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1.
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
2.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1598468

ABSTRACT

mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.


Subject(s)
/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , /therapeutic use , Adaptive Immunity/genetics , Adaptive Immunity/immunology , Adult , Aged , Antigens, Viral , B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carrier State , Convalescence , Epitopes , Female , Humans , Immunity, Cellular/genetics , Immunity, Humoral/genetics , Immunogenicity, Vaccine , Immunologic Memory , Male , Middle Aged , RNA-Seq , SARS-CoV-2 , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells , Th17 Cells , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Young Adult , /therapeutic use
5.
Ann Med ; 53(1): 2099-2109, 2021 12.
Article in English | MEDLINE | ID: covidwho-1514452

ABSTRACT

BACKGROUND: Patients appear to maintain sequelae post-coronavirus disease 2019 (COVID-19) affecting daily life and physical health. We investigated the changes in and the effects of pulmonary rehabilitation (PR) on exercise capacity and immunology six months after COVID-19 hospitalization. METHODS: This retrospective cohort reviewed 233 COVID-19 patients admitted from 17 January 2020 to 29 February 2020. Ninety-eight patients who completed 2-week and 6-month follow-ups and tests were included. Among 98 patients, 27 completed at least five sessions of PR at the First Hospital of Changsha, China, during the 6-month convalescence were allocated to the PR group; the reminder who had not performed any PR were assigned to the control group. The primary outcome was the change in six-minute walk distance (6-MWD) between the 2-week and 6-month follow-ups, which was assessed via analysis of covariance with a covariate of propensity score that adjusted for the potential confounders. Secondary outcomes were the changes in 6-MWD, SARS-CoV-2 immunoglobulins, T-lymphocytes and blood chemistry, which were evaluated via paired tests. RESULTS: Participants' ages ranged from 19 to 84 years (M = 47, standard deviation (SD)=15) 45.9% identified as male. During the 6-month convalescence, 6-MWD increased 27.0%, with a mean [95% CI] of 113 [92-134] m (p < .001). SARS-CoV-2 IgG and IgM decreased 33.3% (p = .002) and 43.8% (p = .009), CD4+ T cells increased 7.9% (p = .04), and the majority of blood chemistry significantly changed. The patients in the PR group acquired a greater increase in 6-MWD than those in control (unadjusted, 194 [167-221] m, p < .001; adjusted, 123 [68-181] m, p < .001), dose-responsiveness of PR on 6-MWD was observed (p < .001). No differences in immunity variables and blood chemistry were observed between groups. CONCLUSIONS: These findings suggest PR may be a strategy to promote the improvement of exercise capacity after COVID-19.


Subject(s)
COVID-19/rehabilitation , Convalescence , Exercise , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/psychology , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , SARS-CoV-2 , Young Adult
6.
BMC Pulm Med ; 21(1): 136, 2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1511742

ABSTRACT

BACKGROUND: All over the world, SARS-CoV-2 pneumonia is causing a significant short-term morbidity and mortality, but the medium-term impact on lung function and quality of life of affected patients are still unknown. METHODS: In this prospective observational study, 39 patients with SARS-CoV-2 pneumonia were recruited from a single COVID-19 hospital in Southern Switzerland. At three months patients underwent radiological and functional follow-up through CT scan, lung function tests, and 6 min walking test. Furthermore, quality of life was assessed through self-reported questionnaires. RESULTS: Among 39 patients with SARS-CoV-2 pneumonia, 32 (82% of all participants) presented abnormalities in CT scan and 25 (64.1%) had lung function tests impairment at three months. Moreover, 31 patients (79.5%) reported a perception of poor health due to respiratory symptoms and all 39 patients showed an overall decreased quality of life. CONCLUSIONS: Medium-term follow up at three months of patients diagnosed with SARS-CoV-2 pneumonia shows the persistence of abnormalities in CT scans, a significant functional impairment assessed by lung function tests and a decreased quality of life in affected patients. Further studies evaluating the long-term impact are warranted to guarantee an appropriate follow-up to patients recovering from SARS-CoV-2 pneumonia.


