Objectives There is a lack of large studies on long-COVID symptoms with symptoms measurements before the onset of COVID-19. Therefore, long-COVID is still poorly defined. Methods The Norwegian COVID-19 Cohort Study is a population-based, open cohort of adult participants (aged 18-96 years) from Norway. From March 27, 2020, participants were recruited through social media, invitations, and nationwide media coverage. Fourteen somatic and cognitive symptoms were assessed at baseline and four follow-ups for up to 22 months. SARS-CoV-2 test status was obtained from a mandatory national registry or from self-report. Results After follow-up, 15 737 participants had a SARS-CoV-2-positive test, 67 305 had a negative test, and 37 563 were still untested. Persistent symptoms reported more frequently by positive compared with negative participants one month after infection, were memory problems (3-6 months: adjusted odds ratio (aOR) = 6.8, CI = 5.7-8.1; >18 months: aOR = 9.4, CI = 4.1-22), and concentration problems (3-6 months: aOR = 4.1, CI = 3.5-4.7; >18 months: aOR = 4.4, CI = 2.0-9.7) as well fatigue, dyspnea, anosmia and dysgeusia. Conclusions COVID-19 was associated with cognitive symptoms, anosmia, dysgeusia, dyspnea, and fatigue as well as worsening of overall health up to 22 months after a SARS-CoV-2 test, even when correcting for symptoms before the onset of COVID-19.

Importance:Post-acute sequelae of SARS-CoV-2, referred to as "long COVID", are a globally pervasive threat. While their many clinical determinants are commonly considered, their plausible social correlates are often overlooked. Objective:To compare social and clinical predictors of differences in quality of life (QoL) with long COVID. Additionally, to measure how much adjusted associations between social factors and long COVID-associated quality of life are unexplained by important clinical intermediates. Design Setting and Participants:Data from the ISARIC long COVID multi-country prospective cohort study. Subjects from Norway, the United Kingdom (UK), and Russia, aged 16 and above, with confirmed acute SARS-CoV-2 infection reporting >= 1 long COVID-associated symptoms 1+ month following infection. Exposure:The social exposures considered were educational attainment (Norway), employment status (UK and Russia), and female vs male sex (all countries). Main outcome and measures:Quality of life-adjusted days, or QALDs, with long COVID. Results:This cohort study included a total of 3891 participants. In all three countries, educational attainment, employment status, and female sex were important predictors of long COVID QALDs. Furthermore, a majority of the estimated relationships between each of these social correlates and long COVID QALDs could not be attributed to key long COVID-predicting comorbidities. In Norway, 90% (95% CI: 77%, 100%) of the adjusted association between the top two quintiles of educational attainment and long COVID QALDs was not explained by clinical intermediates. The same was true for 86% (73%, 100%) and 93% (80%,100%) of the adjusted associations between full-time employment and long COVID QALDs in the United Kingdom (UK) and Russia. Additionally, 77% (46%,100%) and 73% (52%, 94%) of the adjusted associations between female sex and long COVID QALDs in Norway and the UK were unexplained by the clinical mediators. Conclusions and Relevance:This study highlights the role of socio-economic status indicators and female sex, in line with or beyond commonly cited clinical conditions, as predictors of long COVID-associated QoL, and further reveal that other (non-clinical) mechanisms likely drive their observed relationships. Our findings point to the importance of COVID interventions which go further than an exclusive focus on comorbidity management in order to help redress inequalities in experiences with this chronic disease.

Objectives We aimed to describe the trajectories of cognitive and physical symptoms before, during, and after a positive- or negative SARS-CoV-2 test and in untested controls. Design A prospective cohort study. Setting Norway, 27 March 2020 to 6 July 2022 Participants A total of 146 065 volunteers were recruited. Of these, 120 605 participants (mean age 49 (SD 13.7), 69% female), were initially untested for the SARS-CoV-2 virus, completed one or more follow-up questionnaires (response rates 72-90%) and were included for analysis. After 22 months of follow-up, 15 737 participants had a positive SARS-CoV-2 test, 67 305 a negative test, and 37 563 were still untested. Main outcome measures We assessed reported symptoms the past three weeks of memory or concentration problems, anosmia and dysgeusia, dyspnoea, fatigue, fever, headache, cough, muscular pain, nasal symptoms, sore throat and abdominal pain at baseline and through four follow-up questionnaires. In addition, overall health compared to a year before was measured with a five-point scale and memory problems were measured using the Everyday Memory Questionnaire-13 at two timepoints. The exposure, SARS-CoV-2 test status (positive, negative or untested), was obtained from a mandatory national registry or from self-report, and data were analysed using mixed model logistic regression. Results A positive SARS-CoV-2-test was associated with the following persistent symptoms, compared with participants with a negative test (1-3 months after a negative test); memory problems (3 to 6 months after a positive test: adjusted odds ratio (OR) 9.1, 95% confidence interval (CI) 7.5 to 10.9; 12 to 18 months: OR 7.8, CI 5.7 to 10.8), concentration problems (3 to 6 months: OR 6.1, CI 4.8 to 6.5; 12 to 18 months: OR 5.3, CI 3.9 to 7.1), anosmia and dysgeusia, dyspnoea and fatigue as well as self-assessed worsening of overall health. Conclusion A positive SARS-CoV-2 test was associated with new onset memory- and concentration problems, anosmia and dysgeusia, dyspnoea and fatigue as well as self-assessed worsening of overall health, which persisted for the length of the follow-up of 22 months, even when correcting for symptoms before COVID-19 and compared to symptoms in negative controls. Trial registration ClinicalTrials ID: [NCT04320732][1] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This work was funded by the Research Council of Norway (no: 324274) and Southern and Eastern Norway Regional Health Authority (internal funding). The funder had no role in the conduction, collection of data or interpretation of results. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Norwegian Regional Committee for Research Ethics (REK 151 124170), and all participants submitted electronic informed consent forms. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04320732&atom=%2Fmedrxiv%2Fearly%2F2024%2F05%2F01%2F2024.04.30.24306604.atom

