Literature DB >> 33270691

Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19.

Mina Psichogiou1, Andreas Karabinis2, Ioanna D Pavlopoulou3, Dimitrios Basoulis1, Konstantinos Petsios4, Sotirios Roussos5, Maria Pratikaki6, Edison Jahaj6, Konstantinos Protopapas7, Konstantinos Leontis8, Vasiliki Rapti8, Anastasia Kotanidou6, Anastasia Antoniadou7, Garyphallia Poulakou8, Dimitrios Paraskevis5, Vana Sypsa5, Angelos Hatzakis5.   

Abstract

INTRODUCTION: Greece is a country with limited spread of SARS-CoV-2 and cumulative infection attack rate of 0.12% (95% CI 0.06-0.26). Health care workers (HCWs) are a well-recognized risk group for COVID-19. The study aimed to estimate the seroprevalence of antibodies to SARS-CoV-2 in a nosocomial setting and assess potential risk factors.
METHODS: HCWs from two hospitals participated in the study. Hospital-1 was a tertiary university affiliated center, involved in the care of COVID-19 patients while hospital-2 was a tertiary specialized cardiac surgery center not involved in the care of these patients. A validated, CE, rapid, IgM/IgG antibody point-of-care test was used. Comparative performance with a reference globally available assay was assessed.
RESULTS: 1,495 individuals consented to participate (response rate 77%). The anti-SARS-CoV-2 weighted prevalence was 1.26% (95% CI 0.43, 3.26) overall and 0.53% (95% CI 0.06, 2.78) and 2.70% (95% CI 0.57, 9.19) in hospital-1 and hospital-2, respectively although the study was underpowered to detect statistically significant differences. The overall, hospital-1, and hospital-2 seroprevalence was 10, 4 and 22 times higher than the estimated infection attack rate in general population, respectively. Suboptimal use of personal protective equipment was noted in both hospitals.
CONCLUSIONS: These data have implications for the preparedness of a second wave of COVID-19 epidemic, given the low burden of SARS-CoV-2 infection rate, in concordance with national projections.

Entities:  

Year:  2020        PMID: 33270691      PMCID: PMC7714091          DOI: 10.1371/journal.pone.0243025

Source DB:  PubMed          Journal:  PLoS One        ISSN: 1932-6203            Impact factor:   3.240


Introduction

Coronavirus disease 2019 (COVID-2019) caused by a novel coronavirus [severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)] emerged in Wuhan, China in December 2019 and spread worldwide in 212 countries and territories causing more than 5.8 million cases and 360,000 deaths within a period of 5 months [1]. In Greece, the first COVID-19 case was diagnosed on February 26. On March 23, a nation-wide lockdown was enforced to reduce ongoing virus transmission as a response to this pandemic. As of May 30, there were 2,915 confirmed cases and 175 related deaths in Greece with a death rate of 16 per 1,000,000 population, which is one of the lowest in Europe [2]. Modelling data suggest that by the end of April 2020, when the first wave of epidemic was completed, the infection attack rate in Greece was 0.12% (95% Crl: 0.06–0.26) which corresponds to 13,200 total infections (95% Crl: 6,206–27,700) and a case ascertainment rate of 19.1% (95% CI 9.1–40.6) [3]. Health care workers (HCWs) is a well-known risk group for coronavirus infections [4, 5], accounted for a significant proportion of COVID-19 infections worldwide. By February 24, 2020, 3,387 HCWs out of 77,262 (4.4%) cases reported in China were HCWs [6]. The majority of these HCWs were documented at Hubei province, the epicentre of the epidemic. In a comprehensive analysis of 9,684 HCWs from Tongji Hospital in Wuhan, Hubei, the symptomatic infection rate was 1.1% while the respective asymptomatic infection rate was estimated at 0.9%. Nurses held a higher infection risk than physicians [OR: 2.07 (95% CI 1.7–4.3)] [7]. The city of Daegu, South Korea, had the first large outbreak of COVID-19 outside China. 121 HCWs were infected with infection rates 4.42 cases/1000 compared with 2.72 in the general population. Among HCWs, the infection rates were 2.37, 4.85, and 5.14 cases/1,000 among doctors, nurses, and nurse assistants, respectively [8]. In a large study among HCWs from the Netherlands, of whom 9,705 were hospital employees, a total of 1,353 (14%) reported fever and respiratory symptoms. Of those, 86 (6%) were infected with SARS-CoV-2, representing 1% of all HCWs employed [9]. Higher infection rates of SARS-CoV-2 by RT-PCR, ranging from 5–44%, were observed in HCWs from UK, Spain, Italy and US [10-17]. Serologic methods based on antibody testing (anti-SARS-CoV-2) could provide a more accurate estimate of epidemic size by detecting diagnosed and undiagnosed cases. Antibody methods rely on detection of IgM, IgG, IgA, or total antibodies by a variety of methods [18, 19]. The prevalence of the SARS-CoV-2 antibodies among HCWs was assessed in a number of studies from countries with high burden of SARS-CoV-2 infection where the reported anti-SARS-CoV-2 seroprevalence ranges from 1.6–45.3% [20-25]. Few studies used serological methods in the context of outbreak investigation [26, 27]. This study aimed to assess the seroprevalence of antibodies to SARS-CoV-2 in HCWs of two Greek hospitals during the current epidemic and identify potential risk factors for infection.

