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1.
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.

2.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-331791

ABSTRACT

Background: Vaccines based on the Wuhan strain of SARS-CoV-2 are a cornerstone of the global management of the COVID-19 pandemic. However, variants of concern have continuously evolved and may erode previously induced immunity. This study aimed to determine risk of breakthrough infection in a fully vaccinated cohort. Methods: Participants were enrolled before their first SARS-CoV-2 vaccination and SARS-CoV-2 anti-spike IgG levels were measured after 21–28, 90 and 180 days of follow-up, as well as day -7 and 28 after booster vaccination. Rate of breakthrough infections were ascertained from two weeks after the second vaccine dose, and captured through the Danish National Microbiology database. Poisson regression analysis was used to determine the risk of breakthrough infection at time-updated anti-spike IgG levels after adjustment for age, sex, being health care worker, and time-updated SARS-CoV-2 transmission level. Findings: Among 6076 participants (median age 64 years, interquartile range 55–75) included in this analysis, breakthrough infections due to the Delta variant were observed in 127 participants and in 363 due to the Omicron variant. The incidence rate ratio (IRR) for breakthrough infection with the Delta variant decreased with higher levels of anti-spike IgG yielding an IRR of 0.28 (95% CI 0·15–0·55) when comparing the highest and lowest quintiles of anti-spike IgG. For the Omicron variant, no significant differences in IRR of breakthrough infection between quintiles of anti-spike IgG was observed. Notably, 1 of 127 (0·8%) SARS-CoV-2 Delta variant and 0 of 336 (0%) Omicron variant breakthrough infections resulted in severe COVID-19. Interpretation: We observed a strong association between increasing levels of anti-spike antibodies and reduced risk of breakthrough infections with the Delta but not the Omicron variant. However, despite a high proportion of elderly participants, severe COVID-19 was rare in both Delta and Omicron infections.

3.
Clin Microbiol Infect ; 2022 Mar 11.
Article in English | MEDLINE | ID: covidwho-1734287

ABSTRACT

OBJECTIVES: To identify individual characteristics associated with serological COVID-19 vaccine responsiveness and the durability of vaccine-induced antibodies. METHODS: Adults without history of SARS-CoV-2 infection from the Danish population scheduled for SARS-CoV-2 vaccination were enrolled in this parallel group, phase 4 study. SARS-CoV-2 Spike IgG and Spike-ACE2-receptor-blocking antibodies were measured at days 0, 21, 90, and 180. Vaccine responsiveness was categorized according to Spike IgG and Spike-ACE2-receptor-blocking levels at day 90 after first vaccination. Nondurable vaccine response was defined as day-90 responders who no longer had significant responses by day 180. RESULTS: Of 6544 participants completing two vaccine doses (median age 64 years; interquartile range: 54-75), 3654 (55.8%) received BTN162b2, 2472 (37.8%) mRNA-1273, and 418 (6.4%) ChAdOx1 followed by an mRNA vaccine. Levels of both types of antibodies increased from baseline to day 90 and then decreased to day 180. The decrease was more pronounced for levels of Spike-ACE2-receptor-blocking antibodies than for Spike IgG. Proportions with vaccine hyporesponsiveness and lack of durable response were 5.0% and 12.1% for Spike IgG and 12.7% and 39.6% for Spike-ACE2-receptor-blocking antibody levels, respectively. Male sex, vaccine type, and number of comorbidities were associated with all four outcomes. Additionally, age ≥75 years was associated with hyporesponsiveness for Spike-ACE2-receptor-blocking antibodies (adjusted odds ratio: 1.59; 95% confidence interval: 1.25-2.01) but not for Spike IgG. DISCUSSION: Comorbidity, male sex, and vaccine type were risk factors for hyporesponsiveness and nondurable response to COVID-19 vaccination. The functional activity of vaccine-induced antibodies declined with increasing age and had waned to pre-second-vaccination levels for most individuals after 6 months.

