A statewide population-based approach to examining Long COVID symptom prevalence and predictors in Michigan.

OBJECTIVE: The current broad definition of Long COVID, and an overreliance on clinical and convenience samples, is leading to a wide array of Long COVID estimates with limited generalizability. Our objective was to examine Long COVID symptoms using a statewide population-based probability sample. METHODS: Among 8000 sampled adults with polymerase-chain-reaction-confirmed SARS-CoV-2 between June 2020 and July 2021 in the Michigan Disease Surveillance System, 2533 completed our survey (response rate 32.2%). Using modified Poisson regression, we examined sociodemographic, behavioral, and clinical predictors of eight Long COVID symptom clusters, defined as at least one applicable symptom lasting 90 or more days post COVID-19 onset. RESULTS: Neuropsychiatric Long COVID symptoms, including brain fog, were most prevalent (23.7%), followed by systemic symptoms (17.1%), including fatigue, musculoskeletal (11.4%), pulmonary (10.4%), dermatologic (6.7%), cardiovascular (6.1%), gastrointestinal (5.4%), and ear, nose, and throat symptoms (5.3%). In adjusted analyses, female sex, a pre-existing psychological condition, and intensive care unit admission were strong predictors of most Long COVID symptom clusters. Older age was not associated with a higher prevalence of all symptoms - cardiovascular and dermatologic symptoms were most prevalent among middle-aged adults and age was not associated with neuropsychiatric or gastrointestinal symptoms. Additionally, there were fewer associations between pre-existing conditions and cardiovascular, neuropsychiatric, and dermatologic symptoms compared to other symptom clusters. CONCLUSIONS: While many predictors of Long COVID symptom clusters were similar, the relationship with age and pre-existing conditions varied across clusters. Cardiovascular, neuropsychiatric, and dermatologic symptoms require further study as potentially distinct from other Long COVID symptoms.

Trends in Laboratory-Confirmed SARS-CoV-2 Reinfections and Associated Hospitalizations and Deaths Among Adults Aged ≥18 Years - 18 U.S. Jurisdictions, September 2021-December 2022.

Although reinfections with SARS-CoV-2 have occurred in the United States with increasing frequency, U.S. epidemiologic trends in reinfections and associated severe outcomes have not been characterized. Weekly counts of SARS-CoV-2 reinfections, total infections, and associated hospitalizations and deaths reported by 18 U.S. jurisdictions during September 5, 2021-December 31, 2022, were analyzed overall, by age group, and by five periods of SARS-CoV-2 variant predominance (Delta and Omicron [BA.1, BA.2, BA.4/BA.5, and BQ.1/BQ.1.1]). Among reported reinfections, weekly trends in the median intervals between infections and frequencies of predominant variants during previous infections were calculated. As a percentage of all infections, reinfections increased substantially from the Delta (2.7%) to the Omicron BQ.1/BQ.1.1 (28.8%) periods; during the same periods, increases in the percentages of reinfections among COVID-19-associated hospitalizations (from 1.9% [Delta] to 17.0% [Omicron BQ.1/BQ.1.1]) and deaths (from 1.2% [Delta] to 12.3% [Omicron BQ.1/BQ.1.1]) were also substantial. Percentages of all COVID-19 cases, hospitalizations, and deaths that were reinfections were consistently higher across variant periods among adults aged 18-49 years compared with those among adults aged ≥50 years. The median interval between infections ranged from 269 to 411 days by week, with a steep decline at the start of the BA.4/BA.5 period, when >50% of reinfections occurred among persons previously infected during the Alpha variant period or later. To prevent severe COVID-19 outcomes, including those following reinfection, CDC recommends staying up to date with COVID-19 vaccination and receiving timely antiviral treatments, when eligible.

Lack of access to personal protective equipment is associated with severe COVID-19 symptoms among in-person workers.

