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1.
Clin Infect Dis ; 73(12): 2155-2162, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1592795

ABSTRACT

BACKGROUND: Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample. METHODS: Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the spike S1 protein of SARS-CoV-2 (N = 353), with up to 3 consecutive serum samples per seroconverted participant (N = 738). Immunoglobulin M (IgM), immunoglobulin A (IgA), and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined. RESULTS: While SARS-CoV-2-specific IgM and IgA antibodies declined rapidly after the first month after disease onset, specific IgG was still present in 92% (95% confidence interval [CI], 89%-95%) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI, 136-189 days). Concentrations were sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (P = .022). CONCLUSIONS: SARS-CoV-2-specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2, providing insight into protection of the general unvaccinated part of the population. CLINICAL TRIALS REGISTRATION: NL8473 (the Dutch trial registry).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Netherlands/epidemiology , Prospective Studies
2.
Clin Infect Dis ; 73(9): e3066-e3073, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501031

ABSTRACT

BACKGROUND: Reports suggest that some persons previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lack detectable immunoglobulin G (IgG) antibodies. We aimed to determine the proportion IgG seronegative and predictors for seronegativity among persons previously infected with SARS-CoV-2. METHODS: We analyzed serologic data collected from healthcare workers and first responders in New York City and the Detroit metropolitan area with a history of a positive SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) test result and who were tested for IgG antibodies to SARS-CoV-2 spike protein at least 2 weeks after symptom onset. RESULTS: Of 2547 persons with previously confirmed SARS-CoV-2 infection, 160 (6.3%) were seronegative. Of 2112 previously symptomatic persons, the proportion seronegative slightly increased from 14 to 90 days post symptom onset (P = .06). The proportion seronegative ranged from 0% among 79 persons previously hospitalized to 11.0% among 308 persons with asymptomatic infections. In a multivariable model, persons who took immunosuppressive medications were more likely to be seronegative (31.9%; 95% confidence interval [CI], 10.7%-64.7%), while participants of non-Hispanic Black race/ethnicity (vs non-Hispanic White; 2.7%; 95% CI, 1.5%-4.8%), with severe obesity (vs under/normal weight; 3.9%; 95% CI, 1.7%-8.6%), or with more symptoms were less likely to be seronegative. CONCLUSIONS: In our population with previous RT-PCR-confirmed infection, approximately 1 in 16 persons lacked IgG antibodies. Absence of antibodies varied independently by illness severity, race/ethnicity, obesity, and immunosuppressive drug therapy. The proportion seronegative remained relatively stable among persons tested up to 90 days post symptom onset.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Cohort Studies , Humans , Spike Glycoprotein, Coronavirus
4.
Transpl Int ; 34(10): 1908-1913, 2021 10.
Article in English | MEDLINE | ID: covidwho-1268132

ABSTRACT

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d'Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.


Subject(s)
COVID-19 , Liver Transplantation , Adult , Antibodies, Viral , Cross-Sectional Studies , Humans , SARS-CoV-2 , Seroepidemiologic Studies
5.
PLoS One ; 16(6): e0252818, 2021.
Article in English | MEDLINE | ID: covidwho-1264219

ABSTRACT

Most deaths from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in older subjects. We assessed the utility of serum inflammatory markers interleukin-6 (IL-6), C reactive protein (CRP), and ferritin (Roche, Indianapolis, IN), and SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin M (IgM), and neutralizing antibodies (Diazyme, Poway, CA). In controls, non-hospitalized subjects, and hospitalized subjects assessed for SARS-CoV-2 RNA (n = 278), median IgG levels in arbitrary units (AU)/mL were 0.05 in negative subjects, 14.83 in positive outpatients, and 30.61 in positive hospitalized patients (P<0.0001). Neutralizing antibody levels correlated significantly with IgG (r = 0.875; P<0.0001). Having combined values of IL-6 ≥10 pg/mL and CRP ≥10 mg/L occurred in 97.7% of inpatients versus 1.8% of outpatients (odds ratio 3,861, C statistic 0.976, P = 1.00 x 10-12). Antibody or ferritin levels did not add significantly to predicting hospitalization. Antibody testing in family members and contacts of SARS-CoV-2 RNA positive cases (n = 759) was invaluable for case finding. Persistent IgM levels were associated with chronic COVID-19 symptoms. In 81,624 screened subjects, IgG levels were positive (≥1.0 AU/mL) in 5.21%, while IgM levels were positive in 2.96% of subjects. In positive subjects median IgG levels in AU/mL were 3.14 if <30 years of age, 4.38 if 30-44 years of age, 7.89 if 45-54 years of age, 9.52 if 55-64 years of age, and 10.64 if ≥65 years of age (P = 2.96 x 10-38). Our data indicate that: 1) combined IL-6 ≥10 pg/mL and CRP ≥10 mg/L identify SARS-CoV-2 positive subjects requiring hospitalization; 2) IgG levels were significantly correlated with neutralizing antibody levels with a wide range of responses; 3) IgG levels have significant utility for case finding in exposed subjects; 4) persistently elevated IgM levels are associated with chronic symptoms; and 5) IgG levels are significantly higher in positive older subjects than their younger counterparts.


