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1.
Nat Commun ; 13(1): 4738, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-1991583

ABSTRACT

Given the emergence of the SARS-CoV-2 Omicron BA.1 and BA.2 variants and the roll-out of booster COVID-19 vaccination, evidence is needed on protection conferred by primary vaccination, booster vaccination and previous SARS-CoV-2 infection by variant. We employed a test-negative design on S-gene target failure data from community PCR testing in the Netherlands from 22 November 2021 to 31 March 2022 (n = 671,763). Previous infection, primary vaccination or both protected well against Delta infection. Protection against Omicron BA.1 infection was much lower compared to Delta. Protection was similar against Omicron BA.1 compared to BA.2 infection after previous infection, primary and booster vaccination. Higher protection was observed against all variants in individuals with both vaccination and previous infection compared with either one. Protection against all variants decreased over time since last vaccination or infection. We found that primary vaccination with current COVID-19 vaccines and previous SARS-CoV-2 infections offered low protection against Omicron BA.1 and BA.2 infection. Booster vaccination considerably increased protection against Omicron infection, but decreased rapidly after vaccination.


Subject(s)
COVID-19 , Viral Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
2.
Eur J Epidemiol ; 37(10): 1035-1047, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1990695

ABSTRACT

The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700-290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620-1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions.


Subject(s)
COVID-19 , Disabled Persons , Humans , Middle Aged , Quality-Adjusted Life Years , Disability-Adjusted Life Years , Seroepidemiologic Studies , Netherlands/epidemiology , SARS-CoV-2 , Cost of Illness
3.
Microorganisms ; 10(5)2022 May 05.
Article in English | MEDLINE | ID: covidwho-1820340

ABSTRACT

COVID-19 control measures have resulted in a decline in invasive bacterial disease caused by Neisseria meningitidis (IMD), Streptococcus pneumoniae (IPD), and Haemophilus influenzae (Hi-D). These species comprise different serogroups and serotypes that impact transmissibility and virulence. We evaluated type- and pathogen-specific changes in invasive bacterial disease epidemiology in the Netherlands during the first year of the SARS-CoV-2 pandemic. Cases were based on nationwide surveillance for five bacterial species with either respiratory (IMD, IPD, Hi-D) or non-respiratory (controls) transmission routes and were compared from the pre-COVID period (April 2015-March 2020) to the first COVID-19 year (April 2020-March 2021). IMD, IPD, and Hi-D cases decreased by 78%, 67%, and 35%, respectively, in the first COVID-19 year compared to the pre-COVID period, although effects differed per age group. Serogroup B-IMD declined by 61%, while serogroup W and Y-IMD decreased >90%. IPD caused by serotypes 7F, 15A, 12F, 33F, and 8 showed the most pronounced decline (≥76%). In contrast to an overall decrease in Hi-D cases, vaccine-preventable serotype b (Hib) increased by 51%. COVID-19 control measures had pathogen- and type-specific effects related to invasive infections. Continued surveillance is critical to monitor potential rebound effects once restriction measures are lifted and transmission is resumed.

4.
Sci Rep ; 12(1): 5935, 2022 04 08.
Article in English | MEDLINE | ID: covidwho-1784029

ABSTRACT

mRNA- and vector-based vaccines are used at a large scale to prevent COVID-19. We compared Spike S1-specific (S1) IgG antibodies after vaccination with mRNA-based (Comirnaty, Spikevax) or vector-based (Janssen, Vaxzevria) vaccines, using samples from a Dutch nationwide cohort. In adults 18-64 years old (n = 2412), the median vaccination interval between the two doses was 77 days for Vaxzevria (interquartile range, IQR: 69-77), 35 days (28-35) for Comirnaty and 33 days (28-35) for Spikevax. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines. For all vaccines, one dose resulted in boosting of S1 antibodies in adults with a history of SARS-CoV-2 infection. For Comirnaty, two to four months following the second dose (n = 196), S1 antibodies in adults aged 18-64 years old (436 BAU/mL, IQR: 328-891) were less variable and median concentrations higher compared to those in persons ≥ 80 years old (366, 177-743), but differences were not statistically significant (p > 0.100). Nearly all participants seroconverted following COVID-19 vaccination, including the aging population. These data confirm results from controlled vaccine trials in a general population, including vulnerable groups.


