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1.
PLoS One ; 17(5): e0268057, 2022.
Article in English | MEDLINE | ID: covidwho-1846933

ABSTRACT

BACKGROUND: The availability of valid Severe Acute Respiratory Syndrome Coronvirus-2 (SARS-CoV-2) serological tests overcome the problem of underestimated cumulative Coronavirus Disease 2019 (COVID-19) cases during the first months of the pandemic in The Netherlands. The possibility to reliably determine the number of truly infected persons, enabled us to study initial drivers for exposure risk in the absence of routine testing. Numerous activities or circumstances can accelerate virus spread, here defined as exposure factors. Hence, we aimed to evaluate a wide variety of demographic, behavioural and social exposure factors associated with seropositivity during the first eight months of the pandemic in Limburg, The Netherlands. METHODS: SARS-CoV-2 point-seroprevalence was determined cross-sectionally to indicate previous infection in a convenience sample of minimal 10,000 inhabitants of the study province. All adult (18+ years) inhabitants of the study province were eligible to register themselves for participation. Once the initial 10,000 registrations were reached, a reserve list was kept to ensure sufficient participants. Possible exposure factors were mapped by means of an extensive questionnaire. Associated exposure factors were determined using univariable and multivariable logistic regression models. RESULTS: Seropositivity was established in 19.5% (n = 1,948) of the 10,001 participants (on average 49 years old (SD = 15; range 18-90 years), majority women (n = 5,829; 58.3%). Exposure factors associated with seropositivity included current education, working in healthcare and not working from home, and being a member of three or four associations or clubs. Specifically for February-March 2020, visiting an après-ski bar during winter sports in Austria, travelling to Spain, celebrating carnival, and participating in a singing activity or ball sport were associated with seropositivity. CONCLUSIONS: Our results confirm that relevant COVID-19 exposure factors generally reflected circumstances where social distancing was impossible, and the number and duration of contacts was high, in particular for indoor activities.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/epidemiology , Cross-Sectional Studies , Female , Humans , Middle Aged , Netherlands/epidemiology , Pandemics , Seroepidemiologic Studies
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334368

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several variants of concern (VOC) have emerged and became the dominant strain. These are considered VOC because of traits like increased transmissibility, increased severity, and immune-evasion. Understanding their viral load dynamics, with the use of longitudinal follow-up data, can help to understand transmission and could inform policy makers on for example infection prevention guidelines. However, longitudinal follow-up studies are scarce. In this study, we were able to monitor the viral load dynamics of the Delta, Omicron BA.1 and BA.2 variants via an unique dataset that was obtained as a consequence of the implemented infection prevention guidelines for healthcare workers at our institution, based on longitudinal follow-up of viral load. We found that the dynamics are different between Delta, Omicron BA.1, and Omicron BA.2 variants, the latter having the highest viral load on day 5 (5.7 log 10 copies/mL compared to 4.3 log 10 copies/mL for Delta and 4.8 log 10 copies/mL for BA.1) and day 7 (4.4 log 10 copies/mL compared to 3.3 log 10 copies/mL for Delta and 3.8 log 10 copies/mL for BA.1). However, the infection duration does not appear to be different between these variants. Still, considerable viral loads even after the suggested quarantine period were observed, in particular for the Omicron BA.2 sub variant. This highlights the need for a tailored approach per variant as results of previously circulating variants do not always match. This is in particular important for healthcare workers as they can transmit SARS-CoV-2 to vulnerable patients.

3.
BMC Infect Dis ; 22(1): 139, 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1690952

ABSTRACT

BACKGROUND: Individuals with intellectual and developmental disabilities (IDD) living in congregated settings have increased risk of COVID-19 infection and mortality. Little is known about variant B.1.1.519 with spike mutation T478K, dominant in Mexico. We describe a linked SARS-CoV-2 B.1.1.519 outbreak in three IDD facilities in the Netherlands. METHODS: Following notification of the index, subsequent cases were identified through serial PCR group testing. Positive specimens were submitted for whole-genome-sequencing. Clinical information was gathered through interviews with staff members of the three facilities. RESULTS: Attack rate (AR) in clients of the index facility was 92% (23/25), total AR in clients 45% (33/73) and in staff members 24% (8/34). 55% (18/33) of client cases were asymptomatic, versus 25% (2/8) of staff members. Five client cases (15%) were hospitalized, two died (6%). Sequencing yielded the same specific B.1.1.519 genotype in all three facilities. No significant difference in median viral load was established comparing the B.1.1.519 variant with other circulating variants. The index of the linked outbreak reported no travel history or link to suspected or confirmed cases suggesting regional surveillance. Observed peak regional prevalence of B.1.1.519 during the outbreak supports this. CONCLUSION: AR, morbidity and mortality prior to control measures taking effect were high, probably related to the specific characteristics of the IDD setting and its clients. We assessed no evidence for intrinsic contributing properties of variant B.1.1.519. Our study argues for enhanced infection prevention protocols in the IDD setting, and prioritization of this group for vaccination against COVID-19.