Subject(s)
COVID-19/blood , Inflammation/blood , Adult , Age Factors , Aged , Aging , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , C-Reactive Protein/analysis , C-Reactive Protein/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , Female , Ferritins/blood , Ferritins/immunology , Hospitalization , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Inflammation/diagnosis , Inflammation/epidemiology , Inflammation/immunology , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
6.
Front Microbiol ; 12: 643275, 2021.
Article in English | MEDLINE | ID: covidwho-1241180

ABSTRACT

A novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in December 2019, causing an ongoing, rapidly spreading global pandemic. Worldwide, vaccination is now expected to provide containment of the novel virus, resulting in an antibody-mediated immunity. To verify this, serological antibody assays qualitatively as well as quantitatively depicting the amount of generated antibodies are of great importance. Currently available test methods are either laboratory based or do not have the ability to indicate an estimation about the immune response. To overcome this, a novel and rapid serological magnetic immunodetection (MID) point-of-care (PoC) assay was developed, with sensitivity and specificity comparable to laboratory-based DiaSorin Liaison SARS-CoV-2 S1/S2 IgG assay. To specifically enrich human antibodies against SARS-CoV-2 in immunofiltration columns (IFCs) from patient sera, a SARS-CoV-2 S1 antigen was transiently produced in plants, purified and immobilized on the IFC. Then, an IgG-specific secondary antibody could bind to the retained antibodies, which was finally labeled using superparamagnetic nanoparticles. Based on frequency magnetic mixing technology (FMMD), the magnetic particles enriched in IFC were detected using a portable FMMD device. The obtained measurement signal correlates with the amount of SARS-CoV-2-specific antibodies in the sera, which could be demonstrated by titer determination. In this study, a MID-based assay could be developed, giving qualitative as well as semiquantitative results of SARS-CoV-2-specific antibody levels in patient's sera within 21 min of assay time with a sensitivity of 97% and a specificity of 92%, based on the analysis of 170 sera from hospitalized patients that were tested using an Food and Drug Administration (FDA)-certified chemiluminescence assay.

7.
J Electroanal Chem (Lausanne) ; 894: 115341, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1225286

ABSTRACT

Rapid distribution of airborne contagious pathogenic viruses such as SRAS-CoV-2 and their severely adverse impacts on different aspects of the human society, along with significant weaknesses of traditional diagnostic platforms, raised the global requirement for the design/fabrication of precise, sensitive, and rapid nanosystems capable of specific detection of viral illnesses with almost negligible false-negative results. To address this indispensable requirement, we have developed an ultra-precise fast diagnostic platform capable of detecting the trace of monoclonal IgG antibody against S1 protein of SARS-CoV-2 within infected patients' blood specimens with COVID-19 in about 1 min. The as-developed electrochemical-based nanosensor consists of a highly activated graphene-based platform in conjunction with Au nanostars, which can detect SARS-CoV-2 antibodies with a fantastic detection limit (DL) and sensitivity of 0.18 × 10-19%V/V and 2.14 µA.%V/V.cm-2, respectively, in human blood plasma specimens even upon the presence of a high amount of interfering compound/antibodies. The nanosensor also exhibited remarkable sensitivity/specificity compared with the gold standard (i.e., ELISA assay), which furtherly confirmed its superb performance.

