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1.
Cell Rep ; 37(13): 110169, 2021 12 28.
Article in English | MEDLINE | ID: covidwho-1616407

ABSTRACT

The importance of pre-existing immune responses to seasonal endemic coronaviruses (HCoVs) for the susceptibility to SARS-CoV-2 infection and the course of COVID-19 is the subject of an ongoing scientific debate. Recent studies postulate that immune responses to previous HCoV infections can either have a slightly protective or no effect on SARS-CoV-2 pathogenesis and, consequently, be neglected for COVID-19 risk stratification. Challenging this notion, we provide evidence that pre-existing, anti-nucleocapsid antibodies against endemic α-coronaviruses and S2 domain-specific anti-spike antibodies against ß-coronavirus HCoV-OC43 are elevated in patients with COVID-19 compared to pre-pandemic donors. This finding is particularly pronounced in males and in critically ill patients. Longitudinal evaluation reveals that antibody cross-reactivity or polyclonal stimulation by SARS-CoV-2 infection are unlikely to be confounders. Thus, specific pre-existing immunity to seasonal coronaviruses may increase susceptibility to SARS-CoV-2 and predispose individuals to an adverse COVID-19 outcome, guiding risk management and supporting the development of universal coronavirus vaccines.


Subject(s)
COVID-19/immunology , Coronavirus/immunology , SARS-CoV-2/immunology , Adult , Antibodies/immunology , Antibodies, Viral/immunology , COVID-19/etiology , Coronavirus Infections/immunology , Coronavirus OC43, Human/immunology , Coronavirus OC43, Human/pathogenicity , Cross Reactions/immunology , Female , Germany , Humans , Immunity, Humoral/immunology , Immunoglobulin G/immunology , Longitudinal Studies , Male , Middle Aged , Pandemics , SARS-CoV-2/pathogenicity , Seasons , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology
3.
PLoS One ; 16(3): e0247797, 2021.
Article in English | MEDLINE | ID: covidwho-1605332

ABSTRACT

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31-60 days PSO. By 61-90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1-4 days PSO with 86% positivity observed at 5-7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection.


Subject(s)
Antibodies, Viral/blood , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Serological Testing/instrumentation , COVID-19 Serological Testing/methods , Equipment Design , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , SARS-CoV-2/isolation & purification , Young Adult
4.
BMC Infect Dis ; 22(1): 10, 2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1608186

ABSTRACT

BACKGROUND: Serosurveillance is crucial in estimating the range of SARS-CoV-2 infections, predicting the possibility of another wave, and deciding on a vaccination strategy. To understand the herd immunity after the COVID-19 pandemic, the seroprevalence was measured in 3062 individuals with or without COVID-19 from the clinic. METHODS: The levels of SARS-CoV-2 antibody IgM and IgG were measured by the immuno-colloidal gold method. A fusion fragment of nucleocapsid and spike protein was detected by a qualitative test kit with sensitivity (89%) and specificity (98%). RESULTS: The seroprevalence rate for IgM and IgG in all outpatients was 2.81% and 7.51%, respectively. The sex-related prevalence rate of IgG was significantly higher (P < 0.05) in women than men. The highest positive rate of IgM was observed in individuals < 20 years of age (3.57%), while the highest seroprevalence for IgG was observed in persons > 60 years of age (8.61%). Positive rates of IgM and IgG in the convalescent patients were 31.82% and 77.27%, respectively, which was significantly higher than individuals with suspected syndromes or individuals without any clinical signs (P < 0.01). Seroprevalence for IgG in medical staff was markedly higher than those in residents. No significant difference of seroprevalence was found among patients with different comorbidities (P > 0.05). CONCLUSIONS: The low positive rate of the SARS-CoV-2 IgM and nucleic acid (NA) test indicated that the SARS-CoV-2 outbreak is subsiding after 3 months, and the possibility of reintroduction of the virus from an unidentified natural reservoir is low. Seroprevalence provides information for humoral immunity and vaccine in the future.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Communicable Disease Control , Female , Humans , Immunoglobulin G , Immunoglobulin M , Male , Pandemics , Seroepidemiologic Studies
5.
PLoS One ; 17(1): e0262162, 2022.
Article in English | MEDLINE | ID: covidwho-1605852

