Factors influencing the immune response over 15 months after SARS-CoV-2 infection: A longitudinal population-wide study in the Faroe Islands.

BACKGROUND: The durability of SARS-CoV-2 antibody response and the resulting immunity to COVID-19 is unclear. OBJECTIVES: To investigate long-term humoral immunity to SARS-CoV-2. METHODS: In this nationwide, longitudinal study, we determined antibody response in 411 patients aged 0-93 years from two waves of infections (March to December 2020) contributing 1063 blood samples. Each individual had blood drawn on 4-5 occasions 1-15 months after disease onset. We measured total anti-SARS-CoV-2 receptor-binding domain (RBD) antibody using a qualitative RBD sandwich ELISA, IgM, IgG and IgA levels using an quantitative in-house ELISA-based assay  and neutralizing antibodies (NAbs) using an in-house ELISA-based pseudoneutralizing assay. IgG subclasses were analyzed in a subset of samples by ELISA-based assay. We used nonlinear models to study the durability of SARS-CoV-2 antibody responses and its influence over time. RESULTS: After 15 months, 94% still had detectable circulating antibodies, mainly the IgG isotype, and 92% had detectable NAbs. The distribution of IgG antibodies varied significantly over time, characterized by a biphasic pattern with an initial decline followed by a plateau after approximately 7 months. However, the NAbs remained relatively stable throughout the period. The strength of the antibody response was influenced by smoking and hospitalization, with lower IgG levels in smokers and higher levels in hospitalized individuals. Antibody stability over time was mainly associated with male sex and older age with higher initial levels but more marked decrease. CONCLUSIONS: The humoral immune response to SARS-CoV-2 infection varies depending on behavioral factors and disease severity, and antibody stability over 15 months was associated with sex and age.

Omicron Outbreak at a Private Gathering in the Faroe Islands, Infecting 21 of 33 Triple-Vaccinated Healthcare Workers.

There are concerns that the severe acute respiratory syndrome coronavirus 2 Omicron variant evades immune responses due to an unusually high number of mutations on the spike protein. Here, we report a superspreading event of Omicron infections among 21 of 33 triple-vaccinated healthcare workers who attended a private gathering.

Low Seroprevalence among Undetected COVID-19 Cases, Faroe Islands, November 2020.

We conducted a second nationwide severe acute respiratory syndrome coronavirus 2 seroprevalence study in the Faroe Islands during November 2020. We found crude seroprevalence was 0.3% and prevalence was 0.4% after adjusting for test sensitivity and specificity. This low seroprevalence supports the prevention strategies used in the Faroe Islands.

Polygenic risk of Alzheimer's disease in the Faroe Islands.

BACKGROUND AND PURPOSE: The Faroe Islands are a geographically isolated population in the North Atlantic with a similar prevalence of Alzheimer's disease (AD) and all-cause dementia as other European populations. However, the genetic risk underlying AD and other dementia susceptibility has yet to be elucidated. METHODS: Forty-nine single-nucleotide polymorphisms (SNPs) were genotyped in 174 patients with AD and other dementias and 159 healthy controls. Single variant and polygenic risk score (PRS) associations, with/without APOE variability, were assessed by logistic regression. Performance was examined using receiver operating characteristic area under the curve (ROC AUC) analysis. RESULTS: APOErs429358 was associated with AD in the Faroese cohort after correction for multiple testing (odds ratio [OR] 6.32, 95% confidence interval [CI] 3.98-10.05, p = 6.31e-15 ), with suggestive evidence for three other variants: NECTIN2 rs41289512 (OR 2.05, 95% CI 1.20-3.51, p = 0.01), HLA-DRB1 rs6931277 (OR 0.67, 95% CI 0.48-0.94, p = 0.02) and APOE rs7412 [ε2] (OR 0.28, 95% CI 0.11-0.73, p = 0.01). PRSs were associated with AD with or without the inclusion of APOE (PRS+APOE OR = 4.5, 95% CI 2.90-5.85, p = 4.56e-15 , and PRS-APOE OR = 1.53, 95% CI 1.21-1.98, p = 6.82e-4 ). AD ROC AUC analyses demonstrated a PRS+APOE AUC = 80.3% and PRS-APOE AUC = 63.4%. However, PRS+APOE was also significantly associated with all-cause dementia (OR = 3.39, 95% CI 2.51-4.71, p = 2.50e-14 ) with an AUC = 76.9%, that is, all-cause dementia showed similar results albeit less significant. DISCUSSION: In the Faroe Islands, SNP analyses highlighted APOE and immunogenomic variability in AD and dementia risk. PRS+APOE , based on 25 SNPs/loci, had excellent sensitivity and specificity for AD with an AUC of 80.3%. High PRSs were also associated with an earlier onset of late-onset AD.

