CoVHORT) study and participated in a reproductive sub-cohort who were pre-menopausal, not pregnant, and had received a COVID-19 vaccine in 2021 (n = 545). EXPOSURE(S): Demographic and reproductive characteristics were collected via self-reports. MAIN OUTCOME MEASURE(S): Information on self-reported changes in the menstrual cycle after COVID-19 vaccination was collected from May 2021 to December 2021. We looked at demographic and reproductive characteristics as predictors of menstrual cycle change. RESULT(S): The majority of our vaccinated sample received the Pfizer-BioNTech vaccine (58%), and were 26-35 years old (51%), non-Hispanic (84%), and White (88%). Approximately 25% of vaccinated participants reported a change in their menstrual cycle after vaccination; the majority reported changes after their second dose (56%) as compared with their first (18%) and third (14%) doses. The most commonly reported changes were irregular menstruation (43%), increased premenstrual symptoms (34%), increased menstrual pain or cramps (30%), and abnormally heavy or prolonged bleeding (31%). High self-reported perceived stress levels compared with low perceived stress (OR, 2.22; 95% CI 1.12-4.37) and greater body mass index (OR, 1.04; 95% CI 1.00-1.07) were associated with greater odds of experiencing the menstrual cycle changes after the vaccination. Participants having a history of SARS-CoV-2 infection were less likely to report changes in their menstrual cycle after vaccination compared with the participants with no history of SARS-CoV-2 infection (OR, 0.58; 95% CI 0.32-1.04). CONCLUSION(S): Among vaccinated participants, approximately 25% of them reported predominantly temporary changes in the menstrual cycle, however, we are unable to determine whether these changes are due to normal cycle variability. The COVID-19 vaccines are safe and effective for everyone, including pregnant people and people trying to conceive; hence, these findings should not discourage vaccination.

Pre-existing conditions associated with post-acute sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC) are conditions that occur or remain at least 28 days after SARS-CoV-2 infection. While some risk factors for PASC have been identified, little is known about pre-existing conditions that render one susceptible to developing PASC. Data from participants (n = 1224) in a longitudinal COVID-19 cohort study in Arizona were used to investigate comorbid conditions associated with PASC. After adjustment of the models for age, BMI, gender, race, and smoking, the following pre-existing conditions were statistically significantly associated with the development of PASC: asthma (OR = 1.54; 95% CI = 1.10-2.15); chronic constipation (OR = 4.29; 95% CI = 1.15-16.00); reflux (OR = 1.54; 95% CI = 1.01-2.34); rheumatoid arthritis (OR = 3.69; 95%CI = 1.15-11.82); seasonal allergies (OR = 1.56; 95% CI = 1.22-1.98); and depression/anxiety (OR = 1.72; 95% CI = 1.17-2.52). When grouping conditions together, statistically significant associations with PASC were observed for respiratory (OR = 1.47; 95% CI = 1.06-2.14); gastrointestinal (OR = 1.62; 95% CI = 1.16-2.26), and autoimmune conditions (OR = 4.38; 95% CI = 1.59-12.06). After adjustment for severity of acute SARS-CoV-2 infection and depression/anxiety, seasonal allergies (OR = 1.48; 95% CI 1.15-1.91) and autoimmune disease (OR = 3.78; 95% CI - 1.31-10.91) remained significantly associated with risk for PASC. These findings indicate that numerous pre-existing conditions may be associated with an increased risk for the development of PASC. Patients with these conditions should consider taking extra steps to avoid infection.

Design and implementation of a health messaging protocol employed for use within a COVID-19 health dissemination platform

Introduction AZCOVIDTXT, a bilingual, two-way information sharing platform was created in April of 2020 in response to rising COVID-19 cases in Arizona. The aim of this paper is to delineate the protocol and processes used to develop and disseminate health messaging to serve as guidance for other groups, universities, or public health programs in the implementation or enhancement of health communication services. Methods Health messaging formats included website articles, published on the system's website (azcovidtxt.org), infographics posted on social media, and SMS. Social media and SMS infographics were intended to highlight and augment the topics covered in the weekly website articles, to create a seamless multimodal source of reliable COVID-19 information for AZCOVIDTXT enrollees and the broader public. All health messaging information, text message and social media content was planned and reviewed collaboratively by the AZCOVIDTXT team topic experts for accuracy, efficacy, and content consistency. Results As of July 2021, AZCOVIDTXT provided weekly COVID-19-related health communication to 3,747 participating households located across 225 Arizona zip codes. AZCOVIDTXT has developed and sent 446 unique, bilingual SMS for a total of 271,977 contact points. The team has produced and published 179 website articles, which averaged a combined 7,000-page views per month, and 173 social media posts were made available to 268 followers across three platforms. Discussion Several programmatic aspects were deemed essential to the success of AZCOVIDTXT. These included (1) addressing community specific needs, (2) creating timely and relevant content, (3) developing an adaptable system, and (4) prioritizing system automation where possible, (5) having an interdisciplinary team approach to identifying and crafting key messages.

