Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2.

Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.

Development of a prognostic model of COVID-19 severity: a population-based cohort study in Iceland.

BACKGROUND: The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. METHODS: All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. RESULTS: The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke's R2 was 23.4% (95%CI, 22.7-24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96-0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], Emax 0.014 [95%CI, 0.008-0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], Emax 0.018 [95%CI, 0.010-0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and Emax 0.027 [95%CI, 0.013-0.041]). CONCLUSION: Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

Clinical spectrum of coronavirus disease 2019 in Iceland: population based cohort study.

OBJECTIVE: To characterise the symptoms of coronavirus disease 2019 (covid-19). DESIGN: Population based cohort study. SETTING: Iceland. PARTICIPANTS: All individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) between 17 March and 30 April 2020. Cases were identified by three testing strategies: targeted testing guided by clinical suspicion, open invitation population screening based on self referral, and random population screening. All identified cases were enrolled in a telehealth monitoring service, and symptoms were systematically monitored from diagnosis to recovery. MAIN OUTCOME MEASURES: Occurrence of one or more of 19 predefined symptoms during follow-up. RESULTS: Among 1564 people positive for SARS-CoV-2, the most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 83 (5.3%) individuals reported no symptoms, of whom 49 (59%) remained asymptomatic during follow-up. At diagnosis, 216 (14%) and 349 (22%) people did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. Most (67%) of the SARS-CoV-2-positive patients had mild symptoms throughout the course of their disease. CONCLUSION: In the setting of broad access to RT-PCR testing, most SARS-CoV-2-positive people were found to have mild symptoms. Fever and dyspnoea were less common than previously reported. A substantial proportion of SARS-CoV-2-positive people did not meet recommended case definitions at the time of diagnosis.

Humoral Immune Response to SARS-CoV-2 in Iceland.

BACKGROUND: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Disease duration, age at diagnosis and organ damage are important factors for cardiovascular disease in SLE.

OBJECTIVE: To report the incidence rate ratios (IRR) of acute myocardial infarctions (AMI) and cerebrovascular events (CVE) in incident SLE cases from a defined population. To study the risk factors for cardiovascular events in all patients with SLE at our unit. METHODS: Patients with SLE diagnosed from 1981 to 2006 were followed through to 2016. IRRs of AMI and CVE were calculated. The AMI and CVE incidence patterns for patients with SLE were studied in relation to hypertension, smoking, renal dysfunction, anticardiolipin (aCL) antibodies at diagnosis, disease duration and organ damage before an event. RESULTS: 262 patients with SLE were included in the study; of these 175 were from the defined population. Overall, 37 AMI and 44 CVE were recorded. An increased IRR of 3 for AMI was found (p<0.001). Smoking, hypertension and reduced renal function were risk factors for AMI. An increased IRR of 3.3 for ischaemic CVE was found for women (p<0.001). Hypertension and aCL were risk factors for CVE. Organ damage before events was increased. CONCLUSIONS: Cardiovascular events are increased in SLE and are associated with hypertension, smoking and increased damage rate.

Comparative long-term adverse effects elicited by invasive group B and C meningococcal infections.

BACKGROUND: Given the identity between Neisseria meningitidis serogroup B (MenB) capsular polysaccharide (polysialic acid; PSA) and PSA found on neural cell adhesion molecules, it has been proposed that infection with MenB or vaccination with PSA may be associated with subsequent autoimmune or neurological disease. METHODS: We conducted 2 studies. The first was a retrospective nationwide study of invasive meningococcal disease (IMD) in Iceland (with 541 subjects) during the period 1975-2004, and we cross referenced this cohort with databases with respect to subsequent diagnosis of autoimmune disorders. A follow-up study involving 120 survivors of IMD was performed. The study included 70 patients with a history of MenB and 50 patients with N. meningitidis serogroup C (MenC) infection, who served as control subjects. Participants answered standardized questionnaires (Beck's Depression Inventory [BDI] II, Depression Anxiety Stress Scales [DASS], and Patient Health Questionnaire [PHQ]), and serum levels of immunoglobulin (Ig) G against MenB and MenC capsular polysaccharides were measured. RESULTS: The nationwide cohort had 9166 patient-years of follow up. No evidence of increased autoimmunity was found to be associated with MenB, compared with MenC. In the follow-up study, patients were evaluated 16.6 years after the infection, representing 2022 patient-years of observation. Comparable rates of most complications were recorded, but MenC infections were associated with arthritis (P = .008) and migraine headaches (P = .01) more frequently than were MenB infections. No difference was observed with respect to scores on BDI-II, DASS, or PHQ. IgG anti-MenB and anti-MenC capsular polysaccharide levels were not related to patient complaints. CONCLUSIONS: This study does not support the hypothesis that MenB infection may predispose to autoimmunity. MenC infections are associated with a higher prevalence of arthritis and migraine headaches. No evidence of antibody-associated pathology was detected at long-term follow-up.

