scholarly journals The Importance and Challenges of Identifying SARS-CoV-2 Reinfections

2020 ◽  
Author(s):  
Ahmed Babiker ◽  
Charles Marvil ◽  
Jesse J. Waggoner ◽  
Matthew Collins ◽  
Anne Piantadosi
Keyword(s):  
Immune Response ◽  
Viral Genome ◽  
Primary Infection ◽  
Genomic Data ◽  
Medical Community ◽  
Immune Protection ◽  
Key Factors ◽  
Clinical Laboratories ◽  
Strength And Durability ◽  
Total Immunoglobulin

Reports of SARS-CoV-2 reinfection have raised important questions about the strength and durability of the immune response to primary infection, which are key factors in predicting the course of the pandemic. Identifying reinfection requires detecting the virus at two different time points and using viral genomic data to distinguish reinfection from persistent viral carriage. This process is hindered by challenges of logistics and capacity, such as banking samples from primary infection and performing viral genome sequencing. These challenges may help to explain why very few cases have been described to date. In addition, reinfection may be a rare phenomenon, but detailed prospective studies are needed to rigorously assess its frequency. To provide context for future investigations of SARS-CoV-2 reinfection, we review 16 cases that have been published to date or are available in pre-print. Reinfection occurred across demographic spectra and in patients whose initial infections were both asymptomatic/mild and moderate/severe. For cases in which severity could be compared between episodes, half of reinfections were less severe, raising the possibility of partial immune protection. Although many patients had a positive total immunoglobulin or IgG result at the time of reinfection, very little examination of their immune response was performed. Further work is needed to elucidate the frequency, determinants, and consequences of SARS-CoV-2 reinfection. Establishing the necessary frameworks for surveillance and investigation will rely heavily on clinical laboratories and clinical investigators, and we propose several considerations to guide the medical community in identifying and characterizing SARS-CoV-2 reinfections.

scholarly journals Seropositivity to Nucleoprotein to detect SARS-CoV-2 infections: a tool to detect breakthrough infections after COVID-19 vaccination

2021 ◽  
Author(s):  
Lotus Leonie van den Hoogen ◽  
Gaby Smits ◽  
Cheyenne CE van Hagen ◽  
Denise Wong ◽  
Eric RA Vos ◽  
...  
Keyword(s):  
Immune Response ◽  
Primary Infection ◽  
Spike Protein ◽  
Multiplex Immunoassay ◽  
Specific Immunoglobulin ◽  
Vaccination History ◽  
Specific Igg ◽  
Exposure History ◽  
Asymptomatic Individuals ◽  
Roll Out

Background With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Methods Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) with a primary infection and no vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). Results The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥7 days after the second dose (p=0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in naïve participants. Conclusions Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

scholarly journals Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection

2020 ◽  
Author(s):  
Jianmin Zuo ◽  
Alex Dowell ◽  
Hayden Pearce ◽  
Kriti Verma ◽  
Heather Long ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Antibody Level ◽  
Primary Infection ◽  
Natural Infection ◽  
T Cell Responses ◽  
Symptomatic Infection ◽  
Cell Responses ◽  
Cell Immunity

Abstract The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection.

scholarly journals Papain-Like Proteases as Coronaviral Drug Targets: Current Inhibitors, Opportunities, and Limitations

2020 ◽  
Vol 13 (10) ◽  
pp. 277 ◽  
Author(s):  
Anastasiia I. Petushkova ◽  
Andrey A. Zamyatnin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Severe Acute Respiratory Syndrome ◽  
Viral Genome ◽  
Drug Targets ◽  
Structural Features ◽  
The Third ◽  
Frequent Mutations ◽  
Near Future ◽  
Viral Reproduction

Papain-like proteases (PLpro) of coronaviruses (CoVs) support viral reproduction and suppress the immune response of the host, which makes CoV PLpro perspective pharmaceutical targets. Their inhibition could both prevent viral replication and boost the immune system of the host, leading to the speedy recovery of the patient. Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the third CoV outbreak in the last 20 years. Frequent mutations of the viral genome likely lead to the emergence of more CoVs. Inhibitors for CoV PLpro can be broad-spectrum and can diminish present and prevent future CoV outbreaks as PLpro from different CoVs have conservative structures. Several inhibitors have been developed to withstand SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV). This review summarizes the structural features of CoV PLpro, the inhibitors that have been identified over the last 20 years, and the compounds that have the potential to become novel effective therapeutics against CoVs in the near future.

