Impact of post-COVID-19 condition on health status and activities of daily living: the PRIME post-COVID study.

OBJECTIVE: To assess health and activities of daily living (ADL) in SARS-CoV-2-positive adults with and without post-COVID-19 condition (PCC) and compare this with negative tested individuals. Furthermore, different PCC case definitions were compared with SARS-CoV-2-negative individuals. METHODS: All adults tested PCR positive for SARS-CoV-2 at the Public Health Service South Limburg (Netherlands) between June 2020 and November 2021 (n=41 780) and matched PCR negative individuals (2:1, on age, sex, year-quarter test, municipality; n=19 875) were invited by email. Health (five-level EuroQol five-dimension (EQ5D) index and EuroQol visual analogue scale (EQVAS)) and ADL impairment were assessed. PCC classification was done using the WHO case definition and five other common definitions. RESULTS: In total, 8409 individuals (6381 SARS-CoV-2 positive; 53±15 years; 57% female; 9 (7-11) months since test) were included. 39.4% of positives had PCC by the WHO case definition (EQVAS: 71±20; EQ5D index: 0.800±0.191; ADL impairment: 30 (10-70)%) and perceived worse health and more ADL impairment than negatives, that is, difference of -8.50 points (95% CI -9.71 to -7.29; p<0.001) for EQVAS, which decreased by 1.49 points (95% CI 0.86 to 2.12; p<0.001) in individuals with PCC for each comorbidity present, and differences of -0.065 points (95% CI -0.074 to -0.056; p<0.001) for EQ5D index, and +16.72% (95% CI 15.01 to 18.43; p<0.001) for ADL impairment. Health and ADL impairment were similar in negatives and positives without PCC. Replacing the WHO case definition with other PCC definitions yielded comparable results. CONCLUSIONS: Individuals with PCC have substantially worse health and more ADL impairment than negative controls, irrespective of the case definition. Authorities should inform the public about the associated burden of PCC and enable adequate support.

Sex and age differences in the proportion of experienced symptoms by SARS-CoV-2 serostatus in a community-based cross-sectional study.

We examined the possible sex and age differences in the proportion of experienced Coronavirus Disease 2019 (COVID-19) symptoms in unaware (previously) infected adults, and their uninfected counterparts, estimated by serostatus prior to vaccination, at the end of 2020 (Wuhan strain). A cross-sectional community-based study using a convenience sample of 10 001 adult inhabitants of a southern Dutch province, heavily affected by COVID-19, was conducted. Participants donated a blood sample to indicate past infection by serostatus (positive/negative). Experienced symptoms were assessed by questionnaire, before the availability of the serological test result. Only participants without confirmed SARS-CoV-2 infection were included (n = 9715, age range 18-90 years). The seroprevalence was comparable between men (17.3%) and women (18.0%), and participants aged 18-60 years (17.3%) and aged 60 years and older (18.6%). We showed sex and age differences in the proportion experienced symptoms by serostatus in a large cohort of both unaware (untested) seropositive compared with seronegative reference participants. Irritability only differed by serostatus in men (independent of age), while stomach ache, nausea and dizziness only differed by serostatus in women aged 60 years and older. Besides, the proportion of experiencing pain when breathing and headache differed by serostatus in men aged 18-60 years only. Our study highlights the importance of taking possible sex and age differences into account with respect to acute and long-term COVID-19 outcomes. Identifying symptom profiles for sex and age subgroups can contribute to timely identification of infection, gaining importance once governments currently move away from mass testing again.

High proportions of post-exertional malaise and orthostatic intolerance in people living with post-COVID-19 condition: the PRIME post-COVID study.