[Attitudes and knowledge on sexual matters among 16-year old teenagers]. / Vidhorf og thekking 16 ára unglinga á kynlífstengdu efni.

OBJECTIVE: Sexually transmitted diseases and unplanned pregnancies are social and health issues among Icelandic teenagers and are more prevalent than in neighbouring countries. In 2001 knowledge and attitudes to sexual education, sexually transmitted disease and contraception among 16-year olds were investigated by questionnaire. Knowledge was defective. The study was repeated in 2005-2006 in a larger sample and change over five years estimated after an educational effort on sexual issues was launched by medical students (www.astradur.is). MATERIAL AND METHODS: A survey with 69 multiple choice questions was administered in conjunction with sexual education by medical students. Changes in replies to the same questions were compared between 2001 and 2005-2006 as well as before and after teaching. RESULTS: A total of 201 teenagers were in the first and 417 in the latter study. There was a wish for sexual education in schools and by outside advisers. The parental role was relatively small. Knowledge was inadequate in both, but significant improvement was seen between periods and after the educational effort (p<0.001). Misconceptions were common, such as 13% of boys believing that oral contraceptives protected against sexually transmitted disease, that herpes infection was curable by antibiotics (70% of respondents) and that modern medicine cured HIV (10% of respondents). Attitudes to sexual behavior had not changed by 2005-6 and 66% thought it normal for 14-16 year olds to have sexual intercourse, while only 8% were ready to handle the consequences. CONCLUSION: Misconception and inadequate knowledge on various key aspects of sexuality is common, not least on serious sexually transmitted diseases, which suggests a need for improved sexual education in late primary and early secondary school.

[Actinomycosis in a 70 year old woman with a forgotten intrauterine contraceptive device]. / Geislagerlabólga í sjötugri konu med gleymda lykkju. Sjúkratilfelli og yfirlit um sjúkdóminn.

Actinomycosis is an infectious disease that has been known since the late nineteenth century. In the pre-antibiotic era it was thought to be rather common but with increased use of antimicrobial agents its incidence has decreased significantly. The causative agent, most commonly Actinomyces israelii, is part of the commensal bacterial flora. It can infect any tissue, respects no tissue boundaries and can spread throughout the body. The clinical presentation of this illness can be similar to malignant disease and definite diagnosis is sometimes not apparent until after surgery and histologic examination. We report the case of a 71 year old woman who suffered from actinomycosis of the uterus and ovaries due to a forgotten intrauterine contraceptive device that had been in place for over four decades. The disease presentation was consistent with malignant disease and tumor markers, CA 125, CA 19-9 and CEA, measured in blood were elevated. She was treated successfully with total hysterectomy and bilateral salphingo-oophorectomy, as well as penicillin for six months.

The effects of smoking in pregnancy on factors influencing fetal growth.

AIM: To evaluate the influence of maternal smoking during pregnancy on factors influencing fetal growth. METHODS: Thirty newborns of smoking mothers were prospectively compared with 60 newborns of non-smoking mothers. Pre-albumin, albumin, triglycerides, glucose, insulin, insulin-like growth factor I, IGF binding protein 3, pH, lactic acid, erythropoietin and hemoglobin concentrations were measured in umbilical cord blood. RESULTS: Infants of smoking mothers had a significantly lower birth weight (3418 +/- 533 vs. 3863 +/- 503 g; p < 0.001), length (50.5 +/- 2,6 vs. 52.3 +/- 1.9 cm; p < 0.001) and head circumference (34.6 +/- 1.8 vs. 35.8 +/- 1.1 cm; p < 0.001) than controls. They also had significantly lower insulin (3.2 (2.0-4.9) vs. 5.8 (4.6-7.1) mU/L; p = 0.008), insulin-like growth factor I (54.4 +/- 32.5 vs. 93.8 +/- 54.5 microg/L; p = 0.001) and IGF binding protein 3 (1664 +/- 432 vs. 1943 +/- 421 microg/L; p = 0.01) concentrations, than controls. Infants of smoking mothers also had significantly higher hemoglobin (167 +/- 14 vs. 157 +/- 13 g/L; p = 0.002) and erythropoietin (42.3 (25.1-72.4) vs. 26.3 (21.9-30.9) U/L; p = 0.03) than controls, but not pH or lactate concentrations. There was no significant difference in pre-albumin, albumin, triglycerides and glucose concentrations. CONCLUSIONS: Smoking during pregnancy causes symmetrical fetal growth impairment, possibly due to decreased oxygen transport to the fetus and decreased concentrations of fetal insulin, insulin-like growth factor I and IGF binding protein 3.