Patients and methods

Study design

This cross-sectional study recruited HCWs aged more than 18 years from two hospitals. The designated hospital-1 is a 500-bed tertiary, university-affiliated General Hospital providing care to COVID-19 patients. Hospital-2 with 134 beds is a Cardiac Surgery Center not involved in the care of COVID-19. The eligible personnel was in total 1,952, 1,120 in hospital-1, and 832 in hospital-2. Two groups were investigated 1) first-line health care workers (FL-HCWs), defined as personnel whose activities involve contact with patients, and 2) second-line health care workers (SL-HCWs), such as office employees, technical personnel, cleaning personnel etc. Testing was offered at one specified location in each hospital for a period of 4 weeks, 13 April-14 May 2020, and 30 April– 15 May 2020 in hospital-1 and -2, respectively. Up to the date of testing, hospital-1 diagnosed or offered care in 38 individuals with COVID-19 while none was cared for COVID-19 in hospital -2. Written informed consent was obtained from all participants who participated in the study. Participants were interviewed using a structured questionnaire including demographics, education, position within hospital, exposure to COVID-19, use of personal protective equipment (PPE), and symptoms related to COVID-19. The data were directly recorded in a secure database. All participants were immediately informed on their test results, and they were offered a short posttest counseling session. The study was approved by the Laiko General Hospital Scientific and Ethics Review Board (protocol number: 291/02-04-2020) and the Onassis Cardiac Surgery Center Scientific and Ethics Review Board (protocol number: 681/06-04-2020).

Validation of SARS-CoV-2 antibody testing

Testing was based on the GeneBody COVID-19 IgM/IgG detection, which is a lateral flow chromatographic immunoassay for the rapid and differential test of immunoglobulin M and immunoglobulin G against SARS-CoV-2. Serologic testing for SARS-CoV-2 antibodies was performed using capillary blood according to the manufacturer’s instructions (Genebody Inc.). Testing is conducted in cassettes provided by the manufacturers including positive and negative control bands. Samples were concluded as reactive if the IgM or the IgG or both bands were positive using a colorimetric reader (Confiscope G20 analyser). According to the manufacturer, the detection limit of the assay is 1.84 s/co for IgM and 1.57 s/co for IgG. Samples with s/co between 1.0 and 1.84 for IgM and between 1.0 and 1.57 for IgG are considered a grey zone or weakly positive. All positive or weekly positive individuals were immediately retested as well as 1–2 weeks later. Concordant results were considered positive. Sixteen individuals with weekly positive samples were retested 1–2 weeks later, 13 were negative, 1 seroconverted to positive and 2 were unavailable. Positive individuals were immediately retested as well as 1–2 weeks later. The concordant results were considered positive. The GeneBody assay was validated with serological panel from 116 symptomatic, positive by RT-PCR. COVID-19 patients (panel A) and with a second panel (panel B) including 250 samples collected during 2018 before SARS-CoV-2 pandemic All samples of panel A were also tested with an FDA approved (EUA) CLIA assay (anti-SARS-CoV-2 IgG, Abbott Diagnostics). Samples with Index s/c ≥ 1.4 and < 1.4 were considered positive and negative respectively. Both assays were based on nucleocapsid protein as antigen. Manufacturers’ clinical sensitivity estimates were 95% and 100% for GeneBody and Abbott respectively for samples collected >14 days from symptom onset. Manufacturer’s clinical specificity estimates for GeneBody were 98% for IgM and 99% for IgG while for Abbott was 99.6%. Concordance of capillary and venous sample was assessed in 15 samples of panel A tested in the same day The seropositivity rates of GeneBody and Abbott from symptoms onset is shown in Table 1. The clinical sensitivity of both assays peaked at days 20–29 and ranged from 60.1–92.3% for GeneBody and 50.0–92.3% for Abbott. The overall clinical sensitivity was 74.1% (95% CI, 65.2–81.8%) for GeneBody and 81.9% (95% CI, 73.7–88.4%) for Abbott (McNemar’s P = 0.108).
Table 1

Seropositivity rates from symptoms onset of SARS-CoV-2 antibody using GeneBody and Abbott assays.