8.
Sci Rep ; 11(1): 9819, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1223112

ABSTRACT

The simplicity and low cost of rapid point-of-care tests greatly facilitate large-scale population testing, which can contribute to controlling the spread of the COVID-19 virus. We evaluated the applicability of a self-testing strategy for SARS-CoV2 in a population-based, cross-sectional study in Cantabria, Spain, between April and May 2020. For the self-testing strategy, participants received the necessary material for the self-collection of blood and performance of a rapid antibody test using lateral flow immunoassay at home without the supervision of healthcare personnel. A total of 1,022 participants were enrolled. Most participants correctly performed the COVID-19 self-test the first time (91.3% [95% CI 89.4-92.9]). Only a minority of the participants (0.7%) needed the help of healthcare personnel, while 6.9% required a second kit delivery, for a total valid test result in 96.9% of the participants. Incorrect use of the self-test was not associated with the educational level, age over 65, or housing area. Prevalence of IgG antibodies against SARS-CoV2 for subjects with a valid rapid test result was 3.1% (95% CI 2.2-4.4), similar to the seroprevalence result obtained using a conventional approach carried out by healthcare professionals. In conclusion, COVID-19 self-testing should be considered as a screening tool.


Subject(s)
COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Self-Testing , Adolescent , Adult , Aged , COVID-19/virology , Cohort Studies , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Immunoglobulin G , Male , Middle Aged , SARS-CoV-2/physiology , Spain , Young Adult
9.
Clin Microbiol Infect ; 27(9): 1349.e1-1349.e6, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1222883

ABSTRACT

OBJECTIVES: The worldwide spread of coronavirus disease 2019 (COVID-19) highlights the need for assessment of long-term humoral immunity in convalescent subjects. Our objectives were to evaluate long-term IgG antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and B-cell memory response in COVID-19 convalescent subjects. METHODS: Blood samples were collected from a cohort of subjects recovering from COVID-19 and from healthy subjects who donated blood. SARS-CoV-2 IgG antibodies were quantitatively detected by ELISA using anti-S1 spike IgG. SARS-CoV-2 spike-specific IgG memory B cells were evaluated by reversed B-cell FluroSpot based on human IgG SARS-CoV-2 receptor-binding domain in a randomly selected group of subjects recovering from COVID-19. Statistical analysis was performed with clinical variables and time post COVID-19 infection. RESULTS: Antibody response was not detected in 26 of 392 COVID-19 convalescent subjects (6.6%). Over a period of 9 months, the level of antibodies decreased by 50% but stabilized at 6 months, and a protective level prevailed for up to 9 months. No differences were found regarding IgG SARS-CoV-2 antibody levels for age, gender, and major blood types over time. Over time, asymptomatic COVID-19 subjects did not differ in antibody level from subjects with mild to severe disease. Repeated paired IgG SARS-CoV-2 antibody level analyses disclosed that, over 6 and 9 months, 15.3% (nine of 59) and 15.8% (three of 19) of subjects became SARS-CoV-2 IgG-seronegative, respectively, all with a low antibody level at 3 months. Rate of antibody decline was not affected by age, gender, or clinical symptomatology. In a subgroup of recovering subjects, memory B-cell response up to 9 months post-COVID-19 infection was undetectable in 31.8% of subjects (14/44), and there was no correlation with age, SARS-CoV-2 antibody level, or time post infection. CONCLUSIONS: The majority of convalescent COVID-19 subjects develop an IgG SARS-CoV-2 antibody response and a protective level prevails over a period of up to 9 months, regardless of age, gender, major blood types or clinical symptomatology.


Subject(s)
Antibodies, Viral/blood , B-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Case-Control Studies , Convalescence , Cross-Sectional Studies , Female , Humans , Immunoglobulin G/blood , Immunologic Memory , Longitudinal Studies , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
10.
Front Immunol ; 12: 580147, 2021.
Article in English | MEDLINE | ID: covidwho-1211807