ABSTRACT

Analysis of convalescent plasma derived from individuals has shown that IgG3 has the most important role in binding to SARS-CoV-2 antigens; however, this has not yet been confirmed in large studies, and the link between binding and neutralization has not been confirmed. By analyzing plasma pools consisting of 247-567 individual convalescent donors, we demonstrated the binding of IgG3 and IgM to Spike-1 protein and the receptor-binding domain correlates strongly with viral neutralization in vitro. Furthermore, despite accounting for only approximately 12% of total immunoglobulin mass, collectively IgG3 and IgM account for approximately 80% of the total neutralization. This may have important implications for the development of potent therapies for COVID-19, as it indicates that hyperimmune globulins or convalescent plasma donations with high IgG3 concentrations may be a highly efficacious therapy.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , Convalescence , Immunoglobulin G/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Chlorocebus aethiops , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunoglobulin M/immunology , SARS-CoV-2/physiology , Vero Cells
6.
J Int Med Res ; 50(1): 3000605211069279, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1598885

ABSTRACT

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, antibody screening is a critical tool to assess anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity. We examined variation in antibody titers associated with age and sex among patients with confirmed COVID-19. METHODS: Blood IgG levels were tested in 1081 patients with positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests between 1 September and 31 December 2020. Patients who did not experience reinfection were identified. Serum IgG levels were measured by immunofluorescence assay. Antibody positivity and antibody titers were analyzed according to time since infection, sex, and age. RESULTS: The mean (standard deviation) age was 41.2 (14.2) years and 41.2% of patients were women. The lowest antibody positivity rate between the first and ninth month post-infection was detected in the sixth month. The lowest antibody titers among patients aged 20 to 80 years occurred in those aged 30 to 39 years. The IgG titer was positively correlated with age in years (r = 0.125) and decades (r = 0.126). CONCLUSIONS: Six months after infection, anti-SARS-CoV-2 antibody titers increased. Anti-SARS-CoV-2 antibody titers also increased with age. Immunity and pathogenicity should be investigated in addition to antibody positivity rates and antibody titers.


Subject(s)
COVID-19 , Adult , Antibodies, Viral , Female , Fluorescent Antibody Technique , Humans , Immunoglobulin G , Pandemics , SARS-CoV-2
7.
Microbiol Spectr ; 9(3): e0137621, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1592250

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 and caused a dramatic pandemic. Serological assays are used to check for immunization and assess herd immunity. We evaluated commercially available assays designed to quantify antibodies directed to the SARS-CoV-2 Spike (S) antigen, either total (Wantaï SARS-CoV-2 Ab ELISA) or IgG (SARS-CoV-2 IgG II Quant on Alinity, Abbott, and Liaison SARS-CoV-2 TrimericS IgG, Diasorin). The specificities of the Wantaï, Alinity, and Liaison assays were evaluated using 100 prepandemic sera and were 98, 99, and 97%, respectively. The sensitivities of all three were around 100% when tested on 35 samples taken 15 to 35 days postinfection. They were less sensitive for 150 sera from late infections (>180 days). Using the first WHO international standard (NIBSC), we showed that the Wantai results were concordant with the NIBSC values, while Liaison and Alinity showed a proportional bias of 1.3 and 7, respectively. The results of the 3 immunoassays were significantly globally pairwise correlated and for late infection sera (P < 0.001). They were correlated for recent infection sera measured with Alinity and Liaison (P < 0.001). However, the Wantai results of recent infections were not correlated with those from Alinity or Liaison. All the immunoassay results were significantly correlated with the neutralizing antibody titers obtained using a live virus neutralization assay with the B1.160 SARS-CoV-2 strain. These assays will be useful once the protective anti-SARS-CoV-2 antibody titer has been determined. IMPORTANCE Standardization and correlation with virus neutralization assays are critical points to compare the performance of serological assays designed to quantify anti-SARS-CoV-2 antibodies in order to identify their optimal use. We have evaluated three serological immunoassays based on the virus spike antigen that detect anti-SARS-CoV-2 antibodies: a microplate assay and two chemiluminescent assays performed with Alinity (Abbott) and Liaison (Diasorin) analysers. We used an in-house live virus neutralization assay and the first WHO international standard to assess the comparison. This study could be useful to determine guidelines on the use of serological results to manage vaccination and treatment with convalescent plasma or monoclonal antibodies.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoassay/methods , Antibodies, Neutralizing/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Immunization , Immunoglobulin G/blood , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology , Vaccination
9.
Sci Rep ; 11(1): 24198, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1585789