Time from symptom onset (Days)Genbody Positive/N (%)Abbott Positive/N (%)P
0–76/10 (60)5/10 (50)0.99
8–1418/30 (60)22/30 (73.3)0.344
15–2116/22 (72.7)19/22 (86.4)0.250
22–2924/26 (92.3)24/26 (92.3)0.99
30–5922/28 (78.6)25/28 (89.3)0.375

McNemar’s P = 0.108.

McNemar’s P = 0.108. The seropositivity rate of GeneBody in panel B was 0 out of 250 with an estimated clinical specificity 100% (95% CI, 97.6% - 100.0%). The concordance of antibody testing of capillary and venous samples with GeneBody in 15 patients from panel A tested the same day was 100%.

Statistical analysis

To calculate the prevalence of antibodies to SARS-CoV-2, firstly, we calculated the unweighted proportions of positive tests and then we obtained the prevalence after weighting for the age distribution of the adult population (18–69 years old) in Athens Metropolitan area from the 2011 census. Secondly, we adjusted the weighted proportion for the sensitivity (74.1%) and specificity (100.0%) of the test, as assessed from the validation in the serological panels A and B, using the epiR package (R version 3.6.3, R Foundation for Statistical Computing, Vienna, Austria).

Results

Anti-SARS-CoV-2 prevalence among health care workers

A total of 1,495 HCWs consented to participate. The overall participation rate was 77% (81% and 71% in hospitals-1 and 2, respectively). Of 1,495 individuals tested, 69.7% were women, 61.7% were aged 35 to 54 years old, with a mean age (SD) of 46.4 (10.3) years. FL-HCWs accounted for 73.4% (1,097/1,495) of those tested (714/898 and 383/597 for the two hospitals respectively). Participants reporting direct exposure to known cases of COVID-19 during clinical work amounted to 11.5% (82/714), out of which 95% reported full use of PPEs. Subjects’ characteristics are listed in Table. A total of 15 individuals tested positive for anti-SARS-CoV-2, eleven of them for IgG only, three for IgM only and one for both IgM/IgG. After adjusting for age and test performance—assuming 74.1% sensitivity and 100% specificity the weighted seroprevalence for anti-SARS-CoV-2 in the total population was 1.26% (95% CI 0.43, 3.26). The weighed seroprevalence in hospital-1 was 0.53% (95% CI 0.06, 2.78) and in hospital-2 2.82% (95% CI 0.60, 9.62) (Table 2). The seroprevalence was 10, 4 times and 22 times higher in the overall hospital population, in hospital-1 and in hospital-2, respectively compared with the general population [0.12%, (95% Crl: 0.06–0.26)] [3] although the differences were not statistically significant. No significant associations were noted in the seroprevalence according to gender, country of birth, education, number of members in the household, FL-HCWs, SL-HCWs and use of PPE. Anti-SARS-CoV-2 prevalence was higher with increasing age, but the trend was not statistically significant (p = 0.10). The use of PPE was suboptimal in both hospitals. In hospital-1 and among the personnel treating COVID-19 the use of gloves, masks, glasses, gown was 96%, 99%, 56% and 63%, respectively. In hospital-2 the use of gloves and mask was reported in 99.7% and 100% while the use of glasses and gown occasionally (15%). Amongst seropositive individuals, only 9 reported full use of PPE.
Table 2

Socio-demographic characteristics and weighted prevalence of anti-SARS CoV-2 of 1,495 participants in two hospitals in Athens.

CovariatePopulation (N)Anti-SARS-CoV-2 (+)Weighted prevalence with 95% CIa
Overall1,495151.26 (0.43, 3.26)
Hospital
Hospital-190640.53 (0.06, 2.78)
Hospital-2589112.82 (0.60, 9.62)
Gender
Male45351.60 (0.13, 6.92)
Female1,042101.14 (0.36, 3.68)
Age (y)
18–3423110.58 (0.01, 3.22)
35–5492281.17 (0.51, 2.30)
55–7034262.37 (0.87, 5.10)
Country of birth
Greece1,355141.29 (0.42, 3.45)
Other14010.79 (0.02, 17.02)
Marital status
Married910111.19 (0.41, 7.03)
Divorced / widowed13400.00 (0.00, 4.75)
Single45141.62 (0.09, 7.66)
Members of household
126021.07 (0.03, 7.97)
240720.77 (0.02, 5.17)
331351.80 (0.33, 10.85)
438351.55 (0.24, 12.28)
5+13210.65 (0.02, 19.87)
Highest completed level of education
Master’s degree/Doctorate41620.46 (0.06, 5.82)
University or equivalent632102.12 (0.55, 6.09)
Technical education or below44730.66 (0.06, 9.68)
Job title
Healthcare workers1,097111.20 (0.34, 3.61)
Nonhealthcare workers39841.04 (0.29, 8.66)
Symptomsb
Any symptom15032.38 (0.18, 16.18)
No symptom1,345121.15 (0.33, 3.29)

a Weighted prevalence for age and test performance.