The use of personal protective equipment (PPE) at work can greatly reduce risk of SARS-CoV-2 transmission. However, it is unclear whether adequate PPE reduces disease severity if transmission occurs. This study investigated associations between workplace access to adequate PPE and self-reported COVID-19 symptom severity among in-person workers. We used data from the Michigan COVID-19 Recovery Surveillance Study (MI CReSS), a population-based survey of Michigan adults with a PCR-confirmed positive SARS-CoV-2 test. The sample was restricted to employed, in-person respondents with COVID-19 onset on or before November 15, 2020 (n = 893). Access to adequate PPE at work was categorized as often/always, sometimes, or rarely/never. Self-reported symptom severity was dichotomized as severe (severe or very severe) or not severe (mild, moderate, or asymptomatic). We used modified Poisson regression to estimate prevalence ratios for the relationship between adequate PPE at work and severe COVID-19 symptoms. We examined effect modification of the relationship by occupation by including a multiplicative interaction term for healthcare worker versus other occupations. After adjusting for sociodemographic and clinical covariates, respondents who rarely/never had access to PPE at work had a 24.7 % higher prevalence of self-reported severe COVID-19 symptoms (PR: 1.25, 95 % CI 1.03-1.51, p-value = 0.024) compared to respondents who often/always had access to PPE at work. Healthcare worker status did not modify the association between access to PPE and symptom severity. The findings from this study suggest an added benefit of PPE in reducing prevalence of severe COVID-19 among all in-person workers.

Impact of the Tips From Former Smokers Anti-Smoking Media Campaign on Youth Smoking Behaviors and Anti-Tobacco Attitudes.

INTRODUCTION: Anti-tobacco media campaigns can prevent youth smoking, but there is little research on how adult-targeted campaigns affect youth. We investigated the association between the Tips From Former Smokers (Tips) campaign and youth smoking behaviors and anti-tobacco attitudes, and variation by sex, race and/or ethnicity, or socioeconomic status. AIMS AND METHODS: We used data from the monitoring of the future study, a nationally representative survey on 8th, 10th, and 12th graders, from 2013-2015. Quartiles of Tips gross rating points (GRPs) were used to estimate exposure. Youth smoking behavior outcomes included smoking prevalence, initiation, and susceptibility. The anti-tobacco attitude outcomes included the extent that anti-tobacco ads made participants (1) less favorable towards smoking or (2) less likely to smoke cigarettes. Modified Poisson regression models estimated average marginal effects; separate additive interactions between Tips GRP exposure and sex, race and/or ethnicity, parents' highest education, and college plans (12th graders only) were used to test for effect modification. RESULTS: Tips GRPs were not associated with smoking behaviors within any grade. However, 12th graders in the highest quartile of Tips had a 7.0 percentage point higher probability (95% CI = 0.023-0.116) of responding that anti-tobacco ads made them less likely to smoke. Tips GRPs were associated with a lower probability of past 30-day smoking prevalence among 10th grade females, but not males (joint P-value = .002). No additional statistically significant interactions were found for any other outcomes for any grade. CONCLUSIONS: This study revealed the potential for adult-targeted campaigns to increase youth's anti-smoking attitudes, but campaign exposure was not associated with smoking behaviors. IMPLICATIONS: Few studies have examined the potential for anti-smoking media campaigns to influence audiences outside their targeted audience. In this study, we show the potential for adult-targeted campaigns to impact youth and suggest that Tips exposure may promote anti-smoking attitudes among youth.

Population-Based Estimates of Post-acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection (PASC) Prevalence and Characteristics.

