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1.
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
2.
Front Immunol ; 12: 781843, 2021.
Article in English | MEDLINE | ID: covidwho-1581326

ABSTRACT

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/prevention & control , Immunogenicity, Vaccine/drug effects , Multiple Sclerosis/drug therapy , Adult , Antibodies, Viral/immunology , Female , Humans , Italy , Male , Middle Aged , SARS-CoV-2 , Seroconversion/drug effects
3.
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
4.
J Med Virol ; 94(1): 178-185, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544336

ABSTRACT

Many aspects of the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as its role in protection after natural infection, are still unclear. We evaluated IgA and IgG response to spike subunits 1 and 2 (S1 and S2) and Nucleocapsid proteins of SARS-COV-2 in serum samples of 109 volunteers with viral RNA detected or seroconversion with different clinical evolution (asymptomatic, mild, moderate, and severe coronavirus disease 2019), using the ViraChip® Test Kit. We observed that the quantification of antibodies to all antigens had a positive correlation to disease severity, which was strongly associated with the presence of comorbidities. Seroreversion was not uncommon even during the short (median of 77 days) observation, occurring in 15% of mild-asymptomatic cases at a median of 55 days for IgG and 46 days for IgA. The time to reach the maximal antibody response did not differ significantly among recovered and deceased volunteers. Our study illustrated the dynamic of anti-S1, anti-N, and anti-S2 IgA and IgG antibodies, and suggests that high production of IgG and IgA does not guarantee protection to disease severity and that functional responses that have been studied by other groups, such as antibody avidity, need further attention.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Male , Middle Aged , Phosphoproteins/immunology , Seroconversion , Young Adult
5.
Clin Infect Dis ; 73(9): e2932-e2942, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1500989

ABSTRACT

BACKGROUND: Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. METHODS: We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. RESULTS: Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9-18) days for IgM and 15.0 (12-20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. CONCLUSIONS: We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.


Subject(s)
COVID-19 , Pneumonia, Viral , Antibodies, Viral , Female , Humans , Immunoglobulin M , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Seroconversion
6.
Mikrobiyol Bul ; 55(4): 519-538, 2021 Oct.
Article in Turkish | MEDLINE | ID: covidwho-1478366

ABSTRACT

In this study, it was aimed to prospectively evaluate the efficacy, side effects and seroconversion data of inactive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), CoronaVac® (Sinovac, China) vaccine in healthcare workers. A total of 1053 healthcare workers who were initially seronegative (COV2T® SARS-CoV-2 Total Siemens, USA) and vaccinated with inactivated SARS-CoV-2 were included in the study. Quantitative IgG antibodies (ADVIA Centaur® SARS-CoV-2 IgG, Siemens, USA) were investigated 28 days after the first vaccine (n= 939) and the second vaccine (n= 771). In addition, neutralizing antibodies were evaluated via "enzyme linked immunosorbent assay (ELISA)" test (ACE2-RBD Neutralization Assay, Dia-Pro, Italy) 28 days after the first vaccine. Antibody response of the vaccine was evaluated statistically by univariate (Chi-square, Fisher's exact test, Student's t test, Mann-Whitney U, one-way ANOVA and Kruskall Wallis ANOVA tests) analysis and linear regression models. The consistency between quantitative IgG test and neutralizing antibody test was also evaluated in blood samples taken 28 days after second vaccination. Statistical analysis was determined in logarithmically transformed data with statistical analysis with SPSS 23.0 and Stata, and type 1 error level was accepted as 0.05. At least one side effect was reported by 31.3% and 26.8% of the participants after the first and second vaccine, respectively. The most frequent side effect was pain at the injection site with a frequency of 20.4% vs 21.7%. The frequency of applying to a health center due to side effects was 1.0% after the first vaccine and 0.8% after the second vaccine. The percentage of those who produced sufficient quantitative IgG was found as 25.3% (95% CI= 22.5-28.1) 28 days after the first vaccine and 97.9% (95% CI= 96.91- 98.93) after the second vaccine. Neutralizing test antibody positivity was found as 97.7% 28 days after the second vaccine. In univariate analysis, the characteristics that significantly increased the quantitative IgG response against inactivated SARS-CoV-2 vaccine were young age (p<0.01), female gender (p<0.01), being a non smoker (p<0.001), not having a chronic disease (p= 0.019), having had the flu vaccine this year (p= 0.012), not being overweight or obese (p= 0.020), and having a SARS-CoV2 infection prior to vaccination (p<0.001). In addition, allied health personnel showed significantly lower antibody responses than the other workers (p<0.001). Multiple linear regression models revealed that, female gender, younger age, smoking and previous COVID-19 polymerase chain reaction test positivity significantly affected the quantitative IgG response after vaccination. A 99% agreement was found between the ELISA-based neutralizing antibody test and the quantitative IgG test (Kappa p= 0.783) performed on the 28th day after the second vaccination. CoronaVac® provides adequate antibody response in 25% of healthcare workers aged 18-64, after 28 days from a single vaccine, and 97% after 28 days from the second vaccine. Antibody response was significantly higher in younger ages, women, non-smokers, and those who had previously encountered SARS-CoV-2. Phase 3 and phase 4 results are needed to Show effectiveness of this vaccine in real life.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Antibodies, Viral , Antibody Formation , Female , Health Personnel , Humans , Male , Middle Aged , RNA, Viral , SARS-CoV-2 , Seroconversion , Vaccination , Young Adult
7.
Microbiol Spectr ; 9(2): e0090421, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1476401

