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1.
Pan Afr Med J ; 38: 55, 2021.
Article in French | MEDLINE | ID: covidwho-1547713

ABSTRACT

The first outbreak of epidemic respiratory disease due to unknown etiology was reported in the Chinese city of Wuhan December 2019. The World Health Organization (WHO) firstly used the term "new coronavirus 2019" on December 29, 2019. This pandemic, which is currently called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disease caused by SARS-CoV-2. It was subsequently called coronavirus disease 2019 (COVID-19) by the WHO. The purpose of this study was to determine the prevalence of antibodies against SARS-CoV-2 in all employees of the Nouakchott National Hospital Center (CHN). The study was conducted during the week 20/05/2020 to 27/05/2020. It involved 853 employees of all ranks (doctors, pharmacists, nurses, secretaries, security personnel, administrators...) of whom 504 were male and 331 were female, with a sex ratio of 1,52 with an average age of 39 years, ranging from 20 to 60 years. The screening for IgG and IgM antibodies to SARS-CoV-2 was performed using Biotime (Xiamen Biotime Biotechnology Co., Ltd.) immunochromatographic technique. Out of 835 employees included in our study, 14 were positive (1.67%) of whom 12 had IgM and IgG anti-SARS-CoV-2 antibodies and 2 had isolated IgM. Nasopharyngeal swab polymerase chain reaction (PCR) was performed in these 14 patients and was positive in six. While PCR is the gold standard for the diagnosis of SARS-CoV-2, serological tests for SARS-CoV-2 antibodies, in particular rapid tests (RDTs) are a diagnostic complement to COVID-19. They have the advantage of being easy to realize, of being safe both in the laboratories and outside the laboratories. RDTs enabled us to detect asymptomatic SARS-CoV-2 carriers within CHN employees. This allowed for patients management and isolation to protect patients and their environments.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Health Personnel , SARS-CoV-2/isolation & purification , Adult , Antibodies, Viral/blood , COVID-19/epidemiology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Male , Mauritania/epidemiology , Middle Aged , Serologic Tests/methods , Young Adult
2.
Front Med (Lausanne) ; 8: 631769, 2021.
Article in English | MEDLINE | ID: covidwho-1389197

ABSTRACT

Background: SARS-CoV-2 infection may not provide long lasting post-infection immunity. While hundreds of reinfections have reported only a few have been confirmed. Whole genome sequencing (WGS) of the viral isolates from the different episodes is mandatory to establish reinfection. Methods: Nasopharyngeal (NP), oropharyngeal (OP) and whole blood (WB) samples were collected from paired samples of four individuals who were suspected of SARS-CoV-2 reinfection based on distinct clinical episodes and RT-PCR tests. Details from their case record files and investigations were documented. RNA was extracted from the NP and OP samples and subjected to WGS, and the nucleotide and amino acid sequences were subjected to genome and protein-based functional annotation analyses. Serial serology was performed for Anti-N IgG, Anti- S1 RBD IgG, and sVNT (surrogate virus neutralizing test). Findings: Three patients were more symptomatic with lower Ct values and longer duration of illness. Seroconversion was detected soon after the second episode in three patients. WGS generated a genome coverage ranging from 80.07 to 99.7%. Phylogenetic analysis revealed sequences belonged to G, GR and "Other" clades. A total of 42mutations were identified in all the samples, consisting of 22 non-synonymous, 17 synonymous, two in upstream, and one in downstream regions of the SARS-CoV-2 genome. Comparative genomic and protein-based annotation analyses revealed differences in the presence and absence of specific mutations in the virus sequences from the two episodes in all four paired samples. Interpretation: Based on the criteria of genome variations identified by whole genome sequencing and supported by clinical presentation, molecular and serological tests, we were able to confirm reinfections in two patients, provide weak evidence of reinfection in the third patient and unable to rule out a prolonged infection in the fourth. This study emphasizes the importance of detailed analyses of clinical and serological information as well as the virus's genomic variations while assessing cases of SARS-CoV-2 reinfection.