Cancer in the Faroe Islands from 1960-2019 - incidence, mortality, and comparisons with the other Nordic countries.

Purpose: In this paper, we present age-standardized cancer incidence and mortality rates in the Faroe Islands. We also compare with the Nordic rates and show incidence rate ratios (IRR) and mortality rate ratios (MRR).Materials and methods: The Faroese cancer registry (FCR) was established in 1994, with incidence available from 1960 and mortality from 1983. The FCR is a part of the NORDCAN collaboration, where the different Nordic countries all report anonymized cancer data by standardized methods, ensuring comparability. Validation efforts revealed that 13% of cases had not been reported to the FCR from 2006 to 2019, emphasizing the need for continued validation efforts of cancer registries. After validation, we submitted the updated cancer cases to NORDCAN and now present this data, taken directly from the NORDCAN website (2019 data).Results: We found that the incidence of the summary group all cancers in the Faroe Islands increased from 1960 to 2019, while cancer mortality decreased from 1983 to 2019. Comparisons with Nordic rates showed significantly lower IRRs for cancer in all cancers, bladder and urinary tract, and skin cancer for both sexes, while IRR was lower for breast cancer in women and prostate cancer in men. Contrary, IRR was higher for rectum and kidney cancer in women and esophagus and testicular cancer in men. There was an increased MRR for cancer in female organs, bladder and urinary tract, and kidney cancer in women, and esophagus and pancreas cancer in men. In contrast, malignant hematopoietic diseases and melanoma in women had a lower MRR.Conclusions: Cancer incidence in the Faroe Islands was lower than in the other Nordic countries. Of particular interest, the incidence of testicular cancer saw a steep increase during the last 20 years, and an investigation into possible causes for this is needed.

The Faroese Septuagenarians cohort: A comparison of well-being before and during the COVID-19 pandemic among older home-dwelling Faroese.

AIMS: Despite success in avoiding morbidity and mortality in the oldest members of the population during the COVID-19 pandemic, the crisis may have affected the well-being of older adults, for example due to social distancing measures. The aim of this study was to examine the well-being of older Faroese by conducting a direct comparison of well-being indicators on the same group of elderly people before and during the COVID-19 pandemic. METHODS: Data were collected from 227 home-dwelling adults aged 82-86 years from the Faroese Septuagenarians cohort. The pre-COVID-19 period was from December 2017 to January 2019, and the COVID-19 period was from 8 June to 15 July 2020. Three aspects of well-being were assessed: loneliness, self-rated health and quality of life (WHOQOL-BREF). RESULTS: During the COVID-19 pandemic, there were significant increases in loneliness (21.8% vs. 6.8%; p<0.001) and in worse self-rated health compared to the previous year (37.2% vs. 19.0%; p<0.001). In terms of quality of life, the domains of overall quality of life (74.33±14.96 vs. 71.88±15.21; p=0.04) and physical health (73.81±17.11 vs. 71.66±17.37; p=0.03) deteriorated. On the other hand, the domains of social relationships (78.87±16.52 vs. 85.81±13.35; p<0.001), environment (82.49±10.78 vs. 87.06±7.88; p<0.001) and psychological health (77.07±11.52 vs. 80.53±10.89; p<0.001) improved during the pandemic. CONCLUSIONS: Our findings suggest that attention should be directed to loneliness and physical well-being amongst home-dwelling old adults, despite the elderly showed resilience and improved psychological health, social relations and environment domains in a quality of life assessment during the COVID-19 pandemic.

Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021.

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID). Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration. Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022. Exposures: Symptomatic SARS-CoV-2 infection. Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age. Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months. Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

Long COVID in the Faroe Islands: A Longitudinal Study Among Nonhospitalized Patients.

