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1.
Pak J Med Sci ; 36(COVID19-S4): S121-S123, 2020 May.
Article in English | MEDLINE | ID: covidwho-1726834

ABSTRACT

Currently Covid-19 pandemic is a leading challenge across the globe. It is mandatory to attain and maintain good nutritional status to fight against virus. Nutritional status of individual is affected by several factors such as age, sex, health status, life style and medications. Nutritional status of individuals has been used as resilience towards destabilization during this COVID-19 pandemic. Optimal nutrition and dietary nutrient intake impact the immune system, therefore the only sustainable way to survive in current context is to strengthen the immune system. There is no evidence found that supplement can cure the immune system except Vit C, which is one of the best way to improve immune system. A proper diet can ensure that the body is in proper state to defeat the virus. However along with the dietary management guidelines the food safety management and good food practices is compulsory. This article explores the importance of nutrition to boost immunity and gives some professional and authentic dietary guidelines about nutrition and food safety to withstand COVID-19.

2.
Viruses ; 12(5)2020 05 24.
Article in English | MEDLINE | ID: covidwho-1726014

ABSTRACT

Feline infectious peritonitis (FIP) is a viral disease with a high morbidity and mortality by the FIP virus (FIPV, virulent feline coronavirus). Several antiviral drugs for FIP have been identified, but many of these are expensive and not available in veterinary medicine. Hydroxychloroquine (HCQ) is a drug approved by several countries to treat malaria and immune-mediated diseases in humans, and its antiviral effects on other viral infections (e.g., SARS-CoV-2, dengue virus) have been confirmed. We investigated whether HCQ in association with interferon-ω (IFN-ω) is effective for FIPV in vitro. A total of 100 µM of HCQ significantly inhibited the replication of types I and II FIPV. Interestingly, the combination of 100 µM of HCQ and 104 U/mL of recombinant feline IFN-ω (rfIFN-ω, veterinary registered drug) increased its antiviral activity against type I FIPV infection. Our study suggested that HCQ and rfIFN-ω are applicable for treatment of FIP. Further clinical studies are needed to verify the combination of HCQ and rIFN-ω will be effective and safe treatment for cats with FIP.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus, Feline/drug effects , Hydroxychloroquine/pharmacology , Interferon Type I/pharmacology , Analysis of Variance , Animals , Antiviral Agents/therapeutic use , Antiviral Agents/toxicity , Cats , Cell Line/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Coronavirus, Feline/pathogenicity , Drug Combinations , Feline Infectious Peritonitis/drug therapy , Feline Infectious Peritonitis/virology , Fluorescent Antibody Technique/veterinary , Hydroxychloroquine/therapeutic use , Hydroxychloroquine/toxicity , Interferon Type I/therapeutic use , Interferon Type I/toxicity , Virulence
4.
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.

5.
J Leukoc Biol ; 110(1): 21-26, 2021 07.
Article in English | MEDLINE | ID: covidwho-1574077

ABSTRACT

The global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic RNA virus causing coronavirus disease 2019 (COVID-19) in humans. Although most patients with COVID-19 have mild illness and may be asymptomatic, some will develop severe pneumonia, acute respiratory distress syndrome, multi-organ failure, and death. RNA viruses such as SARS-CoV-2 are capable of hijacking the epigenetic landscape of host immune cells to evade antiviral defense. Yet, there remain considerable gaps in our understanding of immune cell epigenetic changes associated with severe SARS-CoV-2 infection pathology. Here, we examined genome-wide DNA methylation (DNAm) profiles of peripheral blood mononuclear cells from 9 terminally-ill, critical COVID-19 patients with confirmed SARS-CoV-2 plasma viremia compared with uninfected, hospitalized influenza, untreated primary HIV infection, and mild/moderate COVID-19 HIV coinfected individuals. Cell-type deconvolution analyses confirmed lymphopenia in severe COVID-19 and revealed a high percentage of estimated neutrophils suggesting perturbations to DNAm associated with granulopoiesis. We observed a distinct DNAm signature of severe COVID-19 characterized by hypermethylation of IFN-related genes and hypomethylation of inflammatory genes, reinforcing observations in infection models and single-cell transcriptional studies of severe COVID-19. Epigenetic clock analyses revealed severe COVID-19 was associated with an increased DNAm age and elevated mortality risk according to GrimAge, further validating the epigenetic clock as a predictor of disease and mortality risk. Our epigenetic results reveal a discovery DNAm signature of severe COVID-19 in blood potentially useful for corroborating clinical assessments, informing pathogenic mechanisms, and revealing new therapeutic targets against SARS-CoV-2.