ABSTRACT

Certain immunizations including vaccination against tick-borne encephalitis virus (TBEV) have been suggested to confer cross-protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with ≥ 1 previous TBEV vaccination (n = 2018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7-1.0, P = 0.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p = 0.001) and total IgG (P < 0.0001), irrespective of SARS-CoV-2 serostatus. Based on these data, we conclude that the observed association of previous TBEV vaccination and reduced risk of SARS-CoV-2 infection is likely due to residual confounding factors. The increase in TBEV follow-up antibody titers can be explained by natural TBEV exposure or potential non-specific immune activation upon exposure to various pathogens, including SARS-CoV-2. We believe that these findings, although negative, contribute to the current knowledge on potential cross-immunity against SARS-CoV-2 from previous immunizations.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Encephalitis Viruses, Tick-Borne/immunology , Encephalitis, Tick-Borne/immunology , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , COVID-19/epidemiology , COVID-19/virology , Cross Protection/immunology , Encephalitis Viruses, Tick-Borne/physiology , Encephalitis, Tick-Borne/virology , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Pandemics/prevention & control , Prospective Studies , SARS-CoV-2/physiology , Seroconversion , Vaccination
10.
Sci Rep ; 11(1): 24448, 2021 12 27.
Article in English | MEDLINE | ID: covidwho-1585777

ABSTRACT

COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.


Subject(s)
Antibodies, Viral/analysis , Immunoglobulin G/analysis , Mouth Mucosa/metabolism , Respiratory System/metabolism , /immunology , Adult , Aged , COVID-19/prevention & control , COVID-19/virology , Female , Health Personnel , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Time Factors , Vaccination , Young Adult , /administration & dosage
11.
Commun Biol ; 4(1): 1389, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1585764

ABSTRACT

In light of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants potentially undermining humoral immunity, it is important to understand the fine specificity of the antiviral antibodies. We screened 20 COVID-19 patients for antibodies against 9 different SARS-CoV-2 proteins observing responses against the spike (S) proteins, the receptor-binding domain (RBD), and the nucleocapsid (N) protein which were of the IgG1 and IgG3 subtypes. Importantly, mutations which typically occur in the B.1.351 "South African" variant, significantly reduced the binding of anti-RBD antibodies. Nine of 20 patients were critically ill and were considered high-risk (HR). These patients showed significantly higher levels of transforming growth factor beta (TGF-ß) and myeloid-derived suppressor cells (MDSC), and lower levels of CD4+ T cells expressing LAG-3 compared to standard-risk (SR) patients. HR patients evidenced significantly higher anti-S1/RBD IgG antibody levels and an increased neutralizing activity. Importantly, a large proportion of S protein-specific antibodies were glycosylation-dependent and we identified a number of immunodominant linear epitopes within the S1 and N proteins. Findings derived from this study will not only help us to identify the most relevant component of the anti-SARS-CoV-2 humoral immune response but will also enable us to design more meaningful immunomonitoring methods for anti-COVID-19 vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Viral Proteins/immunology , Adaptive Immunity/immunology , Adult , Aged , COVID-19/virology , COVID-19 Vaccines/immunology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/immunology , Coronavirus Nucleocapsid Proteins/metabolism , Female , Humans , Immunity, Humoral/immunology , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Male , Middle Aged , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Viral Proteins/genetics , Viral Proteins/metabolism
12.
MAbs ; 14(1): 2002236, 2022.
Article in English | MEDLINE | ID: covidwho-1585298