3.
Continuum (Minneap Minn) ; 27(1): 93-120, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1354739

ABSTRACT

PURPOSE OF REVIEW: This article reviews infectious etiologies of spinal cord dysfunction, emphasizing the importance of recognizing common clinicoradiographic syndromes and interpreting them in the context of exposure risk and individual host susceptibilities. RECENT FINDINGS: This article discusses the shifting spectrum of neurologic infectious diseases, the growing population of patients who are immunocompromised, and the emergence of effective antiretroviral therapies. In addition, it discusses new molecular and serologic tests that have the potential to enhance our ability to rapidly and accurately diagnose infectious diseases of the spine. SUMMARY: When evaluating patients with suspected infectious myelopathies, it is imperative to narrow the range of pathogens under consideration. The geography, seasonality, and clinicoradiographic presentation and immunocompetence status of the patient define the range of potential pathogens and should guide testing and initial management.


Subject(s)
Communicable Diseases , HIV Infections , Spinal Cord Diseases , Humans , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/therapy
4.
Drug Test Anal ; 13(7): 1238-1248, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1258052

ABSTRACT

The outbreak of the new coronavirus disease changed the world upside down. Every day, millions of people were subjected to diagnostic testing for Covid-19, all over the world. Molecular tests helped in the diagnosis of current infection by detecting the presence of viral genome whereas serological tests helped in detecting the presence of antibody in blood as well as contributed to vaccine development. This testing helped in understanding the immunogenicity, community prevalence, geographical spread and conditions post-infection. However, with the contagious nature of the virus, biological specimen sampling involved the risk of transmission and spread of infection. Clinic or pathology visit was the most concerning part. Trained personnel and resources was another barrier. In this scenario, microsampling played an important role due to its most important advantage of remote, contactless, small volume and self-sampling. Minimum requirements for sample storage and ease of shipment added value in this situation. The highly sensitive instruments and validated assay formats assured the accuracy of results and stability of samples. Microsampling techniques are contributing effectively to the Covid-19 pandemic by reducing the demand for clinical staff in population-level testing. The validated and established applications supported the use of microsampling in diagnosis, therapeutic drug monitoring, development of treatment or vaccines and clinical trials for Covid-19.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , Specimen Handling , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines/therapeutic use , Clinical Trials as Topic , Drug Monitoring , Humans , Population Surveillance , Predictive Value of Tests
5.
mSphere ; 6(3)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226714

ABSTRACT

Serology (antibody) tests to detect previous SARS-CoV-2 infection have been in high demand from the beginning of the COVID-19 pandemic. The initial shortage of diagnostic tests coupled with asymptomatic infections led to a significant demand for serology tests to identify past infections. Despite serious limitations on the interpretation of a positive antibody test in terms of immunity to SARS-CoV-2, antibody testing was initially considered for release from social distancing, return to employment, and "immunity passports." The regulatory approach to antibody tests was limited; manufacturers were encouraged to develop and market antibody tests without submitting validation data to the FDA. FDA guidance grew more stringent, but many poor-quality tests were already on the market-potentially inappropriately used for individual decision-making. This is a case study describing COVID-19 serology tests and the U.S. market and describes lessons learned for a future health security crisis.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Pandemics , SARS-CoV-2/immunology , Asymptomatic Infections , COVID-19 Serological Testing/history , COVID-19 Serological Testing/standards , Forecasting , Health Policy , Health Services Needs and Demand , History, 21st Century , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Marketing of Health Services , Politics , Quality Control , Sensitivity and Specificity , United States , United States Food and Drug Administration , Validation Studies as Topic
6.
Clin Microbiol Infect ; 27(7): 981-986, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1222881

