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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22280990

ABSTRACT

BackgroundPost-acute symptoms are not uncommon after SARS-CoV-2 infection with pre-Omicron variants. How the Omicron variant and COVID-19 booster vaccination influences the risk of post-acute symptoms is less clear. ObjectivesTo evaluate the effects of the Omicron variant and COVID-19 booster vaccination on post-acute symptoms, four months after infection with SARS-CoV-2. MethodsA nationwide Danish questionnaire study comprising 44,004 individuals aged 15 years or older with outcomes on post-acute symptoms and new-onset general health problems, four months after testing. Risk differences (RDs) were estimated by comparing Omicron -cases to controls, Omicron to Delta -cases, and Omicron vaccinated cases with three to -two doses, adjusted for age, sex, BMI, self-reported chronic diseases, Charlson comorbidity index, healthcare occupation, and vaccination status. ResultsFour months after testing for SARS-CoV-2 during the Omicron period, the largest RD comparing Omicron cases to controls was observed for memory issues (RD=7.2%, 95% CI: 6.4 to 8.1). Compared to cases from the Delta period, Omicron cases reported reduced risks of post-acute dysosmia (RD=-15.5%, 95% CI: -17.5 to -13.4) and dysgeusia (RD=-11.8%, 95% CI: -13.9 to -9.8). Cases vaccinated with three doses prior to Omicron infection reported reduced risk of 13/26 post-acute symptoms and of 4/5 new-onset general health problems, compared to those vaccinated with two doses. ConclusionsCases infected during the Omicron period experienced substantial post-acute symptoms and new-onset health problems, four months after testing, although milder than Delta cases. Booster vaccination was associated with fewer post-acute symptoms and new-onset health problems, four months after Omicron infection, compared to two doses of COVID-19 vaccine.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22271328

ABSTRACT

BackgroundA considerable number of individuals infected with SARS-CoV-2 continue to experience symptoms after the acute phase. More information on duration and prevalence of these symptoms in non-hospitalized populations is needed. MethodsWe conducted a nationwide cross-sectional study including 152 880 individuals aged 15-years or older, consisting of RT-PCR confirmed SARS-CoV-2 cases between September 2020-April 2021 (N=61 002) and a corresponding test-negative control group (N=91 878). Data were collected 6, 9 or 12 months after the test using web-based questionnaires. The questionnaire covered acute and post-acute symptoms, selected diagnoses, sick leave and general health, together with demographics and life style at baseline. Risk differences (RDs) between test-positives and -negatives were reported, adjusted for age, sex, single comorbidities, Charlson comorbidity score, obesity and healthcare-occupation. FindingsSix to twelve months after the test date, the risks of 18 out of 21 physical symptoms were elevated among test-positives and one third (29.6%) of the test-positives experienced at least one physical post-acute symptom. The largest risk differences were observed for dysosmia (RD = 10.92%, 95%CI 10.68-11.21%), dysgeusia (RD=8.68%, 95%CI 8.43-8.93%), fatigue/exhaustion (RD=8.43%, 95%CI 8.14-8.74%), dyspnea (RD=4.87%, 95%CI 4.65-5.09%) and reduced strength in arms/legs (RD=4.68%, 95%CI 4.45-4.89%). More than half (53.1%) of test-positives reported at least one of the following conditions: concentration difficulties (RD=28.34%, 95%CI 27.34-28.78%), memory issues (RD=27.25%, 95%CI 26.80-27.71%), sleep problems (RD=17.27%, 95%CI 16.81-17.73%), mental (RD=32.58%, 95%CI 32.11-33.09%) or physical exhaustion (RD=40.45%, 95%CI 33.99-40.97%), compared to 11.5% of test-negatives. New diagnoses of anxiety (RD=1.15%, 95%CI 0.95-1.34%) or depression (RD=1.00%, 95%CI 0.81-1.19%) were also more common among test-positives. InterpretationAt the population-level, where the majority of test-positives (96.0%) were not hospitalized during acute infection, a considerable proportion experience post-acute symptoms and sequelae 6-12 months after infection. FundingNone Research in contextO_ST_ABSEvidence before the studyC_ST_ABSTo identify existing studies on the epidemiology and clinical nature of post-acute COVID-19 symptoms, we searched PubMed for articles published until January 4, 2022 using the search string (((SARS-CoV-2[Title/Abstract]) OR (COVID-19[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND ((post-acute[Title/Abstract]) OR ("post acute"[Title/Abstract]) OR ("long haul*"[Title/Abstract]) OR ("long-term symptoms"[Title/Abstract]) OR ("long-term disease"[Title/Abstract]) OR ("long-term illness"[Title/Abstract]) OR ("persistent symptoms"[Title/Abstract]) OR ("persistent disease"[Title/Abstract]) OR ("persistent illness"[Title/Abstract]) OR ("prolonged symptoms"[Title/Abstract]) OR ("prolonged disease"[Title/Abstract]) OR ("prolonged illness"[Title/Abstract]))) OR (long-covid[Title/Abstract]) OR ("Post-COVID-19 syndrome"[Title/Abstract]) OR ("Post-COVID-19 condition"[Title/Abstract]) OR ("Post-COVID-19 symptoms"[Title/Abstract]). This resulted in 870 articles. When screening these, we focused on articles covering symptoms comprehensively or a broader area, e.g. mental health problems, rather than in-depth studies of symptoms within a single area, case stories or studies focusing on clinical management. A very wide range of post-acute symptoms originating from many different organ systems have been reported. This includes pulmonary, cardiovascular, hematologic, gastrointestinal, renal, endocrine, dermatologic, neurological and cognitive symptoms, as well as more general health problems, in particular fatigue. Based on two systematic reviews covering the period December 2019-March 2021, the majority of studies of persistent COVID-19 symptoms had until then been conducted among hospitalized patients and thus were not representative of the general population, where the majority will only have suffered mild or moderate disease. Since then some larger register-based studies as well as some smaller questionnaire- or interview-based studies have been conducted among non-hospitalized patients. Both types of studies offer advantages and disadvantages in relation to obtaining the full overview of long-term effects. Register-based studies are best suited for capturing more severe conditions confirmed by a trained physician and defined by diagnostic classification schemes, whereas questionnaires including self-reported symptoms are able to capture symptoms and health outcomes that do not easily confirm to disease diagnoses, but which are nevertheless critical to our understanding of the burden of post-acute symptoms. The number of sstudies of post-acute conditions among non-hospitalized patients with a follow-up time of more than 6 months is still limited. Some of the major remaining knowledge gaps regarding post-acute symptoms are: 1) What is the prevalence and variety of post-acute symptoms in the general population of infected persons, where the majority will only have suffered mild or moderate disease, 2) For how long do post-acute symptoms persist, and 3) Which subgroups of individuals, if any, are at higher risk of post-acute symptoms. Added value of this studyThe present nationwide questionnaire-study is based on a large, mainly adult study population (N=152 880), where all individuals in Denmark, who tested positive during the study period, were invited to participate along with comparable test-negative controls. Marked levels of post-acute symptoms and conditions were reported with changes in sense of smell and taste being the most frequently reported single physical symptoms. As many as half (53.1%) of the participants report having experienced general health problems in the form of either mental or physical exhaustion, sleep problems or cognitive problems, compared to 11.5% of control persons 6 to 12 months after the test. Our results suggest that a considerable proportion of the general population, who did not experience severe disease, are still affected 6 to 12 months after infection and that post-acute symptoms are more often experienced by females and middle-aged individuals. Implications of all available evidenceDiverse post-acute symptoms following infection with SARS-CoV-2 occur frequently. Even up to 12 months after the onset of infection, a considerable proportion of individuals, who did not experience severe disease, continue to experience symptoms. Post-acute symptoms are generally more often reported by females than males, whereas the influence of age remains unclear.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-21261777