ABSTRACT

The coronavirus disease 2019 (COVID-19) is widely spread and remains a global pandemic. Limited evidence on the systematic evaluation of the impact of treatment regimens on antibody responses exists. Our study aimed to analyze the role of antibody response on prognosis and determine factors influencing the IgG antibodies' seroconversion. A total of 1,111 patients with mild to moderate COVID-19 symptoms admitted to Leishenshan Hospital in Wuhan were retrospectively analyzed. A serologic SARS-CoV-2 IgM/IgG antibody test was performed on all the patients 21 days after the onset of symptoms. Patient clinical characteristics were compared. In the study, 42 patients progressed to critical illness, with 6 mortalities reported while 1,069 patients reported mild to moderate disease. Advanced age (P = 0.028), gasping (P < 0.001), dyspnea (P = 0.024), and IgG negativity (P = 0.006) were associated with progression to critical illness. The mortality rate in critically ill patients with IgG antibody was 6.45% (95% CI 1.12-22.84%) and 36.36% (95% CI 12.36-68.38%) in patients with no IgG antibody (P = 0.003). Symptomatic patients were more likely to develop IgG antibody responses than asymptomatic patients. Using univariable analysis, fever (P < 0.001), gasping (P = 0.048), cancer (P < 0.001), cephalosporin (P = 0.015), and chloroquine/hydroxychloroquine (P = 0.021) were associated with IgG response. In the multivariable analysis, fever, cancer, cephalosporins, and chloroquine/hydroxychloroquine correlated independently with IgG response. We determined that the absence of SARS-CoV-2 antibody IgG in the convalescent stage had a specific predictive role in critical illness progression. Importantly, risk factors affecting seropositivity were identified, and the effect of antimalarial drugs on antibody response was determined.


Subject(s)
Antibodies, Viral/immunology , Antimalarials/adverse effects , COVID-19/immunology , Immunoglobulin G/immunology , Adolescent , Adult , Aged , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , Cephalosporins/adverse effects , China , Chloroquine/adverse effects , Convalescence , Female , Fever/complications , Fever/virology , Humans , Hydroxychloroquine/adverse effects , Immunoglobulin M/immunology , Male , Middle Aged , Multivariate Analysis , Neoplasms/complications , Neoplasms/virology , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2 , Seroconversion , Serologic Tests
11.
Open Forum Infect Dis ; 7(9): ofaa387, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1205747

ABSTRACT

BACKGROUND: Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibodies has become an important tool, complementing nucleic acid tests (NATs) for diagnosis and for determining the prevalence of coronavirus disease 2019 (COVID-19) in population serosurveys. The magnitude and persistence of antibody responses are critical for assessing the duration of immunity. METHODS: A SARS-CoV-2-specific immunofluorescent antibody (IFA) assay for immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) was developed and prospectively evaluated by comparison to the reference standard of NAT on respiratory tract samples from individuals with suspected COVID-19. Neutralizing antibody responses were measured in a subset of samples using a standard microneutralization assay. RESULTS: A total of 2753 individuals were eligible for the study (126 NAT-positive; prevalence, 4.6%). The median "window period" from illness onset to appearance of antibodies (range) was 10.2 (5.8-14.4) days. The sensitivity and specificity of either SARS-CoV-2 IgG, IgA, or IgM when collected ≥14 days after symptom onset were 91.3% (95% CI, 84.9%-95.6%) and 98.9% (95% CI, 98.4%-99.3%), respectively. The negative predictive value was 99.6% (95% CI, 99.3%-99.8%). The positive predictive value of detecting any antibody class was 79.9% (95% CI, 73.3%-85.1%); this increased to 96.8% (95% CI, 90.7%-99.0%) for the combination of IgG and IgA. CONCLUSIONS: Measurement of SARS-CoV-2-specific antibody by IFA is an accurate method to diagnose COVID-19. Serological testing should be incorporated into diagnostic algorithms for SARS-CoV-2 infection to identify additional cases where NAT was not performed and resolve cases where false-negative and false-positive NATs are suspected. The majority of individuals develop robust antibody responses following infection, but the duration of these responses and implications for immunity remain to be established.