Subject(s)
COVID-19/genetics , DNA Methylation/genetics , Epigenesis, Genetic , Genome, Human , COVID-19/virology , HIV Infections/genetics , Humans , Influenza, Human/genetics , SARS-CoV-2/physiology
6.
Sci Immunol ; 5(44)2020 02 21.
Article in English | MEDLINE | ID: covidwho-1575907

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.


Subject(s)
Breast Neoplasms/pathology , Myeloid-Derived Suppressor Cells/pathology , Single-Cell Analysis , Transcriptome , Animals , Biomarkers, Tumor/genetics , Biomarkers, Tumor/immunology , Breast Neoplasms/immunology , Cell Differentiation/genetics , Female , Humans , Mice , Mice, Inbred Strains , Mice, Transgenic , Myeloid-Derived Suppressor Cells/immunology , RNA, Neoplasm/genetics , RNA, Neoplasm/immunology , Signaling Lymphocytic Activation Molecule Family/genetics , Signaling Lymphocytic Activation Molecule Family/immunology
7.
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.

8.
Obstet Gynecol ; 138(2): 189-197, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1364849

ABSTRACT

OBJECTIVE: To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer. METHODS: We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti-receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency. RESULTS: Thirty-two paired samples were analyzed. Detectable anti-receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti-receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5-2.4] vs log 2.7 [2.9-1.4], P=.03). Median (interquartile range) maternal anti-receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5-2.4] vs log 2.67 [2.8-1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67-0.88). CONCLUSIONS: These results demonstrate robust maternal neutralizing and anti-receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study.


Subject(s)
Antibody Formation , COVID-19/immunology , Maternal-Fetal Exchange , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Neutralizing , Asymptomatic Infections , Female , Humans , Pregnancy , Prospective Studies , Young Adult
9.
Front Immunol ; 12: 624703, 2021.
Article in English | MEDLINE | ID: covidwho-1354863

ABSTRACT

Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.


Subject(s)
Autoimmune Diseases/metabolism , Autoimmunity , Cardiomyopathies/metabolism , Inflammation Mediators/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Tenascin/metabolism , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/pathology , Cardiomyopathies/immunology , Cardiomyopathies/pathology , Cellular Microenvironment , Humans , Myocarditis/immunology , Myocarditis/pathology , Myocardium/immunology , Myocardium/pathology , Self Tolerance , Signal Transduction
10.
J Headache Pain ; 22(1): 51, 2021 Jun 04.
Article in English | MEDLINE | ID: covidwho-1346199

ABSTRACT

BACKGROUND: The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. METHODS: An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. RESULTS: One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). CONCLUSIONS: The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.


Subject(s)
COVID-19 , Cytokines , Case-Control Studies , Female , Headache/complications , Humans , Interleukins , Male , SARS-CoV-2
11.
Clin Infect Dis ; 73(3): 376-385, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338654