Objective: We aimed to describe post-acute sequelae of SARS-CoV-2 infection (PASC) related symptoms 3-15 months after a positive test in SARS-CoV-2 unvaccinated and vaccinated participants with a breakthrough infection. Methods: Participants of the Norwegian COVID-19 cohort, without a positive SARS-CoV-2 test, completed a questionnaire about PASC-related symptoms between November 2020 and January 2021. About a year later, a second questionnaire (which also included the Everyday Memory Questionnaire [EMQ]-13) was completed by the same participants, most still without a positive SARS-CoV-2 test, but also by unvaccinated and vaccinated participants with a positive test 3-15 months before the questionnaire. Laboratory-confirmed SARS-CoV-2 status (positive or negative swab test determined by reverse transcriptase quantitative polymerase chain reaction) at the time of completing the questionnaire was ascertained from the Mandatory Norwegian Surveillance System for Communicable Diseases. Results: No differences were found in the self-reported PASC symptoms, dyspnea, fatigue, smell/taste changes, concentration problems, or the EMQ-13 score between unvaccinated and vaccinated participants 3-15 months after the positive test. Fewer memory problems were reported among vaccinated than unvaccinated participants. Conclusion: SARS-CoV-2 vaccines offer minor protection against PASC symptoms, although fewer memory problems were reported among the vaccinated than the unvaccinated participants.

Abstract Background For many people public transport is the only mode of travel, and it can be challenging to keep the necessary distances in such a restricted space. The exact role of public transportation and risk of SARS-CoV-2 transmission is not known. Methods Participants (n = 121,374) were untested adult Norwegian residents recruited through social media who in the spring of 2020 completed a baseline questionnaire on demographics and the use of public transport. Incident cases (n = 1069) had a positive SARS-CoV-2 polymerase chain reaction test registered at the Norwegian Messaging System for Infectious Diseases by January 27, 2021. We investigated the association between the use of public transport and SARS-CoV-2 using logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for age, calendar time, gender, municipality, smoking, income level, fitness and underlying medical conditions were estimated. Frequency of the use of public transport was reported for 2 week-periods. Results Before lockdown, those who tested positive on SARS-CoV-2 were more likely to have used public transport 1–3 times (OR = 1.28, CI 1.09–1.51), 4–10 times (OR = 1.49, CI 1.26–1.77) and ≥ 11 times (OR = 1.50, CI 1.27–1.78, p for trend < 0.0001) than those who had not tested positive. Conclusion The use of public transport was positively associated with contracting SARS-CoV-2 both before and after lockdown.

Objective To determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in Norway. Design Quadruple blinded, randomised placebo controlled trial. Setting Norway, 10 November 2020 to 2 June 2021. Participants 34 601 adults (aged 18-75 years), not taking daily vitamin D supplements. Intervention 5 mL/day of cod liver oil (10 mu g of vitamin D, n=17 278) or placebo (n=17 323) for up to six months. Main outcome measures Four co-primary endpoints were predefined: the first was a positive SARS-CoV-2 test result determined by reverse transcriptase-quantitative polymerase chain reaction and the second was serious covid-19, defined as self-reported dyspnoea, admission to hospital, or death. Other acute respiratory infections were indicated by the third and fourth co-primary endpoints: a negative SARS-CoV-2 test result and self-reported symptoms. Side effects related to the supplementation were self-reported. The fallback method was used to handle multiple comparisons. Results Supplementation with cod liver oil was not associated with a reduced risk of any of the co-primary endpoints. Participants took the supplement (cod liver oil or placebo) for a median of 164 days, and 227 (1.31%) participants in the cod liver oil group and 228 (1.32%) participants in the placebo group had a positive SARS-CoV-2 test result (relative risk 1.00, multiple comparison adjusted confidence interval 0.82 to 1.22). Serious covid-19 was identified in 121 (0.70%) participants in the cod liver oil group and in 101 (0.58%) participants in the placebo group (1.20, 0.87 to 1.65). 8546 (49.46%) and 8565 (49.44%) participants in the cod liver oil and placebo groups, respectively, had >= 1 negative SARS-CoV-2 test results (1.00, 0.97 to 1.04). 3964 (22.94%) and 3834 (22.13%) participants in the cod liver oil and placebo groups, respectively, reported >= 1 acute respiratory infections (1.04, 0.97 to 1.11). Only low grade side effects were reported in the cod liver oil and placebo groups. Conclusion Supplementation with cod liver oil in the winter did not reduce the incidence of SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections compared with placebo.

