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1.
Transplant Direct ; 6(7): e572, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1794966

ABSTRACT

BACKGROUND: The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. METHODS: To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. RESULTS: We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. CONCLUSIONS: These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

2.
Vox Sang ; 117(2): 185-192, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1685455

ABSTRACT

BACKGROUND AND OBJECTIVES: Passive immunization using investigational COVID-19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti-SARS-CoV-2 antibodies. We report the management of a national CCP collection and distribution program in Israel. MATERIALS AND METHODS: From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti-nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut-off (S/CO) level of 4.0. RESULTS: Ninety-six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4-3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. CONCLUSIONS: An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody-rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID-19.


Subject(s)
COVID-19 , Blood Donors , COVID-19/therapy , Humans , Immunization, Passive , Israel , SARS-CoV-2
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.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Immunotherapy, Adoptive , T-Lymphocytes
4.
Transfusion ; 61(1): 17-23, 2021 01.
Article in English | MEDLINE | ID: covidwho-1388418

ABSTRACT

BACKGROUND: The transfer of passive immunity with convalescent plasma is a promising strategy for treatment and prevention of COVID-19, but donors with a history of nonsevere disease are serologically heterogenous. The relationship between SARS-Cov-2 antigen-binding activity and neutralization activity in this population of donors has not been defined. STUDY DESIGN AND METHODS: Convalescent plasma units from 47 individuals with a history of nonsevere COVID-19 were assessed for antigen-binding activity of using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. These results were compared with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. RESULTS: Positive correlations of varying strength (Spearman r = 0.37-0.52) between antigen binding and viral neutralization were identified. Donors age 48 to 75 years had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75%-82%) for those with the highest levels of neutralization. CONCLUSION: The strength of the relationship between antigen-binding activity and neutralization varies depending on the clinical assay used. Units in the highest tertile of binding activity for each assay are predominantly comprised of those with the greatest neutralization activity.


Subject(s)
SARS-CoV-2/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/therapy , COVID-19 Serological Testing , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Passive , Immunoglobulin G/immunology , SARS-CoV-2/pathogenicity , Serologic Tests
6.
Clin Infect Dis ; 73(Suppl 2): S154-S162, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1334204

ABSTRACT

BACKGROUND: Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment. METHODS: An online assessment that included demographic, clinical, and exposure information and a blood sample was collected from 20 614 participants out of ~43 000 total employees at Beaumont Health, which includes 8 hospitals distributed across the Detroit metropolitan area in southeast Michigan. The presence of anti-SARS-CoV-2 IgG was determined using the EUROIMMUN assay. RESULTS: A total of 1818 (8.8%) participants were seropositive between April 13 and May 28, 2020. Among the seropositive individuals, 44% reported that they were asymptomatic during the month prior to blood collection. Healthcare roles such as phlebotomy, respiratory therapy, and nursing/nursing support exhibited significantly higher seropositivity. Among participants reporting direct exposure to a Coronavirus Disease 2019 (COVID-19) positive individual, those wearing an N95/PAPR mask had a significantly lower seropositivity rate (10.2%) compared to surgical/other masks (13.1%) or no mask (17.5%). CONCLUSIONS: Direct contact with COVID-19 patients increased the likelihood of seropositivity among employees but study participants who wore a mask during COVID-19 exposures were less likely to be seropositive. Additionally, a large proportion of seropositive employees self-reported as asymptomatic. (Funded by Beaumont Health and by major donors through the Beaumont Health Foundation). CLINICALTRIALS.GOV NUMBER: NCT04349202.