ABSTRACT

BACKGROUND: The recent identification of a novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2, has caused a global outbreak of respiratory illnesses. The rapidly developing pandemic has posed great challenges to diagnosis of this novel infection. However, little is known about the metatranscriptomic characteristics of patients with coronavirus disease 2019 (COVID-19). METHODS: We analyzed metatranscriptomics in 187 patients (62 cases with COVID-19 and 125 with non-COVID-19 pneumonia). Transcriptional aspects of 3 core elements, pathogens, the microbiome, and host responses, were evaluated. Based on the host transcriptional signature, we built a host gene classifier and examined its potential for diagnosing COVID-19 and indicating disease severity. RESULTS: The airway microbiome in COVID-19 patients had reduced alpha diversity, with 18 taxa of differential abundance. Potentially pathogenic microbes were also detected in 47% of the COVID-19 cases, 58% of which were respiratory viruses. Host gene analysis revealed a transcriptional signature of 36 differentially expressed genes significantly associated with immune pathways, such as cytokine signaling. The host gene classifier built on such a signature exhibited the potential for diagnosing COVID-19 (area under the curve of 0.75-0.89) and indicating disease severity. CONCLUSIONS: Compared with those with non-COVID-19 pneumonias, COVID-19 patients appeared to have a more disrupted airway microbiome with frequent potential concurrent infections and a special trigger host immune response in certain pathways, such as interferon-gamma signaling. The immune-associated host transcriptional signatures of COVID-19 hold promise as a tool for improving COVID-19 diagnosis and indicating disease severity.


Subject(s)
COVID-19 , Microbiota , COVID-19 Testing , Humans , Microbiota/genetics , Pandemics , SARS-CoV-2
12.
Front Immunol ; 12: 681449, 2021.
Article in English | MEDLINE | ID: covidwho-1314554

ABSTRACT

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group.


Subject(s)
Aging/immunology , Host-Pathogen Interactions/immunology , Immunity , Virus Diseases/immunology , Adaptive Immunity , Age Factors , Animals , Clinical Decision-Making , Disease Management , Disease Susceptibility/immunology , Humans , Immune System/immunology , Immune System/metabolism , Immunity, Innate , Virus Diseases/therapy , Virus Diseases/virology
13.
J Virol ; 95(17): e0066721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1274527

ABSTRACT

Cellular immune responses play a key role in the control of viral infection. The nucleocapsid (N) protein of infectious bronchitis virus (IBV) is a major immunogenic protein that can induce protective immunity. To screen for potential T-cell epitopes on IBV N protein, 40 overlapping peptides covering the entirety of the N protein were designed and synthesized. Four T-cell epitope peptides were identified by gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining, and carboxyfluorescein succinimidyl ester (CFSE) lymphocyte proliferation assays; among them, three peptides (N211-230, N271-290, and N381-400) were cytotoxic T lymphocyte (CTL) epitopes, and one peptide (N261-280) was a dual-specific T-cell epitope, which can be recognized by both CD8+ and CD4+ T cells. Multi-epitope gene transcription cassettes comprising four neutralizing epitope domains and four T-cell epitope peptides were synthesized and inserted into the genome of Newcastle disease virus strain La Sota between the P and M genes. Recombinant IBV multi-epitope vaccine candidate rLa Sota/SBNT was generated via reverse genetics, and its immune protection efficacy was evaluated in specific-pathogen-free chickens. Our results show that rLa Sota/SBNT induced IBV-specific neutralizing antibody and T-cell responses and provided significant protection against homologous and heterologous IBV challenge. Thus, the T-cell epitope peptides identified in this study could be good candidates for IBV vaccine development, and recombinant Newcastle disease virus-expressing IBV multi-epitope genes represent a safe and effective vaccine candidate for controlling infectious bronchitis. IMPORTANCE T-cell-mediated immune responses are critical for the elimination of IBV-infected cells. To screen conserved T-cell epitopes in the IBV N protein, 40 overlapping peptides covering the entirety of the N protein were designed and synthesized. By combining IFN-γ ELISpot, intracellular cytokine staining, and CFSE lymphocyte proliferation assays, we identified three CTL epitopes and one dual-specific T-cell epitope. The value of T-cell epitope peptides identified in the N protein was further verified by the design of an IBV multi-epitope vaccine. Results show that IBV multi-epitope vaccine candidate rLa Sota/SBNT provided cross protection against challenges with a QX-like or a TW-like IBV strain. So, T-cell-mediated immune responses play an important role in the control of viral infection, and conserved T-cell epitopes serve as promising candidates for use in multi-epitope vaccine construction. Our results provide a new perspective for the development of a safer and more effective IBV vaccine.


