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1.
Clin Infect Dis ; 2020 Jul 01.
Article in English | MEDLINE | ID: covidwho-1621566

ABSTRACT

We are learning that the host response to SARS-CoV-2 infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a "one size fits all" approach to immunomodulation in patients with COVID-19.  We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anti-cytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.

2.
Biophys J ; 120(14): 2902-2913, 2021 07 20.
Article in English | MEDLINE | ID: covidwho-1605015

ABSTRACT

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 continues to rage with devastating consequences on human health and global economy. The spike glycoprotein on the surface of coronavirus mediates its entry into host cells and is the target of all current antibody design efforts to neutralize the virus. The glycan shield of the spike helps the virus to evade the human immune response by providing a thick sugar-coated barrier against any antibody. To study the dynamic motion of glycans in the spike protein, we performed microsecond-long molecular dynamics simulation in two different states that correspond to the receptor binding domain in open or closed conformations. Analysis of this microsecond-long simulation revealed a scissoring motion on the N-terminal domain of neighboring monomers in the spike trimer. The roles of multiple glycans in shielding of spike protein in different regions were uncovered by a network analysis, in which the high betweenness centrality of glycans at the apex revealed their importance and function in the glycan shield. Microdomains of glycans were identified featuring a high degree of intracommunication in these microdomains. An antibody overlap analysis revealed the glycan microdomains as well as individual glycans that inhibit access to the antibody epitopes on the spike protein. Overall, the results of this study provide detailed understanding of the spike glycan shield, which may be utilized for therapeutic efforts against this crisis.

3.
Clin Infect Dis ; 73(11): 2073-2082, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1560084

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an urgent need for the development of effective therapies for coronavirus disease 2019 (COVID-19). METHODS: We first tested SARS-CoV-2-specific T-cell (CοV-2-ST) immunity and expansion in unexposed donors, COVID-19-infected individuals (convalescent), asymptomatic polymerase chain reaction (PCR)-positive subjects, vaccinated individuals, non-intensive care unit (ICU) hospitalized patients, and ICU patients who either recovered and were discharged (ICU recovered) or had a prolonged stay and/or died (ICU critical). CoV-2-STs were generated from all types of donors and underwent phenotypic and functional assessment. RESULTS: We demonstrate causal relationship between the expansion of endogenous CoV-2-STs and the disease outcome; insufficient expansion of circulating CoV-2-STs identified hospitalized patients at high risk for an adverse outcome. CoV-2-STs with a similarly functional and non-alloreactive, albeit highly cytotoxic, profile against SARS-CoV-2 could be expanded from both convalescent and vaccinated donors generating clinical-scale, SARS-CoV-2-specific T-cell products with functional activity against both the unmutated virus and its B.1.1.7 and B.1.351 variants. In contrast, critical COVID-19 patient-originating CoV-2-STs failed to expand, recapitulating the in vivo failure of CoV-2-specific T-cell immunity to control the infection. CoV-2-STs generated from asymptomatic PCR-positive individuals presented only weak responses, whereas their counterparts originating from exposed to other seasonal coronaviruses subjects failed to kill the virus, thus disempowering the hypothesis of protective cross-immunity. CONCLUSIONS: Overall, we provide evidence on risk stratification of hospitalized COVID-19 patients and the feasibility of generating powerful CoV-2-ST products from both convalescent and vaccinated donors as an "off-the shelf" T-cell immunotherapy for high-risk patients.