Subject(s)
COVID-19 , Antibodies, Viral , Health Personnel , Humans , Michigan , SARS-CoV-2
7.
Clin Biochem ; 95: 77-80, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1265657

ABSTRACT

INTRODUCTION: Commercially available serological assays for SARS-CoV-2 detect antibodies to either the nucleocapsid or spike protein. Here we compare the performance of the Beckman-Coulter SARS-CoV-2 spike IgG assay to that of the Abbott SARS-CoV-2 nucleocapsid IgG and Roche Anti-SARS-CoV-2 nucleocapsid total antibody assays. In addition, we document the trend in nucleocapsid and spike antibodies in sequential samples collected from convalescent plasma donors. METHODS: Plasma or serum samples from 20 individual SARS-CoV-2 RT-PCR-positive inpatients (n = 172), 20 individual convalescent donors with a previous RT-PCR-confirmed SARS-CoV-2 infection (n = 20), were deemed positive SARS-CoV-2 samples. RT-PCR-negative inpatients (n = 24), and 109 pre-SARS-CoV-2 samples were determined to be SARS-CoV-2 negative. Samples were assayed by the Abbott, Roche, and Beckman assays. RESULTS: All three assays demonstrated 100% specificity. Abbott, Beckman, and Roche platforms had sensitivities of 98%, 93%, and 90% respectively, with the difference in sensitivity attributed primarily to samples from immunocompromised patients. After the exclusion of samples immunocompromised patients, all assays exhibited ≥ 95% sensitivity. In sequential samples collected from the same individuals, the Roche nucleocapsid antibody assay demonstrated continually increasing signal intensity, with maximal values observed at the last time point examined. In contrast, the Beckman spike IgG antibody signal peaked between 14 and 28 days post positive SARS-CoV-2 PCR and steadily declined in subsequent samples. Subsequent collections 51-200 days (median of 139 days) post positive SARS-CoV-2 RT-PCR from five inpatients and five convalescent donors revealed that spike and nucleocapsid antibodies remained detectable for several months after confirmed infection. CONCLUSIONS: The three assays are sensitive and specific for SARS-CoV-2 antibodies. Nucleocapsid and spike antibodies were detectable for up to 200 days post-positive SARS-CoV-2 PCR but demonstrated markedly different trends in signal intensity.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Nucleocapsid/blood , SARS-CoV-2/metabolism , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , Humans , Immunoassay/methods , Longitudinal Studies , Nucleocapsid/immunology , SARS-CoV-2/isolation & purification
8.
J Clin Invest ; 131(10)2021 05 17.
Article in English | MEDLINE | ID: covidwho-1255762

ABSTRACT

BACKGROUNDRecent studies have reported T cell immunity to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unexposed donors, possibly due to crossrecognition by T cells specific for common cold coronaviruses (CCCs). True T cell crossreactivity, defined as the recognition by a single TCR of more than one distinct peptide-MHC ligand, has never been shown in the context of SARS-CoV-2.METHODSWe used the viral functional expansion of specific T cells (ViraFEST) platform to identify T cell responses crossreactive for the spike (S) glycoproteins of SARS-CoV-2 and CCCs at the T cell receptor (TCR) clonotype level in convalescent COVID-19 patients (CCPs) and SARS-CoV-2-unexposed donors. Confirmation of SARS-CoV-2/CCC crossreactivity and assessments of functional avidity were performed using a TCR cloning and transfection system.RESULTSMemory CD4+ T cell clonotypes that crossrecognized the S proteins of SARS-CoV-2 and at least one other CCC were detected in 65% of CCPs and unexposed donors. Several of these TCRs were shared among multiple donors. Crossreactive T cells demonstrated significantly impaired SARS-CoV-2-specific proliferation in vitro relative to monospecific CD4+ T cells, which was consistent with lower functional avidity of their TCRs for SARS-CoV-2 relative to CCC.CONCLUSIONSOur data confirm, for what we believe is the first time, the existence of unique memory CD4+ T cell clonotypes crossrecognizing SARS-CoV-2 and CCCs. The lower avidity of crossreactive TCRs for SARS-CoV-2 may be the result of antigenic imprinting, such that preexisting CCC-specific memory T cells have reduced expansive capacity upon SARS-CoV-2 infection. Further studies are needed to determine how these crossreactive T cell responses affect clinical outcomes in COVID-19 patients.FUNDINGNIH funding (U54CA260492, P30CA006973, P41EB028239, R01AI153349, R01AI145435-A1, R21AI149760, and U19A1088791) was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the National Institute of Biomedical Imaging and Bioengineering. The Bloomberg~Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University Provost, and The Bill and Melinda Gates Foundation provided funding for this study.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Epitopes, T-Lymphocyte/immunology , Immunologic Memory , Receptors, Antigen, T-Cell/immunology , SARS-CoV-2/immunology , Adult , Aged , Cross Reactions , Female , Humans , Jurkat Cells , Male , Middle Aged
9.
Sci Immunol ; 6(59)2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243688