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an evolving global public health crisis in need of therapeutic options. Passive immunization of monoclonal antibodies (mAbs) represents a promising therapeutic strategy capable of conferring immediate protection from SARS-CoV-2 infection. Herein, we describe the discovery and characterization of neutralizing SARS-CoV-2 IgG and VHH antibodies from four large-scale phage libraries. Each library was constructed synthetically with shuffled complementarity-determining region loops from natural llama and human antibody repertoires. While most candidates targeted the receptor-binding domain of the S1 subunit of SARS-CoV-2 spike protein, we also identified a neutralizing IgG candidate that binds a unique epitope on the N-terminal domain. A select number of antibodies retained binding to SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa and Delta. Overall, our data show that synthetic phage libraries can rapidly yield SARS-CoV-2 S1 antibodies with therapeutically desirable features, including high affinity, unique binding sites, and potent neutralizing activity in vitro, and a capacity to limit disease in vivo.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Cell Surface Display Techniques , Immunoglobulin G/immunology , Peptide Library , SARS-CoV-2/immunology , Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/metabolism , Antibodies, Neutralizing/pharmacology , Antibodies, Viral/genetics , Antibodies, Viral/metabolism , Antibody Specificity , Binding Sites, Antibody , COVID-19/metabolism , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Disease Models, Animal , Epitopes , Female , Host-Pathogen Interactions , Immunoglobulin G/genetics , Immunoglobulin G/metabolism , Immunoglobulin G/pharmacology , Mesocricetus , SARS-CoV-2/pathogenicity , Single-Domain Antibodies/genetics , Single-Domain Antibodies/metabolism , Single-Domain Antibodies/pharmacology , Vero Cells
13.
MAbs ; 14(1): 2005507, 2022.
Article in English | MEDLINE | ID: covidwho-1585297

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/therapeutic use , Antibody Affinity/immunology , Antibody Specificity/immunology , CHO Cells , COVID-19/prevention & control , COVID-19/virology , Chromatography, High Pressure Liquid/methods , Circular Dichroism , Clone Cells , Cricetinae , Cricetulus , Humans , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Immunoglobulin G/therapeutic use , Isoelectric Point , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism
15.
Microbiol Spectr ; 9(3): e0133021, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1583201

ABSTRACT

"Testing Denmark" is a national, large-scale, epidemiological surveillance study of SARS-CoV-2 in the Danish population. Between September and October 2020, approximately 1.3 million people (age >15 years) were randomly invited to fill in an electronic questionnaire covering COVID-19 exposures and symptoms. The prevalence of SARS-CoV-2 antibodies was determined by point-of care rapid test (POCT) distributed to participants' home addresses. In total, 318,552 participants (24.5% invitees) completed the study and 2,519 (0.79%) were seropositive. Of the participants with a prior positive PCR test (n = 1,828), 29.1% were seropositive in the POCT. Although seropositivity increased with age, participants 61 years and over reported fewer symptoms and were tested less frequently. Seropositivity was associated with physical contact with SARS-CoV-2 infected individuals (risk ratio [RR] 7.43, 95% CI: 6.57-8.41), particular in household members (RR 17.70, 95% CI: 15.60-20.10). A greater risk of seropositivity was seen in home care workers (RR 2.09, 95% CI: 1.58-2.78) compared to office workers. A high degree of adherence with national preventive recommendations was reported (e.g., >80% use of face masks), but no difference were found between seropositive and seronegative participants. The seroprevalence result was somewhat hampered by a lower-than-expected performance of the POCT. This is likely due to a low sensitivity of the POCT or problems reading the test results, and the main findings therefore relate to risk associations. More emphasis should be placed on age, occupation, and exposure in local communities. IMPORTANCE To date, including 318,522 participants, this is the largest population-based study with broad national participation where tests and questionnaires have been sent to participants' homes. We found that more emphasis from national and local authorities toward the risk of infection should be placed on age of tested individuals, type of occupation, as well as exposure in local communities and households. To meet the challenge that broad nationwide information can be difficult to gather. This study design sets the stage for a novel way of conducting studies. Additionally, this study design can be used as a supplementary model in future general test strategy for ongoing monitoring of COVID-19 immunity in the population, both from past infection and from vaccination against SARS-CoV-2, however, with attention to the complexity of performing and reading the POCT at home.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , SARS-CoV-2 , Adult , Antibodies, Viral , COVID-19/immunology , Denmark , Female , Humans , Immunity , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Odds Ratio , Point-of-Care Testing , Population Surveillance , Prevalence , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Surveys and Questionnaires
16.
BMC Microbiol ; 21(1): 351, 2021 12 18.
Article in English | MEDLINE | ID: covidwho-1582113

