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1.
Virology ; 569: 37-43, 2022 04.
Article in English | MEDLINE | ID: covidwho-1692814

ABSTRACT

Risk factors for disease progression and severity of SARS-CoV-2 infections require an understanding of acute and long-term virological and immunological dynamics. Fifty-one RT-PCR positive COVID-19 outpatients were recruited between May and December 2020 in Munich, Germany, and followed up at multiple defined timepoints for up to one year. RT-PCR and viral culture were performed and seroresponses measured. Participants were classified applying the WHO clinical progression scale. Short symptom to test time (median 5.0 days; p = 0.0016) and high viral loads (VL; median maximum VL: 3∙108 copies/mL; p = 0.0015) were indicative for viral culture positivity. Participants with WHO grade 3 at baseline had significantly higher VLs compared to those with WHO 1 and 2 (p = 0.01). VLs dropped fast within 1 week of symptom onset. Maximum VLs were positively correlated with the magnitude of Ro-N-Ig seroresponse (p = 0.022). Our results describe the dynamics of VLs and antibodies to SARS-CoV-2 in mild to moderate cases that can support public health measures during the ongoing global pandemic.


Subject(s)
COVID-19/diagnosis , COVID-19/virology , SARS-CoV-2/physiology , Viral Load , Adolescent , Adult , COVID-19/complications , Child , Cohort Studies , Host-Pathogen Interactions , Humans , Longitudinal Studies , Middle Aged , Outpatients , Pandemics , Serologic Tests/methods , Symptom Assessment , Young Adult
2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-319369

ABSTRACT

Background: Population-based studies investigating the dynamics of the SARS-CoV-2 pandemic are needed. Here, we report on baseline findings from April through June 2020 of a prospective cohort study in Munich, Germany.Methods: We drew a representative sample of 2994 private households. The 5313 participating household members 14 years and older completed questionnaires and provided blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0·4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests.Findings: Seropositivity for SARS-CoV-2 specific antibodies was 1·82% (95% confidence interval (CI) 1·28-2·37%) as compared to 0·46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47·4;95% CI 7·2-307·0) and infections clustered within households. Participants suffering from respiratory allergies (OR 2·7;95% CI 0·9-8·6) and working in high-risk jobs (OR 2·0;95% CI 0·5-6·7) showed non-significantly increased odds for SARS-CoV-2 seropositivity.Interpretation: Applying a validated assay, we demonstrate a low SARS-CoV-2 seroprevalence in the Munich population 14 years and older towards the end of the first pandemic wave. However, we noted official sub-registration at this early stage of the pandemic.Funding: Bavarian State Ministry of Science and the Arts, University Hospital of LMU Munich, Helmholtz Centre Munich, University of Bonn, and University of Bielefeld.Declaration of Interests: FF, TF, DM, LO, and VT report grants from the Bavarian State Ministry of Science and the Arts during the conduct oft he study. TF reports grants from the University Hospital of LMU Munich, Helmholtz Center Munich, University of Bonn, University of Bielefeld, and German Ministry for Education and Research during the conduct of the study. JH reports grants from the German Federal Ministry of Education and Research during the conduct of the study. MH and AW report personal fees and non-financial support, LO and MP report non-financial support from Roche Diagnostics. MH, LO, MP, and AW report non-financial support from Euroimmun, Viramed, and Mikrogen. MH, MP, and AW report grants, non-financial support, and other from German Center for Infection Research (DZIF). FF, MH, LO, MP, VT, and AW report grants and non-financial support from the Government of Bavaria. MH, LO, MP, and AW report non-financial support from BMW, Mercedes Benz, Munich Police, and Accenture. MH and AW report personal fees and non-financial support from Dr. Box Betrobox during the conduct of the study. LO and MP report non-financial support from Dr. Box Betrobox. MH and AW have a patent Sample System for Sputum Diagnostics of SARS-CoV-2 pending. DM reports to be a a sub-investigator on a Phase I SARS-CoV-2 vaccine trial and on a Phase I rabies vaccine trial, both sponsored by CureVac AG. MP and AW report non-financial support from Dr. Becker MVZ. VT reports support from CureVac AG outside the submitted work. AW reports personal fees and other from Haeraeus Sensors. AW reports non-financial support from Bruker Daltronics outside the submitted work. AW is involved in other different patents and companies not in relation with the serology of SARS-CoV-2. All other authors report nothing to disclose.Ethics Approval Statement: Prior to study initiation, this study had been approved by therespective Institutional Review Board.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294856