ABSTRACT

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , Health Personnel/statistics & numerical data , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19 Nucleic Acid Testing , Cohort Studies , Coronavirus Nucleocapsid Proteins/immunology , Denmark , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Phosphoproteins/immunology , Polymerase Chain Reaction , RNA, Viral/analysis , Seroconversion , Spike Glycoprotein, Coronavirus/immunology
8.
Vaccine ; 39(47): 6902-6906, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1475108

ABSTRACT

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide vaccination development efforts. In December 2020 the Pfizer BNT162b2 vaccine was approved in the United States. This study describes the first BNT162b2 vaccine dose effect on a large cohort. METHODS: This retrospective study examined first vaccine dose effect on serology and investigated the associations between seroconversion and age or sex. RESULTS: Serological blood tests were performed on 1898 participants following first vaccine dose; 81% were tested on day 21, before receiving the second dose (mean age 47.5 ± 12.45; median 47.7, range 18-90). Positive serology was found in 92.7% of day 21 tests. Overall positivity was 86.8%, with rates increasing from 2.5% within 1-14 days to 89.8% (14-20 days), 92.7% (21 days), and 95.9% (>21 days). Mean antibody levels 21 days after first dose were 64.3 ± 33.01 AU/ml, (range 15-373 AU/ml, median 61 AU/ml). Seropositivity was greater in females than males (88.3%. vs 83.3% respectively, p < 0.001; OR1.515; 95% CI 1.152-1.994). Older age > 60 years was associated with decreased likelihood of seropositivity (p < 0.001; OR 0.926; 95% CI 0.911-0.940). Longer time between first vaccination and serology tests was associated with increased likelihood for seropositivity (p < 0.001; OR 1.350; 95% CI 1.298-1.404). CONCLUSIONS: The high seroconversion rate following first BNT162b2 dose among individuals < 60 may justify delayed delivery of the second dose, potentially help relieve the worldwide vaccination supply shortage, enable vaccination of twice this population within a shorter period, and ultimately reduce COVID-19 contagion.


Subject(s)
COVID-19 , Vaccines , Adult , Aged , COVID-19 Vaccines , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Seroconversion
9.
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
10.
Lancet Glob Health ; 9(11): e1508-e1516, 2021 11.
Article in English | MEDLINE | ID: covidwho-1472215