BACKGROUND: Little is known about long-term recovery from coronavirus disease 2019 (COVID-19) disease, especially in nonhospitalized individuals. In this longitudinal study we present symptoms registered during the acute phase as well as long COVID (ie, long-lasting COVID-19 symptoms) in patients from the Faroe Islands. METHODS: All consecutive patients with confirmed reverse transcription-polymerase chain reaction testing from April to June 2020 were invited to participate in this study for the assessment of long COVID. Demographic and clinical characteristics and self-reported acute and persistent symptoms were assessed using a standardized detailed questionnaire administered at enrollment and at repeated phone interviews in the period 22 April to 16 August. RESULTS: Of the 180 participants (96.3% of the 187 eligible COVID-19 patients), 53.1% reported persistence of at least 1 symptom after a mean of 125 days after symptoms onset, 33.0% reported 1 or 2 symptoms, and 20.1% reported 3 or more symptoms. At the last follow-up, 46.9% were asymptomatic compared with 4.4% during the acute phase. The most prevalent persistent symptoms were fatigue, loss of smell and taste, and arthralgias. CONCLUSIONS: Our results show that it might take months for symptoms to resolve, even among nonhospitalized persons with mild illness course in the acute phase. Continued monitoring for long COVID is needed.

Seroprevalence of SARS-CoV-2-Specific Antibodies among Quarantined Close Contacts of COVID-19 Patients, Faroe Islands, 2020.

Close contacts of coronavirus disease (COVID-19) patients are at high risk for severe acute respiratory syndrome 2 (SARS-CoV-2) infection. We assessed the seroprevalence of SARS-CoV-2-specific antibodies among quarantined close contacts of COVID-19 patients in the Faroe Islands. We invited quarantined close contacts of COVID-19 index patients identified during March 3-April 22, 2020, to participate in this study; 584 (81%) contacts consented and underwent serologic testing. Among the 584 participants, 32 (5.5%) were seropositive for total antibody against SARS-CoV-2. Household and young or elderly contacts had higher risk for seropositivity than other contacts. We found a secondary attack rate of 19.2%. Seroprevalence among close contacts was almost 10-fold higher than among the general population of the Faroe Islands. Regularly testing household close contacts of COVID-19 patients might help track the transmission of SARS-CoV-2.

Epidemiology and Clinical Course of First Wave Coronavirus Disease Cases, Faroe Islands.

The Faroe Islands was one of the first countries in the Western Hemisphere to eliminate coronavirus disease (COVID-19). During the first epidemic wave in the country, 187 cases were reported between March 3 and April 22, 2020. Large-scale testing and thorough contact tracing were implemented early on, along with lockdown measures. Transmission chains were mapped through patient history and knowledge of contact with prior cases. The most common reported COVID-19 symptoms were fever, headache, and cough, but 11.2% of cases were asymptomatic. Among 187 cases, 8 patients were admitted to hospitals but none were admitted to intensive care units and no deaths occurred. Superspreading was evident during the epidemic because most secondary cases were attributed to just 3 infectors. Even with the high incidence rate in early March, the Faroe Islands successfully eliminated the first wave of COVID-19 through the early use of contact tracing, quarantine, social distancing, and large-scale testing.

Incidence, gender influence, and neuropsychological predictors of all cause dementia in the Faroe Islands-the Faroese Septuagenarian cohort.

BACKGROUND: Using the Faroese Septuagenarian cohort, we aimed to describe the incidence of dementia and assess the validity of neurocognitive tests to predict subsequent dementia diagnosis. METHODS: In this population-based cohort, 713 Faroese septuagenarians aged 70-74 years without dementia, underwent clinical and neuropsychological examinations. After 10-years of follow-up, information was collected on all participants referred for cognitive evaluations and diagnosed with dementia. Incidence rates were calculated and presented with 95% confidence intervals (CIs), assuming a Poisson distribution. We then performed discriminant analysis to determine the best set of neuropsychological tests to identify those who would develop dementia. RESULTS: Over the 10-years, 65 participants (9.1%) were diagnosed with dementia, with a 10-year incidence rate of 1063 cases per 100,000 person years (95% CI 825, 1343). Women had a greater incidence than men (incidence rate ratio (IRR) = 1.58; 95% CI 0.93, 2.71). After stepwise selection, gender and six neuropsychological measures were selected to discriminate between those who would and would not develop dementia. Overall, the model was able to correctly identify 82% of those who would not develop dementia (specificity) and 71% of those who would (sensitivity). CONCLUSIONS: These results indicate that among a greater number of tests covering a broad range of cognitive abilities, tests reflecting verbal and visual learning and recall, visuospatial function, attention, and encoding into and retrieval from long-term memory may be helpful in identifying patients in the pre-symptomatic phase of dementia. Thus, helping care-givers identify patients at a higher risk of developing dementia and adjusting management of care accordingly.