ABSTRACT

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.


Subject(s)
Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19 Vaccines/immunology , Cell Line , Cross Reactions/immunology , Humans , Immunologic Memory/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
10.
Cell ; 184(13): 3452-3466.e18, 2021 06 24.
Article in English | MEDLINE | ID: covidwho-1240207

ABSTRACT

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection. However, the effects of antibodies against other spike protein domains are largely unknown. Here, we screened a series of anti-spike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner. The antibodies against this infectivity-enhancing site were detected at high levels in severe patients. Moreover, we identified antibodies against the infectivity-enhancing site in uninfected donors, albeit at a lower frequency. These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , COVID-19/immunology , Cell Line , Chlorocebus aethiops , HEK293 Cells , Humans , Protein Binding/immunology , Protein Domains/immunology , Spike Glycoprotein, Coronavirus/genetics , Vero Cells
11.
Trials ; 22(1): 342, 2021 May 17.
Article in English | MEDLINE | ID: covidwho-1232436

ABSTRACT

OBJECTIVES: The general objective of this study is to test the hypothesis that administration of convalescent plasma from donors with previous diagnosis of severe COVID-19 pneumonia is safe and associated with a decrease in all-cause in-hospital mortality among hospitalized patients with COVID-19 at 30 days in comparison with standard treatment alone. The secondary objectives are as follows: (1) to assess the efficacy of convalescent plasma to reduce the length of hospitalization, (2) to assess the efficacy of convalescent plasma to reduce the length of ICU stay, and (3) to assess the efficacy of convalescent plasma on reducing the requirement of invasive mechanical ventilation or ICU stay. TRIAL DESIGN: PERUCONPLASMA is a IIb phase open label, randomized, superiority clinical trial with 1:1 allocation taking place in real life routine clinical practice at public hospitals in Lima, Peru. Participants will be randomized to receive convalescent plasma along with local standard treatment or local standard treatment alone. After allocation, all participants will be followed for a total of 30 days or until hospital discharge, whichever occurs first. PARTICIPANTS: The population for the study are patients with severe disease with a confirmed laboratory test for SARS-CoV-2 infection hospitalized in 3 tertiary-care hospitals in Lima, Peru. Subjects are eligible for the trial if they meet all of the following inclusion criteria: 1. Age 18 or older 2. Hospitalization due to COVID-19 with laboratory confirmation (either with serologic, molecular, or antigen test along with a compatible clinical presentation) 3. Severe or critical COVID-19 disease Severe illness was defined by 2 or more of the following: Respiratory rate of 22 or more Hypoxemia with oxygen saturation equal or less than 93% Abnormal blood gas analysis (PaO2 < 60 mmHg, PaCO2 > 50 mmHg, or Pa/FiO2 < 300) Critical disease was defined by either: Mechanical ventilation requirement less than 72 h. Shock. 4. Capacity to provide informed consent (patient or patient's direct relative) 5. Availability of convalescent plasma units compatible with ABO blood type of the subject. EXCLUSION CRITERIA: Subjects are not eligible for the trial if they meet any of the following criteria: 1. Contraindication for transfusion (e.g., prior anaphylaxis, congestive heart failure) 2. Hemodynamic instability (PA < 60 mmHg refractory to vasopressors) 3. Uncontrolled concomitant infections\ 4. Stupor or coma 5. Platelets < 50,000/µL or disseminated intravascular coagulation 6. Serum creatinine > 3.5 mg/dL or dialysis requirement 7. Total bilirubin > 6 mg/dL or jaundice of unknown etiology 8. Myocardial infarction or acute coronary syndrome 9. Active or recent (< 7 days) intracranial hemorrhage 10. Pregnancy Donors: The donors have to meet the following criteria: male between 30 and 60 years with a previous diagnosis