ABSTRACT

BACKGROUND: Although molecular tests are considered the reference standard for coronavirus disease 2019 (COVID-19) diagnostics, serological and immunological tests may be useful in specific settings. OBJECTIVES: This review summarizes the underlying principles and performance of COVID-19 serological and immunological testing. SOURCES: Selected peer-reviewed publications on COVID-19 related serology and immunology published between December 2019 and March 2021. CONTENT: Serological tests are highly specific but heterogeneous in their sensitivity for the diagnosis of COVID-19. For certain indications, including delayed disease presentations, serological tests can have added value. The presence of antibodies against SARS-CoV-2 may indicate a recent or past COVID-19 infection. Lateral flow immunoassay (LFIA) antibody tests have the advantages of being easy and fast to perform, but many have a low sensitivity in acute settings. Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassays (CLIAs) have higher sensitivities. Besides humoral immunity, cellular immunity is also essential for successful host defences against viruses. Enzyme-linked immunospot (ELISpot) assays can be used to measure T-cell responses against SARS-CoV-2. The presence of cross-reactive SARS-CoV-2-specific T cells in never exposed patients suggests the possibility of cellular immunity induced by other circulating coronaviruses. T-cell responses against SARS-CoV-2 have also been detected in recovered COVID-19 patients with no detectable antibodies. IMPLICATIONS: Serological and immunological tests are primarily applied for population-based seroprevalence studies to evaluate the effectiveness of COVID-19 control measures and increase our understanding of the immunology behind COVID-19. Combining molecular diagnostics with serological tests may optimize the detection of COVID-19. As not all infected patients will develop antibodies against SARS-CoV-2, assessment of cellular immunity may provide complementary information on whether a patient has been previously infected with COVID-19. More studies are needed to understand the correlations of these serological and immunological parameters with protective immunity, taking into account the different circulating virus variants.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , COVID-19/immunology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , Humans , Immunity, Cellular , Immunity, Humoral , Immunoassay , Sensitivity and Specificity
7.
J Immunol ; 206(10): 2393-2401, 2021 05 15.
Article in English | MEDLINE | ID: covidwho-1215527

ABSTRACT

Serological tests for detection of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Abs in blood are expected to identify individuals who have acquired immunity against SARS-CoV-2 and indication of seroprevalence of SARS-CoV-2 infection. Many serological tests have been developed to detect Abs against SARS-CoV-2. However, these tests have considerable variations in their specificity and sensitivity, and whether they can predict levels of neutralizing activity is yet to be determined. This study aimed to investigate the kinetics and neutralizing activity of various Ag-specific Ab isotypes against SARS-CoV-2 in serum of coronavirus disease 2019 (COVID-19) patients confirmed via PCR test. We developed IgG, IgM, and IgA measurement assays for each Ag, including receptor-binding domain (RBD) of spike (S) protein, S1 domain, full-length S protein, S trimer, and nucleocapsid (N) domain, based on ELISA. The assays of the S protein for all isotypes showed high specificity, whereas the assays for all isotypes against N protein showed lower specificity. The sensitivity of all Ag-specific Ab isotypes depended on the timing of the serum collection and all of them, except for IgM against N protein, reached more than 90% at 15-21 d postsymptom onset. The best correlation with virus-neutralizing activity was found for IgG against RBD, and levels of IgG against RBD in sera from four patients with severe COVID-19 increased concordantly with neutralizing activity. Our results provide valuable information regarding the selection of serological test for seroprevalence and vaccine evaluation studies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Specificity , Antigens, Viral/immunology , COVID-19/immunology , Immunoglobulin Isotypes/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged
8.
Epidemiology ; 32(4): 518-524, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1211432