4.
Pan Afr Med J ; 38: 93, 2021.
Article in French | MEDLINE | ID: covidwho-1547720

ABSTRACT

Introduction: SARS-CoV-2 serology tests could play a crucial role in estimating the prevalence of COVID-19. The purpose of this study was to estimate the prevalence of COVID-19 among travellers and workers in Bukavu, a city in eastern Democratic Republic of the Congo. Methods: between May and August 2020, the Cellex qSARS-CoV-2 IgG/IgM Rapid Test (Cellex, Inc., USA), lateral flow immunoassay was used to rapidly detect and differentiate antibodies against SARS-CoV-2 among travellers and workers seeking medical certification. Results: among the 684 residents of the city of Bukavu screened for COVID-19 (4.2% Hispanic, 2.8% other African, 0.9% Asian), the seroprevalence anti-SARS-CoV-2 antibodies was 40.8% (IgG+/IgM+: 34.6%; IgG+/IgM-: 0.5%; IgG-/IgM+: 5.4%). Cumulative seroprevalence of anti-SARS-CoV-2 IgG antibodies increased from 24.5% to 35.2% from May to August 2020. Independent predictors of SARS-CoV-2 antibodies were age > 60 years [adjusted OR = 2.07(1.26-3.38)] and non-membership of the medical staff [adjusted OR = 2.28 (1.22-4.26)]. Thirteen point nine percent of patients seropositive for SARS-CoV-2 antibodies were symptomatic and hospitalized. Conclusion: this study shows a very high seroprevalence of SARS-CoV-2 antibodies among travellers and workers in Bukavu, a city in eastern Democratic Republic of the Congo, which may positively affect community immunity in the study population. Thus, the management of COVID-19 should be contextualized according to local realities.


Subject(s)
Antibodies, Viral/blood , COVID-19/epidemiology , SARS-CoV-2/isolation & purification , Travel , Adult , Age Factors , Aged , COVID-19/diagnosis , Democratic Republic of the Congo/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Immunoassay , Male , Middle Aged , SARS-CoV-2/immunology , Seroepidemiologic Studies
5.
World J Clin Cases ; 8(21): 5099-5103, 2020 Nov 06.
Article in English | MEDLINE | ID: covidwho-1527033

ABSTRACT

The coronavirus disease 2019 pandemic has become a major global public health problem. Governments are taking the necessary steps to reduce the movement of people to contain the spread of the virus. However, these measures have caused considerable distress to patients with gastric cancer who are newly diagnosed or are undergoing treatment. In addition to the cancer, they must deal with longer waiting times for surgery and poor communication with doctors. Furthermore, gastric cancer patients generally have low immunity and a poor nutritional status, so they are a high-risk group for infection with the novel coronavirus. Therefore, it is necessary to formulate reasonable outpatient management strategies to reduce the adverse effects of the pandemic on their treatment. We summarize the management strategies for patients with gastric cancer during the pandemic.

6.
J Infect Dis ; 224(9): 1473-1488, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1522215

ABSTRACT

BACKGROUND: Postdischarge immunity and its correlation with clinical features among patients recovered from coronavirus disease 2019(COVID-19) are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of patients with COVID-19 at 3 months after hospital discharge. METHODS: Patients with COVID-19 discharged from 4 hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed. RESULTS: The72 age-, sex- and body mass index-matched participants included 19 patients with severe/critical COVID-19 (SPs), 20 patients with mild/moderate COVID-19 (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of proinflammatory cytokines and factors related to vascular injury/repair in patients recovered from COVID-19 had not returned to those of the HCs, especially among recovered SPs compared with recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest computed tomographic abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features. CONCLUSION: Vascular injury, inflammation, and chemotaxis persisted in patients with COVID-19 and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.