ABSTRACT

Background: Over a year since the first reported case, COVID-19 burden in Ethiopia remains unknown due to limited surveillance. We aimed to investigate seroepidemiology of SARS-CoV-2 among frontline healthcare workers (HCW) and communities in Ethiopia.<br><br>Methods: We conducted a population-based, prospective, longitudinal cohort study involving HCW, urban residents, and rural communities in Jimma and Addis Ababa. Serology was performed with Elecsys® Anti-SARS-CoV-2 anti-nucleocapsid assay (Roche Diagnostics, Switzerland) in three consecutive rounds with a mean interval of six weeks between tests to obtain seroprevalence and incidence estimates within the cohorts.<br><br>Findings: SARS-CoV-2 seroprevalence among HCW increased dramatically during the study period: in Addis Ababa from 10·9% (95% Credible Interval: 8·3%;13·8%) in August 2020 to 53·7% (44·8;62·5) in February 2021, incidence rate 2,223 (1,785;2,696) per 100,000 person-weeks;in Jimma from 30·8% (26·9;34·8) in November 2020 to 56·1% (51·1;61·1) in February 2021, incidence rate 3,810 (3,149;4,540) per 100,000 person-weeks. Among urban communities, an almost 40% increase in seroprevalence was observed in early 2021, with incidence rates of 1,622 (1,004;2,429) in Jimma and 4,646 (2,797;7,255) per 100,000 person-weeks in Addis Ababa. Seroprevalence in rural communities increased from 18·0% (13·5, 23·2) in November 2020 to 31·0% (22·3, 40·3) in March 2021.<br><br>Interpretation: SARS-CoV-2 spread in Ethiopia has been highly dynamic among HCW and urban communities. It can be speculated that the greatest wave of SARS-CoV-2 infections is currently evolving in rural Ethiopia and thus requires focused attention in respect to healthcare burden and disease prevention.<br><br>Funding Information: Bavarian State Ministry of Sciences, Research and the Arts (Bayerisches Staatsministerium, F.4-V0122.4/3/20), Germany Ministry of Education and Research (MoKoCo19;01KI20271), EU Horizon2020 program (ORCHESTRA;101016167), Deutsche Forschungsgemeinschaft (SEPAN;HA 7376/3-1), Volkswagenstiftung (E2;99450).<br><br>Declaration of Interests: The authors declare no competing interests.<br><br>Ethics Approval Statement: This research was approved by the institutional review boards of (i) the Jimma University Institute of Health, (ii) St. Paul’s Hospital Millennium Medical College, and (iii) Ludwig Maximilian University of Munich. Additional approvals were obtained from Addis Ababa and Oromia Regional Health Bureaus. Written informed consent was obtained from all participants.

4.
J Gen Virol ; 102(10)2021 10.
Article in English | MEDLINE | ID: covidwho-1488154

ABSTRACT

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer's cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer's/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , Neutralization Tests/methods , SARS-CoV-2/immunology , COVID-19 Nucleic Acid Testing , Cohort Studies , Humans
5.
Lancet Glob Health ; 9(11): e1517-e1527, 2021 11.
Article in English | MEDLINE | ID: covidwho-1472216

ABSTRACT

BACKGROUND: Over 1 year since the first reported case, the true COVID-19 burden in Ethiopia remains unknown due to insufficient surveillance. We aimed to investigate the seroepidemiology of SARS-CoV-2 among front-line hospital workers and communities in Ethiopia. METHODS: We did a population-based, longitudinal cohort study at two tertiary teaching hospitals involving hospital workers, rural residents, and urban communities in Jimma and Addis Ababa. Hospital workers were recruited at both hospitals, and community participants were recruited by convenience sampling including urban metropolitan settings, urban and semi-urban settings, and rural communities. Participants were eligible if they were aged 18 years or older, had provided written informed consent, and were willing to provide blood samples by venepuncture. Only one participant per household was recruited. Serology was done with Elecsys anti-SARS-CoV-2 anti-nucleocapsid assay in three consecutive rounds, with a mean interval of 6 weeks between tests, to obtain seroprevalence and incidence estimates within the cohorts. FINDINGS: Between Aug 5, 2020, and April 10, 2021, we did three survey rounds with a total of 1104 hospital workers and 1229 community residents participating. SARS-CoV-2 seroprevalence among hospital workers increased strongly during the study period: in Addis Ababa, it increased from 10·9% (95% credible interval [CrI] 8·3-13·8) in August, 2020, to 53·7% (44·8-62·5) in February, 2021, with an incidence rate of 2223 per 100 000 person-weeks (95% CI 1785-2696); in Jimma Town, it increased from 30·8% (95% CrI 26·9-34·8) in November, 2020, to 56·1% (51·1-61·1) in February, 2021, with an incidence rate of 3810 per 100 000 person-weeks (95% CI 3149-4540). Among urban communities, an almost 40% increase in seroprevalence was observed in early 2021, with incidence rates of 1622 per 100 000 person-weeks (1004-2429) in Jimma Town and 4646 per 100 000 person-weeks (2797-7255) in Addis Ababa. Seroprevalence in rural communities increased from 18·0% (95% CrI 13·5-23·2) in November, 2020, to 31·0% (22·3-40·3) in March, 2021. INTERPRETATION: SARS-CoV-2 spread in Ethiopia has been highly dynamic among hospital worker and urban communities. We can speculate that the greatest wave of SARS-CoV-2 infections is currently evolving in rural Ethiopia, and thus requires focused attention regarding health-care burden and disease prevention. FUNDING: Bavarian State Ministry of Sciences, Research, and the Arts; Germany Ministry of Education and Research; EU Horizon 2020 programme; Deutsche Forschungsgemeinschaft; and Volkswagenstiftung.