12.
Healthcare (Basel) ; 9(5)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1202061

ABSTRACT

(1) Background: Healthcare workers (HCWs) are prone to intensified exposure to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in the ongoing pandemic. We prospectively analyzed the prevalence of antibodies against SARS-CoV-2 in HCWs at baseline and follow up with regard to clinical signs and symptoms in two university hospitals in Brandenburg, Germany. (2) Methods: Screening for anti-SARS-CoV-2 IgA and IgG antibodies was offered to HCWs at baseline and follow up two months thereafter in two hospitals of Brandenburg Medical School during the first wave of the COVID-19 pandemic in Germany in an ongoing observational cohort study. Medical history and signs and symptoms were recorded by questionnaires and analyzed. (3) Results: Baseline seroprevalence of anti-SARS-CoV-2 IgA was 11.7% and increased to 15% at follow up, whereas IgG seropositivity was 2.1% at baseline and 2.2% at follow up. The rate of asymptomatic seropositive cases was 39.5%. Symptoms were not associated with general seropositivity for anti-SARS-CoV-2; however, class switch from IgA to IgG was associated with increased symptom burden. (4) Conclusions: The seroprevalence of antibodies against SARS-CoV-2 was low in HCWs but higher compared to population data and increased over time. Screening for antibodies detected a significant proportion of seropositive participants cases without symptoms.

13.
Curr Opin Infect Dis ; 34(3): 181-186, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1201884

ABSTRACT

PURPOSE OF REVIEW: Despite its crucial role in protection against viral infections, mucosal immunity has been largely understudied in the context of coronavirus disease 2019 (COVID-19). This review outlines the current evidence about the role of mucosal immune responses in the clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as potential mucosal mechanisms of protection against (re-)infection. RECENT FINDINGS: The angiotensin-converting enzyme 2 cellular entry receptor for SARS-CoV-2 is most highly expressed in the upper respiratory tract and most SARS-CoV-2 shedding occurs from the upper respiratory tract. Viral shedding peaks early during infection around the onset of symptoms, before dropping rapidly in most individuals within 7 days of symptom onset, suggesting mucosal inhibition of viral infection. Serum and mucosal immunoglobulin G and immunoglobulin M responses were found to be strongly correlated in infected patients, whereas correlations were much weaker for immunoglobulin A (IgA). Mucosal IgA responses have been detected in infected cases in the absence of serum antibody responses, with mucosal antibody levels correlating strongly with virus neutralization. Bulk and single-cell RNA sequencing analysis of nasopharyngeal swabs and bronchoalveolar lavage samples of COVID-19 patients revealed the induction of mucosal chemokine and cytokine genes, complement pathways, Janus Kinase/Signal Transducer and Activator of Transcription signaling and cytotoxic T cells. SUMMARY: Although most clinical studies focus on antibodies and cellular immunity in peripheral blood, mucosal immune responses in the respiratory tract play a key role in the early restriction of viral replication and the clearance of SARS-CoV-2. Identification of mucosal biomarkers associated with viral clearance will allow monitoring of infection-induced immunity. Further studies are needed to understand how the systemic immunological endpoints measured in vaccination studies translate to mucosal protection against SARS-CoV-2 infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunity, Mucosal , Immunoglobulin A/immunology , Virus Shedding , COVID-19/prevention & control , Humans , Immunoglobulin A/blood , SARS-CoV-2/immunology , Vaccination
14.
J Med Virol ; 93(2): 803-811, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196402

ABSTRACT

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests is massive. The external validation of their performance is needed before use in clinical routine practice. Our study aims at assessing the analytical and clinical performance of two enzyme-linked immunosorbent assay tests detecting antibodies directed against the virus nucleocapsid protein: The NovaLisa SARS-CoV-2 immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) test (NovaTec) allowing a separate detection of each antibody and the Platelia SARS-CoV-2 Total Ab test (Bio-Rad) detecting total antibodies (IgM, IgA, and IgG). Two-hundred and eight coronavirus disease 2019 samples from 48 quantitative reverse transcription-polymerase chain reaction (RT-qPCR) confirmed patients were used to perform the sensitivity analysis. Non-SARS-CoV-2 sera (n = 79) with a potential cross-reaction to SARS-CoV-2 immunoassays were included in the specificity analysis. In addition, using receiver operator characteristic curves, adapted cut-off for improvement of the performances were proposed. The kinetics of these antibodies was also assessed over 8 weeks. Two weeks after the RT-qPCR positive detection, the NovaLisa test shows a sensitivity and specificity of 94.9% (95% confidence interval [CI]: 83.1%-98.6%) and 96.2% (95% CI: 89.4%-98.7%) for IgG, of 89.7% (95% CI: 76.4%-95.9%) and 98.7% (95% CI: 93.2%-98.8%) for IgA, and of 48.7% (95% CI: 33.9%-63.8%) and 98.7% (95% CI: 93.2%-99.8%) for IgM. With the Platelia system, the specificity and sensitivity were 97.4% (95% CI: 92.1%-99.7%) and 94.9% (95% CI: 87.7%-98.0%) for total antibodies using the adapted cut-offs. The NovaLisa and the Platelia tests have satisfactory analytical performances. The clinical performances are excellent for IgG, IgA, and total antibodies especially if the cut-off is optimized.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Enzyme-Linked Immunosorbent Assay/standards , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Female , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/pathogenicity , Sensitivity and Specificity , Severity of Illness Index , Survival Analysis
15.
J Orthop Sci ; 27(3): 713-716, 2022 May.
Article in English | MEDLINE | ID: covidwho-1188813