7.
Infect Disord Drug Targets ; 21(4): 541-552, 2021.
Article in English | MEDLINE | ID: covidwho-1496791

ABSTRACT

BACKGROUND: Since December 2019, a novel coronavirus, SARS-CoV-2, has caused global public health issues after being reported for the first time in Wuhan province of China. So far, there have been approximately 14.8 million confirmed cases and 0.614 million deaths due to the SARS-CoV-2 infection globally, and still, numbers are increasing. Although the virus has caused a global public health concern, no effective treatment has been developed. OBJECTIVE: One of the strategies to combat the COVID-19 disease caused by SARS-CoV-2 is the development of vaccines that can make humans immune to these infections. Considering this approach, in this study, an attempt has been made to design epitope-based vaccine for combatting COVID-19 disease by analyzing the complete proteome of the virus by using immuno-informatics tools. METHODS: The protein sequence of the SARS-CoV-2 was retrieved and the individual proteins were checked for their allergic potential. Then, from non-allergen proteins, antigenic epitopes were identified that could bind with MHCII molecules. The epitopes were modeled and docked to predict the interaction with MHCII molecules. The stability of the epitope-MHCII complex was further analyzed by performing a molecular dynamics simulation study. The selected vaccine candidates were also analyzed for their global population coverage and conservancy among SARS-related coronavirus species. RESULTS: The study has predicted 5 peptide molecules that can act as potential candidates for epitope- based vaccine development. Among the 5 selected epitopes, the peptide LRARSVSPK can be the most potent epitope because of its high geometric shape complementarity score, low ACE and very high response towards it by the world population (81.81% global population coverage). Further, molecular dynamic simulation analysis indicated the formation of a stable epitope-MHCII complex. The epitope LRARSVSPK was also found to be highly conserved among the SARS-CoV- -2 isolated from different countries. CONCLUSION: The study has predicted T-cell epitopes that can elicit a robust immune response in the global human population and act as potential vaccine candidates. However, the ability of these epitopes to act as vaccine candidate needs to be validated in wet lab studies.


Subject(s)
COVID-19 , Vaccines , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte , Humans , Molecular Docking Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
J Clin Microbiol ; 59(7): e0083721, 2021 06 18.
Article in English | MEDLINE | ID: covidwho-1486488

ABSTRACT

We assessed the performance of the CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Plasma samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive individuals (Uganda, 78 samples from 78 individuals, and Baltimore, 266 samples from 38 individuals) and from prepandemic individuals (Uganda, 1,077, and Baltimore, 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test. After the first positive PCR in Ugandan samples, the sensitivity was 45% (95% confidence interval [CI], 24,68) at 0 to 7 days, 79% (95% CI, 64 to 91) at 8 to 14 days, and 76% (95% CI, 50 to 93) at >15 days. In samples from Baltimore, sensitivity was 39% (95% CI, 30 to 49) at 0 to 7 days, 86% (95% CI, 79 to 92) at 8 to 14 days, and 100% (95% CI, 89 to 100) at 15 days after positive PCR. The specificity of 96.5% (95% CI, 97.5 to 95.2) in Ugandan samples was significantly lower than that in samples from Baltimore, 99.3% (95% CI, 98.1 to 99.8; P < 0.01). In Ugandan samples, individuals with a false-positive result were more likely to be male (PR, 2.04; 95% CI, 1.03,3.69) or individuals who had had a fever more than a month prior to sample acquisition (PR, 2.87; 95% CI, 1.12 to 7.35). Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False-positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Female , Humans , Male , Sensitivity and Specificity , Uganda
9.
Front Pediatr ; 9: 638871, 2021.
Article in English | MEDLINE | ID: covidwho-1457675

ABSTRACT

With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called "immunology blunting," i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.