ABSTRACT

BACKGROUND: The city of Manaus, Brazil, has seen two collapses of the health system due to the COVID-19 pandemic. We report anti-SARS-CoV-2 nucleocapsid IgG antibody seroconversion rates and associated risk factors in Manaus residents before the second wave of the epidemic in Brazil. METHODS: A convenience sample of adult (aged ≥18 years) residents of Manaus was recruited through online and university website advertising into the DETECTCoV-19 study cohort. The current analysis of seroconversion included a subgroup of DETECTCoV-19 participants who had at least two serum sample collections separated by at least 4 weeks between Aug 19 and Oct 2, 2020 (visit 1), and Oct 19 and Nov 27, 2020 (visit 2). Those who reported (or had no data on) having a COVID-19 diagnosis before visit 1, and who were positive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at visit 1 were excluded. Using an in-house ELISA, the reactivity index (RI; calculated as the optical density ratio of the sample to the negative control) for serum anti-SARS-CoV-2 nucleocapsid IgG antibodies was measured at both visits. We calculated the incidence of seroconversion (defined as RI values ≤1·5 at visit 1 and ≥1·5 at visit 2, and a ratio >2 between the visit 2 and visit 1 RI values) during the study period, as well as incidence rate ratios (IRRs) through cluster-corrected and adjusted Poisson regression models to analyse associations between seroconversion and variables related to sociodemographic characteristics, health access, comorbidities, COVID-19 exposure, protective behaviours, and symptoms. FINDINGS: 2496 DETECTCoV-19 cohort participants returned for a follow-up visit between Oct 19 and Nov 27, 2020, of whom 204 reported having COVID-19 before the first visit and 24 had no data regarding previous disease status. 559 participants were seropositive for anti-SARS-CoV-2 nucleocapsid IgG antibodies at baseline. Of the remaining 1709 participants who were seronegative at baseline, 71 did not meet the criteria for seroconversion and were excluded from the analyses. Among the remaining 1638 participants who were seronegative at baseline, 214 showed seroconversion at visit 2. The seroconversion incidence was 13·06% (95% CI 11·52-14·79) overall and 6·78% (5·61-8·10) for symptomatic seroconversion, over a median follow-up period of 57 days (IQR 54-61). 48·1% of seroconversion events were estimated to be asymptomatic. The sample had higher proportions of affluent and higher-educated people than those reported for the Manaus city population. In the fully adjusted and corrected model, risk factors for seroconversion before visit 2 were having a COVID-19 case in the household (IRR 1·49 [95% CI 1·21-1·83]), not wearing a mask during contact with a person with COVID-19 (1·25 [1·09-1·45]), relaxation of physical distancing (1·31 [1·05-1·64]), and having flu-like symptoms (1·79 [1·23-2·59]) or a COVID-19 diagnosis (3·57 [2·27-5·63]) between the first and second visits, whereas working remotely was associated with lower incidence (0·74 [0·56-0·97]). INTERPRETATION: An intense infection transmission period preceded the second wave of COVID-19 in Manaus. Several modifiable behaviours increased the risk of seroconversion, including non-compliance with non-pharmaceutical interventions measures such as not wearing a mask during contact, relaxation of protective measures, and non-remote working. Increased testing in high-transmission areas is needed to provide timely information about ongoing transmission and aid appropriate implementation of transmission mitigation measures. FUNDING: Ministry of Education, Brazil; Fundação de Amparo à Pesquisa do Estado do Amazonas; Pan American Health Organization (PAHO)/WHO.


Subject(s)
COVID-19/prevention & control , Epidemics , Immunoglobulin G/blood , SARS-CoV-2/immunology , Seroconversion , Adolescent , Adult , Aged , Antibodies, Viral , Brazil/epidemiology , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Prospective Studies , Social Behavior , Young Adult
11.
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
12.
PLoS Pathog ; 17(8): e1009865, 2021 08.
Article in English | MEDLINE | ID: covidwho-1443861

ABSTRACT

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.


Subject(s)
COVID-19/transmission , COVID-19/virology , Macaca fascicularis , Seroconversion , Animals , Chlorocebus aethiops , Disease Models, Animal , Female , Fever/virology , Inhalation Exposure , Male , Vero Cells , Viral Load
13.
PLoS One ; 16(9): e0258041, 2021.
Article in English | MEDLINE | ID: covidwho-1443855