ABSTRACT

BACKGROUND: Serology tests can identify previous infections and facilitate estimation of the number of total infections. However, immunoglobulins targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to wane below the detectable level of serologic assays (which is not necessarily equivalent to the duration of protective immunity). We estimate the cumulative incidence of SARS-CoV-2 infection from serology studies, accounting for expected levels of antibody acquisition (seroconversion) and waning (seroreversion), and apply this framework using data from New York City and Connecticut. METHODS: We estimated time from seroconversion to seroreversion and infection fatality ratio (IFR) using mortality data from March to October 2020 and population-level cross-sectional seroprevalence data from April to August 2020 in New York City and Connecticut. We then estimated the daily seroprevalence and cumulative incidence of SARS-CoV-2 infection. RESULTS: The estimated average time from seroconversion to seroreversion was 3-4 months. The estimated IFR was 1.1% (95% credible interval, 1.0%, 1.2%) in New York City and 1.4% (1.1, 1.7%) in Connecticut. The estimated daily seroprevalence declined after a peak in the spring. The estimated cumulative incidence reached 26.8% (24.2%, 29.7%) at the end of September in New York City and 8.8% (7.1%, 11.3%) in Connecticut, higher than maximum seroprevalence measures (22.1% and 6.1%), respectively. CONCLUSIONS: The cumulative incidence of SARS-CoV-2 infection is underestimated using cross-sectional serology data without adjustment for waning antibodies. Our approach can help quantify the magnitude of underestimation and adjust estimates for waning antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Connecticut/epidemiology , Cross-Sectional Studies , Humans , Incidence , New York City , Seroepidemiologic Studies
9.
Pediatr Infect Dis J ; 40(2): e72-e76, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1207336

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), an entity in children initially characterized by milder case presentations and better prognoses as compared with adults. Recent reports, however, raise concern for a new hyperinflammatory entity in a subset of pediatric COVID-19 patients. METHODS: We report a fatal case of confirmed COVID-19 with hyperinflammatory features concerning for both multi-inflammatory syndrome in children (MIS-C) and primary COVID-19. RESULTS: This case highlights the ambiguity in distinguishing between these two entities in a subset of pediatric patients with COVID-19-related disease and the rapid decompensation these patients may experience. CONCLUSIONS: Appropriate clinical suspicion is necessary for both acute disease and MIS-C. SARS-CoV-2 serologic tests obtained early in the diagnostic process may help to narrow down the differential but does not distinguish between acute COVID-19 and MIS-C. Better understanding of the hyperinflammatory changes associated with MIS-C and acute COVID-19 in children will help delineate the roles for therapies, particularly if there is a hybrid phenotype occurring in adolescents.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Myocarditis/complications , Myocarditis/physiopathology , Adolescent , African Americans , COVID-19/diagnosis , COVID-19/pathology , Female , Humans , Intensive Care Units , Myocarditis/diagnosis , Myocarditis/pathology , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome
10.
J Clin Med ; 10(9)2021 Apr 21.
Article in English | MEDLINE | ID: covidwho-1201827

ABSTRACT

BACKGROUND: There is much data available concerning the initiation of the immune response after SARS-CoV-2 infection, but long-term data are scarce. METHODS: We thus longitudinally evaluated and compared the total and neutralizing immune response of 61 patients to SARS-CoV-2 infection up to eight months after diagnosis by RT-PCR using several commercial assays. RESULTS: Among the 208 samples tested, the percentage of seropositivity was comparable between assays up to four months after diagnosis and then tended to be more heterogeneous between assays (p < 0.05). The percentage of patients with a neutralizing titer decreased from 82% before two months postdiagnosis to 57% after six months. This decrease appeared to be more marked for patients under 65 years old and those not requiring hospitalization. The percentage of serology reversion at 6 months was from 11% with the WANTAI total assay to over 39% with the ABBOTT IgG assay. The neutralizing antibody titers decreased in parallel with the decrease of total antibody titers, with important heterogeneity between assays. CONCLUSIONS: In conclusion, serological tests show equivalent sensitivity in the first months after the diagnosis of SARS-CoV-2 infection, but their performance later, postinfection, must be considered when interpreting the results.