Subject(s)
Assisted Living Facilities , COVID-19 , Cross Infection , COVID-19/epidemiology , COVID-19/virology , Cross Infection/epidemiology , Cross Infection/virology , Developmental Disabilities , Disease Outbreaks , Humans , Mutation , Netherlands/epidemiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311402

ABSTRACT

Background: Individuals with intellectual and developmental disabilities (IDD) living in congregated settings have increased risk of COVID-19 infection and mortality. Little is known about variant B.1.1.519 with spike mutation T478K, dominant in Mexico. We describe a linked SARS-CoV-2 B.1.1.519 outbreak in three IDD facilities in the Netherlands. Methods: Following notification of the index, subsequent cases were identified through serial PCR group testing. Positive specimens were submitted for whole-genome-sequencing. Clinical information was gathered through interviews with staff members of the three facilities. Results: Attack rate (AR) in clients of the index facility was 92% (23/25), total AR in clients 45% (33/73) and in staff members 24% (8/34). 55% (18/33) of client cases were asymptomatic, versus 25% (2/8) of staff members. Five client cases (15%) were hospitalized, two died (6%). Sequencing yielded the same specific B.1.1.519 genotype in all three facilities. No significant difference in median viral load was established comparing the B.1.1.519 variant with other circulating variants. The index of the linked outbreak reported no travel history or link to suspected or confirmed cases suggesting regional surveillance. Observed peak regional prevalence of B.1.1.519 during the outbreak supports this. Conclusion: AR, morbidity and mortality prior to control measures taking effect were high, probably related to the specific characteristics of the IDD setting and its clients. We assessed no evidence for intrinsic contributing properties of variant B.1.1.519. Our study argues for enhanced infection prevention protocols in the IDD setting, and prioritization of this group for vaccination against COVID-19.

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324029

ABSTRACT

Background: Infection with SARS-CoV-2 causes Corona Virus Disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19 positive- and negative persons based on volatile organic compounds (VOCs) analysis. Methods: : Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, presence of SARS-CoV-2 specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine-learning and used for pattern recognition. The result is a value between -1 and +1, indicating the infection probability. Results: : 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96. Conclusions: : The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296690

ABSTRACT

Background: Variant of concern (VOC) SARS-CoV-2 alpha variant (B.1.1.7) was the dominant strain in the Netherlands between March 2021 – June 2021. We describe three primary school outbreaks due to the alpha variant using whole genome sequencing with evidence of large-scale transmission among children, teachers and their household contacts. MethodAll outbreaks described were investigated by the South Limburg Public Health Service, the Netherlands. A case was defined as an individual with a real-time polymerase chain reaction test or antigen test positive for SARS-CoV-2. Whole genome sequencing was performed on random samples from at least one child and one teacher of each affected class.ResultsPeak attack rates in classes were 53%, 33% and 39%, respectively. Specific genotypes were identified for each school across a majority of affected classes. Attack rates were high among staff members, likely to promote staff-to-children transmission. Cases in some classes were limited to children, indicating child-to-child transmission. At 39%, the secondary attack rate (SAR) in household contacts of infected children was remarkably high, similar to SAR in household contacts of staff members (42%). SAR of household contacts of asymptomatic children was only 9%. Conclusion Our findings suggest increased transmissibility of the alpha variant in children compared to preceding non-VOC variants, consistent with a substantial rise in the incidence of cases observed in primary schools and children aged 5-12 since the alpha variant became dominant in March 2021. Lack of mandatory masking, insufficient ventilation and lack of physical distancing also probably contributed to the school outbreaks. The rise of the delta variant (B.1.617.2) since July 2021 which is estimated to be 55% more transmissible than the alpha variant, provides additional urgency to adequate infection prevention in school settings.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292902

ABSTRACT

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, in spite of the high efficacy of the currently available vaccines, proven in trials and real-world studies. Several variants of concern (VOC) have been proffered to be associated with breakthrough infections following immunization. In this study, we investigated 378 breakthrough infections recorded between January and July 2021 and compared the distribution of SARS-CoV-2 genotypes identified in 225 fully vaccinated individuals to the frequency of circulating community lineages in the region of South Limburg (The Netherlands) in a week-by-week comparison. Although the proportion of breakthrough infections was relatively low and stable when the Alpha variant was predominant, the rapid emergence of the Delta variant lead to a strong increase in breakthrough infections, with a higher relative proportion of individuals vaccinated with Oxford-AstraZeneca or J&J/Janssen being infected compared to those immunized with mRNA-based vaccines. A significant difference in median age was observed when comparing fully vaccinated individuals with severe symptoms (83 years) to asymptomatic cases (46.5 years) or individuals with mild-to-moderate symptoms (42 years). There was no association between SARS-CoV-2 genotype or vaccine type and disease symptoms. Interestingly, symptomatic individuals harbored significantly higher SARS-CoV-2 loads than asymptomatic vaccinated individuals and breakthrough infections caused by the Delta variant are associated with increased viral loads compared to those caused by the Alpha variant. Altogether, these results indicate that the emergence of the Delta variant might have lowered the efficiency of particular vaccine types to prevent SARS-CoV-2 infections and that, although rare, the elderly are particularly at risk of becoming severely infected as the consequence of a breakthrough infection.