Subject(s)
COVID-19/physiopathology , Lung/physiopathology , Quality of Life , Aged , COVID-19/diagnostic imaging , Convalescence , Female , Forced Expiratory Volume , Health Status , Humans , Length of Stay , Lung/diagnostic imaging , Male , Middle Aged , Prospective Studies , Pulmonary Diffusing Capacity , Recovery of Function , Respiratory Function Tests , SARS-CoV-2 , Switzerland , Tomography, X-Ray Computed , Vital Capacity , Walk Test
7.
J Ethnopharmacol ; 284: 114830, 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1509995

ABSTRACT

BACKGROUND: As of September 17, 2021, coronavirus disease 2019 (COVID-19) has infected more than 226 million people in a worldwide pandemic, with conservative estimates suggesting that there are more than 204 million convalescent patients with COVID-19. Previous studies have indicated that patients in the recovery phase exhibit decreased function of multiple organs. In China, traditional Chinese medicine (TCM) treatment is recommended in the rehabilitation period of COVID-19; however, the safety and efficacy of such treatment remain to be confirmed. AIM OF STUDY: The present study aimed to evaluate the efficacy and safety of Bufei Huoxue (BFHX) in restoring the functional status and exercise tolerance of patients recovering from COVID-19. METHODS: A total of 131 patients in the rehabilitation period of COVID-19 infection were randomly divided into a Bufei Huoxue (BFHX) group (n = 66) and a placebo group (n = 65). BFHX or placebo was given orally three times a day (1.4 g/dose) for 90 days. The primary outcomes was to evaluate improvements in exercise tolerance and imaging manifestations on chest computed tomography (CT). RESULTS: After the exclusion of two patients who withdrew prior to receiving any medications, 129 patients were recruited, including 64 patients in the BFHX group and 65 patients in the placebo group. After 3 months of treatment, the BFHX group exhibited greater attenuation of pneumonia lesions on chest CT than the placebo group (P<0.05). Improvements in 6-min walk distance (6MWD) relative to baseline were also significantly better in the BFHX group than in the placebo group (P<0.01). Scores on the Fatigue Assessment Inventory (FAI) were lower in the BFHX group than in the placebo group (P<0.05). Although the rate of adverse events was higher in the BFHX group than in the placebo group (9.38% vs. 4.62%), the difference was not significant (P=0.3241). CONCLUSIONS: BFHX may exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19, which may in turn attenuate symptoms of fatigue and improve exercise tolerance.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , SARS-CoV-2 , Adolescent , Adult , Aged , Convalescence , Double-Blind Method , Female , Humans , Male , Middle Aged , Young Adult
8.
Front Immunol ; 12: 769059, 2021.
Article in English | MEDLINE | ID: covidwho-1505989

ABSTRACT

The prognosis of severe COVID-19 patients has motivated research communities to uncover mechanisms of SARS-CoV-2 pathogenesis also on a regional level. In this work, we aimed to understand the immunological dynamics of severe COVID-19 patients with different degrees of illness, and upon long-term recovery. We analyzed immune cellular subsets and SARS-CoV-2-specific antibody isotypes of 66 COVID-19 patients admitted to the Hospital Clínico Universidad de Chile, which were categorized according to the WHO ten-point clinical progression score. These included 29 moderate patients (score 4-5) and 37 severe patients under either high flow oxygen nasal cannula (18 patients, score 6), or invasive mechanical ventilation (19 patients, score 7-9), plus 28 convalescent patients and 28 healthy controls. Furthermore, six severe patients that recovered from the disease were longitudinally followed over 300 days. Our data indicate that severe COVID-19 patients display increased frequencies of plasmablasts, activated T cells and SARS-CoV-2-specific antibodies compared to moderate and convalescent patients. Remarkably, within the severe COVID-19 group, patients rapidly progressing into invasive mechanical ventilation show higher frequencies of plasmablasts, monocytes, eosinophils, Th1 cells and SARS-CoV-2-specific IgG than patients under high flow oxygen nasal cannula. These findings demonstrate that severe COVID-19 patients progressing into invasive mechanical ventilation show a distinctive type of immunity. In addition, patients that recover from severe COVID-19 begin to regain normal proportions of immune cells 100 days after hospital discharge and maintain high levels of SARS-CoV-2-specific IgG throughout the study, which is an indicative sign of immunological memory. Thus, this work can provide useful information to better understand the diverse outcomes of severe COVID-19 pathogenesis.