Background Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals. Methods We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters. Interpretation The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant. Funding The study was funded by the Oslo University Hospital, and by grants from The Coalition for Epidemic Preparedness Innovations, Research Council of Norway (no 312780, 324272), South-Eastern Norway Regional Health Authority (no 2019067, 2021071, 10357, 2021047, 33612, 2021087, 2017092), EU Horizon 2020 grant no 848099, a philantropic donation from Vivaldi Invest A/S, and The European Virus Archive Global.

A total of four strains of the 'environmental superbug' Pedobacter isolated from sludge produced at Norwegian drinking water treatment plants, were characterized by whole genome sequencing and antibiotic susceptibility assays. As with previous studies on members of this genus, we found that the isolates were multi-drug resistant, and that this resistance included clinically important beta-lactams, aminoglycosides and the fluoroquinolone ciprofloxacin. Using the minION sequencing platform (Oxford Nanopore Technologies) combined with HiSeq PE150 Illumina sequencing data, the four isolates were assembled into genomes of single contigs. Analysis of the genomes revealed potential genetic factors possibly underlying some of the specific resistances observed. Metallo-beta-lactamase activity was detected in one isolate, and the same isolate contained a putative metallo-betalactamase gene resembling pedo-2. Furthermore, several genes related to multidrug efflux systems were found using the resistance database CARD. Additionally, the present study extends our knowledge on the phylogeny of this genus, adding four new genomes to the existing 50.

There is a growing awareness of the importance of indoor microbiomes for human health. Given their complexity, these microbiomes can only be adequately surveyed using high throughput sequencing techniques. Oxford Nanopore’s MinION is the newest third generation sequencing technology on the market. With its many advantages such as portability, user friendliness, simplicity, speed of sequencing and long read length, the technology is now an actual contender to established sequencing platforms. MinION’s main disadvantage is a relatively low read accuracy compared to several other platforms, although this is constantly improving. The present study, which appears to be the first of its kind, provides the results of a preliminary analysis of the microbial communities in indoor environments based on 16S rRNA gene amplicon sequencing, using both the Oxford Nanopore Technologies (ONT) MinIOn and the Illumina MiSeq DNA sequencers. At the level of family and above, there was no significant difference between the microbial compositions as revealed by the two platforms. However, at the genus, and particularly at the species level, the ONT MinION reported greater taxonomic resolution than Illumina MiSeq.

In Norway, 91% of children aged 1–5 attend kindergarten where they are exposed to indoor microbiomes which can have relevance for development and health. In order to gain a better understanding of the composition of the indoor microbiome and how it is affected by occupancy over time, floor dust samples from a newly opened kindergarten were investigated. Samples were collected during an 11-month period. Samples were analyzed for bacterial composition using 16S rRNA gene sequencing. Samples were also screened for four clinically relevant antibiotic resistance genes. In addition, Petrifilm analyses were used to evaluate surface hygiene.

The microbial content of dust collected from intake and exhaust air filters in six Norwegian nurseries was determined using 16S rRNA pyrosequencing and plate count analyses. The concentration of endotoxins was also estimated. About 96% of the sequences were classified as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidetes and Cyanobacteria. At the genus level, about 30% of sequences from the exhaust filter were classified as bacteria of probable human origin, such as Streptococcus and Corynebacterium species. These were close to absent in intake dust samples (<1%). This suggests that occupancy shapes the indoor microbiota, creating an environment relatively rich in genera of potential health significance. There were significantly greater counts of culturable bacteria and fungi in exhaust samples, indicating that passage of air through the nursery causes deterioration in the general air quality. Although there was more endotoxin in exhaust dust, the endotoxin levels per colony forming unit were similar in both samples. This study explores, for the first time, the bacterial composition of ventilation filter dust in Norwegian nurseries, and is important as it reveals what types of microorganisms nursery users are exposed to. In addition to possible direct health issues, the nature of our early exposure to microbes may be significant in the development of immunological conditions.