Subject(s)
COVID-19 , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , Kinetics , Middle Aged , RNA, Messenger , SARS-CoV-2/genetics , Vaccination , Young Adult
5.
Vaccine ; 40(15): 2251-2257, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1730146

ABSTRACT

BACKGROUND: With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. METHODS: Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). RESULTS: The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants. CONCLUSIONS: Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , COVID-19/diagnosis , COVID-19/prevention & control , Humans , Nucleoproteins , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
6.
Clin Infect Dis ; 73(12): 2318-2321, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1599037

ABSTRACT

This large, nationwide, population-based, seroepidemiological study provides evidence of the effectiveness of physical distancing (>1.5 m) and indoor group size reductions in reducing severe acute respiratory syndrome coronavirus 2 infection. Additionally, young adults may play an important role in viral spread, contrary to children up until age 12 years with whom close contact is permitted. CLINICAL TRIALS REGISTRATION: NTR8473.


Subject(s)
COVID-19 , SARS-CoV-2 , Child , Humans , Netherlands/epidemiology , Physical Distancing , Research , Young Adult
7.
Clin Infect Dis ; 73(12): 2155-2162, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1592795

ABSTRACT

BACKGROUND: Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample. METHODS: Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the spike S1 protein of SARS-CoV-2 (N = 353), with up to 3 consecutive serum samples per seroconverted participant (N = 738). Immunoglobulin M (IgM), immunoglobulin A (IgA), and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined. RESULTS: While SARS-CoV-2-specific IgM and IgA antibodies declined rapidly after the first month after disease onset, specific IgG was still present in 92% (95% confidence interval [CI], 89%-95%) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI, 136-189 days). Concentrations were sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (P = .022). CONCLUSIONS: SARS-CoV-2-specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2, providing insight into protection of the general unvaccinated part of the population. CLINICAL TRIALS REGISTRATION: NL8473 (the Dutch trial registry).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Netherlands/epidemiology , Prospective Studies
9.
Vaccine ; 40(1): 59-66, 2022 01 03.
Article in English | MEDLINE | ID: covidwho-1565666

ABSTRACT

BACKGROUND: Meningococcal serogroup C (MenC) vaccination was introduced for 14-month-olds in the Netherlands in 2002, alongside a mass campaign for 1-18 year-olds. Due to an outbreak of serogroup W disease, MenC vaccination was replaced for MenACWY vaccination in 2018, next to introduction of a booster at 14 years of age and a catch-up campaign for 14-18 year-olds. We assessed meningococcal ACWY antibodies across the Dutch population in 2016/17 and 2020. METHODS: In a nationwide cross-sectional serosurvey in 2016/17, sera from participants aged 0-89 years (n = 6886) were tested for MenACWY-polysaccharide-specific (PS) serum IgG concentrations, and functional MenACWY antibody titers were determined in subsets. Moreover, longitudinal samples collected in 2020 (n = 1782) were measured for MenACWY-PS serum IgG concentrations. RESULTS: MenC antibody levels were low, except in recently vaccinated 14-23 month-olds and individuals who were vaccinated as teenagers in 2002, with seroprevalence of 59% and 20-46%, respectively. Meningococcal AWY antibody levels were overall low both in 2016/17 and in 2020. Naturally-acquired MenW immunity was limited in 2020 despite the recent serogroup W outbreak. CONCLUSIONS: This study demonstrates waning of MenC immunity 15 years after a mass campaign in the Netherlands. Furthermore, it highlights the lack of meningococcal AWY immunity across the population and underlines the importance of the recently introduced MenACWY (booster) vaccination.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup C , Adolescent , Antibodies, Bacterial , Cross-Sectional Studies , Humans , Immunization, Secondary , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Netherlands/epidemiology , Seroepidemiologic Studies , Vaccines, Conjugate
10.
Euro Surveill ; 26(44)2021 11.
Article in English | MEDLINE | ID: covidwho-1503826

ABSTRACT

We estimated SARS-CoV-2 vaccine effectiveness against onward transmission by comparing secondary attack rates among household members for vaccinated and unvaccinated index cases, based on source and contact tracing data collected when the Delta variant was dominant. Effectiveness of full vaccination of the index case against transmission to unvaccinated and fully vaccinated household contacts, respectively, was 63% (95% confidence interval (CI): 46-75) and 40% (95% CI: 20-54), in addition to the direct protection of vaccination of contacts against infection.


Subject(s)
COVID-19 , Vaccines , COVID-19 Vaccines , Family Characteristics , Humans , Netherlands/epidemiology , SARS-CoV-2
11.
Euro Surveill ; 26(42)2021 10.
Article in English | MEDLINE | ID: covidwho-1485004

ABSTRACT

The incidence of most respiratory-transmitted diseases decreased during the COVID-19 pandemic as a result of containment measures. In contrast, in the Netherlands we noted an increase in invasive disease caused by Haemophilus influenzae b (Hib) (from < 0.3/100,000 before 2019 to 0.39 and 0.33/100,000 in 2020 and 2021) in vaccinated and unvaccinated age groups. We did not find a change in vaccine effectiveness against Hib invasive disease (effectiveness > 90%). We discuss factors that may have contributed to this rise.