ABSTRACT

Numerous assays evaluating serological and cellular responses have been developed to characterize immune responses against SARS-CoV-2. Serological assays are both cost- and time-effective compared to cellular assays, but cellular immune responses may provide a diagnostic value to determine previous SARS-CoV-2 infection in seronegative individuals. However, potential cross-reactive T cell responses stemming from prior encounters with human coronaviruses (HCoVs) may affect assay specificity. In this study, we evaluated the specificity and sensitivity of a SARS-CoV-2 IFN-γ Release Assay (IGRA) based on the FluoroSpot method employing commercially available SARS-CoV-2-specific peptide pools, as well as an in-house designed SARS-CoV-2 peptide pool restricted to 5 amino acid stretches or less aligning with endemic HCoVs. Blood samples were obtained from healthcare workers (HCW) 5-6 months post SARS-CoV-2 spike (S) IgG and nucleocapsid (N) IgG dual seroconversion (n = 187) and HCW who had been S IgG and N IgG dual seronegative at repeated occasions, including the current sampling time point (n = 102). In addition, samples were obtained 4 to 5 months post infection from 55 polymerase chain reaction (PCR)-confirmed COVID-19 patients. Assay specificity and sensitivity were calculated with serology as a reference standard for HCW. The in-house generated peptide pool displayed a specificity of 96.1%, while the commercially available peptide pools displayed specificities of 80.4% and 85.3%, respectively. Sensitivity was higher in a cohort of previously hospitalized COVID-19 patients (96.4% and 84.0% for the commercially available peptide pools and 92.7% for the in-house generated peptide pool) compared to the HCW cohort (92.0% and 66.8% for the commercially available peptide pools and 76.0% for the in-house generated peptide pool). Based on these findings, the individual diagnostic value of T cell immune responses against SARS-CoV-2 currently appears to be limited but remain an important research tool ahead.


Subject(s)
COVID-19 Testing/methods , COVID-19/immunology , Immunity, Cellular , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/diagnosis , Health Personnel , Humans , Interferon-gamma/blood , Interferon-gamma/immunology , Sensitivity and Specificity , Seroconversion
14.
J Med Virol ; 93(10): 5777-5782, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432408

ABSTRACT

High antibody titers have been found to correlate with the severity of coronavirus disease 2019 (COVID-19) disease. Therefore, antibody titers may be higher in older adults, whose disease is known to have a more severe course than younger ones. This study aimed to compare the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody level in the reverse transcription-polymerase chain reaction (RT-PCR) to test positive older adults with young. Patients aged ≥18 with positive RT-PCR and checked serum IgG antibodies between November 1, 2020 and January 13, 2021 were included. The IgG antibody levels and the time between RT-PCR positivity with the antibody levels were recorded. A total of 1071 patients were divided into two groups as Group 1 <60 years old (n = 902) and Group 2 ≥60 years old (n = 169). The SARS-CoV-2 IgG antibody titers were higher in Group 2 (p = 0.001). This height was present in the first 3 months after positive RT-PCR. While the antibody titers were compared by dividing Group 2 into the three groups according to age ranges (60-69, 70-79, and ≥80 years), the antibody titer was higher in ≥80 years patients (p = 0.044). High COVID-19 IgG antibody levels may be associated with the severity of the disease. Also, the humoral immunity advantage was seen in the first 3 months in the older patients, which suggests that older adults with COVID-19 may develop reinfection in the long term.


Subject(s)
COVID-19/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Age Factors , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/diagnosis , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , SARS-CoV-2/isolation & purification , Time Factors
15.
Emerg Infect Dis ; 27(9): 2454-2458, 2021 09.
Article in English | MEDLINE | ID: covidwho-1435936

ABSTRACT

Not all persons recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop SARS-CoV-2-specific antibodies. We show that nonseroconversion is associated with younger age and higher reverse transcription PCR cycle threshold values and identify SARS-CoV-2 viral loads in the nasopharynx as a major correlate of the systemic antibody response.


Subject(s)
COVID-19 , Antibody Formation , COVID-19/immunology , COVID-19 Serological Testing , Humans , Nasopharynx , SARS-CoV-2 , Seroconversion
16.
Microbiol Spectr ; 9(2): e0108221, 2021 10 31.
Article in English | MEDLINE | ID: covidwho-1434911