Subject(s)
Coronavirus Infections/prevention & control , Epitopes, T-Lymphocyte/immunology , Immunity, Cellular/immunology , Infectious bronchitis virus/immunology , Nucleocapsid Proteins/immunology , Poultry Diseases/prevention & control , Viral Vaccines/administration & dosage , Animals , Chickens , Coronavirus Infections/immunology , Coronavirus Infections/virology , Immunity, Cellular/drug effects , Poultry Diseases/immunology , Specific Pathogen-Free Organisms , T-Lymphocytes, Cytotoxic/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Vaccines/immunology
14.
Int J Clin Pract ; 75(10): e14544, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1273093

ABSTRACT

BACKGROUND: Prognostic nutritional index (PNI) and systemic immune-inflammatory index (SII) are inflammation-based novel markers that predict the prognosis in various patient populations. We have investigated the relationship between the disease severity in COVID-19, and the PNI and SII scores in the present study. MATERIALS AND METHODS: This cross-sectional retrospective study included 118 hospitalised patients with a confirmed diagnosis of COVID-19. The patients were divided into two groups as those who were hospitalised at the intensive care unit (ICU) and those who had been internalised at the clinic (non-ICU). RESULTS: Of the 118 patients, 50.8% were male. The mean age was 57.7 ± 17.5 years in non-ICU patients and 70.3 ± 11.7 years in ICU patients and the difference was statistically significant (P < .001). The lymphocyte count and the albumin levels were significantly lower in ICU patients (P < .001, P < .001, respectively). The PNI score was significantly lower in ICU patients compared with non-ICU patients (P < .001). The SII score was found to be significantly higher in ICU patients compared with non-ICU patients (P < .001). The value of PNI and SII scores in prediction of the disease severity in COVID-19 was evaluated with the ROC analysis (PNI: AUC = 0.796, 95%CI: 0.715-0.877, P < .001; SII: AUC =0.689, 95% CI: 0.559-0.819, P=.004). When the cut-off value was taken as ≤36.7 for the PNI score, it was found to have 73.4% sensitivity and 70.8% specificity for predicting of the disease severity and ICU admission probability was 4.4 times higher. When the cut-off value was taken as ≥813.6 for SII score, it was found to have 70.8% sensitivity and 66.0% specificity for predicting of the disease severity and ICU admission probability was six times higher. CONCLUSION: The PNI and the SII scores are independent predictors of the prognosis and the disease severity in COVID-19 patients who require hospitalisation at the ICU.


Subject(s)
COVID-19 , Nutrition Assessment , Adult , Aged , Cross-Sectional Studies , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
15.
mSystems ; 6(3): e0035321, 2021 Jun 29.
Article in English | MEDLINE | ID: covidwho-1269773

