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1.
Ann Intern Med ; 175(2): 234-243, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753917

ABSTRACT

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/blood , Antigens, Viral/blood , Antiviral Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Medical Futility , Middle Aged , RNA, Viral/blood , SARS-CoV-2 , Treatment Failure
2.
J Med Virol ; 94(4): 1723-1727, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1718404

ABSTRACT

To assist in the clinical management of patients and to support infection control, we tested the use of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care antigen test (AgPOC) for unplanned hospitalization, coupled with a nucleic acid amplification test (NAAT) using specimens collected at the same time upon arrival. The aim of this study was to assess the performance of the AgPOC in this specific use compared to NAAT for SARS-CoV-2 diagnosis, in the context of the low prevalence of infection. For 5 months (between two peaks in France of the SARS-CoV-2 pandemic), all patients admitted who undertook the AgPOC/NAAT paired tests were included in the study. AgPOC performances were determined considering the clinical status and the delay of symptoms onset. NAAT and AgPOC results were available for 4425 subjects. AgPOC results showed a homogeneous specificity (>97%) but a low sensitivity at 45.8%. Considering the national guidelines, sensitivity dropped to 32.5% in cases of symptomatic patients with symptoms older than 5 days or more. This study shows the poor performance of AgPOC for entry screening of patients in hospitals. AgPOC may represent a useful tool in the hospital setting only if the use is restricted to patients with consistent symptoms less than 4 days old.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , Hospitals , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Viral/blood , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Time Factors , Young Adult
4.
Microbiol Spectr ; 10(1): e0122021, 2022 02 23.
Article in English | MEDLINE | ID: covidwho-1636464

ABSTRACT

Accurate tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical in efforts to control its spread. The accuracy of tests for SARS-CoV-2 has been assessed numerous times, usually in reference to a gold standard diagnosis. One major disadvantage of that approach is the possibility of error due to inaccuracy of the gold standard, which is especially problematic for evaluating testing in a real-world surveillance context. We used an alternative approach known as Bayesian latent class modeling (BLCM), which circumvents the need to designate a gold standard by simultaneously estimating the accuracy of multiple tests. We applied this technique to a collection of 1,716 tests of three types applied to 853 individuals on a university campus during a 1-week period in October 2020. We found that reverse transcriptase PCR (RT-PCR) testing of saliva samples performed at a campus facility had higher sensitivity (median, 92.3%; 95% credible interval [CrI], 73.2 to 99.6%) than RT-PCR testing of nasal samples performed at a commercial facility (median, 85.9%; 95% CrI, 54.7 to 99.4%). The reverse was true for specificity, although the specificity of saliva testing was still very high (median, 99.3%; 95% CrI, 98.3 to 99.9%). An antigen test was less sensitive and specific than both of the RT-PCR tests, although the sample sizes with this test were small and the statistical uncertainty was high. These results suggest that RT-PCR testing of saliva samples at a campus facility can be an effective basis for surveillance screening to prevent SARS-CoV-2 transmission in a university setting. IMPORTANCE Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been vitally important during the COVID-19 pandemic. There are a variety of methods for testing for this virus, and it is important to understand their accuracy in choosing which one might be best suited for a given application. To estimate the accuracy of three different testing methods, we used a data set collected at a university that involved testing the same samples with multiple tests. Unlike most other estimates of test accuracy, we did not assume that one test was perfect but instead allowed for some degree of inaccuracy in all testing methods. We found that molecular tests performed on saliva samples at a university facility were similarly accurate as molecular tests performed on nasal samples at a commercial facility. An antigen test appeared somewhat less accurate than the molecular tests, but there was high uncertainty about that.