Quantifying SARS-CoV-2 Infection Risk Within the Google/Apple Exposure Notification Framework to Inform Quarantine Recommendations.

Most early Bluetooth-based exposure notification apps use three binary classifications to recommend quarantine following SARS-CoV-2 exposure: a window of infectiousness in the transmitter, ≥15 minutes duration, and Bluetooth attenuation below a threshold. However, Bluetooth attenuation is not a reliable measure of distance, and infection risk is not a binary function of distance, nor duration, nor timing. We model uncertainty in the shape and orientation of an exhaled virus-containing plume and in inhalation parameters, and measure uncertainty in distance as a function of Bluetooth attenuation. We calculate expected dose by combining this with estimated infectiousness based on timing relative to symptom onset. We calibrate an exponential dose-response curve based on infection probabilities of household contacts. The probability of current or future infectiousness, conditioned on how long postexposure an exposed individual has been symptom-free, decreases during quarantine, with shape determined by incubation periods, proportion of asymptomatic cases, and asymptomatic shedding durations. It can be adjusted for negative test results using Bayes' theorem. We capture a 10-fold range of risk using six infectiousness values, 11-fold range using three Bluetooth attenuation bins, ∼sixfold range from exposure duration given the 30 minute duration cap imposed by the Google/Apple v1.1, and ∼11-fold between the beginning and end of 14 day quarantine. Public health authorities can either set a threshold on initial infection risk to determine 14-day quarantine onset, or on the conditional probability of current and future infectiousness conditions to determine both quarantine and duration.

Outdoor Activity Associated with Higher Self-Reported Emotional Well-Being During COVID-19.

Shifts in activity patterns during the COVID-19 pandemic might have impacted the benefits of outdoor activities for mental health. By leveraging an existing mobile application, we collected self-reported data on daily outdoor activities, emotional well-being, and the influence of COVID-19 on participant's outdoor activity levels during April-July 2020. Individuals reporting outdoor activities, in greenspaces or in their residence, had higher well-being scores and this effect increased with age. Self-reported impacts of COVID-19 on emotional well-being were associated with lower well-being scores. This work suggests that outdoor activities may have improved mental health during the COVID-19 pandemic.

COVID-19 lockdowns: Employment and business disruptions, water access and hygiene practices in Nairobi's informal settlements.

Host to one billion people around the world, informal settlements are especially vulnerable to COVID-19 lockdown measures as they already lack basic services such as water, toilets, and secure housing. Additionally, many residents work in informal labor markets that have been affected by the lockdowns, resulting in further reductions in access to resources, including clean water. This study uses a cross-sectional design (n = 532) to examine the vulnerabilities of households to employment and business disruptions, water access and hygiene practices during the COVID-19 lockdowns between April and June 2020 in three informal settlements in Nairobi, Kenya. We used survey questions from the Household Water Insecurity Experience Scale (HWISE) to investigate the relationship between employment and business disruptions, water access, and hygiene practices (i.e., hand washing, body washing, clothes washing, and being able to use or drink clean water). Of the sampled households, 96% were forced to reduce work hours during the lockdowns, and these households had 92% lower odds of being able to afford water than households who did not experience a work hour reduction (OR = 0.08, p < .001). Household challenges in affording water were likely due to a combination of reduced household income, increased water prices, and pre-existing poverty, and were ultimately associated with lower hygiene scores (Beta = 1.9, p < .001). Our results highlight a compounding tragedy of reduced water access in informal settlements that were already facing water insecurities at a time when water is a fundamental requirement for following hygiene guidelines to reduce disease burden during an ongoing pandemic. These outcomes emphasize the need for targeted investments in permanent water supply infrastructures and improved hygiene behaviors as a public health priority among households in informal settlements.