Subject(s)
COVID-19/immunology , Eosinophils/immunology , Plasma Cells/immunology , SARS-CoV-2/physiology , Th1 Cells/immunology , Aged , Antibodies, Viral/blood , Convalescence , Disease Progression , Female , Humans , Immunity, Cellular , Immunoglobulin G/blood , Immunologic Memory , Male , Middle Aged , Severity of Illness Index
9.
Front Immunol ; 12: 741639, 2021.
Article in English | MEDLINE | ID: covidwho-1497078

ABSTRACT

Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/physiology , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Convalescence , Environmental Exposure , Family Characteristics , Female , Humans , Immunity, Cellular , Immunologic Memory , Infant , Male , Middle Aged , Young Adult
11.
J Infect Dis ; 224(8): 1305-1315, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493821

ABSTRACT

BACKGROUND: A notable feature of coronavirus disease 2019 (COVID-19) is that children are less susceptible to severe disease. Children are known to experience more infections with endemic human coronaviruses (HCoVs) compared to adults. Little is known whether HCoV infections lead to cross-reactive anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. METHODS: We investigated the presence of cross-reactive anti-SARS-CoV-2 IgG antibodies to spike 1 (S1), S1-receptor-binding domain (S1-RBD), and nucleocapsid protein (NP) by enzyme-linked immunosorbent assays, and neutralizing activity by a SARS-CoV-2 pseudotyped virus neutralization assay, in prepandemic sera collected from children (n = 50) and adults (n = 45), and compared with serum samples from convalescent COVID-19 patients (n = 16). RESULTS: A significant proportion of children (up to 40%) had detectable cross-reactive antibodies to SARS-CoV-2 S1, S1-RBD, and NP antigens, and the anti-S1 and anti-S1-RBD antibody levels correlated with anti-HCoV-HKU1 and anti-HCoV-OC43 S1 antibody titers in prepandemic samples (P < .001). There were marked increases of anti-HCoV-HKU1 and - OC43 S1 (but not anti-NL63 and -229E S1-RBD) antibody titers in serum samples from convalescent COVID-19 patients (P < .001), indicating an activation of cross-reactive immunological memory to ß-coronavirus spike. CONCLUSIONS: We demonstrated cross-reactive anti-SARS-CoV-2 antibodies in prepandemic serum samples from children and young adults. Promoting this cross-reactive immunity and memory response derived from common HCoV may be an effective strategy against SARS-COV-2 and future novel coronaviruses.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/virology , Child , Child, Preschool , Convalescence , Coronavirus 229E, Human/immunology , Coronavirus Envelope Proteins/immunology , Coronavirus OC43, Human/immunology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Female , HEK293 Cells , Humans , Immunoglobulin G/immunology , Immunologic Memory , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Young Adult
12.
Front Immunol ; 12: 743422, 2021.
Article in English | MEDLINE | ID: covidwho-1472388

ABSTRACT

Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1st and 3 weeks after 2nd vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2nd vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , COVID-19/prevention & control , Convalescence , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Long-Term Care , Middle Aged , Prospective Studies , Vaccination , Young Adult
13.
Sci Rep ; 11(1): 20254, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1467135