scholarly journals Vaccination of Mice with a Novel Trypsin from Trichinella spiralis Elicits the Immune Protection against Larval Challenge

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 437 ◽  
Author(s):  
Yao Zhang ◽  
Jie Zeng ◽  
Yan Yan Song ◽  
Shao Rong Long ◽  
Ruo Dan Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Trichinella Spiralis ◽  
Biological Properties ◽  
Target Antigen ◽  
Immune Protection ◽  
Humoral Immune ◽  
Meat Safety ◽  
Muscle Larvae ◽  
Candidate Target ◽  
Cellular Immune

Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel T. spiralis trypsin (TsT) and its elicited immune protection against larval challenge. The cDNA sequence of TsT gene was cloned and expressed. Western blotting showed rTsT was identified by infection serum and anti-TsT serum. RT-PCR results revealed that TsT gene was transcribed at diverse T. spiralis lifecycle stages. The IIFT results showed that natural TsT was principally expressed at epicuticle of 5-6 day adult worms, indicating that TsT is a worm somatic antigen and adult-stage specific surface antigen. Vaccination of mice with rTsT triggered an evident humoral immune response (high levels of serum IgG, IgG1/IgG2a, and enteral sIgA), and it also induced the systemic and enteral local cellular immune response, demonstrated by an significantly elevation of cytokines IFN-γ and IL-4. The mice vaccinated with rTsT exhibited a 33.17% reduction of enteral adult worms and a 37.80% reduction of muscle larvae after larval challenge. The results showed that TsT might be considered as a candidate target antigen for anti-T. spiralis vaccines.

Fluctuations in rat liver alanine-amino-transferase activity during experimental nippostrongylosis

Parasitology ◽  
1989 ◽  
Vol 98 (2) ◽  
pp. 301-306
Author(s):  
Lucy J. Robertson
Keyword(s):  
Immune Response ◽  
Primary Infection ◽  
Parasitic Infection ◽  
Transferase Activity ◽  
Nippostrongylus Brasiliensis ◽  
Alanine Amino Transferase ◽  
A Value ◽  
Gluconeogenic Enzyme ◽  
Alt Activity

SUMMARYThe activity of the gluconeogenic enzyme, alanine-amino-transferase (ALT), in a preparation from the liver of rats was studied by means of an in vitro assay throughout the course of a primary infection of Nippostrongylus brasiliensis, established by a subcutaneous injection of approximately 4000 3rd-stage larvae. The activity was measured on days 1–14 p.i. in both uninfected and infected rats and a marked pattern in the enzyme's activity was observed. In infected rats, the activity increased from 1·46±0·19 U/g liver on day 1 p.i. to a peak on day 4 p.i. of 10·75±1·62 U/g liver, then decreased to a trough of 0·44±0·18 U/g liver on day 10 p.i. before returning to original levels by day 14 p.i., by which time the infection had been largely eliminated. In uninfected rats the activity of the liver enzyme remained constant throughout this period with a value of 2·54±0·12 U/g liver. The activity of the enzyme in vitro was found to be related to the size of the inoculum on days 4 and 10 p.i. It was proposed that these observations could be due to either (1) a direct effect of the parasite, or (2) a consequence of the host immune response to the infection. In order to investigate the second proposition more fully, liver ALT activity was investigated by in vitro assay on selected days p.i. in rats experiencing a secondary N. brasiliensis infection. In these rats the liver ALT activity was observed to reach a peak on day 2 p.i., with an activity of 3·87 ± 0-28 U/g liver, and a trough on day 4 p.i. with an activity of 0·11 ±0·03 U/g liver, returning to similar levels to those measured in uninfected rats by day 7 p.i. When serum prepared from rats having secondary N. brasiliensis infections collected on day 4 p.i. was added to the assay, a reduction in the activity of liver ALT activity from both the infected and uninfected rats was measured by in vitro assay. The results are discussed in relation to protein metabolism and gluconeogenesis in rats infected with N. brasiliensis, and also in relation to the host’s immune response to the parasitic infection.