Subject(s)
COVID-19/epidemiology , Personnel, Hospital/statistics & numerical data , Residence Characteristics/statistics & numerical data , Adult , Ethiopia/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Models, Statistical , Seroepidemiologic Studies , Young Adult
6.
BMC Infect Dis ; 21(1): 925, 2021 Sep 08.
Article in English | MEDLINE | ID: covidwho-1398842

ABSTRACT

BACKGROUND: In the 2nd year of the COVID-19 pandemic, knowledge about the dynamics of the infection in the general population is still limited. Such information is essential for health planners, as many of those infected show no or only mild symptoms and thus, escape the surveillance system. We therefore aimed to describe the course of the pandemic in the Munich general population living in private households from April 2020 to January 2021. METHODS: The KoCo19 baseline study took place from April to June 2020 including 5313 participants (age 14 years and above). From November 2020 to January 2021, we could again measure SARS-CoV-2 antibody status in 4433 of the baseline participants (response 83%). Participants were offered a self-sampling kit to take a capillary blood sample (dry blood spot; DBS). Blood was analysed using the Elecsys® Anti-SARS-CoV-2 assay (Roche). Questionnaire information on socio-demographics and potential risk factors assessed at baseline was available for all participants. In addition, follow-up information on health-risk taking behaviour and number of personal contacts outside the household (N = 2768) as well as leisure time activities (N = 1263) were collected in summer 2020. RESULTS: Weighted and adjusted (for specificity and sensitivity) SARS-CoV-2 sero-prevalence at follow-up was 3.6% (95% CI 2.9-4.3%) as compared to 1.8% (95% CI 1.3-3.4%) at baseline. 91% of those tested positive at baseline were also antibody-positive at follow-up. While sero-prevalence increased from early November 2020 to January 2021, no indication of geospatial clustering across the city of Munich was found, although cases clustered within households. Taking baseline result and time to follow-up into account, men and participants in the age group 20-34 years were at the highest risk of sero-positivity. In the sensitivity analyses, differences in health-risk taking behaviour, number of personal contacts and leisure time activities partly explained these differences. CONCLUSION: The number of citizens in Munich with SARS-CoV-2 antibodies was still below 5% during the 2nd wave of the pandemic. Antibodies remained present in the majority of SARS-CoV-2 sero-positive baseline participants. Besides age and sex, potentially confounded by differences in behaviour, no major risk factors could be identified. Non-pharmaceutical public health measures are thus still important.


Subject(s)
COVID-19 , Pandemics , Follow-Up Studies , Germany/epidemiology , Humans , Infant, Newborn , Male , SARS-CoV-2
7.
EBioMedicine ; 70: 103502, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1330765