10.
Ann Intern Med ; 174(8): 1073-1080, 2021 08.
Article in English | MEDLINE | ID: covidwho-1456490

ABSTRACT

BACKGROUND: Assessing the evolution of SARS-CoV-2 immune response among patients receiving dialysis can define its durability in a highly clinically relevant context because patients receiving dialysis share the characteristics of persons most susceptible to SARS-CoV-2 infection. OBJECTIVE: To evaluate the persistence of SARS-CoV-2 receptor-binding domain (RBD) IgG in seroprevalent patients receiving dialysis. DESIGN: Prospective. SETTING: Nationwide sample from dialysis facilities. PATIENTS: 2215 patients receiving dialysis who had evidence of SARS-CoV-2 infection as of July 2020. MEASUREMENTS: Remainder plasma from routine monthly laboratories was used to measure semiquantitative RBD IgG index value over 6 months. RESULTS: A total of 2063 (93%) seroprevalent patients reached an assay detectable response (IgG index value ≥1). Most (n = 1323, 60%) had responses in July with index values classified as high (IgG ≥10); 1003 (76%) remained within this stratum. Adjusted median index values declined slowly but continuously (July vs. December values were 21 vs. 13; P < 0.001). The trajectory of the response did not vary by age group, sex, race/ethnicity, or diabetes status. Patients without an assay detectable response (n = 137) were more likely to be White and in the younger (18 to 44 years) or older (≥80 years) age groups and less likely to have diabetes and hypoalbuminemia. LIMITATION: Lack of data on symptoms or reverse transcriptase polymerase chain reaction diagnosis, cohort of persons who survived infection, and use of a semiquantitative assay. CONCLUSION: Despite impaired immunity, most seropositive patients receiving dialysis maintained RBD antibody levels over 6 months. A slow and continual decline in median antibody levels over time was seen, but no indication that subgroups with impaired immunity had a shorter-lived humoral response was found. PRIMARY FUNDING SOURCE: Ascend Clinical Laboratories.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , Protein Domains/immunology , Renal Dialysis , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Young Adult
11.
J Med Virol ; 93(10): 5805-5815, 2021 10.
Article in English | MEDLINE | ID: covidwho-1453606

ABSTRACT

Aggressive immune response, due to overexpressed proinflammatory molecules, has been characterized in coronavirus disease 2019 (COVID-19) patients. Some of those mediators have a dual and opposite role on immune systems at play behind differential disease severities. We investigated the expression of some cytokines and chemokines in COVID-19 patients in Bangladesh. We diagnosed the patients by detecting severe acute respiratory syndrome coronavirus 2 RNA in nasal swab samples by the real-time RT-PCR method. Thirty adult patients were preselected based on their disease severities and grouped into mild, moderate, and severe cases. Nine healthy volunteers participated in this study as a control. Relative expression of nine cytokines/chemokine in total leukocytes was semi-quantified in SYBRgreen-based real-time quantitative reverse-transcriptase polymerase chain reaction. We performed statistical tests on transformed log data using SPSS 24.0. At the onset of symptoms (Day 1), angiotensin-converting enzyme 2 (ACE2) (p < 0.05) and interleukin (IL)-6 (p > 0.05) were upregulated in all COVID-19 groups, although the expression levels did not significantly correlate with disease severities. However, expressions of IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α, tumor necrosis factor-α (TNF-α), RANTES (regulated upon activation, normal T cell expressed and secreted), and ACE2, on Day 14, were positively correlated with disease severities. Relative viral load at Day 1 showed no significant correlation with cytokine expression but had a significant positive correlation with RANTES and ACE2 expression on Day 14 (p < 0.05). Male patients had a higher level of IL-6 than female patients on Day 1 (p < 0.05). All COVID-19 patients showed upregulated cytokines and chemokines on Day 14 compared to Day 1 except TNF-α. Female patients had a higher expression of ACE2 and IL-12 on Day 14. Upregulated cytokines/chemokines at the convalescent stage, especially IL-6, may help in targeting anticytokine therapy in post-COVID-19 patients' management.


Subject(s)
COVID-19/diagnosis , Cytokines/blood , Adult , Bangladesh/epidemiology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/virology , Chemokines/blood , Female , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification , Severity of Illness Index , Viral Load
12.
Res Sq ; 2021 Mar 17.
Article in English | MEDLINE | ID: covidwho-1431222