b Among fever, cough, and shortness of breath.

a Weighted prevalence for age and test performance. b Among fever, cough, and shortness of breath. Among all participants, 150 (10.1%) reported some symptoms indicative of COVID-19 in the previous 3 months; 82 reported fever, and 111 of them cough; 27 reported shortness of breath. Overall, 1,345 (89.9%) reported no symptoms. The prevalence of anti-SARS-CoV-2 was 2.38% (95% CI 0.18, 16.18) and 1.10% (95%CI 0.33, 3.29) in those who reported and those not reporting symptoms, respectively but the difference was not statistically significant.

Discussion

We used a validated point-of-care antibody test. We estimated de-novo the clinical sensitivity, the clinical specificity and the comparative performance of the point-of-care test with a reference globally available assay [28]. The clinical specificity of GeneBody was found 100% (95 CI, 97.6–100.0%). The clinical sensitivity was 74.1% (95 CI, 62.5–81.8%) and did not differ statistically from Abbott reference assay 81.9% (95 CI, 73.7–88.4%) In this survey of SARS-CoV-2 antibodies among hospital personnel, the overall seroprevalence was 1.26% (95% CI 0.43, 3.26). This seroprevalence rate is consistent with the low burden of COVID-19 in Greece. However, in the total hospital population and in that of hospital-2, it was 10 and 22 times higher, respectively, compared to the cumulative infection attack rate estimated by mathematical modeling for the general population in Greece [3] and a recently published population serological survey in Greece [29]. This is not surprising since the spread of SARS-CoV-2 is highly heterogeneous. In New York State the prevalence of anti-SARS-CoV-2 was found 14.0% with a range of 3.6–22.7% [30]. Due to the low burden of infection, the study is underpowered for pointing out risk factors. The difference in the prevalence between hospital-1 [0.51% (95% CI 0.06, 2.66)] and hospital-2 [2.70% (95% CI 0.57, 9.19)] is not significant. However, it is consistent with data suggesting that HCWs in hospitals involved in COVID-19 care could have a lower burden of infection than those not participating in COVID-19 care [7, 31]. This is probably due to the more extensive use of PPE, which is the main determinant for risk of SARS-CoV-2 infection in the health care environment [32]. In this study the use of PPE was suboptimal in both hospitals. Other reported risk factors are working in high- risk departments, long duty hours, practicing suboptimal hand hygiene [33]. Of the 42,600 HCWs caring for COVID-19 patients in the second half of the China epidemic, none was infected, suggesting that sufficient precautions and rigorous enforcement of PPE are the major determinants for eliminating COVID-19 infection [6]. A further challenge is whether SARS-CoV-2 infection can be truly attributed to hospital- acquired infections, especially in countries with a high burden of community infection [28]. In the study of Lai Y et al, contact with patients (59%), colleagues with infection (11%), and community acquired infection (13%) were the main routes of exposure among HCWs [7]. Contradicting results are noted in two large studies from Madrid and Birmingham. The anti-SARS-CoV-2 prevalence is higher in HCWs working in areas with exposure to COVID-19 (31–34%) compared with low-risk area (26%) and external workers (30%) in Madrid [24]. On the contrary in Birmingham study the anti-SARS-CoV-2 prevalence was higher among general medicine and housekeeping general personnel (30–35%) compared with intensive care and emergency medicine (13–15%) [21]. Several study limitations are noted: 1) The sensitivity of the currently existing antibody assays is not well knownbeyond 3 months from infection. However, the study took place at the end of the 1st epidemic wave and the time of testing was within the 3 months period from the 1st reported case in Greece (February 26, 2020). Studies have shown a steady prevalence decrease with time [18, 19]. 2) The study, due to the low anti-SARS-CoV-2 prevalence, is underpowered to detect risk factors. In conclusion, the burden of SARS-CoV-2 infection among hospital personnel in Athens by the end of first wave of SARS-CoV-2 is low, consistent with the low burden of infection in the country. The use of PPE was suboptimal. These findings have implications for the preparedness of a second wave of COVID-19 such as to urgently increase the availability of PPE and expedite hospital preparedness for possible major increase in the demand of hospitals and ICU beds.

Evaluation of sensitivity and specificity of GeneBody COVID-19 IgM/IgG antibody panel.

