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1.
Michaelsen, Thomas Y.; Bennedbæk, Marc, Christiansen, Lasse E.; Jørgensen, Mia S. F.; Møller, Camilla H.; Sørensen, Emil A.; Knutsson, Simon, Brandt, Jakob, Jensen, Thomas B. N.; Chiche-Lapierre, Clarisse, Collados, Emilio F.; Sørensen, Trine, Petersen, Celine, Le-Quy, Vang, Sereika, Mantas, Hansen, Frederik T.; Rasmussen, Morten, Fonager, Jannik, Karst, Søren M.; Marvig, Rasmus L.; Stegger, Marc, Sieber, Raphael N.; Skov, Robert, Legarth, Rebecca, Krause, Tyra G.; Fomsgaard, Anders, Andersen, Kasper S.; Andersen, Martin H.; Berg, Amalie, Bielidt, Susanne R.; Dall, Sebastian M.; Dvarionaite, Erika, Hansen, Susan H.; Jørgensen, Vibeke R.; Kirkegaard, Rasmus H.; Saei, Wagma, Nicolajsen, Trine B.; Østergaard, Stine K.; Brøndum, Rasmus F.; Bøgsted, Martin, Hose, Katja, Sagi, Tomer, Pakanec, Miroslaw, Fuglsang-Damgaard, David, Mølvadgaard, Mette, Krarup, Henrik, Svarrer, Christina W.; Christiansen, Mette T.; Ingham, Anna C.; Johannesen, Thor B.; Basterrechea, Martín, Lilje, Berit, Ellegaard, Kirsten, Matusevicius, Povilas, Christoffersen, Lars B.; Tang, Man-Hung E.; Ng, Kim L.; Edslev, Sofie M.; Baig, Sharmin, Larsen, Ole H.; Skipper, Kristian A.; Vang, Søren, Handberg, Kurt J.; Nielsen, Marc T. K.; Kobel, Carl M.; Andersen, Camilla, Tarpgaard, Irene H.; Ellermann-Eriksen, Svend, Castruita, José A. S.; Schneider, Uffe V.; Jacobsen, Nana G.; Andersen, Christian Ø, Pedersen, Martin S.; Schønning, Kristian, Kirkby, Nikolai, Nielsen, Lene, Nilsson, Line L.; Friis, Martin B.; Sundelin, Thomas, Hansen, Thomas A.; Skov, Marianne N.; Sydenham, Thomas V.; Nielsen, Xiaohui C.; Schouw, Christian H.; Jensen, Anders, Marmolin, Ea S.; Coia, John E.; Andersen, Dorte T.; Albertsen, Mads.
Genome Medicine ; 14(1):47-47, 2022.
Article in English | PMC | ID: covidwho-1822207
2.
The Lancet Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-1799640

ABSTRACT

Summary Background Estimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity. Methods In this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period. Findings Between Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22–0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56–0·75;222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44–0·75) among cases with no or only one dose of vaccine, 0·71 (0·60–0·86) among those who received two doses, and 0·50 (0·32–0·76) among those who received three doses. Interpretation We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness. Funding None.

3.
Euro Surveill ; 27(10)2022 03.
Article in English | MEDLINE | ID: covidwho-1742167

ABSTRACT

Following emergence of the SARS-CoV-2 variant Omicron in November 2021, the dominant BA.1 sub-lineage was replaced by the BA.2 sub-lineage in Denmark. We analysed the first 2,623 BA.2 cases from 29 November 2021 to 2 January 2022. No epidemiological or clinical differences were found between individuals infected with BA.1 versus BA.2. Phylogenetic analyses showed a geographic east-to-west transmission of BA.2 from the Capital Region with clusters expanding after the Christmas holidays. Mutational analysis shows distinct differences between BA.1 and BA.2.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Denmark/epidemiology , Humans , Molecular Epidemiology , Phylogeny , SARS-CoV-2/genetics
4.
BMC Infect Dis ; 22(1): 143, 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1690954