Subject(s)
Antigens, Viral/analysis , COVID-19/diagnosis , SARS Virus/immunology , SARS-CoV-2/isolation & purification , Saliva/virology , Antigens, Viral/blood , Bayes Theorem , COVID-19/epidemiology , COVID-19/virology , COVID-19 Nucleic Acid Testing , Humans , Predictive Value of Tests , Prevalence , Reproducibility of Results , SARS-CoV-2/immunology , Sensitivity and Specificity , Universities , Young Adult
8.
J Med Virol ; 94(4): 1357-1365, 2022 04.
Article in English | MEDLINE | ID: covidwho-1544352

ABSTRACT

At present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is raging worldwide, and the coronavirus disease 2019 outbreak caused by SARS-CoV-2 seriously threatens the life and health of all humankind. There is no specific medicine for novel coronavirus yet. So, laboratory diagnoses of novel coronavirus as soon as possible and isolation of the source of infection play a vital role in preventing and controlling the epidemic. Therefore, selecting appropriate detection techniques and methods is particularly important to improve the efficiency of disease diagnosis and treatment and to curb the outbreak of infectious diseases. In this paper, virus nucleic acid, protein, and serum immunology were reviewed to provide a reference for further developing virus detection technology to provide better prevention and treatment strategies and research ideas for clinicians and researchers.


Subject(s)
COVID-19 Testing , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/epidemiology , Genome, Viral/genetics , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Technology
9.
J Med Virol ; 93(12): 6686-6692, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544320

ABSTRACT

To control the spread of the coronavirus disease 2019 (COVID-19) epidemics, it is necessary to have easy-to-use, reliable diagnostic tests available. The nasopharyngeal sampling method being often uncomfortable, nasal sampling could prove to be a viable alternative to the reference sampling method. We performed a multicentre, prospective validation study of the COVID-VIRO® test, using a nasal swab sampling method, in a point-of-care setting. In addition, we performed a multicentre, prospective, and usability study to validate the use of the rapid antigen nasal diagnostic test by laypersons. In March 2021, 239 asymptomatic and symptomatic patients were included in the validation study. Compared with reverse-transcription polymerase chain reaction on nasopharyngeal samples, the sensitivity and specificity of the COVID-VIRO® Antigen test combined with a nasal sampling method were evaluated as 96.88% and 100%, respectively. A total of 101 individuals were included in the usability study. Among these, 99% of the participants rated the instructions material as good, 98% of the subjects executed the test procedure well, and 98% of the participants were able to correctly interpret the test results. This study validates the relevance of COVID-VIRO® as a diagnostic tool from nasal specimens as well as its usability in the general population. COVID-VIRO® diagnostic performances and ease of use make it suitable for widespread utilization.


Subject(s)
COVID-19 Testing/methods , Diagnostic Tests, Routine/methods , Self-Testing , Adult , Antigens, Viral/blood , Humans , Male , Point-of-Care Testing , Prospective Studies , SARS-CoV-2/immunology , Sensitivity and Specificity
10.
Anal Biochem ; 631: 114360, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1474246

ABSTRACT

To monitor the levels of protecting antibodies raised in the population in response to infection and/or to immunization with SARS-CoV-2, we need a technique that allows high throughput and low-cost quantitative analysis of human IgG antibodies reactive against viral antigens. Here we describe an ultra-fast, high throughput and inexpensive assay to detect SARS-CoV-2 seroconversion in humans. The assay is based on Ni2+ magnetic particles coated with His tagged SARS-CoV-2 antigens. A simple and inexpensive 96 well plate magnetic extraction/homogenization process is described which allows the simultaneous analysis of 96 samples and delivers results in 7 min with high accuracy.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin G/blood , SARS-CoV-2/isolation & purification , Antibodies, Viral/immunology , Antigens, Viral/blood , Antigens, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19 Serological Testing/economics , Enzyme-Linked Immunosorbent Assay/economics , Enzyme-Linked Immunosorbent Assay/methods , Humans , Immunoglobulin G/immunology , Magnets/chemistry , Nickel/chemistry , SARS-CoV-2/immunology , Sensitivity and Specificity , Seroconversion , Time Factors
11.
Anal Bioanal Chem ; 413(29): 7251-7263, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1460298