ABSTRACT

We describe the results of testing health care workers, from a tertiary care hospital in Japan that had experienced a coronavirus disease 2019 (COVID-19) outbreak during the first peak of the pandemic, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody seroconversion. Using two chemiluminescent immunoassays and a confirmatory surrogate virus neutralization test, serological testing revealed that a surprising 42% of overlooked COVID-19 diagnoses (27/64 cases) occurred when case detection relied solely on SARS-CoV-2 nucleic acid amplification testing (NAAT). Our results suggest that the NAAT-positive population is only the tip of the iceberg and the portion left undetected might potentially have led to silent transmissions and triggered the spread. A questionnaire-based risk assessment was further indicative of exposures to specific aerosol-generating procedures (i.e., noninvasive ventilation and airway suctioning) having mediated transmission and served as the origins of the outbreak. Our observations are supportive of a multitiered testing approach, including the use of serological diagnostics, in order to accomplish exhaustive case detection along the whole COVID-19 spectrum. IMPORTANCE We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection. COVID-19 clusters have been continuously striking the health care system around the globe. Our findings illustrate that such clusters are lined with hidden infections eluding detection with diagnostic PCR and that the cluster burden in total is more immense than actually recognized. The mainstays of diagnosing infectious diseases, including COVID-19, generally consist of two approaches, one aiming to detect molecular fragments of the invading pathogen and the other to measure immune responses of the host. Considering antibody testing as one trustworthy option to test our way through the pandemic can aid in the exhaustive case detection of COVID-19 patients with variable presentations.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Serological Testing/statistics & numerical data , COVID-19/epidemiology , Cross Infection/epidemiology , Health Personnel/statistics & numerical data , SARS-CoV-2/isolation & purification , Adult , Antibodies, Viral/blood , Cost of Illness , Female , Humans , Immunoglobulin G/blood , Japan/epidemiology , Male , Neutralization Tests , Occupational Exposure , Risk Assessment , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Seroconversion , Surveys and Questionnaires , Tertiary Care Centers
17.
Front Immunol ; 12: 705441, 2021.
Article in English | MEDLINE | ID: covidwho-1430695

ABSTRACT

The purpose of this study is to monitor specific anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) IgG and IgM antibody production in patients with severe forms of coronavirus disease 2019 (COVID-19) using various commercially available quantitative and qualitative tests. The sera of 23 confirmed COVID-19 patients were processed for anti-SARS-CoV-2 IgG and IgM detection. Three different immunoassays, viz. Abbott Architect® SARS-CoV-2 IgG assay, and two quantitative tests, ANSH® SARS-CoV-2 and AESKULISA® SARS-CoV-2 Nucleocapsid Protein (NP), were performed and the results pooled, from diagnosis to serum collection. Seroconversion rates were computed for all 3 assays, and possible correlations were tested using the Pearson correlation coefficient and Cohen's kappa coefficient. Overall, 70 combinations of qualitative and quantitative IgG and IgM results were pooled and analyzed. In the early phase (0-4 days after diagnosis), in all tests, IgG seroconversion rates were 43%-61%, and increased in all tests gradually to 100% after 15 days. The Pearson correlation coefficient showed a strong positive relationship between the qualitative IgG test results and both quantitative IgG tests. IgM detection was inconsistent, with maximal concentrations and seroconversion rates between 10-15 days after diagnosis and slight-to-fair agreement between the two quantitative immunoassays. There was no significant association between mortality with IgG or IgM seroconversion or concentrations. Patients with severe COVID-19 develop an early, robust anti-SARS-CoV-2 specific humoral immune response involving IgG immunoglobulins. Further comparative studies are warranted to analyze the value of serological testing in predicting the severity of COVID-19 and detecting prior exposure.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , SARS-CoV-2/immunology , Comorbidity , Female , Humans , Immunity, Humoral/immunology , Immunoassay/methods , Male , Middle Aged , Retrospective Studies , Saudi Arabia , Sensitivity and Specificity , Seroconversion
18.
J Infect Dis ; 224(5): 771-776, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1410005

ABSTRACT

We aimed to characterize presence of culturable virus in clinical specimens during acute illness, and antibody kinetics up to 6 months after symptom onset, among 14 early patients with coronavirus disease 2019 in the United States. We isolated viable severe acute respiratory syndrome coronavirus 2 from real-time reverse-transcription polymerase chain reaction-positive respiratory specimens collected during days 0-8 after onset, but not after. All 13 patients with 2 or more serum specimens developed anti-spike antibodies; 12 developed detectable neutralizing antibodies. We did not isolate virus after detection of neutralizing antibodies. Eight participants provided serum at 6 months after onset; all retained detectable anti-spike immunoglobulin G, and half had detectable neutralizing antibodies. Two participants reported not feeling fully recovered at 6 months.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation/immunology , COVID-19/immunology , Seroconversion/physiology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/virology , Follow-Up Studies , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Spike Glycoprotein, Coronavirus/immunology , United States
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