ABSTRACT

Monocytes are thought to play an important role in host defence and pathogenesis of COVID-19. However, a comprehensive examination of monocyte numbers and function has not been performed longitudinally in acute and convalescent COVID-19. We examined the absolute counts of monocytes, the frequency of monocyte subsets, the plasma levels of monocyte activation markers using flowcytometry and ELISA in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the absolute counts of total monocytes and the frequencies of intermediate and non-classical monocytes increases from Days 15-30 to Days 61-90 and plateau thereafter. In contrast, the frequency of classical monocytes decreases from Days 15-30 till Days 121-150. The plasma levels of sCD14, CRP, sCD163 and sTissue Factor (sTF)-all decrease from Days 15-30 till Days 151-180. COVID-19 patients with severe disease exhibit higher levels of monocyte counts and higher frequencies of classical monocytes and lower frequencies of intermediate and non-classical monocytes and elevated plasma levels of sCD14, CRP, sCD163 and sTF in comparison with mild disease. Thus, our study provides evidence of dynamic alterations in monocyte counts, subset frequencies and activation status in acute and convalescent COVID-19 individuals.


Subject(s)
COVID-19/immunology , Monocytes , Acute Disease , Adolescent , Adult , Aged , Biomarkers/blood , Convalescence , Female , Humans , Leukocyte Count , Male , Middle Aged , Monocytes/cytology , Monocytes/immunology , Young Adult
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
15.
Pol J Microbiol ; 70(3): 401-404, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1441450

ABSTRACT

SARS-CoV-2 was found in a recovered patient's stool specimen by combining quantitative reverse transcription PCR (qRT-PCR) and genome sequencing. The patient was virus positive in stool specimens for at least an additional 15 days after he was recovered, whereas respiratory tract specimens were negative. The discovery of the complete genome of SARS-CoV-2 in the stool sample of the recovered patient demonstrates a cautionary warning that the potential mode of the virus transmission cannot be excluded through the fecal-oral route after viral clearance in the respiratory tract.


Subject(s)
COVID-19/virology , Convalescence , Feces/virology , Genome, Viral , SARS-CoV-2/genetics , Whole Genome Sequencing , Adult , COVID-19/diagnostic imaging , COVID-19/transmission , China , Cough/virology , Fever/virology , Humans , Male , SARS-CoV-2/isolation & purification , Tomography, X-Ray Computed
16.
Front Immunol ; 12: 737083, 2021.
Article in English | MEDLINE | ID: covidwho-1430703

ABSTRACT

mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, ß, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, ß, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of ß and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , Convalescence , Female , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Longitudinal Studies , Male , Spain , Spike Glycoprotein, Coronavirus/immunology , Vaccination
17.
Transfusion ; 61(11): 3087-3093, 2021 11.
Article in English | MEDLINE | ID: covidwho-1430132

ABSTRACT

BACKGROUND: Convalescent plasma has emerged as a potential specific treatment for coronavirus disease 2019 (COVID-19), since it contains severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Several studies are currently investigating the efficacy of convalescent plasma for treatment of COVID-19, with a focus on neutralizing antibodies. However, there is little information on whether convalescent plasma may contain additional immunoregulatory constituents produced by the blood donor during convalescence. Therefore, using a standardized whole blood assay employing synthetic toll-like receptor (TLR) ligands, we have investigated the immunoregulatory capacity of convalescent plasma in direct comparison to ABO-matched allogeneic control plasma. STUDY DESIGN AND METHODS: Whole blood samples from healthy blood donors were collected, and autologous plasma was replaced by convalescent plasma or ABO-matched control plasma. Standardized innate immune triggering and monitoring was performed by adding different TLR ligands (Pam3CsK4 [TLR1/2], HKLM [TLR2], LPS [TLR4], flagellin [TLR5], ssRNA40 [TLR8], imiquimod [TLR7], and FSL-1 [TLR2/6]) and subsequent quantitative analysis of pro- and anti-inflammatory cytokines (IP-10, IL-1ß, TNF-α, MCP-1, IL-6, IL-10, and IFN-γ) by cytometric bead array. Negative controls included unstimulated samples as well as samples spiked with autologous plasma. RESULTS: COVID-19 convalescent plasma (CCP) significantly decreased pro-inflammatory cytokines production triggered by different TLR ligands in healthy donors as compared with healthy control plasma. IL-6, MCP-1, and IFN-γ represented the cytokines that are most frequently downregulated by convalescent plasma. CONCLUSION: Our experiments reveal a potential novel, SARS-CoV-2-independent immunomodulatory activity of CCP, which may be beneficial for COVID-19 patients.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19/therapy , Convalescence , SARS-CoV-2 , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunization, Passive , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
18.
Nat Commun ; 12(1): 5215, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1392854