ABSTRACT

Supply shortage for the development and production of preventive, therapeutic, and diagnosis tools during the COVID-19 pandemic is an important issue affecting the wealthy and poor nations alike. Antibodies and antigens are especially needed for the production of immunological-based testing tools such as point-of-care tests. Here, we propose a simple and quick magnetic nanoparticle (MNP)-based separation/isolation approach for the repurposing of infected human samples to produce specific antibodies and antigen cocktails. Initially, an antibody cocktail was purified from serums via precipitation and immunoaffinity chromatography. Purified antibodies were conjugated onto MNPs and used as an affinity matrix to separate antigens. The characterization process was performed by ELISA, SDS-PAGE, electrochemistry, isothermal titration calorimetry, and LC-Q-TOF-MS/MS analyses. The MNP-separated peptides can be used for mass spectrometry-based as well as paper-based lateral flow assay diagnostic. The exploitation of the current workflow for the development of efficient diagnostic tools, specific treatments, and fundamental research can significantly impact the present or eventual pandemic. This workflow can be considered as a two birds, one stone-like strategy.


Subject(s)
Antibodies, Viral/isolation & purification , Antigens, Viral/isolation & purification , COVID-19/diagnosis , Cost-Benefit Analysis , Immunoassay/economics , SARS-CoV-2/isolation & purification , Viremia/virology , Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/virology , Calorimetry , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Humans , SARS-CoV-2/immunology , Specimen Handling , Tandem Mass Spectrometry , Viremia/blood , Workflow
12.
J Intern Med ; 291(2): 232-240, 2022 02.
Article in English | MEDLINE | ID: covidwho-1455598

ABSTRACT

BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19 , COVID-19/immunology , COVID-19/mortality , Critical Illness , Humans , RNA, Viral/blood , SARS-CoV-2
13.
Clin Chem ; 68(1): 204-213, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1450383

ABSTRACT

BACKGROUND: Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antigen in blood has been described, but the diagnostic and prognostic role of antigenemia is not well understood. This study aimed to determine the frequency, duration, and concentration of nucleocapsid antigen in plasma and its association with coronavirus disease 2019 (COVID-19) severity. METHODS: We utilized an ultrasensitive electrochemiluminescence immunoassay targeting SARS-CoV-2 nucleocapsid antigen to evaluate 777 plasma samples from 104 individuals with COVID-19. We compared plasma antigen to respiratory nucleic acid amplification testing (NAAT) in 74 individuals with COVID-19 from samples collected ±1 day of diagnostic respiratory NAAT and in 52 SARS-CoV-2-negative individuals. We used Kruskal-Wallis tests, multivariable logistic regression, and mixed-effects modeling to evaluate whether plasma antigen concentration was associated with disease severity. RESULTS: Plasma antigen had 91.9% (95% CI 83.2%-97.0%) clinical sensitivity and 94.2% (84.1%-98.8%) clinical specificity. Antigen-negative plasma samples belonged to patients with later respiratory cycle thresholds (Ct) when compared with antigen-positive plasma samples. Median plasma antigen concentration (log10 fg/mL) was 5.4 (interquartile range 3.9-6.0) in outpatients, 6.0 (5.4-6.5) in inpatients, and 6.6 (6.1-7.2) in intensive care unit (ICU) patients. In models adjusted for age, sex, diabetes, and hypertension, plasma antigen concentration at diagnosis was associated with ICU admission [odds ratio 2.8 (95% CI 1.2-6.2), P=.01] but not with non-ICU hospitalization. Rate of antigen decrease was not associated with disease severity. CONCLUSIONS: SARS-CoV-2 plasma nucleocapsid antigen exhibited comparable diagnostic performance to upper respiratory NAAT, especially among those with late respiratory Ct. In addition to currently available tools, antigenemia may facilitate patient triage to optimize intensive care utilization.


Subject(s)
Antigens, Viral/blood , COVID-19 Testing/methods , COVID-19 , Coronavirus Nucleocapsid Proteins/blood , COVID-19/diagnosis , Electrochemical Techniques , Hospitalization , Humans , Immunoassay , Luminescent Measurements , Nucleocapsid , Phosphoproteins/blood , SARS-CoV-2 , Sensitivity and Specificity
14.
Front Immunol ; 12: 739037, 2021.
Article in English | MEDLINE | ID: covidwho-1448729

ABSTRACT

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients. Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients. Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients. Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.


