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1.
Turk J Med Sci ; 51(SI-1): 3301-3311, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1884486

ABSTRACT

The COVID-19 pandemic has created a major alteration in the medical literature including the sepsis discussion. From the outset of the pandemic, various reports have indicated that although there are some unique features pertinent to COVID-19, many of its acute manifestations are similar to sepsis caused by other pathogens. As a consequence, the old definitions now require consideration of this new etiologic agent, namely SARS-CoV-2. Although the pathogenesis of COVID-19 has not been fully explained, the data obtained so far in hospitalized patients has revealed that serum cytokine and chemokine levels are high in severe COVID-19 patients, similar to those found with sepsis. COVID-19 may involve multiple organ systems. In addition to the lungs, the virus has been isolated from blood, urine, faeces, liver, and gallbladder. Results from autopsy series in COVID-19 patients have demonstrated a wide range of findings, including vascular involvement, congestion, consolidation, and hemorrhage as well as diffuse alveolar damage in lung tissue consistent with acute respiratory distress syndrome (ARDS). The presence of viral cytopathic-like changes, infiltration of inflammatory cells (mononuclear cells and macrophages), and viral particles in histopathological samples are considered a consequence of both direct viral infection and immune hyperactivation. Thromboembolism and hyper-coagulopathy are other components in the pathogenesis of severe COVID-19. Although the pathogenesis of hypercoagulability is not fully understood, it has been pointed out that all three components of Virchow's triad (endothelial injury, stasis, and hypercoagulable state) play a major role in contributing to clot formation in severe COVID-19 infection. In severe COVID-19 cases, laboratory parameters such as hematological findings, coagulation tests, liver function tests, D-dimer, ferritin, and acute phase reactants such as CRP show marked alterations, which are suggestive of a cytokine storm. Another key element of COVID-19 pathogenesis in severe cases is its similarity or association with hemophagocytic lymphohistiocytosis (HLH). SARS-CoV-2 induced cytokine storm has significant clinical and laboratory findings overlapping with HLH. Viral sepsis has some similarities but also some differences when compared to bacterial sepsis. In bacterial sepsis, systemic inflammation affecting multiple organs is more dominant than in COVID-19 sepsis. While bacterial sepsis causes an early and sudden onset clinical deterioration, viral diseases may exhibit a relatively late onset and chronic course. Consideration of severe COVID-19 disease as a sepsis syndrome has relevance and may assist in terms of determining treatments that will modulate the immune response, limit intrinsic damage to tissue and organs, and potentially improve outcome.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome , Inflammation , Lymphohistiocytosis, Hemophagocytic , Sepsis/complications , Chemokines/blood , Cytokines/blood , Humans , Lymphohistiocytosis, Hemophagocytic/immunology , Pandemics , SARS-CoV-2 , Sepsis/blood
2.
Viruses ; 14(5)2022 05 15.
Article in English | MEDLINE | ID: covidwho-1884377

ABSTRACT

In this study, we investigated the correlation between the mechanism involved in porcine epidemic diarrhea virus (PEDV) replication and autophagic flux. In this study, we found that as PEDV replicated, production of LC3-II was significantly induced up to 24 h post-infection (hpi). Interestingly, although there was significant production of LC3-II, greater p62 accumulation was simultaneously found. Pretreatment with rapamycin significantly induced PEDV replication, but autolysosome formation was reduced. These results were confirmed by the evaluation of ATG5/ATG12 and LAMP1/LAMP2. Taken together, we conclude that PEDV infection induces autophagosome formation but inhibits autolysosome formation during replication.


Subject(s)
Autophagosomes/metabolism , Porcine epidemic diarrhea virus , Animals , Autophagosomes/genetics , Chlorocebus aethiops , Lysosomes/genetics , Lysosomes/metabolism , Macroautophagy , Porcine epidemic diarrhea virus/immunology , Swine , Vero Cells
3.
PLoS One ; 17(2): e0263328, 2022.
Article in English | MEDLINE | ID: covidwho-1883630

ABSTRACT

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.