(DOCX) Click here for additional data file. 21 Sep 2020 PONE-D-20-20858 Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19 PLOS ONE Dear Dr. Psichogiou, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. I would like to apologise for the delay of the decision, but under the current circumstances it was very difficult to find reviewers that were available. Please submit your revised manuscript by Nov 05 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Ronald Dijkman, PhD Academic Editor PLOS ONE Additional Editor Comments: Based on the available literature and deficits of certain early phase commercial serological assays, and reviewer comments, I would recommend that the authors would confirm their finding with an additional serological assay, in order for the revised version of their manuscript to be considered. Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Thank you for stating the following in the Financial Disclosure section: "Gilead Hellas (https://www.gilead.com/utility/global-operations/europe/greece/greek) has funded the study with a grant bearing an approval code number GR-515-03.2020  after the approval by the Gilead Hellas Grants Committee at the colloquy of March 23d, 2020. Recipient of the grant was AH. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript." We note that you received funding from a commercial source: Gilead Sciences. Please provide an amended Competing Interests Statement that explicitly states this commercial funder, along with any other relevant declarations relating to employment, consultancy, patents, products in development, marketed products, etc. Within this Competing Interests Statement, please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests).  If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your amended Competing Interests Statement within your cover letter. We will change the online submission form on your behalf. Please know it is PLOS ONE policy for corresponding authors to declare, on behalf of all authors, all potential competing interests for the purposes of transparency. PLOS defines a competing interest as anything that interferes with, or could reasonably be perceived as interfering with, the full and objective presentation, peer review, editorial decision-making, or publication of research or non-research articles submitted to one of the journals. Competing interests can be financial or non-financial, professional, or personal. Competing interests can arise in relationship to an organization or another person. Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests 3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: No ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: No ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The manuscript by Psichogiou describes a study on health care workers in Greece. A low level of immunity was found which mirrors the low rate on infection in Greece. The low prevalence of people with antibodies to SARS-CoV-2 cannot draw conclusions on risk factors, which is unfortunate. Still the low prevalence is worthwhile sharing with the scientific community. Suggestions for improvement; - line 111, please add the viral protein that is used as target in the GeneBody COVID-19 antibody detection test. - line 140-141 and line 158 – 159: It is mentioned that seroprevalence is 10, 4 or 20 times higher than the general population. However, these numbers are probably not significant as the CI of the hospital tests is so wide. Please provide P-values, and mention whether there is a significant difference (or not). Reviewer #2: Pichogiou et al. perform a serological testing for COVID-19 among health care workers in Greece, a country with low burden of COVID-19. First, the major issue is lack of detailed description for the commercial kit from Genebody Inc they used for antibody testing. what is the catalogue Number? Is it a quantitative or qualitative gold immunochromatography assay? It will be great if the authors use alternative assay to confirm the positive samples. Otherwise, it is hard to know the seropositive individuals identified from this assay were really positive or false positive. Also, the author mentioned that "capillary blood" was used for testing, instead of venous blood. From our practical experience, capillary blood might cause false positivity. Secondly, some key details of socio-demographic characteristics of HCWs in two hospitals were missing. For examples, how many individuals in hospital-1 were front line HCW (FL-HCW)? How many of them directly exposed to COVID-19 patients without proper PPE? How many seropositive HCWs used PPE? Only identifying the seroprevalence among HCWs has limited implication for preparedness of a second wave of COVID-19. ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. 24 Oct 2020 To the Editor of PLOS ONE Dear Dr. Dijkman, Thank you for the valuable comments. To address all the concerns related to anti-SARS-CoV-2 rapid test assay we performed de-novo estimation of clinical sensitivity, clinical specificity, comparative efficacy and we used a strict quality control to accept positivity for capillary blood samples. The clinical sensitivity and the comparative performance of GeneBody with Abbott antibody test (SARS-CoV-2 IgG – Abbott, Chicago. IL, USA) was assessed in panel A. Panel A includes 116 serum or plasma samples from 116 COVID-19 patients with clinical disease and positive RT-PCR. Both assays are based on the nucleocapsid antigen. There was no statistical significance difference in clinical sensitivity of GeneBody and Abbott assays and their peak clinical sensitivity was similar (Table 1). We de-novo estimated the clinical specificity of GeneBody assay on panel B, including 250 serological samples collected before COVID-19 epidemic. The specificity was found 100% , suggesting that the GeneBody assay is appropriate for studies in low prevalence populations. Further quality controls were included. Positive capillary samples by GeneBody were