ABSTRACT

BACKGROUND: Since 2020 SARS-CoV-2 spreads pandemically, infecting more than 119 million people, causing >2·6 million fatalities. Symptoms of SARS-CoV-2 infection vary greatly, ranging from asymptomatic to fatal. Different populations react differently to the disease, making it very hard to track the spread of the infection in a population. Measuring specific anti-SARS-CoV-2 antibodies is an important tool to assess the spread of the infection or successful vaccinations. To achieve sufficient sample numbers, alternatives to venous blood sampling are needed not requiring medical personnel or cold-chains. Dried-blood-spots (DBS) on filter-cards have been used for different studies, but not routinely for serology. METHODS: We developed a semi-automated protocol using self-sampled DBS for SARS-CoV-2 serology. It was validated in a cohort of matched DBS and venous-blood samples (n = 1710). Feasibility is demonstrated with two large serosurveys with 10247 company employees and a population cohort of 4465 participants. FINDINGS: Sensitivity and specificity reached 99·20% and 98·65%, respectively. Providing written instructions and video tutorials, 99·87% (4465/4471) of the unsupervised home sampling DBS cards could be analysed. INTERPRETATION: DBS-sampling is a valid and highly reliable tool for large scale serosurveys. We demonstrate feasibility and accuracy with a large validation cohort including unsupervised home sampling. This protocol might be of big importance for surveillance in resource-limited settings, providing low-cost highly accurate serology data. FUNDING: Provided by Bavarian State Ministry of Science and the Arts, LMU University-Hospital; Helmholtz-Centre-Munich, German Ministry for Education and Research (project01KI20271); University of Bonn; University of Bielefeld; the Medical Biodefense Research Program of Bundeswehr-Medical-Service; Euroimmun, RocheDiagnostics provided discounted kits and machines.


Subject(s)
Antibodies, Viral/immunology , Biological Assay/methods , COVID-19 Serological Testing/methods , COVID-19/blood , COVID-19/immunology , Dried Blood Spot Testing/methods , SARS-CoV-2/immunology , Asymptomatic Infections , Cohort Studies , Humans , Longitudinal Studies , Sensitivity and Specificity , Specimen Handling/methods , Vaccination/methods
8.
Infect Dis Ther ; 10(3): 1505-1518, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1274999

ABSTRACT

BACKGROUND: Quantitative serological assays detecting response to SARS-CoV-2 are needed to quantify immunity. This study analyzed the performance and correlation of two quantitative anti-S1 assays in oligo-/asymptomatic individuals from a population-based cohort. METHODS: In total, 362 plasma samples (108 with reverse transcription-polymerase chain reaction [RT-PCR]-positive pharyngeal swabs, 111 negative controls, and 143 with positive serology without confirmation by RT-PCR) were tested with quantitative assays (Euroimmun Anti-SARS-CoV-2 QuantiVac enzyme-linked immunosorbent assay [EI-S1-IgG-quant]) and Roche Elecsys® Anti-SARS-CoV-2 S [Ro-RBD-Ig-quant]), which were compared with each other and confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript®cPass™. Square roots R of coefficients of determination were calculated for continuous variables and non-parametric tests were used for paired comparisons. RESULTS: Quantitative anti-S1 serology correlated well with each other (true positives, 96%; true negatives, 97%). Antibody titers decreased over time (< 30 to > 240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true positives and true negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed distinct separation between positives and negatives, and less non-specific reactivity versus EI-S1-IgG-quant. Raw values (95% CI) ≥ 28.7 U/mL (22.6-36.4) for Ro-RBD-Ig-quant and ≥ 49.8 U/mL (43.4-57.1) for EI-S1-IgG-quant predicted NT > 1:5 in 95% of cases. CONCLUSIONS: Our findings suggest both quantitative anti-S1 assays (EI-S1-IgG-quant and Ro-RBD-Ig-quant) may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances. However, although the mean antibody titers for both assays tended to decrease over time, a higher proportion of Ro-RBD-Ig-quant values remained positive after 240 days.

9.
Int J Environ Res Public Health ; 18(7)2021 03 30.
Article in English | MEDLINE | ID: covidwho-1160500

ABSTRACT

Given the large number of mild or asymptomatic SARS-CoV-2 cases, only population-based studies can provide reliable estimates of the magnitude of the pandemic. We therefore aimed to assess the sero-prevalence of SARS-CoV-2 in the Munich general population after the first wave of the pandemic. For this purpose, we drew a representative sample of 2994 private households and invited household members 14 years and older to complete questionnaires and to provide blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0.4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests. Seropositivity for SARS-CoV-2-specific antibodies was 1.82% (95% confidence interval (CI) 1.28-2.37%) as compared to 0.46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47.4; 95% CI 7.2-307.0) and infections clustered within households. By this first population-based study on SARS-CoV-2 prevalence in a large German municipality not affected by a superspreading event, we could show that at least one in four cases in private households was reported and known to the health authorities. These results will help authorities to estimate the true burden of disease in the population and to take evidence-based decisions on public health measures.


Subject(s)
COVID-19 , Coronavirus Infections , Humans , Prevalence , Risk Factors , SARS-CoV-2
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