Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 36
Filter
1.
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
2.
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
3.
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
4.
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.

5.
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.

6.
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
7.
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
8.
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
9.
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
10.
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
11.
Front Neurol ; 12: 622130, 2021.
Article in English | MEDLINE | ID: covidwho-1110311

ABSTRACT

Thrombotic complications are common in COVID-19 patients, but cerebral venous system involvement, timing after infection, optimal treatment, and long-term outcome are uncertain. We report a case of massive cerebral venous thrombosis and concomitant internal iliac vein thrombosis occurring in the late phase of paucisymptomatic COVID-19 infection. Mild respiratory symptoms, without fever, started 3 weeks before headache and acute neurological deficits. The patient had silent hypoxemia and typical COVID-19 associated interstitial pneumonia. Brain CT scan showed a left parietal hypodense lesion with associated sulcal subarachnoid hemorrhage. CT cerebral venography showed a massive cerebral venous thrombosis involving the right transverse sinus, the right jugular bulb, the superior sagittal sinus, the straight sinus, the vein of Galen, and both internal cerebral veins. Abdominal CT scan showed no malignancy but revealed an asymptomatic right internal iliac vein thrombosis. Both cerebral venous thrombosis and pelvic vein thrombosis were effectively treated with unfractionated heparin started on the day of admission, then shifted to low molecular weight heparin, with a favorable clinical course. Nasopharyngel swab, repeated twice, tested negative for SARS-CoV-2. Serological tests confirmed SARS-CoV-2 infection. Our case supports active surveillance and prevention of thrombotic complications associated with COVID-19, which may affect both peripheral and cerebral venous system. Early initiation of unfractionated heparin may lead to good neurologic outcome.

12.
Cureus ; 13(1): e12588, 2021 Jan 09.
Article in English | MEDLINE | ID: covidwho-1060102

ABSTRACT

OBJECTIVE: To determine the diagnostic accuracy of fully automated electro-chemiluminescence immunoassay (ECLIA) anti-SARS-CoV-2 serological test for detection of past SARS-CoV-2 infection and to be used in seroprevalence surveys. METHOD:  A total of 426 patients who had tested for anti-SARS-CoV-2 from August 1 to 31, 2020 were selected for the study. Informed consent was obtained and a questionnaire including the patient's age, gender, symptoms, and past polymerase chain reaction (PCR) status was filled by the patient. Samples were analyzed for anti-SARS-CoV-2 antibodies on Roche Cobas e601. RESULTS: The mean age of the patients was 42.43±16.67 years. One hundred and five (24.6%) were PCR positive, while 321 (75.4%) were PCR negative. Most patients were males 241 (56.6%) while 185(43.3%) were females. Over 185(43.3%) patients presented with symptoms, and the rest of the patients 241 (56.6%) were asymptomatic. Anti-SARS-CoV-2 had sensitivity 89.5%, specificity 99.06%, positive predictive value (PPV) 96.90%, negative predictive value (NPV) 96.6%, and positive likelihood ratio 4.26, while negative likelihood ratio 0.1. Diagnostic accuracy of anti-SARS-CoV-2 was 96.7% based on receiver-operating characteristic (ROC) curve analysis. CONCLUSION: Anti-SARS-CoV-2 is very useful for the detection of past COVID-19 infection; it can be proved helpful in the identification of post-COVID complications and actual disease burden in a population.

13.
Front Microbiol ; 11: 628281, 2020.
Article in English | MEDLINE | ID: covidwho-1058428

ABSTRACT

OBJECTIVES: Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples. METHODS: We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) dedicated automated chemiluminescent enzyme immunoassay analyzer AIA-CL1200. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors. RESULTS: All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested. CONCLUSION: Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.