Sepsis

2018 ◽  
Author(s):  
Graham Cooke
Keyword(s):  
Immune Response ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Primary Infection ◽  
Clinical Manifestations ◽  
Host Immune Response ◽  
Organ Damage ◽  
Clinical Syndrome ◽  
Systemic Inflammatory Response ◽  
Physiological Status

Sepsis is a clinical syndrome defined by the presence of both infection and a systemic inflammatory response with or without organ damage. The pathogenesis of sepsis is complex and may differ according to the infecting microbe, the site of primary infection, and the host’s immunological and physiological status prior to infection. The term ‘systemic inflammatory response syndrome’ refers to the clinical manifestations of a dysregulated host immune response, while ‘bacteraemia’, in contrast, refers to the presence of viable organisms that can be cultured from blood.

scholarly journals Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Francesco Romano ◽  
Antonino Giulio Giannone ◽  
Sergio Siragusa ◽  
Rossana Porcasi ◽  
Ada Maria Florena
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Medical Community ◽  
Immune Checkpoints ◽  
Bone Marrow Biopsies ◽  
Underlying Mechanisms ◽  
Acute Myeloid

tumor immunotherapy is a rapidly evolving field. The discovery of the ability of neoplasms to evade the immune response has shifted the attention of the medical community to the underlying mechanisms of the immune response to tumors, highlighting the importance of so-called immune check points, including CTLA4, TIM-3 and PD-1.  an immune escape mechanism is the activation of the immune checkpoint pathway that contributes to the creation of an immunosuppressive microenvironment and therefore to tumor proliferation.although immune checkpoints have been extensively investigated in solid tumors, the same is not true for hematologic neoplasms, particularly for myeloid malignancies. our study is based on the evaluation of the activation of the PD-1 and PD-L1 pathway in the context of the bone marrow tumor microenvironment of patients with acute myeloid leukemia. To do so we evaluated  34 bone marrow biopsies of patients with acute myeloid leukemia comparing them to 10 controls using immunohistochemical methods.

scholarly journals Use of Biopolymers in Mucosally-Administered Vaccinations for Respiratory Disease

Materials ◽  
2019 ◽  
Vol 12 (15) ◽  
pp. 2445 ◽  
Author(s):  
Margaret R. Dedloff ◽  
Callie S. Effler ◽  
Alina Maria Holban ◽  
Monica C. Gestal
Keyword(s):  
Immune Response ◽  
Hyaluronic Acid ◽  
Side Effects ◽  
Respiratory Disease ◽  
Mucosal Immunity ◽  
Respiratory Infections ◽  
Antigen Delivery ◽  
Immune Protection ◽  
Adverse Side Effects ◽  
Robust Immune Response

Communicable respiratory infections are the cause of a significant number of infectious diseases. The introduction of vaccinations has greatly improved this situation. Moreover, adjuvants have allowed for vaccines to be more effective with fewer adverse side effects. However, there is still space for improvement because while the more common injected formulations induce a systematic immunity, they do not confer the mucosal immunity needed for more thorough prevention of the spread of respiratory disease. Intranasal formulations provide systemic and mucosal immune protection, but they have the potential for more serious side effects and a less robust immune response. This review looks at seven different adjuvants—chitosan, starch, alginate, gellan, β-glucan, emulsan and hyaluronic acid—and their prospective ability to improve intranasal vaccines as adjuvants and antigen delivery systems.

Obligatory multiparasitism in the tussock moth,Orgyia leucostigma

Parasitology ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 1-10 ◽  
Author(s):  
D. Guzo ◽  
D. B. Stoltz
Keyword(s):  
Immune Response ◽  
Viral Genome ◽  
Cross Linking ◽  
Viral Dna ◽  
Permissive Host ◽  
Tussock Moth ◽  
Complete Development ◽  
Orgyia Leucostigma ◽  
Cotesia Melanoscela

Orgyia leucostigmahaemocytes were able to encapsulate and destroy eggs ofHyposoterspecies, thereby preventing successful parasitism. When host larvae had previously been parasitized byCotesia melanoscela, however, this response was not observed, and 3 differentHyposoterspecies could be reared to maturity in the normally non-permissive host. Appropriate injection experiments established thatC. melanoscelavirus and venom were both required in order for successful parasitism byHyposoterto occur. Covalent cross-linking ofC. melanoscelaviral DNA led to an immune response againstHyposoterlarvae, but not eggs, suggesting that an active viral genome may be required for complete development ofHyposoterspecies in tussock moth larvae.

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