Seroprevalence of SARS-CoV-2-Specific Antibodies, Faroe Islands.

We conducted a nationwide study of the prevalence of severe acute respiratory syndrome coronavirus 2 infection in the Faroe Islands. Of 1,075 randomly selected participants, 6 (0.6%) tested seropositive for antibodies to the virus. Adjustment for test sensitivity and specificity yielded a 0.7% prevalence. Our findings will help us evaluate our public health response.

Blood Harmane (1-Methyl-9H-Pyrido[3,4-b]indole) and Mercury in Essential Tremor: A Population-Based, Environmental Epidemiology Study in the Faroe Islands.

BACKGROUND: Essential tremor (ET) is among the most prevalent neurological diseases. Its environmental determinants are poorly understood. Harmane (1-methyl-9H-pyrido[3, 4-b]indole), a dietary tremor-producing neurotoxin, has been linked to ET in a few studies in New York and Madrid. Mercury, also a tremor-producing neurotoxin, has not been studied in ET. The Faroe Islands have been the focus of epidemiological investigations of numerous neurological disorders. OBJECTIVE: In this population-based, case-control study, we directly measured blood harmane concentrations (HA) and blood mercury concentrations (Hg) in ET cases and controls. METHODS: In total, 1,328 Faroese adults were screened; 26 ET cases were identified whose (HA) and (Hg) were compared to 197 controls. RESULTS: Although there were no statistically significant differences between diagnostic groups, median (HA) was 2.7× higher in definite ET (4.13 g-10/mL) and 1.5× higher in probable ET (2.28 g-10/mL) than controls (1.53 g-10/mL). Small sample size was a limitation. For definite ET versus controls, p = 0.126. (Hg) were similar between groups. CONCLUSIONS: We demonstrated marginally elevated (HA) in definite and probable ET. These data are similar to those previously published and possibly extend etiological links between this neurotoxin and ET to a third locale. The study did not support a link between mercury and ET.

Prevalence of Essential Tremor in the Faroe Islands: A Population-Based Study.

BACKGROUND: No studies of the prevalence of one of the most common movement disorders, essential tremor (ET), have been undertaken in the Faroe Islands. Given the potential for founder effects in the Islands, and the highly genetic nature of ET, the Faroe Islands provide a particularly interesting setting in which to study the prevalence of ET. OBJECTIVE: To estimate the prevalence of ET and study its characteristics. METHODS: We used a 2-phase, population-based design, screening 1,328 randomly selected Faroese individuals aged ≥40 years. A subsample of 282 individuals who had returned the spirals and questionnaire was selected to participate in an in-person clinical evaluation. Tremor was systematically quantified by a senior movement disorder neurologist with particular specialization in tremor using a reliable and valid clinical rating scale followed by the application of rigorous diagnostic criteria used by tremor investigators internationally. RESULTS: The overall crude prevalence was 2.9%. The age-adjusted prevalence was 3.1%. There was an age-associated rise in prevalence; by age ≥70, prevalence reached 4.8%. Twenty six of 27 (96.2%) were previously undiagnosed. CONCLUSIONS: This is the first population-based study of the prevalence of ET in the Faroe Islands. The estimated prevalence was similar to studies using the same or comparable methodologies.

High Prevalence of Dystonia in the Faroe Islands: A Population-Based Study.

BACKGROUND: There are fewer than 5 population-based studies of dystonia worldwide. Only one utilized a movement disorders neurologist. Given the potential for founder effects, and the highly genetic nature of dystonia, the Faroe Islands provide a particularly interesting setting to study the prevalence of dystonia. OBJECTIVE: To estimate the prevalence of dystonia. METHODS: We used a 2-phase, population-based design, screening 1,334 randomly selected Faroese individuals aged ≥40 years from which a subsample of 227 participated in an in-person clinical evaluation. Dystonia was assessed by 2 movement disorder neurologists using videotaped examinations. RESULTS: Two of 227 (0.88%, 95% CI -0.33 to 2.09%) were diagnosed with cervical or segmental dystonia. An unusual form of thumb flexion dystonia was noted in 75 more, yielding a combined prevalence of 33.92% (95% CI 27.73-40.11%). CONCLUSIONS: The prevalence of cervical or segmental dystonia was as high as in one prior population-based study using similar methods. Furthermore, an unusual form of thumb flexion dystonia was uncovered, which yielded an extraordinarily high prevalence of dystonia in this population. Although our methods likely contributed to more complete capture of subtle dystonia, founder effects are highly likely to have been an additional major contributor to these findings.

