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1.
Food Sci Nutr ; 2020 May 31.
Article in English | MEDLINE | ID: covidwho-1898719

ABSTRACT

This review focused on the use of plant based foods for enhancing the immunity of all aged groups against COVID-19. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and, recently, severe acute respiratory syndrome (SARS). Emerging infectious diseases, such as SARS present a major threat to public health. The novel coronavirus has spread rapidly to multiple countries and has been declared a pandemic by the World Health Organization. COVID-19 is usually caused a virus to which most probably the people with low immunity response are being effected. Plant based foods increased the intestinal beneficial bacteria which are helpful and makes up of 85% of the immune system. By the use of plenty of water, minerals like magnesium and Zinc, micronutrients, herbs, food rich in vitamins C, D & E and better life style one can promote the health and can overcome this infection. Various studies investigated that a powerful antioxidant Glutathione and a bioflavonoid Quercetin may prevent various infections including COVID-19. In conclusion, the plant based foods play a vital role to enhance the immunity of people to control of COVID-19.

2.
J Clin Invest ; 131(12)2021 06 15.
Article in English | MEDLINE | ID: covidwho-1731387

ABSTRACT

The characterization of the adaptive immune response to COVID-19 vaccination in individuals who recovered from SARS-CoV-2 infection may define current and future clinical practice. To determine the effect of the 2-dose BNT162b2 mRNA COVID-19 vaccination schedule in individuals who recovered from COVID-19 (COVID-19-recovered subjects) compared with naive subjects, we evaluated SARS-CoV-2 Spike-specific T and B cell responses, as well as specific IgA, IgG, IgM, and neutralizing antibodies titers in 22 individuals who received the BNT162b2 mRNA COVID-19 vaccine, 11 of whom had a previous history of SARS-CoV-2 infection. Evaluations were performed before vaccination and then weekly until 7 days after second injection. Data obtained clearly showed that one vaccine dose is sufficient to increase both cellular and humoral immune response in COVID-19-recovered subjects without any additional improvement after the second dose. On the contrary, the second dose proved mandatory in naive subjects to further enhance the immune response. These findings were further confirmed at the serological level in a larger cohort of naive (n = 68) and COVID-19-recovered (n = 29) subjects, tested up to 50 days after vaccination. These results question whether a second vaccine injection in COVID-19-recovered subjects is required, and indicate that millions of vaccine doses may be redirected to naive individuals, thus shortening the time to reach herd immunity.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Humoral/drug effects , Immunologic Memory/drug effects , SARS-CoV-2 , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
3.
Int J Vitam Nutr Res ; 92(1): 35-48, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1721399

ABSTRACT

Recently, the outbreak of severe acute respiratory syndrome cornoavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become a great perturbation all around the globe and has many devastating effects on every aspect of life. Apart from the oxygen therapy and extracorporeal membrane oxygenation, Remdesivir and Dexamethasone have been proven to be efficacious against COVID-19, along with various vaccine candidates and monoclonal antibody cocktail therapy for Regeneron. All of these are currently at different stages of clinical trials. People with weak immunity are more prone to a severe infection of SARS-CoV-2. Therefore, early and judicious nutritional supplementation along with pharmacological treatment and clinician collaborations are critical in restituting the current situation. Nutritional supplements help in acquiring strong immunity to prevent the progression of disease any further. Vitamin C, vitamin D, selenium, zinc and many other nutritional and dietary supplements inhibit the production of inflammatory cytokines during a viral infection and prevents several unwanted symptoms of infection. Many dietary components like citrus fruits, black elderberry, ginger, and probiotics have the ability to attack viral replication. These supplements can also tame the overriding immune system during coronavirus infection. Keeping in view these facts, nutritional and dietary supplements can be used along with other management modalities. These nutritional and dietary supplements are potential candidates to curb the convulsive unfolding of novel COVID-19, in combination with other standard treatment protocols. In this review, various search engines were used to exploit available literature in order to provide a comprehensive review on nutritional and dietary supplements with respect to the viral infections. It will also provide a brief overview on some of the clinical trials that are in progress to assess the role of nutritional supplements, either alone or in combination with other pharmacological drugs, in fight against COVID-19.