tested 3 times. Two times at the date of testing and a third time 1-2 weeks later. All samples exceeding the cut-off recommended by manufacturer (1.84 s/co for IgM and 1.57 s/co for IgG) were found positive in all tests. The great majority of samples scored as weakly positive or grey zone (1.0 – 1.84 s/co for IgM and 1.0 – 1.57 s/co for IgG) were found negative when tested 1-2 weeks later (see Validation of SARS-CoV-2 antibody testing). To assess the concordance between capillary and venous blood we tested serum samples and capillary results tested in the same day. There was 100% concordance. Finally, we adjusted the estimated prevalence for the clinical sensitivity and specificity of GeneBody assay (see Statistical analysis). The choice of GeneBody test was based on the preliminary evaluation of a handful number of rapid tests taking advantage of our panel A and panel B. Our study was the first population study of anti-SARS-CoV-2 in Greece and later studies for anti-SARS-CoV-2 confirmed our findings. Therefore, we believe that our results are valid and describe adequately the prevalence of anti-SARS-CoV-2 in the health care workers population in Greece. Our detailed response in Reviewers follows: Reviewer #1 Comments- Suggestions: Suggestions for improvement - line 111, please add the viral protein that is used as target in the GeneBody COVID-19 antibody detection test. - line 140-141 and line 158 – 159: It is mentioned that seroprevalence is 10, 4 or 20 times higher than the general population. However, these numbers are probably not significant as the CI of the hospital tests is so wide. Please provide P-values, and mention whether there is a significant difference (or not). Response to Reviewer #1 Information pertaining to viral protein used in the assays was added in line 134 of the non-tracking final manuscript: “Both assays were based on nucleocapsid protein as antigen.” The statistical non-significance was included in lines 183 of the non-tracking final manuscript: “…although the differences were not statistically significant.” Reviewer #2 Comments- Suggestions: Comment 1: Pichogiou et al. perform a serological testing for COVID-19 among health care workers in Greece, a country with low burden of COVID-19. First, the major issue is lack of detailed description for the commercial kit from Genebody Inc they used for antibody testing. what is the catalogue Number? Is it a quantitative or qualitative gold immunochromatography assay? It will be great if the authors use alternative assay to confirm the positive samples. Otherwise, it is hard to know the seropositive individuals identified from this assay were really positive or false positive. Also, the author mentioned that "capillary blood" was used for testing, instead of venous blood. From our practical experience, capillary blood might cause false positivity. Response to Reviewer #2 Comment 1: The clinical sensitivity and the comparative performance with Abbott test was assessed in panel A. Panel A includes 116 samples from 116 COVID-19 patients with clinical disease and positive RT-PCR. Both assays are based on the nucleocapsid antigen. There was no statistical significance difference in clinical sensitivity of GeneBody and Abbott assays and their peak sensitivity was similar (Table 1). We de-novo estimated the clinical specificity of GeneBody assay which was on panel B, including 250 serological samples collected before COVID-19 epidemic. The specificity was found 100% , suggesting that the GeneBody assay is appropriate for studies in low prevalence populations. Further quality controls were included. Positive samples in capillary blood were tested 3 times. Two times at the date of testing and a third time 1-2 weeks later. All samples exceeding the cut-off recommended by manufacturer (1.84 s/co for IgM and 1.57 s/co for IgG) were found positive. The great majority of samples scored as grey zone were found negative when tested 1-2 weeks later. To assess the concordance between capillary and venous blood we tested serum samples and capillary results tested in the same day. There was 100% concordance. The GeneBody assay is a qualitative lateral flow immunoassay with catalogue number COVI040. The GeneBody Inc. is one of the leaders in rapid diagnostic testing pioneered Zika virus diagnostic tests. Reviewer #2 Comments- Suggestions: Comment 2: Secondly, some key details of socio-demographic characteristics of HCWs in two hospitals were missing. For examples, how many individuals in hospital-1 were front line HCW (FL-HCW)? How many of them directly exposed to COVID-19 patients without proper PPE? How many seropositive HCWs used PPE? Only identifying the seroprevalence among HCWs has limited implication for preparedness of a second wave of COVID-19. Response to Reviewer #2 Comment 2: FL-HCW and PPE use amongst FL-HCWs directly exposed to SARS-COV-2 information has been added at line 166-168 of the manuscript “FL-HCWs accounted for 73.4% (1,097/1,495) of those tested (714/898 and 383/597 for the two hospitals respectively). Participants reporting direct exposure to known cases of COVID-19 during clinical work amounted to 11.5% (82/714), out of which 95% reported full use of PPEs.” Regarding use of PPE amongst seropositive participants, we added line 190-191 “Amongst seropositive individuals, only 9 reported full use of PPE.” Submitted filename: Response to reviewers.docx Click here for additional data file. 16 Nov 2020 Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19 PONE-D-20-20858R1 Dear Dr. Psichogiou, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Ronald Dijkman, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: (No Response) ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No 23 Nov 2020 PONE-D-20-20858R1 Antibodies against SARS-CoV-2 among health care workers in a country with low burden of COVID-19 Dear Dr. Psichogiou: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Ronald Dijkman Academic Editor PLOS ONE
  21 in total