ABSTRACT

Coronavirus-associated acute respiratory disease, called coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 90 million people have been infected with SARS-CoV-2 and more than 2 million people have died of complications due to COVID-19 worldwide. COVID-19, in its severe form, presents with an uncontrolled, hyperactive immune response and severe immunological injury or organ damage that accounts for morbidity and mortality. Even in the absence of complications, COVID-19 can last for several months with lingering effects of an overactive immune system. Dysregulated myeloid and lymphocyte compartments have been implicated in lung immunopathology. Currently, there are limited clinically-tested treatments of COVID-19 with disparities in the apparent efficacy in patients. Accurate model systems are essential to rapidly evaluate promising discoveries but most currently available in mice, ferrets and hamsters do not recapitulate sustained immunopathology described in COVID19 patients. Here, we present a comprehensively humanized mouse COVID-19 model that faithfully recapitulates the innate and adaptive human immune responses during infection with SARS-CoV-2 by adapting recombinant adeno-associated virus (AAV)-driven gene therapy to deliver human ACE2 to the lungs 1 of MISTRG6 mice. Our unique model allows for the first time the study of chronic disease due to infection with SARS-CoV-2 in the context of patient-derived antibodies to characterize in real time the potential culprits of the observed human driving immunopathology; most importantly this model provides a live view into the aberrant macrophage response that is thought to be the effector of disease morbidity and ARDS in patients. Application of therapeutics such as patient-derived antibodies and steroids to our model allowed separation of the two aspects of the immune response, infectious viral clearance and immunopathology. Inflammatory cells seeded early in infection drove immune-patholgy later, but this very same early anti-viral response was also crucial to contain infection.

13.
Life Sci Alliance ; 4(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1389962

ABSTRACT

A critical question in understanding the immunity to SARS-COV-2 is whether recovered patients are protected against re-challenge and transmission upon second exposure. We developed a Syrian hamster model in which intranasal inoculation of just 100 TCID50 virus caused viral pneumonia. Aged hamsters developed more severe disease and even succumbed to SARS-CoV-2 infection, representing the first lethal model using genetically unmodified laboratory animals. After initial viral clearance, the hamsters were re-challenged with 105 TCID50 SARS-CoV-2 and displayed more than 4 log reduction in median viral loads in both nasal washes and lungs in comparison to primary infections. Most importantly, re-challenged hamsters were unable to transmit virus to naïve hamsters, and this was accompanied by the presence of neutralizing antibodies. Altogether, these results show that SARS-CoV-2 infection induces protective immunity that not only prevents re-exposure but also limits transmission in hamsters. These findings may help guide public health policies and vaccine development and aid evaluation of effective vaccines against SARS-CoV-2.


Subject(s)
COVID-19/immunology , COVID-19/transmission , Immunity , Reinfection/immunology , Reinfection/transmission , SARS-CoV-2/immunology , Age Factors , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Chlorocebus aethiops , Cricetinae , Disease Models, Animal , Female , HEK293 Cells , Humans , Male , RNA, Viral/genetics , Reinfection/virology , SARS-CoV-2/genetics , Transfection , Vero Cells , Viral Load
14.
Vaccines (Basel) ; 9(1)2021 Jan 18.
Article in English | MEDLINE | ID: covidwho-1389565

ABSTRACT

In this concise review, we summarize the concepts behind mRNA vaccination. We discuss the innate and adaptive immune response generated by mRNA vaccines in different animal models and in humans. We give examples of viral infections where mRNA vaccines have shown to induce potent responses and we discuss in more detail the recent SARS-CoV-2 mRNA vaccine trials in humans.