ABSTRACT

BACKGROUND: COVID-19 is thought 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. METHODS: We conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning risk factors associated with COVID-19. As a proxy for the general Danish population we accessed data on seroprevalence from Danish blood donors (total Ig ELISA assay) in same time period. RESULTS: Of the 13,279 included participants, 2296 (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 (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 household members (OR 5.0, 95% CI 4.1-6.2 p < 0,001). Living at least four people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.0-1.6, p = 0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.6, p = 0.003). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. CONCLUSIONS: Danish 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 slightly with age. Living in multiple generations households or in households of more than four persons was a strong 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.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , Denmark/epidemiology , Female , Housing , Humans , Male , Middle Aged , Pandemics , Seroepidemiologic Studies
5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327773

ABSTRACT

The newly found Omicron SARS-CoV-2 variant of concern has rapidly spread worldwide. Omicron carries numerous mutations in key regions and is associated with increased transmissibility and immune escape. The variant has recently been divided into four subvariants with substantial genomic differences, in particular between Omicron BA.1 and BA.2. With the surge of Omicron subvariants BA.1 and BA.2, a large number of reinfections from earlier cases has been observed, raising the question of whether BA.2 specifically can escape the natural immunity acquired shortly after a BA.1 infection. To investigate this, we selected a subset of samples from more than 1,8 million cases of infections in the period from November 22, 2021, until February 11, 2022. Here, individuals with two positive samples, more than 20 and less than 60 days apart, were selected. From a total of 187 reinfection cases, we identified 47 instances of BA.2 reinfections shortly after a BA.1 infection, mostly in young unvaccinated individuals with mild disease not resulting in hospitalization or death. In conclusion, we provide evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.

6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327249

ABSTRACT

1 The Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant. Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022. Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19;95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45;95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99;95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1. We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320263

ABSTRACT

Rapid nucleic-acid based tests that can be performed by non-professionals outside laboratory settings could help the containment of the pandemic SARS-CoV-2 virus and may potentially prevent further widespread lockdowns. Here, we present a novel compact portable detection instrument (the Egoo Health System) for extraction-free detection of SARS-CoV-2 using isothermal Reverse Transcription Strand Invasion Based Amplification (RT-SIBA). The SARS-CoV-2 RT-SIBA assay can be performed directly on crude oropharyngeal swabs without nucleic acid extraction with a reaction time of 30 minutes. The Egoo health system uses a capsule system, which is automatically sealed tight in the Egoo instrument after applying the sample, resulting in a closed system optimal for molecular isothermal amplification. The performance of the Egoo Health System is comparable to the PCR instrument with an analytical sensitivity of 25 viral RNA copies per SARS-CoV-2 RT-SIBA reaction and a clinical sensitivity and specificity between 87.0-98.4% and 96.6-98.2% respectively.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-316429

ABSTRACT

Background: The case presented here illustrates that interdisciplinary teamwork can be essential for the understanding of the COVID-19 disease presentation and enlightening of the pathophysiology. Case presentation: A 60-years-old overweight woman without any comorbidities was found dead in her apartment after 14 days of home isolation due to suspicion on the Coronavirus disease 2019 (COVID-19). She had reported symptoms of tachycardia, fever, and increasing respiratory difficulty one day before her death. Due to the Danish legal act on sudden deaths a forensic autopsy was performed including a thorough examination and biosampling. The results of the forensic autopsy displayed sever densified, almost airless, firm lungs, and an unspecific reactive minimal focal perivascular inflammation consisting of macrophages of the brain tissue. The final diagnosis, COVID-19 with involvement of the central nervous system was established by use of the RT-RNA analysis on cerebrospinal fluid, as well as by serologic detection of the specific antibodies for SARS-CoV-2 in cerebrospinal fluid and serum. The genetic analysis displayed a 2 % variation between SARS-CoV-2 isolates recovered from the tracheal sample, cerebrospinal fluid, and tissues from both lungs. Conclusion: The combination of all available results revealed that the cause of death was COVID-19 with severe pulmonary disease and neuroinvasion, as well as renal affection resulting in hyponatremia. To our knowledge, it was not shown previously that neuroinvasion could be confirmed by the detection of specific antibodies for SARS-CoV-2 and SARS-CoV-2 specific RNA in cerebrospinal fluid. This case supports hypotheses that SARS-CoV-2 may cause central nervous system infection. The genetic distinction between SARS-CoV-2 isolates was done by whole-genome sequencing, where the isolate recovered from the cerebrospinal fluid was the most different.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305241