11.
Ann Med Surg (Lond) ; 65: 102320, 2021 May.
Article in English | MEDLINE | ID: covidwho-1198606

ABSTRACT

COVID-19 serological antibody tests are recently needed for a relatively quick, affordable, and valuable assessment of the immunity toward COVID-19 infection. Furthermore, they can help with evaluating the sufficiency of the vaccination process and its longevity. There are limitations in the current approach of choosing the positive and negative control samples for the validation of those tests. Herein, we are proposing the use of blood samples from positive COVID-19 patients, at the beginning of the disease course, as negative control blood samples for the antibody tests. For more precision, both the negative and the positive control samples can be obtained from the same patients where the accuracy of the test will depend on its ability to detect the seroconversion, from negative to positive antibodies detection, within the same patient. Furthermore, when the validation of the test is accompanied by detecting/sequencing the viral genome in those COVID-19 patients, this can also aid in determining the accuracy of the test in detecting the immune response to specific viral variants. The latter notion is needed for the proper management of the COVID-19 crisis, new vaccines' manufacturing, and evaluating the vaccines' efficiencies. Finally, this approach could be requested/formulated by the regulatory agencies as part of the tests' validation and can be "in-house" obtained by health facilities before its clinical use.

12.
ACS Omega ; 6(14): 9667-9671, 2021 Apr 13.
Article in English | MEDLINE | ID: covidwho-1191080

ABSTRACT

SARS-CoV-2 is the etiologic agent of COVID-19, which has led to a dramatic loss of human life and presents an unprecedented challenge to public health worldwide. The gold standard assay for SARS-CoV-2 identification is real-time polymerase chain reaction; however, this assay depends on highly trained personnel and sophisticated equipment and may suffer from false results. Thus, a serological antibody test is a supplement to the diagnosis or screening of SARS-CoV-2. Here, we develop and evaluate the diagnostic performance of an IgM/IgG indirect ELISA method for antibodies against SARS-CoV-2 in COVID-19. The ELISA was constructed by coating with a recombinant nucleocapsid protein of SARS-CoV-2 on an enzyme immunoassay plate, and its sensitivity and specificity for clinical diagnosis of SARS-CoV-2 infection was assessed by detecting the SARS-CoV-2-specific IgM and IgG antibodies in COVID-19 patient's sera or healthy person's sera. The SARS-CoV-2 positive serum samples (n = 168) were collected from confirmed COVID-19 patients. A commercial nucleocapsid protein-based chemiluminescent immunoassay (CLIA) kit and a colloidal gold immunochromatography kit were compared with those of the ELISA assay. The specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of IgM were 100, 95.24, 100, and 91.84%, whereas those of IgG were 100, 97.02, 100, and 94.74%, respectively. We developed a highly sensitive and specific SARS-CoV-2 nucleocapsid protein-based ELISA method for the diagnosis and epidemiologic investigation of COVID-19 by SARS-CoV-2 IgM and IgG antibody detection.

13.
J Clin Microbiol ; 59(4)2021 03 19.
Article in English | MEDLINE | ID: covidwho-1177519

ABSTRACT

The COVID-19 pandemic, caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread worldwide. Serological testing for SARS-CoV-2-specific antibodies plays an important role in understanding and controlling the pandemic, notably through epidemiological surveillance. Well-validated and highly specific SARS-CoV-2 serological assays are urgently needed. We describe here the analytical and clinical performance of Vidas SARS-CoV-2 IgM and Vidas SARS-CoV-2 IgG, two CE-marked, emergency use authorization (EUA)-authorized, automated, qualitative assays for the detection of SARS-CoV-2-specific IgM and IgG, respectively. Both assays showed high within-run and within-laboratory precision (coefficients of variation < 11.0%) and very low cross-reactivity toward sera of patients with a past common coronavirus or respiratory virus infection. Clinical specificity determined on up to 989 prepandemic healthy donors was ≥99% with a narrow 95% confidence interval for both IgM and IgG assays. Clinical sensitivity was determined on up to 232 samples from 130 reverse transcriptase PCR (RT-PCR)-confirmed SARS-CoV-2 patients. The positive percent agreement (PPA) with SARS-CoV-2 PCR reached 100% at ≥16 days (Vidas SARS-CoV-2 IgM) and ≥32 days (Vidas SARS-CoV-2 IgG) of symptom onset. Combined IgM/IgG test results improved the PPA compared to each test alone. SARS-CoV-2 IgG seroconversion followed closely that of SARS-CoV-2 IgM and remained stable over time, while SARS-CoV-2 IgM levels rapidly declined. Interestingly, SARS-CoV-2-specific IgM and IgG responses were significantly higher in COVID-19 hospitalized versus nonhospitalized patients. Altogether, the Vidas SARS-CoV-2 IgM and IgG assays are highly specific and sensitive serological tests suitable for the reliable detection of past acute SARS-CoV-2 infections.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin G , Immunoglobulin M , Pandemics , Sensitivity and Specificity
14.
Expert Rev Clin Immunol ; 17(6): 573-599, 2021 06.
Article in English | MEDLINE | ID: covidwho-1160272