16.
Kidney Int ; 99(6): 1470-1477, 2021 06.
Article in English | MEDLINE | ID: covidwho-1386157

ABSTRACT

Patients with end stage kidney disease receiving in-center hemodialysis (ICHD) have had high rates of SARS-CoV-2 infection. Following infection, patients receiving ICHD frequently develop circulating antibodies to SARS-CoV-2, even with asymptomatic infection. Here, we investigated the durability and functionality of the immune responses to SARS-CoV-2 infection in patients receiving ICHD. Three hundred and fifty-six such patients were longitudinally screened for SARS-CoV-2 antibodies and underwent routine PCR-testing for symptomatic and asymptomatic infection. Patients were regularly screened for nucleocapsid protein (anti-NP) and receptor binding domain (anti-RBD) antibodies, and those who became seronegative at six months were screened for SARS-CoV-2 specific T-cell responses. One hundred and twenty-nine (36.2%) patients had detectable antibody to anti-NP at time zero, of whom 127 also had detectable anti-RBD. Significantly, at six months, 71/111 (64.0%) and 99/116 (85.3%) remained anti-NP and anti-RBD seropositive, respectively. For patients who retained antibody, both anti-NP and anti-RBD levels were reduced significantly after six months. Eleven patients who were anti-NP seropositive at time zero, had no detectable antibody at six months; of whom eight were found to have SARS-CoV-2 antigen specific T cell responses. Independent of antibody status at six months, patients with baseline positive SARS-CoV-2 serology were significantly less likely to have PCR confirmed infection over the following six months. Thus, patients receiving ICHD mount durable immune responses six months post SARS-CoV-2 infection, with fewer than 3% of patients showing no evidence of humoral or cellular immunity.


Subject(s)
Antibodies, Viral/analysis , COVID-19/immunology , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , SARS-CoV-2/immunology , COVID-19 Testing , Female , Humans , Immunity , Male , Pandemics , Polymerase Chain Reaction , Reinfection , SARS-CoV-2/isolation & purification , Serologic Tests/methods
17.
Immunity ; 54(4): 753-768.e5, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1385739

ABSTRACT

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.


Subject(s)
Immunity/genetics , Virus Diseases/immunology , Antigen Presentation/genetics , Cohort Studies , Hematopoiesis/genetics , Humans , Interferons/blood , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Myeloid Cells/immunology , Myeloid Cells/pathology , Prognosis , Severity of Illness Index , Systems Biology , Transcriptome , Virus Diseases/blood , Virus Diseases/classification , Virus Diseases/genetics , Viruses/classification , Viruses/pathogenicity
18.
Cell ; 184(3): 628-642.e10, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-1385216

ABSTRACT

SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Immunoglobulin G/immunology , Maternal-Fetal Exchange/immunology , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Trimester, Third/immunology , Receptors, IgG/immunology , THP-1 Cells
19.
Infection ; 49(4): 781-783, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1384710

ABSTRACT

BACKGROUND: We report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CASE: One patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had a similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. DISCUSSION AND CONCLUSION: Thus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/immunology , Immunoglobulin G/blood , Infectious Disease Transmission, Patient-to-Professional , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing/biosynthesis , COVID-19/transmission , Cross Infection/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/biosynthesis , Male , Middle Aged , Nasopharynx/virology , SARS-CoV-2/classification , SARS-CoV-2/genetics
20.
Curr Nutr Rep ; 10(2): 137-145, 2021 06.
Article in English | MEDLINE | ID: covidwho-1384685

ABSTRACT

PURPOSE OF REVIEW: From single cells to entire organisms, biological entities are in constant communication with their surroundings, deciding what to 'allow' in, and what to reject. In very different ways, the immune and taste systems both fulfill this function, with growing evidence suggesting a relationship between the two, through shared signaling pathways, receptors, and feedback loops. The purpose of this review was to explore recent reports on taste and immunity in model animals and in humans to explore our understanding of the interplay between these systems. RECENT FINDINGS: Acute infections in the upper airway, as with SARS-CoV-2, are associated with a proinflammatory state, and blunted taste perception. Further, recent findings highlight taste receptors working as immune sentinels throughout the body. Work in humans and mice also points to inflammation from obesity impacting taste, altering taste bud abundance and composition. There is accumulating evidence that taste cells, and particularly their receptors, play a role in airway and gut immunity, responsive to invading organisms. Inflammation itself may further act on taste buds and other taste receptor expressing cells throughout the body as a form of homeostatic control.


Subject(s)
COVID-19/immunology , Taste/immunology , Animals , Databases, Factual , Humans , Immunity , Inflammation/immunology , SARS-CoV-2/isolation & purification , Taste Buds
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