14.
Environ Res ; 195: 110793, 2021 04.
Article in English | MEDLINE | ID: covidwho-1051629

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) are highly exposed to SARS-CoV-2 infection given their specific tasks. The IgG-IgM serological assay has demonstrated good accuracy in early detection in symptomatic patients, but its role in the diagnosis of asymptomatic patients is uncertain. The aim of our study was to assess IgM and IgG prevalence in sera in a large cohort of HCWs previously subjected to Nasopharyngeal swab test (NST) after accurate risk assessment due to positive COVID-19 patient exposure during an observation period of 90 days. METHODS: 2407 asymptomatic HCWs that had close contact with COVID-19 patients in the period between April 8th and June 7th were screened with NST based on the RT-PCR method. In parallel, they underwent large-scale chemiluminescence immunoassays involving IgM-IgG serological screening to determine actual viral spread in the same cohort. RESULTS: During the 90-day observation period, 18 workers (0.75%) resulted positive for SARS-CoV-2 infection at the NST, whereas the positivity rates for IgM and IgG were 11.51% and 2.37%, respectively (277 workers). Despite high specificity, serological tests were inadequate for detecting SARS-CoV-2 infection in patients with previous positive NST results (IgM and IgG sensitivities of 27.78% and 50.00%, respectively). CONCLUSIONS: These findings indicate a widespread low viral load of SARS-CoV-2 among hospital workers. However, serological screening showed very low sensitivity with respect to NST in identifying infected workers, and negative IgG and IgM results should not exclude the diagnosis of COVID-19. IgG-IgM chemiluminescence immunoassays could increase the diagnosis of COVID-19 only in association with NST, and this association is considered helpful for decision-making regarding returning to work.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Health Personnel , Hospitals , Humans , Immunoglobulin G , Immunoglobulin M , Italy/epidemiology , Prevalence , Public Health , Sensitivity and Specificity
15.
J Clin Microbiol ; 59(2)2021 01 21.
Article in English | MEDLINE | ID: covidwho-1041778

ABSTRACT

Reliable serological tests are required to determine the prevalence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to characterize immunity to the disease in order to address key knowledge gaps in the coronavirus disease 2019 (COVID-19) pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and enzyme-linked immunosorbent assays (ELISAs) with their higher precision, dynamic range, throughput, miniaturization, cost-efficiency, and multiplexing capacity. We developed three qSAT assays for IgM, IgA, and IgG against a panel of eight SARS-CoV-2 antigens, including spike protein (S), nucleocapsid protein (N), and membrane protein (M) constructs. The assays were optimized to minimize the processing time and maximize the signal-to-noise ratio. We evaluated their performances using 128 prepandemic plasma samples (negative controls) and 104 plasma samples from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 5 were asymptomatic, 51 had mild symptoms, and 48 were hospitalized. Preexisting IgG antibodies recognizing N, M, and S proteins were detected in negative controls, which is suggestive of cross-reactivity to common-cold coronaviruses. The best-performing antibody/antigen signatures had specificities of 100% and sensitivities of 95.78% at ≥14 days and 95.65% at ≥21 days since the onset of symptoms, with areas under the curve (AUCs) of 0.977 and 0.999, respectively. Combining multiple markers as assessed by qSAT assays has the highest efficiency, breadth, and versatility to accurately detect low-level antibody responses for obtaining reliable data on the prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity and their kinetics, required for vaccine development to combat the COVID-19 pandemic.


Subject(s)
Antigens, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin Isotypes/blood , SARS-CoV-2/immunology , Adult , Antibodies, Viral/blood , COVID-19/blood , Cross Reactions , Female , Humans , Immunoassay , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Viral Structural Proteins/immunology
16.
Int J Infect Dis ; 104: 415-422, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1032496

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS: A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS: Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION: These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Pandemics , SARS-CoV-2/immunology , COVID-19/virology , COVID-19 Serological Testing , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Luminescent Measurements , Sensitivity and Specificity , Serologic Tests , Spike Glycoprotein, Coronavirus/immunology
17.
Cochrane Database Syst Rev ; 6: CD013652, 2020 06 25.
Article in English | MEDLINE | ID: covidwho-981322