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.
Clin Infect Dis ; 74(1): 1-7, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621583

ABSTRACT

BACKGROUND: Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity. METHODS: We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2-infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between "critical COVID-19" within and between households with and without secondary cases. RESULTS: From 15 063 multiperson households, 19 773 SARS-CoV-2-positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88-3.34), 2.27 (95% CI, 1.77-2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93-1.30) for index cases with secondary cases vs index cases without secondary cases. CONCLUSIONS: We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Denmark/epidemiology , Family Characteristics , Humans
6.
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
8.
J Glob Health ; 11: 05014, 2021.
Article in English | MEDLINE | ID: covidwho-1365810

ABSTRACT

BACKGROUND: The SARS-CoV-2 pandemic spread across Europe from February 2020. While robust SARS-CoV-2 serological assays were quickly developed, only limited information on applied serological testing is available. We describe the extent and nature of SARS-CoV-2 serological testing used in Europe and assess the links between epidemiology, mitigation strategies applied and seroprevalence. METHODS: An online questionnaire on SARS-CoV-2 serology was sent to the European Society of Clinical Virology and European Non-Polio Enterovirus Network members in September 2020. Data were analysed by comparing mitigation approaches, serological methods and seroprevalance studies performed. RESULTS: About 100 000 laboratory confirmed cases identified between March and June 2020 were reported by 36 participating laboratories from 20 countries. All responders experienced mitigation strategies including lockdowns and other closures. All except one participant had introduced serological testing; most had validated their assays (n = 29), but some had had difficulties in obtaining reference material. Most used commercial assays (n = 35), measuring IgG response against the spike antigen. Serology was used primarily for diagnostic purposes (n = 22) but also for convalescent plasma (n = 13) and research studies (n = 30). Seroprevalence studies targeted mainly health care workers (n = 20; seroprevalance 5% to 22%) and general population (n = 16; seroprevalance 0.88% to 5.6%). Basic demographic and clinical information were collected by most laboratories (n = 28), whereas data on long-term outcomes were rarely collected. CONCLUSIONS: This is first study gathering systematic information on serological testing approaches implemented during the first pandemic wave in Europe.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/therapy , Communicable Disease Control , Humans , Immunization, Passive , Seroepidemiologic Studies
9.
Clin Infect Dis ; 74(1): 1-7, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1203662

ABSTRACT

BACKGROUND: Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity. METHODS: We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2-infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between "critical COVID-19" within and between households with and without secondary cases. RESULTS: From 15 063 multiperson households, 19 773 SARS-CoV-2-positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88-3.34), 2.27 (95% CI, 1.77-2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93-1.30) for index cases with secondary cases vs index cases without secondary cases. CONCLUSIONS: We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.


Subject(s)
COVID-19 , SARS-CoV-2 , Cohort Studies , Denmark/epidemiology , Family Characteristics , Humans
10.
Lancet Infect Dis ; 20(12): 1401-1408, 2020 12.
Article in English | MEDLINE | ID: covidwho-1009965

ABSTRACT

BACKGROUND: Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19. METHODS: In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period. FINDINGS: Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% [95% CI 3·82-4·27]) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 [3·04%] of 4672; risk ratio [RR] 1·33 [95% CI 1·12-1·58]; p<0·001). Seroprevalence was higher in male health-care workers (331 [5·45%] of 6077) than in female health-care workers (832 [3·66%] of 22 715; RR 1·49 [1·31-1·68]; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 [4·55%] of 16 356) than health-care workers in other settings (384 [3·29%] of 11 657; RR 1·38 [1·22-1·56]; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 [7·19%] of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 [4·35%] of 15 983; RR 1·65 [1·34-2·03]; p<0·001). 622 [53·5%] of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 [32·39%] of 1164 participants with this symptom were seropositive vs 786 [2·84%] of 27 628 without this symptom; RR 11·38 [10·22-12·68]). The study is registered at ClinicalTrials.gov, NCT04346186. INTERPRETATION: The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19. FUNDING: Lundbeck Foundation.


Subject(s)
COVID-19/epidemiology , Health Personnel/statistics & numerical data , Occupational Health/statistics & numerical data , Adult , Antibodies, Viral/blood , Blood Donors/statistics & numerical data , COVID-19/diagnosis , COVID-19/immunology , COVID-19/pathology , Cohort Studies , Denmark/epidemiology , Female , Health Personnel/classification , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Point-of-Care Testing , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroconversion , Seroepidemiologic Studies
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