ABSTRACT

During the current COVID-19 pandemic, different methods have been used to evaluate patients suspected with infection of SARS-CoV-2. In this study, we evaluate the longevity of saliva and dry swab samples to retain SARS-CoV-2 for storage and transport at different environmental settings. Our results show that at ambient temperature of 20°C, SARS-CoV-2 RNA remains stable for up to 9 days giving a long span of time for transport and storage without compromising clinical results. Additionally, this study demonstrates that sali­­­va and dry swabs specimens can also be stored at -20°C and +4°C for up to 26 days without affecting RT-qPCR results. Our data is relevant for low-and middle-income countries, which have limited access to rapid refrigerated transport and storage of samples representing an economical alternative. Finally, our study demonstrates that dry swabs provide clear advantages over using transport medium.

10.
NPJ Vaccines ; 6(1): 156, 2021 Dec 20.
Article in English | MEDLINE | ID: covidwho-1585846

ABSTRACT

New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.

11.
Microbiol Spectr ; 9(3): e0133021, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1583201

ABSTRACT

"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (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. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/immunology , Denmark , Female , Humans , Immunity , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Odds Ratio , Point-of-Care Testing , Population Surveillance , Prevalence , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Surveys and Questionnaires
12.
Euro Surveill ; 26(49)2021 12.
Article in English | MEDLINE | ID: covidwho-1566615

ABSTRACT

Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sub-lineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. We evaluated the sensitivity of AY.4.2 to neutralisation by sera from 30 Comirnaty (BNT162b2 mRNA) vaccine recipients in Denmark in November 2021. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sub-lineages. Conversely, the less prevalent B.1.617.2 with E484K showed a significant more than 4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Denmark , Humans , Mutation , RNA, Messenger , SARS-CoV-2
13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-295252

ABSTRACT

Several factors may account for the recent increased spread of the SARS-CoV-2 Delta sublineage AY.4.2 in the United Kingdom, Romania, Poland, and Denmark. Here, we evaluate the sensitivity of AY.4.2 to neutralisation by sera from Pfizer/BioNTech (BNT162b2) vaccine recipients. AY.4.2 neutralisation was comparable to other circulating Delta lineages or sublineages. In contrast, the more rare B.1.617.2+E484K variant showed a significant >4-fold reduction in neutralisation that warrants surveillance of strains with the acquired E484K mutation.

14.
PLoS Pathog ; 17(11): e1010068, 2021 11.
Article in English | MEDLINE | ID: covidwho-1518369

ABSTRACT

Mink, on a farm with about 15,000 animals, became infected with SARS-CoV-2. Over 75% of tested animals were positive for SARS-CoV-2 RNA in throat swabs and 100% of tested animals were seropositive. The virus responsible had a deletion of nucleotides encoding residues H69 and V70 within the spike protein gene as well as the A22920T mutation, resulting in the Y453F substitution within this protein, seen previously in mink. The infected mink recovered and after free-testing of 300 mink (a level giving 93% confidence of detecting a 1% prevalence), the animals remained seropositive. During further follow-up studies, after a period of more than 2 months without any virus detection, over 75% of tested animals again scored positive for SARS-CoV-2 RNA. Whole genome sequencing showed that the viruses circulating during this re-infection were most closely related to those identified in the first outbreak on this farm but additional sequence changes had occurred. Animals had much higher levels of anti-SARS-CoV-2 antibodies in serum samples after the second round of infection than at free-testing or during recovery from initial infection, consistent with a boosted immune response. Thus, it was concluded that following recovery from an initial infection, seropositive mink were readily re-infected by SARS-CoV-2.