BACKGROUND: Emerging evidence suggests many people have persistent symptoms after acute coronavirus disease 2019 (COVID-19) illness. Our objective was to estimate the prevalence and correlates of post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). METHODS: We used a population-based probability survey of adults with COVID-19 in Michigan. Living noninstitutionalized adults aged ≥18 in the Michigan Disease Surveillance System with COVID-19 onset through mid-April 2020 were eligible for selection (N = 28 000). Among 2000 selected, 629 completed the survey between June-December 2020. We estimated PASC prevalence, defined as persistent symptoms ≥30 (30-day COVID-19) or ≥60 (60-day COVID-19) days post-COVID-19 onset, overall and by sociodemographic and clinical factors. We used modified Poisson regression to produce adjusted prevalence ratios (aPRs) for potential risk factors. RESULTS: The analytic sample (n = 593) was predominantly female (56.1%), aged ≥45 years (68.2%), and non-Hispanic White (46.3%) or Black (34.8%). Thirty- and 60-day COVID-19 were highly prevalent (52.5% and 35.0%), even among nonhospitalized respondents (43.7% and 26.9%) and respondents reporting mild symptoms (29.2% and 24.5%). Respondents reporting very severe (vs mild) symptoms had 2.25 times higher prevalence of 30-day COVID-19 (aPR, 2.25; 95% CI, 1.46-3.46) and 1.71 times higher prevalence of 60-day COVID-19 (aPR, 1.71; 95% CI: 1.02-2.88). Hospitalized (vs nonhospitalized) respondents had ~40% higher prevalence of both 30-day (aPR, 1.37; 95% CI: 1.12-1.69) and 60-day (aPR, 1.40; 95% CI: 1.02-1.93) COVID-19. CONCLUSIONS: PASC is highly prevalent among cases reporting severe initial symptoms and, to a lesser extent, cases reporting mild and moderate symptoms.

Collagen and PAPP-A in the Etiology of Postpartum Breast Cancer.

Pregnancy has a dual effect on the risk of breast cancer. On one hand, pregnancy at a young age is known to be protective. However, pregnancy is also associated with a transient increased risk of breast cancer. For women that have children after the age of 30, the risk remains higher than women who never had children for decades. Involution of the breast has been identified as a window of mammary development associated with the adverse effect of pregnancy. In this review, we summarize the current understanding of the role of involution and describe the role of collagen in this setting. We also discuss the role of a collagen-dependent protease, pappalysin-1, in postpartum breast cancer and its role in activating both insulin-like growth factor signaling and discoidin domain collagen receptor 2, DDR2. Together, these novel advances in our understanding of postpartum breast cancer open the way to targeted therapies against this aggressive breast cancer sub-type.

Parity predisposes breasts to the oncogenic action of PAPP-A and activation of the collagen receptor DDR2.

BACKGROUND: Women who had children at a young age (less than 25) show a reduced overall risk of breast cancer. However, epidemiological studies showed that for all other women, pregnancy increases the risk of breast cancer and the risk remains higher for decades. Further, even in women who had children at a young age, there is a transient increase risk that peaks 6 years after pregnancy. Women diagnosed with breast cancer following pregnancy show a higher rate of metastasis. Yet, the factors that increase the predisposition of post-partum breasts to more aggressive cancers remain unknown. Pregnancy-associated plasma protein A (PAPP-A) is a secreted protease that is overexpressed in more than 70% of breast cancers. However, PAPP-A is a collagen-dependent oncogene. We initiated this study to test the effect of PAPP-A on the predisposition of post-partum breasts. METHODS: We used PAPP-A mouse models for the analysis of its effect on virgin, involuting, or post-partum mammary glands. We performed second-harmonic generation microscopy for the analysis of collagen, defined tumor-associated collagen signature (TACS), the rate of mammary tumors, and the status of the collagen-DDR2-Snail axis of metastasis. We knockdown DDR2 by CRISPR and performed invasion assays. A transcriptomic approach was used to define a PAPP-A and parity-dependent genetic signature and assess its correlation with breast cancer recurrence in humans. RESULTS: We confirmed that post-partum mammary glands have a higher level of collagen than virgin glands and that this collagen is characterized by an anti-proliferative architecture. However, PAPP-A converts the anti-proliferative post-partum collagen into pro-tumorigenic collagen. We show that PAPP-A activates the collagen receptor DDR2 and metastasis. Further, deletion of DDR2 by CRISPR abolished the effect of PAPP-A on invasion. We defined a PAPP-A-driven genetic signature that identifies patients at higher risk of metastasis. CONCLUSIONS: These results support the notion that information about pregnancy may be critical in the prognosis of breast cancer as passage through a single pregnancy predisposes to the oncogenic action of PAPP-A. Our data indicate that history of pregnancy combined with the expression of PAPP-A-driven genetic signature may be useful to identify patients at higher risk of metastatic disease.