ABSTRACT

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) is a current worldwide threat for which the immunological features after infection need to be investigated. The aim of this study was to establish a highly sensitive and quantitative detection method for SARS-CoV-2 IgG antibody and to compare the antibody reaction difference in patients with different disease severity. RESULTS: Recombinant SARS-CoV-2 nucleocapsid protein was expressed in Escherichia coli and purified to establish an indirect IgG ELISA detection system. The sensitivity of the ELISA was 100% with a specificity of 96.8% and a 98.3% concordance when compared to a colloidal gold kit, in addition, the sensitivity of the ELISA was 100% with a specificity of 98.9% and a 99.4% concordance when compared to a SARS-CoV-2 spike S1 protein IgG antibody ELISA kit. The increased sensitivity resulted in a higher rate of IgG antibody detection for COVID-19 patients. Moreover, the quantitative detection can be conducted with a much higher serum dilution (1:400 vs 1:10, 1:400 vs 1:100). The antibody titers of 88 patients with differing COVID-19 severity at their early convalescence ranged from 800 to 102,400, and the geometric mean titer for severe and critical cases, moderate cases, asymptomatic and mild cases was 51,203, 20,912, and 9590 respectively. CONCLUSION: The development of a highly sensitive ELISA system for the detection of SARS-CoV-2 IgG antibodies is described herein. This system enabled a quantitative study of rSARS-CoV-2-N IgG antibody titers in COVID-19 patients, the occurrence of higher IgG antibody titers were found to be correlated with more severe cases.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulin G/blood , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/immunology , Child , Child, Preschool , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Middle Aged , Phosphoproteins/immunology , SARS-CoV-2 , Sensitivity and Specificity , Young Adult
17.
Front Immunol ; 12: 777858, 2021.
Article in English | MEDLINE | ID: covidwho-1581332

ABSTRACT

Background: Developing an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method. Methods: Here we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis. Results: In our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study. Conclusions: Based on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Saliva/immunology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Mouth Mucosa/immunology , SARS-CoV-2 , Seroconversion , Spike Glycoprotein, Coronavirus/immunology
18.
Front Immunol ; 12: 794642, 2021.
Article in English | MEDLINE | ID: covidwho-1581317