Subject(s)
COVID-19/veterinary , COVID-19/virology , Mink/immunology , Mink/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Nucleic Acid Testing , COVID-19 Serological Testing , Farms , Follow-Up Studies , Humans , Mutation , Pharynx/virology , Phylogeny , RNA, Viral , Reinfection/virology , Whole Genome Sequencing
15.
Sci Rep ; 11(1): 22214, 2021 11 15.
Article in English | MEDLINE | ID: covidwho-1517639

ABSTRACT

Rapid nucleic-acid based tests that can be performed by non-professionals outside laboratory settings could help the containment of the pandemic SARS-CoV-2 virus and may potentially prevent further widespread lockdowns. Here, we present a novel compact portable detection instrument (the Egoo Health System) for extraction-free detection of SARS-CoV-2 using isothermal reverse transcription strand invasion based amplification (RT-SIBA). The SARS-CoV-2 RT-SIBA assay can be performed directly on crude oropharyngeal swabs without nucleic acid extraction with a reaction time of 30 min. The Egoo Health system uses a capsule system, which is automatically sealed tight in the Egoo instrument after applying the sample, resulting in a closed system optimal for molecular isothermal amplification. The performance of the Egoo Health System is comparable to the PCR instrument with an analytical sensitivity of 25 viral RNA copies per SARS-CoV-2 RT-SIBA reaction and a clinical sensitivity and specificity between 87.0-98.4% and 96.6-98.2% respectively.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Equipment Design , Molecular Diagnostic Techniques/instrumentation , Molecular Diagnostic Techniques/methods , Pandemics/prevention & control , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/genetics , COVID-19/virology , Cell Phone , Humans , Mobile Applications , Oropharynx/virology , Point-of-Care Testing , Polymorphism, Single Nucleotide , RNA, Viral/genetics , Retrospective Studies , Sensitivity and Specificity
16.
Lancet Infect Dis ; 21(11): 1507-1517, 2021 11.
Article in English | MEDLINE | ID: covidwho-1492844

ABSTRACT

BACKGROUND: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. METHODS: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. FINDINGS: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72-0·87; p<0·0001) and an adjusted RR of 1·42 (95% CI 1·25-1·60; p<0·0001). The adjusted RR was increased in all strata of age and calendar period-the two covariates with the largest contribution to confounding of the crude RR. INTERPRETATION: Infection with SARS-CoV-2 lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with that of other lineages in an analysis adjusted for covariates. The overall effect on hospitalisations in Denmark was lessened due to a strict lockdown, but our findings could support hospital preparedness and modelling of the projected impact of the epidemic in countries with uncontrolled spread of B.1.1.7. FUNDING: None.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , Adolescent , Adult , COVID-19/diagnosis , COVID-19/therapy , COVID-19/transmission , COVID-19 Nucleic Acid Testing/statistics & numerical data , Child , Child, Preschool , Cohort Studies , Comorbidity , Denmark/epidemiology , Female , Genome, Viral/genetics , Humans , Infant , Infant, Newborn , Male , Middle Aged , RNA, Viral/genetics , RNA, Viral/isolation & purification , Risk Assessment/statistics & numerical data , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Whole Genome Sequencing/statistics & numerical data , Young Adult
17.
Transbound Emerg Dis ; 69(2): 189-194, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1450581

ABSTRACT

During the current COVID-19 pandemic, different methods have been used to evaluate patients with suspected SARS-CoV-2 infection. In this study, we experimentally evaluate the ability of spiked saliva-moist swabs and spiked swabs without any transport medium to retain SARS-CoV-2 for storage and transport at different environmental settings during different incubation time periods. Our results show that at ambient temperature of 20°C, SARS-CoV-2 RNA remains stable for up to 9 days allowing a long-time span for transport and storage without compromising clinical results. Additionally, this study demonstrates that saliva-moist swabs can also be stored at -20°C and +4°C for up to 26 days without affecting RT-qPCR results. Our data are relevant for low-and middle-income countries, which have limited access to rapid refrigerated transport and storage of samples representing an economical alternative. Finally, our study demonstrates the practical and economic advantage of using swabs without transport medium.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/veterinary , Pandemics , RNA Stability , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva/chemistry , Specimen Handling/methods , Specimen Handling/veterinary , Temperature
18.
EBioMedicine ; 71: 103519, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363986