8.
Transl Vis Sci Technol ; 10(12): 32, 2021 10 04.
Article in English | MEDLINE | ID: covidwho-1484163

ABSTRACT

Purpose: The putative presence of SARS-CoV-2 in ocular specimen puts healthcare workers at risk. We thoroughly examined conjunctival swabs and tear fluid in a large cohort of COVID-19 patients. Methods: A total of 243 symptomatic laboratory-confirmed COVID-19 patients were included in this observational multicenter study. Conjunctival swabs were analyzed by reverse transcription polymerase chain reaction for detection of SARS-CoV-2 RNA. Next-generation sequencing and phylogenetic analysis were performed to identify viral strains and to determine tissue tropism. Schirmer tear samples from 43 hospitalized COVID-19 patients and 25 healthy controls were analyzed by multiplex cytokine immunoassays. Results: Viral SARS-CoV-2 RNA was detected in conjunctival swabs from 17 (7.0%) of 243 COVID-19 patients. Conjunctival samples were positive for viral SARS-CoV-2 RNA as long as 12 days after disease onset. Cycle threshold (Ct) values for conjunctival swabs (mean 34.5 ± 5.1) were significantly higher than nasopharyngeal swabs (mean 16.7 ± 3.6). No correlation between Ct values of conjunctival and nasopharyngeal swabs was observed. The majority of positive conjunctival samples were detected only once and primarily during the first visit. Next-generation sequencing analysis revealed that the virus strain found in the conjunctiva was most often identical to the one found in the nasopharynx. Tear cytokine levels IL-1ß and IL-6 were elevated in COVID-19 patients compared to healthy controls. Conclusions: Conjunctival samples that were positive for SARS-CoV-2 RNA contained the same viral strain as the nasopharynx. Translational Relevance: The presence of SARS-CoV-2 viral RNA and elevated cytokines in tear fluid confirm the involvement of the ocular surface in COVID-19 disease.


Subject(s)
COVID-19 , RNA, Viral , Cohort Studies , Humans , Phylogeny , SARS-CoV-2
9.
Sci Rep ; 11(1): 13476, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1287817

ABSTRACT

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation.


Subject(s)
COVID-19/pathology , Masks/virology , Nasopharynx/virology , SARS-CoV-2/isolation & purification , Adult , Aerosols , Aged , COVID-19/virology , Female , Hospitalization , Humans , Limit of Detection , Male , Middle Aged , Particle Size , RNA, Viral/analysis , Real-Time Polymerase Chain Reaction , SARS-CoV-2/physiology , Static Electricity , Viral Load , Young Adult
10.
Eur J Clin Microbiol Infect Dis ; 40(8): 1695-1703, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1139367

ABSTRACT

A variety of serological tests have been developed to detect the presence of antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the performance of 18 commercially available SARS-CoV-2 antibody assays. Early (6-8 days after the start of symptoms) and late sera (>14 days) from ICU patients (n=10 and n=16, respectively) and healthcare workers (n=5 and n=9, respectively) were included. Additionally, 22 sera were included to detect potential cross-reactivity. Test characteristics were determined for the 18 assays. In >14 days samples, the Vircell IgG and Wantai Ig ELISAs had superior sensitivity compared to the other ELISAs (96%). Furthermore, the Roche Ig, the Epitope Diagnostics IgM, Wantai IgM, Euroimmun IgG, and IgA all showed a specificity of 100%. The POCTs of Boson Biotech and ACRO Biotech showed the highest sensitivities: 100% and 96% (83.5-99.8), respectively. The POCT of Orient Gene Biotech, VOMED Diagnostics, and Coris-Bioconcept showed highest specificities (100%). For the IgM and IgA assays, the Euroimmun IgA test showed the highest sensitivity in early samples: 46.7% (23.5-70.9) to 53.3% (29.1-76.5). In general, all tests performed better in patients with severe symptoms (ICU patients). We conclude that the Wantai Ig and Vircell IgG ELISAs may be suitable for diagnostic purposes. The IgM/IgA tests performed poorer than their IgG/Ig counterparts but may have a role in diagnoses of SARS-CoV-2 in a population in which the background seroprevalence of IgG high, and IgM and/or IgA may distinguish between acute or past infection.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2 , Sensitivity and Specificity
11.
Surg Endosc ; 35(12): 6671-6678, 2021 12.
Article in English | MEDLINE | ID: covidwho-956162

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 causes corona virus disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19-positive and negative persons based on volatile organic compounds (VOCs) analysis. METHODS: Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, the presence of SARS-CoV-2-specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine learning and used for pattern recognition. The result is a value between - 1 and + 1, indicating the infection probability. RESULTS: 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96. CONCLUSIONS: The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery.


Subject(s)
COVID-19 , SARS-CoV-2 , Electronic Nose , Humans , Mass Screening , Predictive Value of Tests
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