Subject(s)
COVID-19 , Clinical Trials as Topic , Dietary Supplements , Humans , SARS-CoV-2 , Vitamin D , Vitamins
4.
J Leukoc Biol ; 111(2): 497-508, 2022 02.
Article in English | MEDLINE | ID: covidwho-1669515

ABSTRACT

Coronaviruses (CoVs) are RNA viruses that cause human respiratory infections. Zoonotic transmission of the SARS-CoV-2 virus caused the recent COVID-19 pandemic, which led to over 2 million deaths worldwide. Elevated inflammatory responses and cytotoxicity in the lungs are associated with COVID-19 severity in SARS-CoV-2-infected individuals. Bats, which host pathogenic CoVs, operate dampened inflammatory responses and show tolerance to these viruses with mild clinical symptoms. Delineating the mechanisms governing these host-specific inflammatory responses is essential to understand host-virus interactions determining the outcome of pathogenic CoV infections. Here, we describe the essential role of inflammasome activation in determining COVID-19 severity in humans and innate immune tolerance in bats that host several pathogenic CoVs. We further discuss mechanisms leading to inflammasome activation in human SARS-CoV-2 infection and how bats are molecularly adapted to suppress these inflammasome responses. We also report an analysis of functionally important residues of inflammasome components that provide new clues of bat strategies to suppress inflammasome signaling and innate immune responses. As spillover of bat viruses may cause the emergence of new human disease outbreaks, the inflammasome regulation in bats and humans likely provides specific strategies to combat the pathogenic CoV infections.


Subject(s)
COVID-19/pathology , Immune Tolerance , Immunity, Innate , Inflammasomes/immunology , SARS-CoV-2/immunology , Animals , COVID-19/immunology , COVID-19/virology , Chiroptera , Humans , Inflammasomes/metabolism , Phylogeny
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.
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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunotherapy, Adoptive , T-Lymphocytes
7.
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
8.
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
9.
PLoS Pathog ; 17(1): e1009161, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388959

ABSTRACT

We report the emergency development and application of a robust serologic test to evaluate acute and convalescent antibody responses to SARS-CoV-2 in Argentina. The assays, COVIDAR IgG and IgM, which were produced and provided for free to health authorities, private and public health institutions and nursing homes, use a combination of a trimer stabilized spike protein and the receptor binding domain (RBD) in a single enzyme-linked immunosorbent assay (ELISA) plate. Over half million tests have already been distributed to detect and quantify antibodies for multiple purposes, including assessment of immune responses in hospitalized patients and large seroprevalence studies in neighborhoods, slums and health care workers, which resulted in a powerful tool for asymptomatic detection and policy making in the country. Analysis of antibody levels and longitudinal studies of symptomatic and asymptomatic SARS-CoV-2 infections in over one thousand patient samples provided insightful information about IgM and IgG seroconversion time and kinetics, and IgM waning profiles. At least 35% of patients showed seroconversion within 7 days, and 95% within 45 days of symptoms onset, with simultaneous or close sequential IgM and IgG detection. Longitudinal studies of asymptomatic cases showed a wide range of antibody responses with median levels below those observed in symptomatic patients. Regarding convalescent plasma applications, a protocol was standardized for the assessment of end point IgG antibody titers with COVIDAR with more than 500 plasma donors. The protocol showed a positive correlation with neutralizing antibody titers, and was used for clinical trials and therapies across the country. Using this protocol, about 80% of convalescent donor plasmas were potentially suitable for therapies. Here, we demonstrate the importance of providing a robust and specific serologic assay for generating new information about antibody kinetics in infected individuals and mitigation policies to cope with pandemic needs.


Subject(s)
COVID-19/virology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody Formation , Argentina/epidemiology , COVID-19/epidemiology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , Pandemics , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies
10.
J Exp Med ; 218(4)2021 04 05.
Article in English | MEDLINE | ID: covidwho-1387677

ABSTRACT

SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals, we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 mo after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen-specific memory that could contribute to rapid recall responses. Recovered individuals also show enduring alterations in relative overall numbers of CD4+ and CD8+ memory T cells, including expression of activation/exhaustion markers, and cell division.


Subject(s)
COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions/immunology , Immunity, Cellular , SARS-CoV-2/immunology , Adult , Aged , Antigens, Viral/immunology , Biomarkers , Female , Humans , Immunophenotyping , Lymphocyte Count , Male , Middle Aged , T-Cell Antigen Receptor Specificity , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Young Adult
11.
J Autoimmun ; 121: 102662, 2021 07.
Article in English | MEDLINE | ID: covidwho-1385817