ABSTRACT

Introduction: The gold standard for diagnosis of coronavirus disease 2019 (COVID-19) is detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR), which is expensive, time-consuming and may result in false-negative results. Serological tests can be employed for RT-PCR negative patients, contact tracing, determining the probability of protection against re-infection, and seroepidemiological studies.Areas covered: The main methodologies of serology-based tests for the detection of SARS-CoV-2 including enzyme-linked immunosorbent assays (ELISAs), chemiluminescent immunoassays (CLIAs) and lateral flow immunoassays (LFIAs) were reviewed and their diagnostic performances were compared. Herein, a literature review on the databases of PubMed, Scopus and Google Scholar between January 1, 2020 and June 30, 2020 based on the main serological methods for COVID-19 detection with the focus on comparative experiments was performed. The review was updated on December 31, 2020.Expert opinion: Serology testing could be considered as a part of diagnostic panel two-week post symptom onset. Higher sensitivity for serology-based tests could be achieved by determining combined IgG/IgM titers. Furthermore, higher sensitive serological test detecting neutralization antibody could be developed by targeting spike (S) antigen. It was also demonstrated that the sensitivity of ELISA/CLIA-based methods are higher than LFIA devices.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/diagnosis , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Biomarkers/blood , COVID-19/immunology , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Host-Pathogen Interactions , Humans , Luminescent Measurements , Predictive Value of Tests , Reproducibility of Results
15.
PLoS Comput Biol ; 17(2): e1008728, 2021 02.
Article in English | MEDLINE | ID: covidwho-1154072

ABSTRACT

Large-scale serological testing in the population is essential to determine the true extent of the current SARS-CoV-2 pandemic. Serological tests measure antibody responses against pathogens and use predefined cutoff levels that dichotomize the quantitative test measures into sero-positives and negatives and use this as a proxy for past infection. With the imperfect assays that are currently available to test for past SARS-CoV-2 infection, the fraction of seropositive individuals in serosurveys is a biased estimator of the cumulative incidence and is usually corrected to account for the sensitivity and specificity. Here we use an inference method-referred to as mixture-model approach-for the estimation of the cumulative incidence that does not require to define cutoffs by integrating the quantitative test measures directly into the statistical inference procedure. We confirm that the mixture model outperforms the methods based on cutoffs, leading to less bias and error in estimates of the cumulative incidence. We illustrate how the mixture model can be used to optimize the design of serosurveys with imperfect serological tests. We also provide guidance on the number of control and case sera that are required to quantify the test's ambiguity sufficiently to enable the reliable estimation of the cumulative incidence. Lastly, we show how this approach can be used to estimate the cumulative incidence of classes of infections with an unknown distribution of quantitative test measures. This is a very promising application of the mixture-model approach that could identify the elusive fraction of asymptomatic SARS-CoV-2 infections. An R-package implementing the inference methods used in this paper is provided. Our study advocates using serological tests without cutoffs, especially if they are used to determine parameters characterizing populations rather than individuals. This approach circumvents some of the shortcomings of cutoff-based methods at exactly the low cumulative incidence levels and test accuracies that we are currently facing in SARS-CoV-2 serosurveys.