1.  "Syndromic surveillance within a hospital" for the early detection of a nosocomial outbreak of acute respiratory infection.

Authors:  Akihiko Kawana; Katsuji Teruya; Teruo Kirikae; Jun-ichiro Sekiguchi; Yasuyuki Kato; Emi Kuroda; Kumi Horii; Sin-ichiro Saito; Hiroshi Ohara; Tadatoshi Kuratsuji; Satoshi Kimura; Koichiro Kudo
Journal:  Jpn J Infect Dis       Date:  2006-12       Impact factor: 1.362

2.  Asymptomatic Seroconversion of Immunoglobulins to SARS-CoV-2 in a Pediatric Dialysis Unit.

Authors:  David S Hains; Andrew L Schwaderer; Aaron E Carroll; Michelle C Starr; Amy C Wilson; Fatima Amanat; Florian Krammer
Journal:  JAMA       Date:  2020-06-16       Impact factor: 56.272

3.  Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study.

Authors:  Adamma Aghaizu; Gillian Elam; Fortune Ncube; Gail Thomson; Emese Szilágyi; Tim Eckmanns; Garyphallia Poulakou; Mike Catchpole
Journal:  BMC Public Health       Date:  2011-07-08       Impact factor: 3.295

4.  Risk Factors of Healthcare Workers With Coronavirus Disease 2019: A Retrospective Cohort Study in a Designated Hospital of Wuhan in China.

Authors:  Li Ran; Xuyu Chen; Ying Wang; Wenwen Wu; Ling Zhang; Xiaodong Tan
Journal:  Clin Infect Dis       Date:  2020-11-19       Impact factor: 9.079

5.  Seroprevalence of antibodies against SARS-CoV-2 among health care workers in a large Spanish reference hospital.

Authors:  Alberto L Garcia-Basteiro; Gemma Moncunill; Marta Tortajada; Marta Vidal; Caterina Guinovart; Alfons Jiménez; Rebeca Santano; Sergi Sanz; Susana Méndez; Anna Llupià; Ruth Aguilar; Selena Alonso; Diana Barrios; Carlo Carolis; Pau Cisteró; Eugenia Chóliz; Angeline Cruz; Silvia Fochs; Chenjerai Jairoce; Jochen Hecht; Montserrat Lamoglia; Mikel J Martínez; Robert A Mitchell; Natalia Ortega; Nuria Pey; Laura Puyol; Marta Ribes; Neus Rosell; Patricia Sotomayor; Sara Torres; Sarah Williams; Sonia Barroso; Anna Vilella; José Muñoz; Antoni Trilla; Pilar Varela; Alfredo Mayor; Carlota Dobaño
Journal:  Nat Commun       Date:  2020-07-08       Impact factor: 14.919

6.  Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York.

Authors:  Eli S Rosenberg; James M Tesoriero; Elizabeth M Rosenthal; Rakkoo Chung; Meredith A Barranco; Linda M Styer; Monica M Parker; Shu-Yin John Leung; Johanne E Morne; Danielle Greene; David R Holtgrave; Dina Hoefer; Jessica Kumar; Tomoko Udo; Brad Hutton; Howard A Zucker
Journal:  Ann Epidemiol       Date:  2020-06-17       Impact factor: 3.797

7.  Lower detection rates of SARS-COV2 antibodies in cancer patients versus health care workers after symptomatic COVID-19.

Authors:  M L Solodky; C Galvez; B Russias; P Detourbet; V N'Guyen-Bonin; A-L Herr; P Zrounba; J-Y Blay
Journal:  Ann Oncol       Date:  2020-05-01       Impact factor: 32.976

8.  COVID-19 screening of health-care workers in a London maternity hospital.

Authors:  Asma Khalil; Robert Hill; Shamez Ladhani; Katherine Pattisson; Pat O'Brien
Journal:  Lancet Infect Dis       Date:  2020-05-18       Impact factor: 25.071

9.  Prevalence of SARS-CoV-2 infection in previously undiagnosed health care workers in New Jersey, at the onset of the U.S. COVID-19 pandemic.

Authors:  Emily S Barrett; Daniel B Horton; Jason Roy; Maria Laura Gennaro; Andrew Brooks; Jay Tischfield; Patricia Greenberg; Tracy Andrews; Sugeet Jagpal; Nancy Reilly; Jeffrey L Carson; Martin J Blaser; Reynold A Panettieri
Journal:  BMC Infect Dis       Date:  2020-11-16       Impact factor: 3.090

10.  Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison.

Authors: 
Journal:  Lancet Infect Dis       Date:  2020-09-23       Impact factor: 25.071

View more
  20 in total

1.  Low seropositivity for SARS-CoV-2 antibodies among healthcare workers after the first COVID-19 pandemic wave in Greece.