Subject(s)
Antibodies, Neutralizing/immunology , Neutralization Tests , Renal Dialysis , SARS-CoV-2/immunology , Vaccination , Animals , Antibodies, Neutralizing/blood , Antibody Affinity , CHO Cells , COVID-19 Vaccines/immunology , Case-Control Studies , Cricetulus , Dose-Response Relationship, Immunologic , Follow-Up Studies , HEK293 Cells , Humans , Immunoglobulin G/blood , Risk Factors , /immunology
4.
Circulation ; 144(6): e123-e135, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1883361

ABSTRACT

Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.


Subject(s)
Myocarditis/diagnosis , Myocarditis/therapy , Animals , Biopsy , Child , Clinical Decision-Making , Combined Modality Therapy , Disease Management , Disease Models, Animal , Disease Susceptibility/immunology , Humans , Multimodal Imaging , Myocarditis/etiology , Myocarditis/mortality , Prognosis , Symptom Assessment , Treatment Outcome
6.
Rinsho Ketsueki ; 63(5): 454-462, 2022.
Article in Japanese | MEDLINE | ID: covidwho-1879648

ABSTRACT

Antiplatelet factor 4 (PF4) antibodies, also known as anti-PF4/heparin complex antibodies, are measured to diagnose heparin-induced thrombocytopenia (HIT). In HIT, anti-PF4 antibodies induced by heparin exposure cause thrombocytopenia and thrombosis. However, in recent years, autoimmune HIT (aHIT) that develops without heparin exposure has been getting attention. In 2021, anti-PF4 antibodies were reported to cause the fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) that developed after adenoviral vector vaccination for COVID-19. HIT, aHIT, and VITT are considered to be caused by anti-PF4 antibodies, and their pathological conditions are similar. However, they have different levels of severity, and the detection sensitivity of their antibodies varies depending on the assay. Herein, we review three pathologies, namely, HIT, aHIT, and VITT, associated with anti-PF4 antibodies.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Antibodies , Heparin/adverse effects , Humans , Platelet Factor 4/immunology , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombosis/etiology , Vaccines/adverse effects
7.
Viruses ; 14(5)2022 04 21.
Article in English | MEDLINE | ID: covidwho-1879492

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.


Subject(s)
Antibodies, Neutralizing , COVID-19 Vaccines , COVID-19 , Cross Reactions , Spike Glycoprotein, Coronavirus , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Mice , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Subunit/genetics , Vaccines, Subunit/immunology
8.
Signal Transduct Target Ther ; 7(1): 172, 2022 Jun 06.
Article in English | MEDLINE | ID: covidwho-1878517

ABSTRACT

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Humans , SARS-CoV-2
9.
BMC Pregnancy Childbirth ; 21(1): 511, 2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1874999

ABSTRACT

BACKGROUND: Although the World Health Organization and health authorities in most countries recommend that pregnant women receive inactivated influenza virus vaccines, coverage remains low. This study aimed to investigate (1) the proportion of pregnant women who received an influenza vaccination and influencing factors and (2) the proportion of obstetrics and gynecology (OBGYN) doctors who routinely recommend influenza vaccination to pregnant women and influencing factors. METHODS: Two separate, anonymized questionnaires were developed for physicians and pregnant and postpartum women and were distributed to multicenters and clinics in South Korea. The proportions of women who received influenza vaccination during pregnancy and OBGYN doctors who routinely recommend the influenza vaccine to pregnant women were analyzed. Independent influencing factors for both maternal influenza vaccination and OBGYN doctors' routine recommendations to pregnant women were analyzed using log-binomial regression analysis. RESULTS: The proportion of self-reported influenza vaccination during pregnancy among 522 women was 63.2%. Pregnancy-related independent factors influencing maternal influenza vaccination were "(ever) received information about influenza vaccination during pregnancy" (OR 8.9, 95% CI 4.17-19.01), "received vaccine information about from OBGYN doctors" (OR 11.44, 95% CI 5.46-24.00), "information obtained from other sources" (OR 4.38, 95% CI 2.01-9.55), and "second/third trimester" (OR 2.41, 95% CI 1.21-4.82).. Among 372 OBGYN doctors, 76.9% routinely recommended vaccination for pregnant women. Independent factors effecting routine recommendation were "working at a private clinic or hospital" (OR 5.33, 95% CI 2.44-11.65), "awareness of KCDC guidelines" (OR 3.11, 95% CI 1.11-8.73), and "awareness of the 2019 national free influenza vaccination program for pregnant women" (OR 4.88, 95% CI 2.34-10.17). OBGYN doctors most commonly chose 'guidelines proposed by the government or public health (108, 46%) and academic committees (59, 25%), as a factor which expect to affect the future recommendation CONCLUSION: This study showed that providing information about maternal influenza vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Closer cooperation between the government and OBGYN academic societies to educate OBGYN doctors might enhance routine recommendations.