Background: Exercise-based treatments can worsen/exacerbate symptoms in people who were SARS-CoV-2 positive and living with post-COVID-19 condition (PL-PCC) and who have post-exertional malaise (PEM) or orthostatic intolerance (OI). Nevertheless, PEM and OI are not routinely assessed by clinicians. We estimated PEM and OI proportions in PL-PCC, as well as in people not living with PCC (PnL-PCC) and negatives (i.e., never reported a SARS-CoV-2 positive test), and identified associated factors. Methods: Participants from the Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study were included. PEM and OI were assessed using validated questionnaires. PCC was defined as feeling unrecovered after SARS-CoV-2 infection. Multivariable regression analyses to study PEM and OI were stratified for sex. Results: Data from 3,783 participants were analyzed. In PL-PCC, the proportion of PEM was 48.1% and 41.2%, and the proportion of OI was 29.3% and 27.9% in women and men, respectively. Proportions were higher in PL-PCC than negatives, for PEM in women OR=4.38 [95%CI:3.01-6.38]; in men OR = 4.78 [95%CI:3.13-7.29]; for OI in women 3.06 [95%CI:1.97-4.76]; in men 2.71 [95%CI:1.75-4.21]. Associated factors were age ≤ 60 years, ≥1 comorbidities, and living alone. Conclusion: High proportions of PEM and OI are observed in PL-PCC. Standard screening for PEM and OI is recommended in PL-PCC to promote appropriate therapies.

Prevalence of Long-term Symptoms Varies When Using Different Post-COVID-19 Definitions in Positively and Negatively Tested Adults: The PRIME Post-COVID Study.

Background: Long-term symptoms after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (ie, post-coronavirus disease 2019 [COVID-19] condition or long COVID) constitute a substantial public health problem. Yet, the prevalence remains currently unclear as different case definitions are used, and negatively tested controls are lacking. We aimed to estimate post-COVID-19 condition prevalence using 6 definitions. Methods: The Prevalence, Risk factors, and Impact Evaluation (PRIME) post-COVID-19 condition study is a population-based sample of COVID-19-tested adults. In 2021, 61 655 adults were invited to complete an online questionnaire, including 44 symptoms plus a severity score (0-10) per symptom. Prevalence was calculated in both positively and negatively tested adults, stratified by time since their COVID-19 test (3-5, 6-11, or ≥12 months ago). Results: In positive individuals (n = 7405, 75.6%), the prevalence of long-term symptoms was between 26.9% and 64.1% using the 6 definitions, while in negative individuals (n = 2392, 24.4%), the prevalence varied between 11.4% and 32.5%. The prevalence of long-term symptoms potentially attributable to COVID-19 ranged from 17.9% to 26.3%. Conclusions: There is a (substantial) variation in prevalence estimates when using different post-COVID-19 condition definitions, as is current practice; there is limited overlap between definitions, indicating that the essential post-COVID-19 condition criteria are still unclear. Including negatives is important to determine long-term symptoms attributable to COVID-19. Trial registration: ClinicalTrials.gov Identifier: NCT05128695.

Exposure factors associated with SARS-CoV-2 seroprevalence during the first eight months of the COVID-19 pandemic in the Netherlands: A cross-sectional study.

BACKGROUND: The availability of valid Severe Acute Respiratory Syndrome Coronvirus-2 (SARS-CoV-2) serological tests overcome the problem of underestimated cumulative Coronavirus Disease 2019 (COVID-19) cases during the first months of the pandemic in The Netherlands. The possibility to reliably determine the number of truly infected persons, enabled us to study initial drivers for exposure risk in the absence of routine testing. Numerous activities or circumstances can accelerate virus spread, here defined as exposure factors. Hence, we aimed to evaluate a wide variety of demographic, behavioural and social exposure factors associated with seropositivity during the first eight months of the pandemic in Limburg, The Netherlands. METHODS: SARS-CoV-2 point-seroprevalence was determined cross-sectionally to indicate previous infection in a convenience sample of minimal 10,000 inhabitants of the study province. All adult (18+ years) inhabitants of the study province were eligible to register themselves for participation. Once the initial 10,000 registrations were reached, a reserve list was kept to ensure sufficient participants. Possible exposure factors were mapped by means of an extensive questionnaire. Associated exposure factors were determined using univariable and multivariable logistic regression models. RESULTS: Seropositivity was established in 19.5% (n = 1,948) of the 10,001 participants (on average 49 years old (SD = 15; range 18-90 years), majority women (n = 5,829; 58.3%). Exposure factors associated with seropositivity included current education, working in healthcare and not working from home, and being a member of three or four associations or clubs. Specifically for February-March 2020, visiting an après-ski bar during winter sports in Austria, travelling to Spain, celebrating carnival, and participating in a singing activity or ball sport were associated with seropositivity. CONCLUSIONS: Our results confirm that relevant COVID-19 exposure factors generally reflected circumstances where social distancing was impossible, and the number and duration of contacts was high, in particular for indoor activities.