ABSTRACT

SARS-CoV-2 variants with multiple amino acid mutations in the spike protein are emerging in different parts of the world, raising concerns regarding their possible impact on human immune response and vaccine efficacy against the virus. Recently, a variant named lineage B.1.1.7 was detected and shown to be rapidly spreading across the UK since November 2020. As surveillance for these SARS-CoV-2 variants of concern (VOCs) becomes critical, we have investigated the use of environmental surveillance (ES) for the rapid detection and quantification of B.1.1.7 viruses in sewage as a way of monitoring its expansion that is independent on the investigation of identified clinical cases. Next-generation sequencing analysis of amplicons synthesized from sewage concentrates revealed the presence of B.1.1.7 mutations in viral sequences, first identified in a sample collected in London on 10 November 2020 and shown to rapidly increase in frequency to >95% in January 2021, in agreement with clinical data over the same period. We show that ES can provide an early warning of VOCs becoming prevalent in the population and that, as well as B.1.1.7, our method can detect VOCs B.1.351 and P.1, first identified in South Africa and Brazil, respectively, and other viruses carrying critical spike mutation E484K, known to have an effect on virus antigenicity. Although we did not detect such mutation in viral RNAs from sewage, we did detect mutations at amino acids 478, 490, and 494, located close to amino acid 484 in the spike protein structure and known to also have an effect on antigenicity. IMPORTANCE The recent appearance and growth of new SARS-CoV-2 variants represent a major challenge for the control of the COVID-19 pandemic. These variants of concern contain mutations affecting antigenicity, which raises concerns on their possible impact on human immune response to the virus and vaccine efficacy against them. Here, we show how environmental surveillance for SARS-CoV-2 can be used to help us understand virus transmission patterns and provide an early warning of variants becoming prevalent in the population. We describe the detection and quantification of variant B.1.1.7, first identified in southeast England in sewage samples from London (UK) before widespread transmission of this variant was obvious from clinical cases. Variant B.1.1.7 was first detected in a sample from early November 2020, with the frequency of B.1.1.7 mutations detected in sewage rapidly increasing to >95% in January 2021, in agreement with increasing SARS-CoV-2 infections associated with B.1.1.7 viruses.

16.
Kidney Int ; 100(4): 915-927, 2021 10.
Article in English | MEDLINE | ID: covidwho-1267774

ABSTRACT

Solid organ transplant recipients are at high risk for the development of severe forms of COVID-19. However, the role of immunosuppression in the morbidity and mortality of the immune phenotype during COVID-19 in transplant recipients remains unknown. In this retrospective study, we compared peripheral blood T and B cell functional and surface markers, as well as serum antibody development during 29 cases of mild (World Health Organization 9-point Ordinal Scale (WOS) of 3-4) and 22 cases of severe COVID-19 (WOS 5-8) in solid organ transplant (72% kidney transplant) recipients hospitalized in our center. Patients who developed severe forms of COVID-19 presented significantly lower CD3+ (median 344/mm3 (inter quartile range 197; 564) vs. 643/mm3 (397; 1251)) and CD8+ T cell counts (124/mm3 (76; 229) vs. 240/mm3 (119; 435)). However, activated CD4+ T cells were significantly more frequent in severe forms (2.9% (1.37; 5.72) vs. 1.4% (0.68; 2.35)), counterbalanced by a significantly higher proportion of Tregs (3.9% (2.35; 5.87) vs. 2.7% (1.9; 3.45)). A marked decrease in the proportion of NK cells was noted only in severe forms. In the B cell compartment, transitional B cells were significantly lower in severe forms (1.2% (0.7; 4.2) vs. 3.6% (2.1; 6.2)). Nonetheless, a majority of transplant recipients developed antibodies against SARS-CoV-2 (77% and 83% in mild and severe forms, respectively). Thus, our data revealed immunological differences between mild and severe forms of COVID-19 in solid organ transplant recipients, similar to previous reports in the immunocompetent population.


Subject(s)
COVID-19 , Organ Transplantation , Humans , Killer Cells, Natural , Organ Transplantation/adverse effects , Retrospective Studies , SARS-CoV-2 , Transplant Recipients
17.
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266400

ABSTRACT

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Subject(s)
COVID-19 , Drug Repositioning , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Immunotherapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Comorbidity , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/immunology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompromised Host/physiology , Immunotherapy/adverse effects , Immunotherapy/methods , Immunotherapy/statistics & numerical data , Mortality , Pandemics , Prognosis , Rheumatic Diseases/epidemiology , SARS-CoV-2/physiology , Transplant Recipients/statistics & numerical data
18.
Front Res Metr Anal ; 6: 683212, 2021.
Article in English | MEDLINE | ID: covidwho-1264397