Assessing the Prevalence of Undetected Possible Dementia in Faroese Nursing Homes.

INTRODUCTION: To assess the prevalence of possible dementia among nursing home residents in the Faroe Islands. METHOD: This cross-sectional study, undertaken in 2017, included all nursing homes in the Faroe Islands (n = 30), housing 591 residents. All residents were invited to participate, except those with an existing clinical diagnosis of dementia or living in dementia units (n = 207). A total of 232 residents participated, while 39 declined and 113 were unable to give consent, had died, or were not permanent residents at the time of examination. Cognitive screening was carried out using the Mini-Mental State Examination (MMSE) and the Informant Questionnaire on Cognitive Decline (IQCODE). RESULTS: Possible dementia was found in 49% to 78% of the participants depending on the method used. According to both MMSE and IQCODE (AND rule), possible dementia was present in 105 participants (49%). According only to IQCODE, 119 participants (55%) scored above the cut-off (≥3.6), according to MMSE alone, 162 participants (72%) scored below the cut-off (≤24 on MMSE), while 175 participants (78%) screened positive according to either MMSE or IQCODE (OR rule). A rough estimate of the prevalence of possible dementia in the entire nursing home population (n = 591) including residents with known dementia and those with possible dementia from this study was between 61% and 73%. CONCLUSION: A high percentage (49-78%) of the participating nursing home residents without a pre-dementia diagnosis were assessed to have possible dementia based on screening with standardized tools, indicating a high degree of dementia underdiagnoses in Faroese nursing homes. This high prevalence of dementia is of significance for the clinical practice, running, and planning of nursing homes and pinpoints a need to act upon this, not only in the Faroes but also worldwide.

Gender differences in cognitive performance and health status in the Faroese Septuagenarians cohort.

The aim was to determine cognitive performance and health status in the Faroese Septuagenarians cohort in relation to gender differences. In this cross-sectional study of 713 Faroese septuagenarians who underwent a clinical, neurophysiological and neuropsychological examinations and questionnaire, women performed better on tests covering the memory domain, while there was no gender difference in other cognitive domains. Men suffered more frequently from cardiovascular events while women more frequently suffered from arthrosis, hypothyroidism and muscle pain. We observed a considerable heterogeneity and gender difference in some cognitive domains and health in Faroese septuagenarians.

Umbilical Cord Serum 25-Hydroxyvitamin D Concentrations and Relation to Birthweight, Head Circumference and Infant Length at Age 14 Days.

BACKGROUND: Insufficient supply of vitamin D during early development may negatively affect offspring growth. METHODS: We examined the association between umbilical cord (UC) serum 25-hydroxyvitamin D (25(OH)D) concentrations and infant size in a study of two Faroese birth cohorts of 1038 singleton infants. In the third trimester, the pregnant women completed questionnaires, and clinical examination included birthweight, head circumference, and infant length at age 14 days. RESULTS: Fifty-three percent of the newborn population had UC 25(OH)D < 25 nmol/L as determined by LC-MS/MS. Using multiple linear regression models with adjustment for pre-pregnancy BMI, sex, parity, gestational age, or infant age at examination, season of birth, smoking, gestational diabetes, examiner, and cohort identity, we found no relationship between birthweight or head circumference and UC 25(OH)D. However, infants with vitamin D status <12 nmol/L had a 0.49 (95% confidence interval 0.05, 0.93) cm lower length than infants with vitamin D status >50 nmol/L in models further adjusted for birthweight. CONCLUSION: Our data suggest that umbilical cord serum 25(OH)D concentrations are positively associated with infant length but not with birthweight and head circumference. Although the paediatric relevance of the observed association is unclear, the possible long-term consequences of late-pregnancy hypovitaminosis D deserve attention.