ABSTRACT

Herein, we consider venous immunothrombotic mechanisms in SARS-CoV-2 infection and anti-SARS-CoV-2 DNA vaccination. Primary SARS-CoV-2 infection with systemic viral RNA release (RNAaemia) contributes to innate immune coagulation cascade activation, with both pulmonary and systemic immunothrombosis - including venous territory strokes. However, anti-SARS-CoV-2 adenoviral-vectored-DNA vaccines -initially shown for the ChAdOx1 vaccine-may rarely exhibit autoimmunity with autoantibodies to Platelet Factor-4 (PF4) that is termed Vaccine-Induced Thrombotic Thrombocytopenia (VITT), an entity pathophysiologically similar to Heparin-Induced Thrombocytopenia (HIT). The PF4 autoantigen is a polyanion molecule capable of independent interactions with negatively charged bacterial cellular wall, heparin and DNA molecules, thus linking intravascular innate immunity to both bacterial cell walls and pathogen-derived DNA. Crucially, negatively charged extracellular DNA is a powerful adjuvant that can break tolerance to positively charged nuclear histone proteins in many experimental autoimmunity settings, including SLE and scleroderma. Analogous to DNA-histone interactons, positively charged PF4-DNA complexes stimulate strong interferon responses via Toll-Like Receptor (TLR) 9 engagement. A chain of events following intramuscular adenoviral-vectored-DNA vaccine inoculation including microvascular damage; microbleeding and platelet activation with PF4 release, adenovirus cargo dispersement with DNA-PF4 engagement may rarely break immune tolerance, leading to rare PF4-directed autoimmunity. The VITT cavernous sinus cerebral and intestinal venous territory immunothrombosis proclivity may pertain to venous drainage of shared microbiotal-rich areas of the nose and in intestines that initiates local endovascular venous immunity by PF4/microbiotal engagement with PF4 autoantibody driven immunothrombosis reminiscent of HIT. According to the proposed model, any adenovirus-vectored-DNA vaccine could drive autoimmune VITT in susceptible individuals and alternative mechanism based on molecular mimicry, vaccine protein contaminants, adenovirus vector proteins, EDTA buffers or immunity against the viral spike protein are secondary factors. Hence, electrochemical DNA-PF4 interactions and PF4-heparin interactions, but at different locations, represent the common denominator in HIT and VITT related autoimmune-mediated thrombosis.


Subject(s)
Autoantibodies/immunology , COVID-19/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , SARS-CoV-2/immunology , Thrombosis/immunology , Vaccines/adverse effects , COVID-19/pathology , COVID-19/prevention & control , Humans , Platelet Activation/immunology , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/pathology , Thrombosis/chemically induced , Thrombosis/pathology , Vaccines/immunology
12.
Int J Infect Dis ; 108: 183-186, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1351694

ABSTRACT

BACKGROUND: The efficacy of COVID-19 vaccines to generate immunological memory post-vaccination has not previously been studied. OBJECTIVE: To assess immunological memory in previously SARS-CoV-2 infected individuals after a single dose of mRNA vaccine. PATIENTS AND METHODS: Healthcare workers (n = 280) were enrolled after obtaining written informed consent and grouped under previously infected and no prior exposure (reverse transcription-polymerase chain reaction positive and negative, respectively). Blood was drawn at baseline and post-vaccination (single dose of COVISHIELD) for enumerating neutralizing antibodies by chemiluminescence and memory T- and B-cells by flow cytometry. RESULTS: Post vaccination, compared with the no prior exposure group, the previously infected group had higher levels of: antibody response (1124.73 ± 869.13 vs 94.23 ± 140.06 AU/ml, p = 0.0001); CD4 memory T-cells: central memory CCR7+CD45RA- (p = 0.0001), effector memory CCR7-/CD45RA- (p = 0.01); total CD8+ T-cells (p = 0.004); CD8+ naïve T-cells CCR7+CD45RA+ (p = 0.01); and memory B-cells CD20+CD27+ (p = 0.0001). DISCUSSION: Single-dose vaccination elicited higher neutralizing antibody response and protective immunity in individuals who had recovered from SARS-CoV-2 infection compared with those with no prior exposure.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , CD8-Positive T-Lymphocytes , Humans , Immunologic Memory , SARS-CoV-2
13.
Brief Bioinform ; 22(2): 1387-1401, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343660

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein-protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.


Subject(s)
COVID-19/complications , Cardiovascular Diseases/complications , Computational Biology , Hypertension/complications , Systems Biology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification
14.
Nature ; 595(7867): 426-431, 2021 07.
Article in English | MEDLINE | ID: covidwho-1267998

ABSTRACT

More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals2,5-8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Monoclonal/immunology , B-Lymphocytes/immunology , Enzyme-Linked Immunosorbent Assay , Epitopes/immunology , Female , Humans , Immunologic Memory/immunology , Male , Middle Aged , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Time Factors
15.
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
16.
Nat Cell Biol ; 23(6): 620-630, 2021 06.
Article in English | MEDLINE | ID: covidwho-1263492

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.