Prevalence and risk factors for SARS-CoV-2 infection in children with and without symptoms seeking care in Managua, Nicaragua: results of a cross-sectional survey

ObjectiveThis study aimed to capture key epidemiological data on SARS-CoV-2 infection in Nicaraguan children (≤18 years) seeking medical care, between 6 October and 16 November 2020.DesignIn this cross-sectional study, 418 children were recruited: 319 with symptoms characteristic of COVID-19 and 99 with no symptoms of illness. Children were tested for SARS-CoV-2 RNA using loop-mediated isothermal amplification. A questionnaire was employed to identify symptoms, risk factors, comorbidities and COVID-19 prevention measures.SettingResearch was carried out in four hospitals and two clinics in Managua, Nicaragua, where schools and businesses remained open throughout the COVID-19 pandemic.ParticipantsChildren were enrolled into a possible COVID-19 group if presenting with clinical symptoms. A comparison group included children lacking any COVID-19 symptoms attending routine check-ups or seeking care for issues unrelated to COVID-19.ResultsA high prevalence (43%) of SARS-CoV-2 infection was found, which was relatively equivalent in symptomatic and non-symptomatic children. Age distribution was similar between symptomatic and non-symptomatic children testing positive for SARS-CoV-2. Symptomatic children who tested positive for SARS-CoV-2 were 2.7 times more likely to have diarrhoea (26.7% in positive vs 12.0% in negative;OR=2.7 (95% CI 1.5 to 4.8), p=0.001) and were 2.0 times more likely to have myalgia (17.8% in positive vs 9.8% in negative;OR=2.0 (95% CI 1.0 to 3.8), p=0.04). Children with COVID-19 symptoms, who tested positive for SARS-CoV-2, were more likely to be under age 5 years and to have a pre-existing comorbid condition than children who tested positive but did not have symptoms.ConclusionsThis is the first paediatric study to provide laboratory-confirmed data on SARS-CoV-2 infection in Nicaragua, crucial for paediatric health services planning and a successful COVID-19 response. The high prevalence of the virus suggests widespread and sustained community transmission, underscoring the urgent need for robust data on the true extent of SARS-CoV-2 infection throughout Nicaragua.

COVID-19 Infection, the COVID-19 Pandemic, and Changes in Sleep

The objective of this study was to investigate the differences in sleep patterns among individuals with and without laboratory-confirmed SARS-CoV-2 infection. Laboratory-confirmed SARS-CoV-2 test results and self-reported measures recalling sleep habits prior to and during the pandemic were collected from May 2020 to March 2021 among 1,848 individuals in The Arizona CoVHORT Study. We used linear and logistic regression to model the association between test status, presentation of symptoms, and time since test result with sleep duration and trouble sleeping, respectively. Mixed models were used to investigate change in sleep duration prior to the pandemic compared to during the pandemic. Overall, 16.2% of the sample were SARS-CoV-2 positive, 64.3% were SARS-CoV-2 negative, and 19.5% were untested for SARS-CoV-2. Independent of SARS-CoV-2 infection status, all participants slept longer during the pandemic compared to pre-pandemic (Δ SARS-CoV-2 positive: 77.7 min, 95% CI 67.9, 87.5;Δ SARS-CoV-2 negative: 13.4 min, 95% CI 8.4, 18.3). However, SARS-CoV-2 positive participants slept 60.9 min longer (95% CI 49.1, 72.8) than SARS-CoV-2 negative participants in multivariable-adjusted models and had greater odds of trouble sleeping three or more times per week since the start of the pandemic (OR: 1.34 95% CI 1.02, 1.77) This greater odds of trouble sleeping persisted for participants who reported sleep habits > 30 days after their positive SARS-CoV-2 (OR: 2.11 95% CI 1.47, 3.03). Sleep patterns among non-hospitalized individuals with COVID-19 were altered following infection, regardless of the presentation of symptoms and time since infection.

A Rasch analysis assessing the reliability and validity of the Arizona CoVHORT COVID-19 vaccine questionnaire.