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and resulting COVID-19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify current infection, rule out infection, identify people in need of care escalation, or to test for past infection and immune response. Serology tests to detect the presence of antibodies to SARS-CoV-2 aim to identify previous SARS-CoV-2 infection, and may help to confirm the presence of current infection. OBJECTIVES: To assess the diagnostic accuracy of antibody tests to determine if a person presenting in the community or in primary or secondary care has SARS-CoV-2 infection, or has previously had SARS-CoV-2 infection, and the accuracy of antibody tests for use in seroprevalence surveys. SEARCH METHODS: We undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We conducted searches for this review iteration up to 27 April 2020. SELECTION CRITERIA: We included test accuracy studies of any design that evaluated antibody tests (including enzyme-linked immunosorbent assays, chemiluminescence immunoassays, and lateral flow assays) in people suspected of current or previous SARS-CoV-2 infection, or where tests were used to screen for infection. We also included studies of people either known to have, or not to have SARS-CoV-2 infection. We included all reference standards to define the presence or absence of SARS-CoV-2 (including reverse transcription polymerase chain reaction tests (RT-PCR) and clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS: We assessed possible bias and applicability of the studies using the QUADAS-2 tool. We extracted 2x2 contingency table data and present sensitivity and specificity for each antibody (or combination of antibodies) using paired forest plots. We pooled data using random-effects logistic regression where appropriate, stratifying by time since post-symptom onset. We tabulated available data by test manufacturer. We have presented uncertainty in estimates of sensitivity and specificity using 95% confidence intervals (CIs). MAIN RESULTS: We included 57 publications reporting on a total of 54 study cohorts with 15,976 samples, of which 8526 were from cases of SARS-CoV-2 infection. Studies were conducted in Asia (n = 38), Europe (n = 15), and the USA and China (n = 1). We identified data from 25 commercial tests and numerous in-house assays, a small fraction of the 279 antibody assays listed by the Foundation for Innovative Diagnostics. More than half (n = 28) of the studies included were only available as preprints. We had concerns about risk of bias and applicability. Common issues were use of multi-group designs (n = 29), inclusion of only COVID-19 cases (n = 19), lack of blinding of the index test (n = 49) and reference standard (n = 29), differential verification (n = 22), and the lack of clarity about participant numbers, characteristics and study exclusions (n = 47). Most studies (n = 44) only included people hospitalised due to suspected or confirmed COVID-19 infection. There were no studies exclusively in asymptomatic participants. Two-thirds of the studies (n = 33) defined COVID-19 cases based on RT-PCR results alone, ignoring the potential for false-negative RT-PCR results. We observed evidence of selective publication of study findings through omission of the identity of tests (n = 5). We observed substantial heterogeneity in sensitivities of IgA, IgM and IgG antibodies, or combinations thereof, for results aggregated across different time periods post-symptom onset (range 0% to 100% for all target antibodies). We thus based the main results of the review on the 38 studies that stratified results by time since symptom onset. The numbers of individuals contributing data within each study each week are small and are usually not based on tracking the same groups of patients over time. Pooled results for IgG, IgM, IgA, total antibodies and IgG/IgM all showed low sensitivity during the first week since onset of symptoms (all less than 30.1%), rising in the second week and reaching their highest values in the third week. The combination of IgG/IgM had a sensitivity of 30.1% (95% CI 21.4 to 40.7) for 1 to 7 days, 72.2% (95% CI 63.5 to 79.5) for 8 to 14 days, 91.4% (95% CI 87.0 to 94.4) for 15 to 21 days. Estimates of accuracy beyond three weeks are based on smaller sample sizes and fewer studies. For 21 to 35 days, pooled sensitivities for IgG/IgM were 96.0% (95% CI 90.6 to 98.3). There are insufficient studies to estimate sensitivity of tests beyond 35 days post-symptom onset. Summary specificities (provided in 35 studies) exceeded 98% for all target antibodies with confidence intervals no more than 2 percentage points wide. False-positive results were more common where COVID-19 had been suspected and ruled out, but numbers were small and the difference was within the range expected by chance. Assuming a prevalence of 50%, a value considered possible in healthcare workers who have suffered respiratory symptoms, we would anticipate that 43 (28 to 65) would be missed and 7 (3 to 14) would be falsely positive in 1000 people undergoing IgG/IgM testing at days 15 to 21 post-symptom onset. At a prevalence of 20%, a likely value in surveys in high-risk settings, 17 (11 to 26) would be missed per 1000 people tested and 10 (5 to 22) would be falsely positive. At a lower prevalence of 5%, a likely value in national surveys, 4 (3 to 7) would be missed per 1000 tested, and 12 (6 to 27) would be falsely positive. Analyses showed small differences in sensitivity between assay type, but methodological concerns and sparse data prevent comparisons between test brands. AUTHORS' CONCLUSIONS: The sensitivity of antibody tests is too low in the first week since symptom onset to have a primary role for the diagnosis of COVID-19, but they may still have a role complementing other testing in individuals presenting later, when RT-PCR tests are negative, or are not done. Antibody tests are likely to have a useful role for detecting previous SARS-CoV-2 infection if used 15 or more days after the onset of symptoms. However, the duration of antibody rises is currently unknown, and we found very little data beyond 35 days post-symptom onset. We are therefore uncertain about the utility of these tests for seroprevalence surveys for public health management purposes. Concerns about high risk of bias and applicability make it likely that the accuracy of tests when used in clinical care will be lower than reported in the included studies. Sensitivity has mainly been evaluated in hospitalised patients, so it is unclear whether the tests are able to detect lower antibody levels likely seen with milder and asymptomatic COVID-19 disease. The design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement. Studies must report data on sensitivity disaggregated by time since onset of symptoms. COVID-19-positive cases who are RT-PCR-negative should be included as well as those confirmed RT-PCR, in accordance with the World Health Organization (WHO) and China National Health Commission of the People's Republic of China (CDC) case definitions. We were only able to obtain data from a small proportion of available tests, and action is needed to ensure that all results of test evaluations are available in the public domain to prevent selective reporting. This is a fast-moving field and we plan ongoing updates of this living systematic review.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Antibody Specificity , COVID-19 , Coronavirus Infections/epidemiology , False Negative Reactions , False Positive Reactions , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Pandemics , Pneumonia, Viral/epidemiology , Reference Standards , Reverse Transcriptase Polymerase Chain Reaction/standards , Reverse Transcriptase Polymerase Chain Reaction/statistics & numerical data , SARS-CoV-2 , Selection Bias , Sensitivity and Specificity , Serologic Tests/methods , Serologic Tests/standards
18.
Lab Chip ; 21(1): 93-104, 2021 01 07.
Article in English | MEDLINE | ID: covidwho-977278