ABSTRACT

BackgroundNational data on the spread of SARS-CoV-2 infection and knowledge on associated risk factors are important for understanding the course of the pandemic. "Testing Denmark" is a national large-scale epidemiological surveillance study of SARS-CoV-2 in the Danish population. MethodsBetween September and October 2020, approximately 1.3 million of 5.8 million Danish citizens (age > 15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by Point-of Care rapid Test (POCT) distributed to participants home addresses. FindingsIn total 318,552 participants (24.5% invitees) completed the questionnaire and provided the result of the POCT. Of these, 2,519 (0.79%) were seropositive (median age 55 years) and women were more often seropositive than men, interquartile range (IQR) 42-64, 40.2% males. Of participants with a prior positive Polymerase Chain Reaction (PCR) test (n=1,828), 29.1% were seropositive in the POCT. Seropositivity increased with age irrespective of sex. Elderly participants (>61 years) reported less symptoms and had less frequently been tested for SARS-CoV-2 compared to younger participants. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (Risk ratio (RR) 7.43, 95% CI: 6.57-8.41) and in particular household members (RR 17.70, 95% CI: 15.60-20.10). Home care workers had a higher risk of seropositivity (RR 2.09 (95% CI: 1.58-2.78) as compared to office workers. Geographic population density was not associated to seropositivity. A high degree of compliance with national preventive recommendations was reported (e.g., > 80% use of face masks), but no difference was found between seropositive and seronegative participants. InterpretationThis study provides insight into the immunity of the Danish population seven to eight months after the first COVID-19 case in Denmark. The seroprevalence was lower than expected probably due to a low sensitivity of the POCT used or due to challenges relating to the reading of test results. Occupation or exposure in local communities were major routes of infection. As elderly participants were more often seropositive despite fewer symptoms and less PCR tests performed, more emphasis should be placed on testing this age group.

4.
Preprint in English | medRxiv | ID: ppmedrxiv-21256388

ABSTRACT

BackgroundPeople experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. Design and methodsIn November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. ResultsWe included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p=0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p <0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (RR 2.1, 95% CI 1.16-3.75, p=0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). InterpretationsThe prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. The subset of the study participants who were also sex workers were at particularly high risk of COVID-19 infection. FundingTrygFonden and HelseFonden.

5.
Preprint in English | medRxiv | ID: ppmedrxiv-21256725

ABSTRACT

BackgroundCOVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas. MethodsAs part of "Testing Denmark", a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population. FindingsOf the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 p<0,001). Adjusted for age, gender and region living at least 4 people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.1-1.6, p=0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.5, p=0.007). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Anosmia (RR 3.2 95% CI 2.8-3.7, p<0.001) and ageusia (RR 3.3, 95% CI 2.9-3.8, p<0.001) were strongest associated with seropositivity. InterpretationDanish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.

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