BACKGROUND: Despite the widespread availability of COVID-19 vaccines in the United States, many that have chosen not to be vaccinated have done so because of vaccine hesitancy. This highlights the need for tools that accurately capture the knowledge, attitudes, and beliefs towards COVID-19 vaccines, and provide steps toward improving vaccine acceptance. METHODS: Participants of the Arizona CoVHORT (COVID-19 Cohort) received a one-time, electronic based cross-sectional questionnaire intended to capture underlying motivations regarding vaccination, as well as hesitations that may prevent people from getting vaccinated. Rasch analysis was conducted among 4703 CoVHORT participants who had completed the vaccine questionnaire to assess questionnaire reliability and validity. Response categories were grouped to optimize scale functioning and to ensure independent probabilities of participant endorsement. RESULTS: A total of 4703 CoVHORT participants completed the questionnaire, of whom 68% were female, and who had a mean age of 48 years. Participants were primarily White (90%), highly educated (63% with a college degree or above, with most respondents (45%) having an income of more than $75,000 per annum. The results indicated the questionnaire has good reliability and construct validity for assessing attitudes and beliefs about the COVID-19 vaccines. In-fit mean-squares for included items ranged from 0.61 to 1.72 and outfit mean-squares ranged from 0.56 to 1.75, and correlation coefficients ranged from 0.25 to 0.75. The person-item map indicated normal distribution of logit scores measuring perceptions about COVID-19 vaccinations. CONCLUSIONS: The CoVHORT vaccine questionnaire demonstrated satisfactory reliability and construct validity in assessing attitudes and beliefs about COVID-19 vaccines. Overall results provide a starting point for a reliable and valid tool to assess knowledge and perceptions about COVID-19 vaccination, ultimately providing public health professionals with an instrument to assess the factors that are associated with vaccine acceptance or hesitancy.

Elucidating symptoms of COVID-19 illness in the Arizona CoVHORT: a longitudinal cohort study.

OBJECTIVE: To elucidate the symptoms of laboratory-confirmed COVID-19 cases as compared with laboratory-confirmed negative individuals and to the untested general population among all participants who reported symptoms within a large prospective cohort study. SETTING AND DESIGN: This work was conducted within the framework of the Arizona CoVHORT, a longitudinal prospective cohort study conducted among Arizona residents. PARTICIPANTS: Eligible participants were any individual living in Arizona and were recruited from across Arizona via COVID-19 case investigations, participation in testing studies and a postcard mailing effort. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was a comparison of the type and frequency of symptoms between COVID-19-positive cases, tested but negative individuals and the general untested population who reported experiencing symptoms consistent with COVID-19. RESULTS: Of the 1335 laboratory-confirmed COVID-19 cases, 180 (13.5%) reported having no symptoms. Of those that did report symptoms, the most commonly reported were fatigue (82.2%), headache (74.6%), aches, pains or sore muscles (66.3%), loss of taste or smell (62.8) and cough (61.9%). In adjusted logistic regression models, COVID-19-positive participants were more likely than negative participants to experience loss of taste and smell (OR 12.1; 95% CI 9.6 to 15.2), bone or nerve pain (OR 3.0; 95% CI 2.2 to 4.1), headache (OR 2.6; 95% CI 2.2 to 3.2), nausea (OR 2.4; 95% CI 1.9 to 3.1) or diarrhoea (OR 2.1; 95% CI 1.7 to 2.6). Fatigue (82.9) and headache (74.9) had the highest sensitivities among symptoms, while loss of taste or smell (87.2) and bone or nerve pain (92.9) had the high specificities among significant symptoms associated with COVID-19. CONCLUSION: When comparing confirmed COVID-19 cases with either confirmed negative or untested participants, the pattern of symptoms that discriminates SARS-CoV-2 infection from those arising from other potential circulating pathogens may differ from general reports of symptoms among cases alone.

Post-acute sequelae of COVID-19 in a non-hospitalized cohort: Results from the Arizona CoVHORT.

Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30-250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1-20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

Design of the Arizona CoVHORT: A Population-Based COVID-19 Cohort.

This study is a prospective, population-based cohort of individuals with a history of SARS-CoV-2 infection and those without past infection through multiple recruitment sources. The main study goal is to track health status over time, within the diverse populations of Arizona and to identify the long-term consequences of COVID-19 on health and well-being. A total of 2,881 study participants (16.2% with a confirmed SARS-CoV-2 infection) have been enrolled as of December 22, 2020, with a target enrollment of 10,000 participants and a planned follow-up of at least 2 years. This manuscript describes a scalable study design that utilizes a wide range of recruitment sources, leveraging electronic data collection to capture and link longitudinal participant data on the current and emerging issues associated with the COVID-19 pandemic. The cohort is built within a collaborative infrastructure that includes new and established partnerships with multiple stakeholders, including the state's public universities, local health departments, tribes, and tribal organizations. Challenges remain for ensuring recruitment of diverse participants and participant retention, although the electronic data management system and timing of participant contact can help to mitigate these problems.