ABSTRACT

BACKGROUND: Elective orthopaedic surgery has been severely curtailed because of coronavirus disease, 2019. There is scant scientific evidence to guide surgeons in assessing the protocols that must be implemented before resuming elective orthopaedic surgery safely after the second wave of the coronavirus disease, 2019. METHODS: A retrospective review of elective orthopaedic surgeries performed between May 15, 2020, and November 20, 2020, was conducted. A screening questionnaire was used, and reverse transcription-polymerase chain reaction and severe acute respiratory syndrome coronavirus-2 immunoglobulin G and IgM antibodies testing were assessed in all admitted patients. Screening and testing data for coronavirus disease was reviewed for all patients. RESULTS: Of 592 patients tested for severe acute respiratory syndrome coronavirus-2 during the study period, 21 (3.5%) tested positive. There were 2 patients (0.3%) with positive reverse transcription-polymerase chain reaction tests, 3 (0.5%) with positive IgG and IgM antibodies, 13 (2.2%) with positive IgG antibodies, and 10 (1.7%) with positive IgM antibodies. Among these 21 patients, 20 (95.2%) were asymptomatic. CONCLUSIONS: Our findings suggest that most elective orthopaedic surgery patients with severe acute respiratory syndrome coronavirus-2 are asymptomatic. In the second wave of coronavirus disease, 2019, universal testing of all patients should be strongly considered as an important measure to prevent clusters of in-hospital transmission of the disease.


Subject(s)
COVID-19 , Orthopedic Procedures , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2
17.
Clin Chim Acta ; 519: 26-31, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1176557

ABSTRACT

BACKGROUND AND AIMS: The reduced fucosylation in the spike glycoprotein of SARS-CoV-2 and the IgG antibody has been observed in COVID-19. However, the clinical relevance of α-l-fucosidase, the enzyme for defucosylation has not been discovered. MATERIALS AND METHODS: 585 COVID-19 patients were included to analyze the correlations of α-l-fucosidase activity with the nucleic acid test, IgM/IgG, comorbidities, and disease progression. RESULTS: Among the COVID-19 patients, 5.75% were double-negative for nucleic acid and antibodies. All of them had increased α-l-fucosidase, while only one had abnormal serum amyloid A (SAA) and C-reactive protein (CRP). The abnormal rate of α-l-fucosidase was 81.82% before the presence of IgM, 100% in the presence of IgM, and 66.2% in the presence of IgG. 73.42% of patients with glucometabolic disorders had increased α-l-fucosidase activity and had the highest mortality of 6.33%. The increased α-l-fucosidase was observed in 55.8% of non-severe cases and 72.9% of severe cases, with an odds ratio of 2.118. The α-l-fucosidase mRNA was irrelevant to its serum activity. CONCLUSION: The change in α-l-fucosidase activity in COVID-19 preceded the IgM and SAA and showed a preferable relation with glucometabolic disorders, which may be conducive to virus invasion or invoke an immune response against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Humans , Immunoglobulin M , alpha-L-Fucosidase
18.
Pathogens ; 10(4)2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1178375