ABSTRACT

Achieving sufficient worldwide vaccination coverage against SARS-CoV-2 will require additional approaches to currently approved viral vector and mRNA vaccines. Subunit vaccines may have distinct advantages when immunizing vulnerable individuals, children and pregnant women. Here, we present a new generation of subunit vaccines targeting viral antigens to CD40-expressing antigen-presenting cells. We demonstrate that targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to CD40 (αCD40.RBD) induces significant levels of specific T and B cells, with long-term memory phenotypes, in a humanized mouse model. Additionally, we demonstrate that a single dose of the αCD40.RBD vaccine, injected without adjuvant, is sufficient to boost a rapid increase in neutralizing antibodies in convalescent non-human primates (NHPs) exposed six months previously to SARS-CoV-2. Vaccine-elicited antibodies cross-neutralize different SARS-CoV-2 variants, including D614G, B1.1.7 and to a lesser extent B1.351. Such vaccination significantly improves protection against a new high-dose virulent challenge versus that in non-vaccinated convalescent animals.


Subject(s)
CD40 Antigens/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antigen-Presenting Cells/immunology , B-Lymphocytes/immunology , Convalescence , Humans , Macaca , Mice , Mutation , Protein Domains , Reinfection/prevention & control , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , T-Lymphocytes/immunology , Vaccination , Vaccines, Subunit/immunology
19.
Front Immunol ; 12: 693775, 2021.
Article in English | MEDLINE | ID: covidwho-1394758

ABSTRACT

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas. A475V and E484Q mutants are highly resistant to neutralization by mAb B38 and 2-4, suggesting that some crucial mutations in spike protein might evolve SARS-CoV-2 variants capable of escaping humoral immune response.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/immunology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Amino Acid Substitution/genetics , Amino Acid Substitution/immunology , Antibodies, Neutralizing/immunology , Convalescence , Humans , Immune Evasion , Immunity, Humoral , Neutralization Tests , Protein Binding
20.
Cells ; 10(9)2021 09 06.
Article in English | MEDLINE | ID: covidwho-1390544

ABSTRACT

Studying the dynamics changes of neutrophils during innate immune response in coronavirus 2019 (COVID-19) can help understand the pathogenesis of this disease. The aim of the study was to assess the usefulness of new neutrophil activation parameters: Immature Granulocyte (IG), Neutrophil Reactivity Intensity (NEUT-RI), Neutrophil Granularity Intensity (NEUT-GI), and data relating to granularity, activity, and neutrophil volume (NE-WX, NE-WY, NE-WZ) available in hematology analyzers to distinguish convalescent patients from patients with active SARS-CoV-2 infection and healthy controls (HC). The study group consisted of 79 patients with a confirmed positive RT-PCR test for SARS-CoV2 infection, 71 convalescent patients, and 20 HC. We observed leukopenia with neutrophilia in patients with active infection compared to convalescents and HC. The IG median absolute count was higher in convalescent patients than in COVID-19 and HC (respectively, 0.08 vs. 0.03 vs. 0.02, p < 0.0001). The value of the NEUT-RI parameter was the highest in HC and the lowest in convalescents (48.3 vs. 43.7, p < 0.0001). We observed the highest proportion of NE-WX, NE-WY, and NE-WZ parameters in HC, without differences between the COVID-19 and convalescent groups. New neutrophil parameters can be useful tools to assess neutrophils' activity and functionalities in the immune response during infection and recovery from COVID-19 disease.


Subject(s)
COVID-19/pathology , Cell Differentiation , Convalescence , Neutrophils/pathology , Case-Control Studies , Female , Humans , Male , Middle Aged , Severity of Illness Index
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