Subject(s)
COVID-19/genetics , Epigenesis, Genetic , Epigenomics , Genes, T-Cell Receptor , Immunologic Memory , Lymphocyte Subsets/immunology , Monocytes/immunology , SARS-CoV-2/immunology , Single-Cell Analysis , Adaptive Immunity , Adolescent , Adult , Aged , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , B-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/virology , COVID-19/immunology , COVID-19/metabolism , COVID-19/virology , Case-Control Studies , Cell Differentiation , Chromatin Assembly and Disassembly , Female , Gene Expression Profiling , Host-Pathogen Interactions , Humans , Immunity, Innate , Lymphocyte Subsets/metabolism , Lymphocyte Subsets/virology , Male , Middle Aged , Monocytes/metabolism , Monocytes/virology , SARS-CoV-2/pathogenicity , Young Adult
17.
iScience ; 24(7): 102710, 2021 Jul 23.
Article in English | MEDLINE | ID: covidwho-1263298

ABSTRACT

Lockdowns and stay-at-home orders have partially mitigated the spread of Covid-19. However, en masse mitigation has come with substantial socioeconomic costs. In this paper, we demonstrate how individualized policies based on disease status can reduce transmission risk while minimizing impacts on economic outcomes. We design feedback control policies informed by optimal control solutions to modulate interaction rates of individuals based on the epidemic state. We identify personalized interaction rates such that recovered/immune individuals elevate their interactions and susceptible individuals remain at home before returning to pre-lockdown levels. As we show, feedback control policies can yield similar population-wide infection rates to total shutdown but with significantly lower economic costs and with greater robustness to uncertainty compared to optimal control policies. Our analysis shows that test-driven improvements in isolation efficiency of infectious individuals can inform disease-dependent interaction policies that mitigate transmission while enhancing the return of individuals to pre-pandemic economic activity.

18.
Rheumatol Int ; 41(8): 1429-1440, 2021 08.
Article in English | MEDLINE | ID: covidwho-1263142

ABSTRACT

OBJECTIVE: To assess antibody response to inactivated COVID-19 vaccine in patients with immune-mediated diseases (IMD) among hospital workers and people aged 65 and older. METHODS: In this cross-sectional study, we studied 82 hospital workers with IMD (mean age: 42.2 ± 10.0 years) and 300 (mean age: 41.7 ± 9.9 years) controls. Among + 65 aged population, we studied 22 (mean age: 71.4 ± 4.5 years) patients and 47 controls (mean age: 70.9 ± 4.8 years). All study subjects had a negative history for COVID-19. Sera were obtained after at least 21 days following the second vaccination. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. RESULTS: Patients with IMD were significantly less likely to have detectable antibodies than healthy controls both among the hospital workers (92.7% vs 99.7%, p < 0.001) and elderly population (77.3% vs 97.9%, p = 0.011). Among patients with IMD, those using immunosuppressive or immune-modulating drugs (64/75, 85.3%) were significantly less likely to have detectable antibodies compared to those off treatment (29/29, 100%) (p = 0.029). Additionally, a negative association between age and the antibody titer categories among patients (r = - 0.352; p < 0.001) and controls (r = - 0.258; p < 0.001) were demonstrated. CONCLUSIONS: Among hospital workers, the vast majority of patients with IMD and immunocompetent controls developed a significant humoral response following the administration of the second dose of inactivated COVID-19 vaccine. This was also true for the elderly population, albeit with lower antibody titers. Immunosuppressive use, particularly rituximab significantly reduced antibody titers. Antibody titers were significantly lower among those aged ≥ 60 years both in patient and control populations. Whether these individuals should get a booster dose warrants further studies.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , Immune System Diseases/immunology , Immunity, Humoral , Immunogenicity, Vaccine , Immunoglobulin G/blood , Mass Vaccination , Personnel, Hospital , Adult , Age Factors , Aged , Biomarkers/blood , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Immune System Diseases/blood , Immune System Diseases/diagnosis , Immunization Schedule , Immunocompromised Host , Male , Middle Aged , Time Factors , Turkey , Vaccines, Inactivated/administration & dosage , Young Adult
19.
Int J Vitam Nutr Res ; 92(1): 35-48, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1260925