ABSTRACT

It is assumed that healthcare workers are at the highest risk to be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, few data from healthcare workers who do not primarily take care of patients with SARS-CoV-2 infection support this assumption. We investigated the prevalence of immunoglobulin G (Ig G) against SARS-CoV-2 among healthcare workers who do not primarily take care of patients with SARS-CoV-2 infection and the general population in a well-defined geographical area. The first part of the study was conducted in May 2020 in Val Mesolcina (Southern Switzerland), a valley with ~8000 inhabitants. All healthcare workers were invited. All participants (n = 488) of the Swiss Longitudinal Cohort Study (SWICOS), a cohort representative of the general population, were also invited. Circulating Ig G against spike protein subunit 1 of SARS-CoV-2 were tested in each subject. Subjects with positive Ig G were tested again after 6 months. The condition of being a healthcare worker, rather than a part of the general population, was tested as a predictor of seroprevalence positivity by both simple and multiple (adjusted for age and sex) logistic regression. Eleven (2.6%) of the 423 SWICOS participants and 46 (16%) out of 289 healthcare workers were positive for antibodies against SARS-CoV-2. The seroprevalence OR was 7.01 (95% CI: 3.53-15.47) for healthcare workers as compared to SWICOS participants. After adjusting for age and gender, the seroprevalence OR was 5.13 (95% CI: 2.54-10.40). About three quarters of the subjects in the SWICOS (73%) and in healthcare (79%) group with a previous positive serology still presented positive Ig G against the SARS-CoV-2 after 6 months. The present seroprevalence data point out that the SARS-CoV-2 infection is seven times higher among healthcare workers than in the general population of Val Mesolcina. Efforts to effectively protect all the healthcare personnel are needed.

19.
Nat Commun ; 12(1): 2117, 2021 04 09.
Article in English | MEDLINE | ID: covidwho-1174671

ABSTRACT

To estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered seroprevalence survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with an immunoassay, followed by confirmatory testing of borderline and positive test results with a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (PRNT). Those with a borderline or positive immunoassay result were retested after 4 to 5 months. At baseline, 4771 persons participated (88% response rate). Between April 24th and June 30th, 2020, seroprevalence was 0.97% (95% CI: 0.72-1.30) by immunoassay and 0.36% (95% CI: 0.21-0.61) when considering only those with two additional positive confirmatory tests. Importantly, about 20% of PRNT+ individuals lost their neutralizing antibodies within five months. Here, we show that neutralizing antibodies are detectable in only one third of those with a positive immunoassay result, and wane relatively quickly.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , COVID-19/virology , Cohort Studies , Female , Germany , Humans , Immunoassay/methods , Male , Middle Aged , Neutralization Tests/methods , Population Surveillance/methods , SARS-CoV-2/physiology , Seroepidemiologic Studies
20.
PLoS One ; 16(4): e0249449, 2021.
Article in English | MEDLINE | ID: covidwho-1171683

ABSTRACT

OBJECTIVES: To determine the seroprevalence of anti-SARS-CoV-2 IgG and IgM antibodies in symptomatic Japanese COVID-19 patients. METHODS: Serum samples (n = 114) from 34 COVID-19 patients with mild to critical clinical manifestations were examined. The presence and titers of IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were determined by a chemiluminescent microparticle immunoassay (CMIA) using Alinity i SARS-CoV-2 IgG and by an immunochromatographic (IC) IgM/IgG antibody assay using the Anti-SARS-CoV-2 Rapid Test. RESULTS: IgG was detected by the CMIA in 40%, 88%, and 100% of samples collected within 1 week, 1-2 weeks, and 2 weeks after symptom onset in severe and critical cases, and 0%, 38%, and 100% in mild/moderate cases, respectively. In severe and critical cases, the positive IgG detection rate with the IC assay was 60% within one week and 63% between one and two weeks. In mild/moderate cases, the positive IgG rate was 17% within one week and 63% between one and two weeks; IgM was positive in 80% and 75% of severe and critical cases, and 42% and 88% of mild/moderate cases, respectively. On the CMIA, no anti-SARS-CoV-2 IgG antibodies were detected in COVID-19 outpatients with mild symptoms within 10 days from onset, whereas 50% of samples from severe inpatients were IgG-positive in the same period. The IC assay detected higher IgM positivity earlier from symptom onset in severe and critical cases than in mild/moderate cases. CONCLUSIONS: A serologic anti-SARS-CoV-2 antibody analysis can complement PCR for diagnosing COVID-19 14 days after symptom onset.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19 , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Immunoassay , Japan/epidemiology , Male , Middle Aged
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