ABSTRACT

The applications of serology tests to the virus SARS-CoV-2 are diverse, ranging from diagnosing COVID-19, understanding the humoral response to this disease, and estimating its prevalence in a population, to modeling the course of the pandemic. COVID-19 serology assays will significantly benefit from sensitive and reliable technologies that can process dozens of samples in parallel, thus reducing costs and time; however, they will also benefit from biosensors that can assess antibody reactivities to multiple SARS-CoV-2 antigens. Here, we report a high-throughput microfluidic device that can assess antibody reactivities against four SARS-CoV-2 antigens from up to 50 serum samples in parallel. This semi-automatic platform measures IgG and IgM levels against four SARS-CoV-2 proteins: the spike protein (S), the S1 subunit (S1), the receptor-binding domain (RBD), and the nucleocapsid (N). After assay optimization, we evaluated sera from infected individuals with COVID-19 and a cohort of archival samples from 2018. The assay achieved a sensitivity of 95% and a specificity of 91%. Nonetheless, both parameters increased to 100% when evaluating sera from individuals in the third week after symptom onset. To further assess our platform's utility, we monitored the antibody titers from 5 COVID-19 patients over a time course of several weeks. Our platform can aid in global efforts to control and understand COVID-19.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoassay/methods , SARS-CoV-2/immunology , Area Under Curve , COVID-19/virology , Coronavirus Nucleocapsid Proteins/immunology , Humans , Immunoassay/instrumentation , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lab-On-A-Chip Devices , Longitudinal Studies , Phosphoproteins/immunology , Protein Domains/immunology , ROC Curve , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology
19.
Euro Surveill ; 25(48)2020 12.
Article in English | MEDLINE | ID: covidwho-961570

ABSTRACT

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.


Subject(s)
COVID-19 , Coronavirus Infections/diagnosis , Coronavirus/genetics , Mucocutaneous Lymph Node Syndrome/virology , Pneumonia, Viral/diagnosis , Systemic Inflammatory Response Syndrome , Case-Control Studies , Child , Child, Preschool , Coronavirus/isolation & purification , France/epidemiology , Humans , Mucocutaneous Lymph Node Syndrome/complications , Pneumonia, Viral/epidemiology , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction
SELECTION OF CITATIONS
SEARCH DETAIL