Subject(s)
COVID-19/therapy , Convalescence , SARS-CoV-2/immunology , Seroconversion , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/blood , Blood Donors , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunization, Passive , Kinetics , Male , Middle Aged , Outpatients , RNA, Viral/blood
16.
J Med Virol ; 94(1): 222-228, 2022 01.
Article in English | MEDLINE | ID: covidwho-1372751

ABSTRACT

The current study aimed at characterizing the dynamics of SARS-CoV-2 nucleocapsid (N) antigenemia in a cohort of critically ill adult COVID-19 patients and assessing its potential association with plasma levels of biomarkers of clinical severity and mortality. Seventy-three consecutive critically ill COVID-19 patients (median age, 65 years) were recruited. Serial plasma (n = 340) specimens were collected. A lateral flow immunochromatography assay and reverse-transcription polymerase chain reaction (RT-PCR) were used for SARS-CoV-2 N protein detection and RNA quantitation and in plasma, respectively. Serum levels of inflammatory and tissue-damage biomarkers in paired specimens were measured. SARS-CoV-RNA N-antigenemia and viral RNAemia were documented in 40.1% and 35.6% of patients, respectively at a median of 9 days since symptoms onset. The level of agreement between the qualitative results returned by the N-antigenemia assay and plasma RT-PCR was moderate (k = 0.57; p < 0.0001). A trend towards higher SARS-CoV-2 RNA loads was seen in plasma specimens testing positive for N-antigenemia assay than in those yielding negative results (p = 0.083). SARS-CoV-2 RNA load in tracheal aspirates was significantly higher (p < 0.001) in the presence of concomitant N-antigenemia than in its absence. Significantly higher serum levels of ferritin, lactose dehydrogenase, C-reactive protein, and D-dimer were quantified in paired plasma SARS-CoV-2 N-positive specimens than in those testing negative. Occurrence of SARS-CoV-2 N-antigenemia was not associated with increased mortality in univariate logistic regression analysis (odds ratio, 1.29; 95% confidence interval, 0.49-3.34; p = 0.59). In conclusion, SARS-CoV-2 N-antigenemia detection is relatively common in ICU patients and appears to associate with increased serum levels of inflammation and tissue-damage markers. Whether this virological parameter may behave as a biomarker of poor clinical outcome awaits further investigations.


Subject(s)
COVID-19/virology , Coronavirus Nucleocapsid Proteins/blood , Critical Illness , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Antigens, Viral/blood , Biomarkers/analysis , Biomarkers/blood , COVID-19/mortality , Coronavirus Nucleocapsid Proteins/immunology , Female , Humans , Inflammation , Male , Middle Aged , Phosphoproteins/blood , Phosphoproteins/immunology , Prospective Studies , RNA, Viral/analysis , RNA, Viral/blood , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Trachea/virology , Young Adult
17.
STAR Protoc ; 2(3): 100815, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1373301

ABSTRACT

The emergence of the coronavirus disease 2019 pandemic increased the interest in analysis of immunoglobulin responses. ELISA and lateral flow assays are widely used but are restricted by a single response value to an antigen or antigen pool. Here, we describe antigen microarrays, an alternative allowing simultaneous assessment of multiple interactions between antigens and the immunoglobulin content of patient sera. The technique requires minimal reagents and sample input and can be adapted to a wide variety of potential antigenic targets of interest.


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/blood , Microarray Analysis/methods , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/immunology , COVID-19/virology , Humans , Spike Glycoprotein, Coronavirus/blood
19.
JCI Insight ; 6(15)2021 08 09.
Article in English | MEDLINE | ID: covidwho-1350084

ABSTRACT

A subset of COVID-19 patients exhibit post-acute sequelae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median = 74 days) compared with 30 who had symptom resolution within 20 days. Individuals with prolonged symptom duration maintained antigen-specific T cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and circulating T follicular helper cell populations during late convalescence, while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 spike protein. Significant correlations between symptom duration and both SARS-CoV-2-specific T cells and antibodies were observed. Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups, suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2-specific immune responses are maintained in patients suffering from prolonged post-COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/blood , Antigens, Viral/immunology , COVID-19/blood , Female , Humans , Immunity , Immunity, Cellular , Male , Middle Aged , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Young Adult
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