ABSTRACT

BACKGROUND: Given the importance of neutralising antibodies in protection against SARS-CoV-2 infection, it is critical to assess neutralisation persistence long-term following recovery. This study investigated neutralisation titres against SARS-CoV-2 up to 6 months post-symptom onset in individuals with mild COVID-19. METHODS: Plasma neutralisation titres in convalescent COVID-19 individuals were determined at baseline and 6 months post-symptom onset using a cell culture infectious SARS-CoV-2 assay. Total SARS-CoV-2 spike-specific IgG and IgA binding was measured using a lectin capture ELISA and compared between timepoints and correlated to neutralising titres. FINDINGS: All 48 convalescent COVID-19 individuals were found to have detectable SARS-CoV-2 50% inhibitory dilution neutralisation titres (ID50) at baseline and 6 months post-symptom onset with mean ID50 of 1/943 and 1/411, respectively. SARS-CoV-2 neutralisation titres peaked within 1-2 months post-symptom onset. However, 50% of individuals showed comparable ID50 at baseline and 6 months post-symptom onset. Both SARS-CoV-2 spike-specific IgG and IgA levels correlated well with neutralising titres. IgG binding was found to be sustained up to 6 months post-symptom onset, whereas IgA levels declined. INTERPRETATION: This study demonstrates durability of SARS-CoV-2 spike-specific IgG and neutralisation responses following recovery from mild COVID-19. Thus, all subjects included in this study might potentially have protective levels of neutralising antibodies 6 months post-symptom onset. This study also demonstrates a relationship between spike-specific IgA and neutralisation decline, with implications for long-term protection against SARS-CoV-2 infection. FUNDING: Novo Nordisk Foundation, Independent Research Fund Denmark and Danish Agency for Science and Higher Education.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/pathogenicity , Adult , COVID-19/epidemiology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Male , Middle Aged
19.
Front Microbiol ; 12: 698944, 2021.
Article in English | MEDLINE | ID: covidwho-1305659

ABSTRACT

In addition to humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit to animals that include hamsters, cats, dogs, mink, ferrets, tigers, lions, cynomolgus macaques, rhesus macaques, and treeshrew. Among these, mink are particularly susceptible. Indeed, 10 countries in Europe and North America reported SARS-CoV-2 infection among mink on fur farms. In Denmark, SARS-CoV-2 spread rapidly among mink farms and spilled-over back into humans, acquiring mutations/deletions with unknown consequences for virulence and antigenicity. Here we describe a mink-associated SARS-CoV-2 variant (Cluster 5) characterized by 11 amino acid substitutions and four amino acid deletions relative to Wuhan-Hu-1. Temporal virus titration, together with genomic and subgenomic viral RNA quantitation, demonstrated a modest in vitro fitness attenuation of the Cluster 5 virus in the Vero-E6 cell line. Potential alterations in antigenicity conferred by amino acid changes in the spike protein that include three substitutions (Y453F, I692V, and M1229I) and a loss of two amino acid residues 69 and 70 (ΔH69/V70), were evaluated in a virus microneutralization assay. Compared to a reference strain, the Cluster 5 variant showed reduced neutralization in a proportion of convalescent human COVID-19 samples. The findings underscore the need for active surveillance SARS-CoV-2 infection and virus evolution in susceptible animal hosts.

20.
Euro Surveill ; 26(27)2021 07.
Article in English | MEDLINE | ID: covidwho-1304570

ABSTRACT

We compared the performance of SARS-CoV-2 neutralising antibody testing between 12 European laboratories involved in convalescent plasma trials. Raw titres differed almost 100-fold differences between laboratories when blind-testing 15 plasma samples. Calibration of titres in relation to the reference reagent and standard curve obtained by testing a dilution series reduced the inter-laboratory variability ca 10-fold. The harmonisation of neutralising antibody quantification is a vital step towards determining the protective and therapeutic levels of neutralising antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Europe , Humans , Immunization, Passive
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