Subject(s)
Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Physicians/statistics & numerical data , Pregnancy Complications, Infectious/prevention & control , Pregnancy/statistics & numerical data , Vaccination/statistics & numerical data , Adult , Female , Gynecology , Health Knowledge, Attitudes, Practice , Humans , Influenza, Human/immunology , Male , Middle Aged , Obstetrics , Pregnancy Complications, Infectious/immunology , Republic of Korea , Surveys and Questionnaires , Vaccination Coverage/statistics & numerical data
10.
Front Cell Infect Microbiol ; 12: 862656, 2022.
Article in English | MEDLINE | ID: covidwho-1875399

ABSTRACT

Objectives: To assess humoral and cellular immune responses against SARS-CoV-2 variants in COVID-19 convalescent and confirmed patients, to explore the correlation between disease severity, humoral immunity, and cytokines/chemokines in confirmed patients, and to evaluate the ADE risk of SARS-CoV-2. Methods: Anti-RBD IgG were quantified using an ELISA. Neutralization potency was measured using pseudovirus and real virus. Cellular immunity was measured using ELISpot. Cytokine/chemokine levels were detected using multiplex immunoassays. In vitro ADE assays were performed using Raji cells. Results: One-month alpha convalescents exhibited spike-specific antibodies and T cells for alpha and delta variants. Notably, the RBD-specific IgG towards the delta variant decreased by 2.5-fold compared to the alpha variant. Besides, serum from individuals recently experienced COVID-19 showed suboptimal neutralizing activity against the delta and omicron variants. Humoral immune response, IL-6, IP-10 and MCP-1 levels were greater in patients with severe disease. Moreover, neither SARS-CoV-1 nor SARS-CoV-2 convalescent sera significantly enhanced SARS-CoV-2 pseudovirus infection. Conclusions: Significant resistance of the delta and omicron variants to the humoral immune response generated by individuals who recently experienced COVID-19. Furthermore, there was a significant correlation among disease severity, humoral immune response, and specific cytokines/chemokine levels. No evident ADE was observed for SARS-CoV-2.


Subject(s)
COVID-19 , Cytokines , Immunity, Cellular , Immunity, Humoral , SARS-CoV-2 , COVID-19/immunology , Cytokines/immunology , Humans , Immunoglobulin G , Severity of Illness Index
12.
Front Immunol ; 12: 785941, 2021.
Article in English | MEDLINE | ID: covidwho-1869377

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.


Subject(s)
Adaptive Immunity , COVID-19/immunology , Exosomes/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Acute Disease , Adult , Aged , COVID-19/blood , Exosomes/metabolism , Female , Humans , Male , Middle Aged , Plasma , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/blood
13.
Front Immunol ; 13: 876306, 2022.
Article in English | MEDLINE | ID: covidwho-1865451

ABSTRACT

The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody affinity to the ancestral strain - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants since high affinity may offer some flexibility to compensate for strain-individual mutations. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.


Subject(s)
B-Lymphocytes , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/metabolism , Humans , Pandemics , SARS-CoV-2/genetics , Vaccination/methods , /immunology
14.
Science ; 376(6596): 906-907, 2022 05 27.
Article in English | MEDLINE | ID: covidwho-1865138
15.
Obstet Gynecol ; 139(3): 373-380, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1864995

ABSTRACT

OBJECTIVE: To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels. METHODS: We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test. RESULTS: We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection. DISCUSSION: Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , Fetal Blood/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Female , Humans , Immunization, Secondary , Pregnancy , Retrospective Studies
16.
N Engl J Med ; 386(23): 2201-2212, 2022 06 09.
Article in English | MEDLINE | ID: covidwho-1864786