Subject(s)
COVID-19 , Haemophilus Infections , Haemophilus Vaccines , Haemophilus influenzae type b , Haemophilus Infections/epidemiology , Haemophilus Infections/prevention & control , Haemophilus influenzae , Humans , Infant , Netherlands/epidemiology , Pandemics , SARS-CoV-2
12.
Euro Surveill ; 26(31)2021 08.
Article in English | MEDLINE | ID: covidwho-1346380

ABSTRACT

Several studies report high effectiveness of COVID-19 vaccines against SARS-CoV-2 infection and severe disease, however an important knowledge gap is the vaccine effectiveness against transmission (VET). We present estimates of the VET to household and other close contacts in the Netherlands, from February to May 2021, using contact monitoring data. The secondary attack rate among household contacts was lower for fully vaccinated than unvaccinated index cases (11% vs 31%), with an adjusted VET of 71% (95% confidence interval: 63-77).


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Vaccines , Family Characteristics , Humans , Netherlands/epidemiology
13.
Eur J Epidemiol ; 36(7): 735-739, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1265533

ABSTRACT

BACKGROUND: The proportion of SARS-CoV-2 positive persons who are asymptomatic-and whether this proportion is age-dependent-are still open research questions. Because an unknown proportion of reported symptoms among SARS-CoV-2 positives will be attributable to another infection or affliction, the observed, or 'crude' proportion without symptoms may underestimate the proportion of persons without symptoms that are caused by SARS-CoV-2 infection. METHODS: Based on two rounds of a large population-based serological study comprising test results on seropositivity and self-reported symptom history conducted in April/May and June/July 2020 in the Netherlands (n = 7517), we estimated the proportion of reported symptoms among those persons infected with SARS-CoV-2 that is attributable to this infection, where the set of relevant symptoms fulfills the ECDC case definition of COVID-19, using inferential methods for the attributable risk (AR). Generalised additive regression modelling was used to estimate the age-dependent relative risk (RR) of reported symptoms, and the AR and asymptomatic proportion (AP) were calculated from the fitted RR. RESULTS: Using age-aggregated data, the 'crude' AP was 37% but the model-estimated AP was 65% (95% CI 63-68%). The estimated AP varied with age, from 74% (95% CI 65-90%) for < 20 years, to 61% (95% CI 57-65%) for the 50-59 years age-group. CONCLUSION: Whereas the 'crude' AP represents a lower bound for the proportion of persons infected with SARS-CoV-2 without COVID-19 symptoms, the AP as estimated via an attributable risk approach represents an upper bound. Age-specific AP estimates can inform the implementation of public health actions such as targetted virological testing and therefore enhance containment strategies.


Subject(s)
Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/virology , COVID-19 Serological Testing , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Netherlands/epidemiology , Poisson Distribution , Regression Analysis , Risk Assessment , Self Report , Seroepidemiologic Studies , Young Adult
14.
Euro Surveill ; 26(8)2021 02.
Article in English | MEDLINE | ID: covidwho-1150673

ABSTRACT

BackgroundDuring the COVID-19 pandemic, many countries have implemented physical distancing measures to reduce transmission of SARS-CoV-2.AimTo measure the actual reduction of contacts when physical distancing measures are implemented.MethodsA cross-sectional survey was carried out in the Netherlands in 2016-17, in which participants reported the number and age of their contacts the previous day. The survey was repeated among a subsample of the participants in April 2020, after strict physical distancing measures were implemented, and in an extended sample in June 2020, after some measures were relaxed.ResultsThe average number of community contacts per day was reduced from 14.9 (interquartile range (IQR): 4-20) in the 2016-17 survey to 3.5 (IQR: 0-4) after strict physical distancing measures were implemented, and rebounded to 8.8 (IQR: 1-10) after some measures were relaxed. All age groups restricted their community contacts to at most 5, on average, after strict physical distancing measures were implemented. In children, the number of community contacts reverted to baseline levels after measures were eased, while individuals aged 70 years and older had less than half their baseline levels.ConclusionStrict physical distancing measures greatly reduced overall contact numbers, which likely contributed to curbing the first wave of the COVID-19 epidemic in the Netherlands. However, age groups reacted differently when measures were relaxed, with children reverting to normal contact numbers and elderly individuals maintaining restricted contact numbers. These findings offer guidance for age-targeted measures in future waves of the pandemic.