ABSTRACT

Recently, the outbreak of severe acute respiratory syndrome cornoavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), has become a great perturbation all around the globe and has many devastating effects on every aspect of life. Apart from the oxygen therapy and extracorporeal membrane oxygenation, Remdesivir and Dexamethasone have been proven to be efficacious against COVID-19, along with various vaccine candidates and monoclonal antibody cocktail therapy for Regeneron. All of these are currently at different stages of clinical trials. People with weak immunity are more prone to a severe infection of SARS-CoV-2. Therefore, early and judicious nutritional supplementation along with pharmacological treatment and clinician collaborations are critical in restituting the current situation. Nutritional supplements help in acquiring strong immunity to prevent the progression of disease any further. Vitamin C, vitamin D, selenium, zinc and many other nutritional and dietary supplements inhibit the production of inflammatory cytokines during a viral infection and prevents several unwanted symptoms of infection. Many dietary components like citrus fruits, black elderberry, ginger, and probiotics have the ability to attack viral replication. These supplements can also tame the overriding immune system during coronavirus infection. Keeping in view these facts, nutritional and dietary supplements can be used along with other management modalities. These nutritional and dietary supplements are potential candidates to curb the convulsive unfolding of novel COVID-19, in combination with other standard treatment protocols. In this review, various search engines were used to exploit available literature in order to provide a comprehensive review on nutritional and dietary supplements with respect to the viral infections. It will also provide a brief overview on some of the clinical trials that are in progress to assess the role of nutritional supplements, either alone or in combination with other pharmacological drugs, in fight against COVID-19.


Subject(s)
COVID-19 , Clinical Trials as Topic , Dietary Supplements , Humans , SARS-CoV-2 , Vitamin D , Vitamins
20.
mSphere ; 6(3): e0017021, 2021 06 30.
Article in English | MEDLINE | ID: covidwho-1255525

ABSTRACT

Neutralizing antibodies are key determinants of protection from future infection, yet well-validated high-throughput assays for measuring titers of SARS-CoV-2-neutralizing antibodies are not generally available. Here, we describe the development and validation of IMMUNO-COV v2.0, a scalable surrogate virus assay, which titrates antibodies that block infection of Vero-ACE2 cells by a luciferase-encoding vesicular stomatitis virus displaying SARS-CoV-2 spike glycoproteins (VSV-SARS2-Fluc). Antibody titers, calculated using a standard curve consisting of stepped concentrations of SARS-CoV-2 spike monoclonal antibody, correlated closely (P < 0.0001) with titers obtained from a gold standard 50% plaque-reduction neutralization test (PRNT50%) performed using a clinical isolate of SARS-CoV-2. IMMUNO-COV v2.0 was comprehensively validated using data acquired from 242 assay runs performed over 7 days by five analysts, utilizing two separate virus lots, and 176 blood samples. Assay performance was acceptable for clinical use in human serum and plasma based on parameters including linearity, dynamic range, limit of blank and limit of detection, dilutional linearity and parallelism, precision, clinical agreement, matrix equivalence, clinical specificity and sensitivity, and robustness. Sufficient VSV-SARS2-Fluc virus reagent has been banked to test 5 million clinical samples. Notably, a significant drop in IMMUNO-COV v2.0 neutralizing antibody titers was observed over a 6-month period in people recovered from SARS-CoV-2 infection. Together, our results demonstrate the feasibility and utility of IMMUNO-COV v2.0 for measuring SARS-CoV-2-neutralizing antibodies in vaccinated individuals and those recovering from natural infections. Such monitoring can be used to better understand what levels of neutralizing antibodies are required for protection from SARS-CoV-2 and what booster dosing schedules are needed to sustain vaccine-induced immunity. IMPORTANCE Since its emergence at the end of 2019, SARS-CoV-2, the causative agent of COVID-19, has caused over 100 million infections and 2.4 million deaths worldwide. Recently, countries have begun administering approved COVID-19 vaccines, which elicit strong immune responses and prevent disease in most vaccinated individuals. A key component of the protective immune response is the production of neutralizing antibodies capable of preventing future SARS-CoV-2 infection. Yet, fundamental questions remain regarding the longevity of neutralizing antibody responses following infection or vaccination and the level of neutralizing antibodies required to confer protection. Our work is significant as it describes the development and validation of a scalable clinical assay that measures SARS-CoV-2-neutraling antibody titers. We have critical virus reagent to test over 5 million samples, making our assay well suited for widespread monitoring of SARS-CoV-2-neutralizing antibodies, which can in turn be used to inform vaccine dosing schedules and answer fundamental questions regarding SARS-CoV-2 immunity.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , High-Throughput Screening Assays/methods , Animals , Chlorocebus aethiops , Humans , Limit of Detection , Neutralization Tests/methods , Severity of Illness Index , Vero Cells
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