ABSTRACT

The COVID-19 pandemic constitutes an ongoing worldwide threat to human society and has caused massive impacts on global public health, the economy and the political landscape. The key to gaining control of the disease lies in understanding the genetics of SARS-CoV-2 and the disease spectrum that follows infection. This study leverages traditional and intelligent bibliometric methods to conduct a multi-dimensional analysis on 5,632 COVID-19 genetic research papers, revealing that 1) the key players include research institutions from the United States, China, Britain and Canada; 2) research topics predominantly focus on virus infection mechanisms, virus testing, gene expression related to the immune reactions and patient clinical manifestation; 3) studies originated from the comparison of SARS-CoV-2 to previous human coronaviruses, following which research directions diverge into the analysis of virus molecular structure and genetics, the human immune response, vaccine development and gene expression related to immune responses; and 4) genes that are frequently highlighted include ACE2, IL6, TMPRSS2, and TNF. Emerging genes to the COVID-19 consist of FURIN, CXCL10, OAS1, OAS2, OAS3, and ISG15. This study demonstrates that our suite of novel bibliometric tools could help biomedical researchers follow this rapidly growing field and provide substantial evidence for policymakers' decision-making on science policy and public health administration.

19.
Endocr Pract ; 27(8): 850-855, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1263262

ABSTRACT

OBJECTIVE: To discuss the use of melatonin as an early treatment option on the first day of diagnosis for COVID-19. METHODS: Medical Subject Headings terms "COVID-19" and "viral diseases" were manually searched on PubMed, and relevant articles were included. RESULTS: The results showed that melatonin acts to reduce reactive oxygen species-mediated damage, cytokine-induced inflammation, and lymphopenia in viral diseases similar to COVID-19. CONCLUSION: These conclusions provide evidence for potential benefits in melatonin use for COVID-19 treatment as early as the day of diagnosis.


Subject(s)
COVID-19 , Coronavirus Infections , Melatonin , COVID-19/drug therapy , Humans , Melatonin/therapeutic use , SARS-CoV-2
20.
Proc Natl Acad Sci U S A ; 118(25)2021 06 22.
Article in English | MEDLINE | ID: covidwho-1258620

ABSTRACT

Low plasma arginine bioavailability has been implicated in endothelial dysfunction and immune dysregulation. The role of arginine in COVID-19 is unknown, but could contribute to cellular damage if low. Our objective was to determine arginine bioavailability in adults and children with COVID-19 vs. healthy controls. We hypothesized that arginine bioavailability would be low in patients with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We conducted a prospective observational study of three patient cohorts; arginine bioavailability was determined in asymptomatic healthy controls, adults hospitalized with COVID-19, and hospitalized children/adolescents <21 y old with COVID-19, MIS-C, or asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection identified on admission screen. Mean patient plasma amino acids were compared to controls using the Student's t test. Arginine-to-ornithine ratio, a biomarker of arginase activity, and global arginine bioavailability ratio (GABR, arginine/[ornithine+citrulline]) were assessed in all three groups. A total of 80 patients were included (28 controls, 32 adults with COVID-19, and 20 pediatric patients with COVID-19/MIS-C). Mean plasma arginine and arginine bioavailability ratios were lower among adult and pediatric patients with COVID-19/MIS-C compared to controls. There was no difference between arginine bioavailability in children with COVID-19 vs. MIS-C. Adults and children with COVID-19 and MIS-C in our cohort had low arginine bioavailability compared to healthy adult controls. This may contribute to immune dysregulation and endothelial dysfunction in COVID-19. Low arginine-to-ornithine ratio in patients with COVID-19 or MIS-C suggests an elevation of arginase activity. Further study is merited to explore the role of arginine dysregulation in COVID-19.


Subject(s)
Amino Acids/blood , COVID-19/blood , Hospitalization , SARS-CoV-2/metabolism , Adult , COVID-19/therapy , Female , Humans , Male , Middle Aged , Retrospective Studies
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