Subject(s)
COVID-19/prevention & control , Pandemics , Physical Distancing , Social Interaction , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Netherlands/epidemiology , Young Adult
15.
Eurosurveillance ; 26(8):1, 2021.
Article in English | ProQuest Central | ID: covidwho-1124144

ABSTRACT

Background: During the COVID-19 pandemic, many countries have implemented physical distancing measures to reduce transmission of SARS-CoV-2. Aim: To measure the actual reduction of contacts when physical distancing measures are implemented. Methods: A cross-sectional survey was carried out in the Netherlands in 2016–17, in which participants reported the number and age of their contacts the previous day. The survey was repeated among a subsample of the participants in April 2020, after strict physical distancing measures were implemented, and in an extended sample in June 2020, after some measures were relaxed. Results: The average number of community contacts per day was reduced from 14.9 (interquartile range (IQR): 4–20) in the 2016–17 survey to 3.5 (IQR: 0–4) after strict physical distancing measures were implemented, and rebounded to 8.8 (IQR: 1–10) after some measures were relaxed. All age groups restricted their community contacts to at most 5, on average, after strict physical distancing measures were implemented. In children, the number of community contacts reverted to baseline levels after measures were eased, while individuals aged 70 years and older had less than half their baseline levels. Conclusion: Strict physical distancing measures greatly reduced overall contact numbers, which likely contributed to curbing the first wave of the COVID-19 epidemic in the Netherlands. However, age groups reacted differently when measures were relaxed, with children reverting to normal contact numbers and elderly individuals maintaining restricted contact numbers. These findings offer guidance for age-targeted measures in future waves of the pandemic.

16.
Vaccine ; 39(7): 1039-1043, 2021 02 12.
Article in English | MEDLINE | ID: covidwho-1009912

ABSTRACT

We aimed to assess the impact of the COVID-19 pandemic on the incidence of vaccine-preventable diseases (VPDs) and participation in the routine infant vaccination programme in the Netherlands. The incidence of various VPDs initially decreased by 75-97% after the implementation of the Dutch COVID-19 response measures. The participation in the first measles-mumps-rubella vaccination among children scheduled for vaccination in March-September 2020 initially dropped by 6-14% compared with the previous year. After catch-up vaccination, a difference in MMR1 participation of -1% to -2% still remained. Thus, the pandemic has reduced the incidence of several VPDs and has had a limited impact on the routine infant vaccination programme.


Subject(s)
COVID-19 , Pandemics , Vaccination/statistics & numerical data , Vaccine-Preventable Diseases/epidemiology , Child , Humans , Immunization Programs , Incidence , Infant , Measles-Mumps-Rubella Vaccine/administration & dosage , Netherlands/epidemiology , Vaccine-Preventable Diseases/prevention & control
17.
J Epidemiol Community Health ; 2020 Nov 28.
Article in English | MEDLINE | ID: covidwho-949241

ABSTRACT

BACKGROUND: We aimed to detect SARS-CoV-2 serum antibodies in the general population of the Netherlands and identify risk factors for seropositivity amidst the first COVID-19 epidemic wave. METHODS: Participants (n=3207, aged 2-90 years), enrolled from a previously established nationwide serosurveillance study, provided a self-collected fingerstick blood sample and completed a questionnaire (median inclusion date 3 April 2020). IgG antibodies targeted against the spike S1-protein of SARS-CoV-2 were quantified using a validated multiplex-immunoassay. Seroprevalence was estimated controlling for survey design, individual pre-pandemic concentration, and test performance. Random-effects logistic regression identified risk factors for seropositivity. RESULTS: Overall seroprevalence in the Netherlands was 2.8% (95% CI 2.1 to 3.7), with no differences between sexes or ethnic background, and regionally ranging between 1.3 and 4.0%. Estimates were highest among 18-39 year-olds (4.9%), and lowest in children 2-17 years (1.7%). Multivariable analysis revealed that persons taking immunosuppressants and those from the Orthodox-Reformed Protestant community had over four times higher odds of being seropositive compared to others. Anosmia/ageusia was the most discriminative symptom between seropositive (53%) and seronegative persons (4%, p<0.0001). Antibody concentrations in seropositive persons were significantly higher in those with fever or dyspnoea in contrast to those without (p=0.01 and p=0.04, respectively). CONCLUSIONS: In the midst of the first epidemic wave, 2.8% of the Dutch population was estimated to be infected with SARS-CoV-2, that is, 30 times higher than reported. This study identified independent groups with increased odds for seropositivity that may require specific surveillance measures to guide future protective interventions internationally, including vaccination once available.

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