Subject(s)
COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/epidemiology , Models, Statistical , Pandemics , SARS-CoV-2 , Antibodies, Viral/blood , Asymptomatic Infections/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/statistics & numerical data , Computational Biology , Computer Simulation , Confidence Intervals , False Negative Reactions , False Positive Reactions , Humans , Incidence , Likelihood Functions , Pandemics/statistics & numerical data , ROC Curve , Reproducibility of Results , SARS-CoV-2/immunology , Sensitivity and Specificity
16.
J Med Virol ; 93(7): 4549-4552, 2021 07.
Article in English | MEDLINE | ID: covidwho-1141366

ABSTRACT

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin G/blood , Immunoglobulin M/blood , Adult , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2/immunology , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Young Adult
17.
Int J Occup Med Environ Health ; 34(2): 203-209, 2021 May 27.
Article in English | MEDLINE | ID: covidwho-1140809

ABSTRACT

OBJECTIVES: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) had spread worldwide since December 2019 and became a pandemic in March 2020. The diagnosis of an active infection is based on the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) from the nasopharyngeal swab specimen. The aim of the current analysis was to assess the usefulness of the rapid serological tests for diagnosing SARS-CoV-2 infections. MATERIAL AND METHODS: The rapid serological tests detecting IgG/IgM antibodies for SARS-CoV-2 were voluntarily performed in asymptomatic employees of 2 companies. The examination was conducted at the date and time selected online by the study participants. The testing team consisted of 2 nurses collecting the samples and 1 doctor who interpreted the results. Each positive rapid test result was verified by an RT-PCR examination from a nasopharyngeal swab. The testing kits named Vazyme: 2019-nCoV IgG/IgM Detection Kit (Colloidal Gold-Based) were provided by the employer along with the manual and certificates. RESULTS: The overall interest in testing among employees was below the employer's expectations and reached 30% and 20% in each of the 2 companies, respectively. A total of 516 participants were included in the analysis. Ten positive results of the rapid tests were documented, including 7 for IgM and 3 for IgG antibodies. No positive result was confirmed by the detection of the genetic material of the SARS-CoV-2 by the RT-PCR examination. CONCLUSIONS: Herein, the authors demonstrated the uselessness of rapid serological tests performed in asymptomatic volunteers for diagnosing SARS-CoV-2 infections. Int J Occup Med Environ Health. 2021;34(2):203-9.


Subject(s)
Antibodies, Viral/analysis , COVID-19/epidemiology , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Pandemics , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19/virology , Female , Humans , Immunoglobulin M/immunology , Male , Middle Aged
18.
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
19.
Indian J Tuberc ; 67(4S): S163-S166, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1124681

ABSTRACT

Accurate and rapid diagnostic tests are critical for achieving control of coronavirus disease 2019 (covid-19), a pandemic illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic tests for covid-19 fall into two main categories: molecular tests that detect viral RNA, and serological tests that detect anti-SARS-CoV-2 immunoglobulins. Reverse transcriptase polymerase chain reaction (RT-PCR), a molecular test, has become the gold standard for diagnosis of covid-19; however, this test has many limitations that include potential false negative results, changes in diagnostic accuracy over the disease course, and precarious availability of test materials. Serological tests have generated substantial interest as an alternative or complement to RT-PCR and other Nucleic acid tests in the diagnosis of acute infection, as some might be cheaper and easier to implement at the point of care. A clear advantage of these tests over RT-PCR is that they can identify individuals previously infected by SARS-CoV-2, even if they never underwent testing while acutely ill. Many serological tests for covid-19 have become available in a short period, including some marketed for use as rapid, point-of-care tests. The pace of development has, however, exceeded that of rigorous evaluation, and important uncertainty about test accuracy remains.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Humans , Sensitivity and Specificity
20.
Elife ; 102021 03 05.
Article in English | MEDLINE | ID: covidwho-1119624

ABSTRACT

Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies have been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that seropositivity indicates immune protection, we propagated estimates and uncertainty through dynamical models to assess uncertainty in the epidemiological parameters needed to evaluate public health interventions and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize serosurvey design given test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions.


Subject(s)
COVID-19/epidemiology , Adolescent , Adult , Age Factors , Aged , Bayes Theorem , COVID-19/diagnosis , COVID-19 Serological Testing , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Uncertainty , Young Adult
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