Authors:  P Galanis; D Kaitelidou; P Prezerakos; I Kotsiopoulos; O Siskou; O Konstantakopoulou; C Hadjichristodoulou; S Tsiodras
Journal:  Public Health       Date:  2021-07-31       Impact factor: 4.984

2.  SARS-CoV-2 seroprevalence in healthcare workers: The experience of a Portuguese COVID-19 front-line hospital during the 1st pandemic wave.

Authors:  Angelica Ramos; Beatriz Araújo; Lisa Lacerda; Ana Lúcia Flora; Luis Ribeiro; Emília Patrício; Maria João Cardoso; João Tiago Guimarães
Journal:  Porto Biomed J       Date:  2022-06-17

3.  Seroprevalence of SARS-CoV-2 IgG antibodies among health care workers prior to vaccine administration in Europe, the USA and East Asia: A systematic review and meta-analysis.

Authors:  Ahmed Hossain; Sarker Mohammad Nasrullah; Zarrin Tasnim; Md Kamrul Hasan; Md Maruf Hasan
Journal:  EClinicalMedicine       Date:  2021-03-08

4.  Seroprevalence of hospital staff in a province with zero COVID-19 cases.

Authors:  Tanawin Nopsopon; Krit Pongpirul; Korn Chotirosniramit; Wutichai Jakaew; Chuenkhwan Kaewwijit; Sawan Kanchana; Narin Hiransuthikul
Journal:  PLoS One       Date:  2021-04-01       Impact factor: 3.240

5.  SARS-CoV-2 seroprevalence in healthcare workers at a frontline hospital in Tokyo.

Authors:  Hiroshi Fukuda; Kuniaki Seyama; Kanami Ito; Tomohiko Ai; Shuko Nojiri; Satoshi Hori; Mitsuru Wakita; Kaori Saito; Yuka Shida; Rie Nagura; Mayu Hasegawa; Chiaki Kanemoto; Mayumi Tokuhara; Katsunobu Okajima; Yukio Yoshikawa; Narimasa Katsuta; Takamasa Yamamoto; Mayumi Idei; Yuki Horiuchi; Kotoko Yamatani; Shigeki Misawa; Toshio Naito; Takashi Miida; Hiroyuki Sato; Nobutaka Hattori; Yoko Tabe; Kazuhisa Takahashi
Journal:  Sci Rep       Date:  2021-04-16       Impact factor: 4.379

6.  Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies Among Market and City Bus Depot Workers in Lima, Peru.

Authors:  Marco Tovar; Jesús Peinado; Santiago Palomino; Fernando Llanos; Claudio Ramírez; Gisella Valderrama; Roger I Calderón; Roger B Williams; Gustavo E Velásquez; Carole D Mitnick; Molly F Franke; Leonid Lecca
Journal:  Clin Infect Dis       Date:  2022-01-29       Impact factor: 9.079

7.  Sero-Prevalence and Sero-Incidence of Antibodies to SARS-CoV-2 in Health Care Workers in Israel, Prior to Mass COVID-19 Vaccination.

Authors:  Khitam Muhsen; Mitchell J Schwaber; Jihad Bishara; Eias Kassem; Alaa Atamna; Wasef Na'amnih; Sophy Goren; Anya Bialik; Jameel Mohsen; Yona Zaide; Nimrod Hazan; Ortal Ariel-Cohen; Regev Cohen; Pnina Shitrit; Dror Marchaim; Shmuel Benenson; Debby Ben-David; Bina Rubinovitch; Tamar Gotessman; Amir Nutman; Yonit Wiener-Well; Yasmin Maor; Yehuda Carmeli; Dani Cohen
Journal:  Front Med (Lausanne)       Date:  2021-06-24

8.  High anti-SARS-CoV-2 antibody seroprevalence in healthcare workers in an Irish university teaching hospital.

Authors:  Ann Leonard; Anna Rose Prior; Phyllis Reilly; Caroline Murray; Meghan O' Brien; Gillian Maguire; Deborah Ennis; Alex Reid; Ana Rakovac; Gerard Boran
Journal:  Ir J Med Sci       Date:  2021-06-30       Impact factor: 2.089

9.  Reactivation of Varicella Zoster Virus after Vaccination for SARS-CoV-2.

Authors:  Mina Psichogiou; Michael Samarkos; Nikolaos Mikos; Angelos Hatzakis
Journal:  Vaccines (Basel)       Date:  2021-06-01

Review 10.  Seroprevalence of SARS-CoV-2 antibodies and associated factors in health care workers: a systematic review and meta-analysis.

Authors:  Petros Galanis; Irene Vraka; Despoina Fragkou; Angeliki Bilali; Daphne Kaitelidou
Journal:  J Hosp Infect       Date:  2020-11-16       Impact factor: 3.926

View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.