ABSTRACT

BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provides natural immunity against reinfection. Recent studies have shown waning of the immunity provided by the BNT162b2 vaccine. The time course of natural and hybrid immunity is unknown. METHODS: Using the Israeli Ministry of Health database, we extracted data for August and September 2021, when the B.1.617.2 (delta) variant was predominant, on all persons who had been previously infected with SARS-CoV-2 or who had received coronavirus 2019 vaccine. We used Poisson regression with adjustment for confounding factors to compare the rates of infection as a function of time since the last immunity-conferring event. RESULTS: The number of cases of SARS-CoV-2 infection per 100,000 person-days at risk (adjusted rate) increased with the time that had elapsed since vaccination with BNT162b2 or since previous infection. Among unvaccinated persons who had recovered from infection, this rate increased from 10.5 among those who had been infected 4 to less than 6 months previously to 30.2 among those who had been infected 1 year or more previously. Among persons who had received a single dose of vaccine after previous infection, the adjusted rate was low (3.7) among those who had been vaccinated less than 2 months previously but increased to 11.6 among those who had been vaccinated at least 6 months previously. Among previously uninfected persons who had received two doses of vaccine, the adjusted rate increased from 21.1 among those who had been vaccinated less than 2 months previously to 88.9 among those who had been vaccinated at least 6 months previously. CONCLUSIONS: Among persons who had been previously infected with SARS-CoV-2 (regardless of whether they had received any dose of vaccine or whether they had received one dose before or after infection), protection against reinfection decreased as the time increased since the last immunity-conferring event; however, this protection was higher than that conferred after the same time had elapsed since receipt of a second dose of vaccine among previously uninfected persons. A single dose of vaccine after infection reinforced protection against reinfection.


Subject(s)
COVID-19 , /immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Immunity, Innate , Reinfection/immunology , Reinfection/prevention & control , SARS-CoV-2 , Time Factors , Viral Vaccines/immunology , Viral Vaccines/therapeutic use
17.
N Engl J Med ; 386(21): e64, 2022 05 26.
Article in English | MEDLINE | ID: covidwho-1864784
18.
Sci Rep ; 12(1): 8890, 2022 May 25.
Article in English | MEDLINE | ID: covidwho-1864769

ABSTRACT

We assessed the feasibility of a highly sensitive immunoassay method based on single molecule array (Simoa) technology to detect IgG and IgA antibodies against SARS-CoV-2 spike protein receptor binding domain (RBD) in saliva from individuals with natural or vaccine-induced COVID-19 immunity. The performance of the method was compared to a laboratory-developed SARS-CoV-2 RBD total antibody enzyme-linked immunosorbent assay (ELISA). Paired serum and saliva specimens were collected from individuals (n = 40) prior to and 2 weeks after receiving an initial prime COVID-19 vaccine dose (Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273). Saliva was collected using a commercially available collection device (OraSure Inc.) and SARS-CoV-2 RBD IgG antibodies were measured by an indirect ELISA using concentrated saliva samples and a Simoa immunoassay using unconcentrated saliva samples. The IgG results were compared with paired serum specimens that were analyzed for total RBD antibodies using the ELISA method. The analytical sensitivity of the saliva-based Simoa immunoassay was five orders of magnitude higher than the ELISA assay: 0.24 pg/mL compared to 15 ng/mL. The diagnostic sensitivity of the saliva ELISA method was 90% (95% CI 76.3-97.2%) compared to 91.7% (95% CI 77.5-98.2%) for the Simoa immunoassay without total IgG-normalization and 100% (95% CI 90.3-100%) for the Simoa immunoassay after total IgG-normalization when compared to the serum ELISA assay. When analyzed using the SARS-CoV-2 RBD IgG antibody ELISA, the average relative increase in antibody index (AI) between the saliva of the post- and pre-vaccinated individuals was 8.7 (AIpost/pre). An average relative increase of 431 pg/mL was observed when the unconcentrated saliva specimens were analyzed using the Simoa immunoassay (SARS-CoV-2 RBD IgGpost/pre). These findings support the suitability of concentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG antibodies via ELISA, and unconcentrated saliva specimens for the measurement of SARS-CoV-2 RBD IgG and IgA using an ultrasensitive Simoa immunoassay.


Subject(s)
COVID-19 Vaccines , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , COVID-19 Vaccines/immunology , Humans , Immunoglobulin A/chemistry , Immunoglobulin A/immunology , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology
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