ABSTRACT

Background: The relationships of the coronavirus disease 2019 (COVID-19) vaccination with reactogenicity and the humoral immune response are important to study. The current study aimed to assess the reactogenicity and immunogenicity of the Pfizer and AstraZeneca COVID-19 vaccines among adults in Madinah, Saudi Arabia. Methods: A cross-sectional study, including 365 randomly selected adult Pfizer or AstraZeneca vaccine recipients who received a homologous prime-boost vaccination between February 1st and June 30th, 2021. Data of height and weight were collected to assess the weight status of percipients. An evaluation of seropositivity for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies was assessed using enzyme-linked immunosorbent assay (ELISA). Results: Among the participants, 69% (n = 250) reported at least one vaccine-related symptom. Pain at the injection site was the most frequently reported vaccine-related symptom. The mean total score for vaccine-related symptoms was significantly higher among participants who received the AstraZeneca vaccine, women, and participants with no previous COVID-19 infection (p < 0.05). Spike-specific IgG antibodies were detected in 98.9% of participants after the receipt of two vaccine doses, including 99.5% of Pfizer vaccine recipients and 98.3% of AstraZeneca vaccine recipients. Significantly, higher proportions of participants in the <35-year age group developed a humoral immune response after the first vaccine dose compared with the participants in other age groups. Conclusion: Participants who received the Pfizer COVID-19 vaccine reported fewer vaccine-related complications compared with those who received the AstraZeneca COVID-19 vaccine, but no serious side effects were reported in response to either vaccine. Health status and age were factors that may influence COVID-19 vaccine effectiveness for the generation of antibodies against the SARS-CoV-2 spike protein.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/standards , COVID-19/prevention & control , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Adult , Aged , Antibody Formation/immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Host-Pathogen Interactions/immunology , Humans , Immunization, Secondary , Immunoglobulin G , Male , Middle Aged , Online Systems , Public Health Surveillance , Surveys and Questionnaires
19.
Front Immunol ; 12: 798859, 2021.
Article in English | MEDLINE | ID: covidwho-1581315

ABSTRACT

SARS-CoV-2 antibodies in saliva serve as first line of defense against the virus. They are present in the mucosa, more precisely in saliva, after a recovered infection and also following vaccination. We report here the antibody persistence in plasma and in saliva up to 15 months after mild COVID-19. The IgG antibody response was measured every two months in 72 participants using an established and validated in-house ELISA assay. In addition, the virus inhibitory activity of plasma antibodies was assessed in a surrogate virus neutralization test before and after vaccination. SARS-CoV-2-specific antibody concentrations remained stable in plasma and saliva and the response was strongly boosted after one dose COVID-19 vaccination.


Subject(s)
Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Saliva/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2
20.
Viruses ; 13(12)2021 12 20.
Article in English | MEDLINE | ID: covidwho-1580419

ABSTRACT

A microarray-based assay to detect IgG and IgM antibodies against betacoronaviruses (SARS-CoV-2, SARS, MERS, OC43, and HKU1), other respiratory viruses and type I interferons (IFN-Is) was developed. This multiplex assay was applied to track antibody cross-reactivity due to previous contact with similar viruses and to identify antibodies against IFN-Is as the markers for severe COVID-19. In total, 278 serum samples from convalescent plasma donors, COVID-19 patients in the intensive care unit (ICU) and patients who recovered from mild/moderate COVID-19, vaccine recipients, prepandemic and pandemic patients with autoimmune endocrine disorders, and a heterogeneous prepandemic cohort including healthy individuals and chronically ill patients were analyzed. The anti-SARS-CoV-2 microarray results agreed well with the ELISA results. Regarding ICU patients, autoantibodies against IFN-Is were detected in 10.5% of samples, and 10.5% of samples were found to simultaneously contain IgM antibodies against more than two different viruses. Cross-reactivity between IgG against the SARS-CoV-2 nucleocapsid and IgG against the OC43 and HKU1 spike proteins was observed, resulting in positive signals for the SARS-CoV-2 nucleocapsid in prepandemic samples from patients with autoimmune endocrine disorders. The presence of IgG against the SARS-CoV-2 nucleocapsid in the absence of IgG against the SARS-CoV-2 spike RBD should be interpreted with caution.


Subject(s)
Antibodies, Viral/immunology , Interferon Type I/immunology , SARS-CoV-2/immunology , Viruses/immunology , Antibodies, Viral/blood , Antigens, Viral/immunology , Autoantibodies/blood , Autoantibodies/immunology , COVID-19/immunology , COVID-19 Serological Testing , Cross Reactions , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Protein Array Analysis , Respiratory Tract Diseases/immunology , Respiratory Tract Diseases/virology , Viruses/classification
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