Design and recruitment of a large-scale cohort study on prevalence, risk factors and impact evaluation of post-COVID-19 condition and its wider long-term social, mental, and physical health impact: The PRIME post-COVID study.

Background: Persistent symptoms, described as long COVID or post-COVID-19 condition, pose a potential public health problem. Here, the design and recruitment of the PRIME post-COVID study is described. PRIME post-COVID is a large-scale population-based observational study that aims to improve understanding of the occurrence, risk factors, social, physical, mental, emotional, and socioeconomic impact of post-COVID-19 condition. Methods: An observational open cohort study was set up, with retrospective and prospective assessments on various health-conditions and health-factors (medical, demographic, social, and behavioral) based on a public health COVID-19 test and by self-report (using online questionnaires in Dutch language). Invited for participation were, as recorded in a public health registry, adults (18 years and older) who were tested for COVID-19 and had a valid Polymerase Chain Reaction (PCR) positive or negative test result, and email address. In November 2021, 61,655 individuals were invited by email to participate, these included all eligible adults who tested PCR positive between 1 June 2020 and 1 November 2021, and a sample of adults who tested negative (2:1), comparable in distribution of age, sex, municipality of residence and year-quarter of testing. New recruitment periods are planned as well. Participants are followed over time by regular follow-up measurements. Data are analyzed using the appropriate data-analyses methods. Discussion: The PRIME post-COVID study will provide insights into various health-related aspects of post-COVID-19 condition in the context of various stages of the COVID-19 pandemic. Results will inform practical guidance for society, clinical and public health practice for the prevention and care for long-term impact of COVID-19. Trial registration ClinicalTrialsgov identifier: NCT05128695.

Glucose Variability Assessed with Continuous Glucose Monitoring: Reliability, Reference Values, and Correlations with Established Glycemic Indices-The Maastricht Study.

Background: Glucose variability (GV) measured by continuous glucose monitoring (CGM) has become an accepted marker of glycemic control. Nevertheless, several methodological aspects of GV assessment require further study. We, therefore, investigated the minimum number of days needed to reliably measure GV, assessed GV reference values, and studied the correlation of GV with established glycemic indices (i.e., HbA1c, seven-point oral glucose tolerance test [OGTT]-derived indices). Methods: We used cross-sectional data from The Maastricht Study, an observational population-based cohort enriched with type 2 diabetes. Participants with more than 48 h of CGM (iPro2; Medtronic) were included for analysis (n = 851; age: 60 ± 9years; 49% women; 23% type 2 diabetes). We used mean sensor glucose (MSG), standard deviation (SD), and coefficient of variation (CV) as CGM-derived indices (the latter two for GV quantification). We calculated reliability using the Spearman-Brown prophecy formula, established reference values by calculating 2.5th-97.5th percentiles, and studied correlations using Spearman's rho. Results: Sufficient reliability (R > 0.80) was achieved with two (MSG and SD), or three monitoring days (CV). The reference ranges, assessed in individuals with normal glucose metabolism (n = 470), were 90.5-120.6 mg/dL (MSG), 7.9-24.8 mg/dL (SD), and 7.74%-22.45% (CV). For MSG, the strongest correlation was found with fasting plasma glucose (rho = 0.65 [0.61; 0.69]); for SD, with the 1-h OGTT value (rho = 0.61 [0.56; 0.65]); and for CV, with both the incremental glucose peak (IGP) during the OGTT (rho = 0.50 [0.45; 0.55]) and the 1-h OGTT value (rho = 0.50 [0.45; 0.55]). Conclusions: The reliability findings and reference values are relevant for studies that aim to investigate CGM-measured GV. One-hour OGTT and IGP values can be used as GV indices when CGM is unavailable.