of severe COVID-19-associated pneumonia within the last 3 months, with resolution of symptoms of at least 28 days. The rationale for including donors with severe disease is to maximize the probability of collecting convalescent plasma units with high titer of neutralizing antibodies, as the technology to measure this specific type of antibodies is not routinely available in Peru. Aliquots of plasma will be stored for future quantification of neutralizing antibodies. INTERVENTION AND COMPARATOR: Convalescent plasma from donors with previous severe COVID-19 is the investigational medical product. The experimental group will receive 1 to 2 units of 200 to 250 ml of convalescent plasma along with local standard treatment. The control group will receive local standard treatment alone. The participants randomized to plasma will have evaluations at 6 h and 24 h to specifically evaluate possible post transfusion events. All the participants will be evaluated at day 3, day 7, and day 30 after enrolment. MAIN OUTCOMES: Safety outcome: Incidence of serious adverse reactions related to convalescent plasma transfusion within 24 h after convalescent plasma administration. Efficacy outcomes: Mortality from any cause during hospitalization at 30 days post randomization. Length of hospitalization at 30 days post randomization or until hospital discharge. Duration of mechanical ventilation at 30 days post randomization or until hospital discharge. Length of hospitalization in an intensive care unit at 30 days post randomization or until hospital discharge. Exploratory: Oxygen requirement evolution at days 3 and 7. Score Sequential Organ Failure Assessment (SOFA) evolution at days 3 and 7. Dynamics of inflammatory marker (lymphocyte, C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH)) evolution at days 3 and 7. Proportion of patients progressing to multi-organ failure at 30 days post randomization or until hospital discharge. Proportion of transfusion related adverse reactions at 30 days post randomization or until hospital discharge. RANDOMIZATION: Randomization will be carried out within the electronic case report form (eCRF) in 1:1 ratio (receive plasma/control) in a randomization process established by blocks of size 2, 4, and 6. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomization process. Randomization blocks will be performed with "ralloc", Stata's randomization process v.16.0. Randomization through the eCRF will be available 24 h every day. BLINDING (MASKING): Both the participants and study staff will be aware of the allocated intervention. Blinded statistical analysis will be performed. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The sample size was calculated using the Fleiss formula with continuity correction to detect a mortality reduction from 50 to 20% between the two treatment arms with a confidence level of 95% and a power of 80%. Based on this information, a total of 45 patients per arm would be needed. After adjustment for a drop-out rate of 10% after enrolment, a total of 50 patients per arm (100 patients in total) will be enrolled. TRIAL STATUS: Current protocol version: 5.0 dated January 04, 2021. Recruitment started on September 21, 2020, and is expected to finish by the end of March 2021. TRIAL REGISTRATION: Peruvian Register of Clinical Trials (REPEC) ID: PER-016-20, registered on June 27, 2020. Clinicaltrials.gov ID: NCT04497324 , registered on August 4, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19 , Adolescent , Blood Component Transfusion , COVID-19/therapy , Humans , Immunization, Passive , Male , Peru , Plasma , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
12.
Vopr Virusol ; 66(2): 152-161, 2021 05 15.
Article in Russian | MEDLINE | ID: covidwho-1229649

ABSTRACT

INTRODUCTION: Immunodeficiency underlying the development of severe forms of new coronavirus infection may be the result of mixed infection with SARS-CoV-2 and other pathogens, including Epstein-Barr virus (EBV).The aim is to study the prevalence and epidemiological features of co-infection with SARS-CoV-2 and EBV. MATERIAL AND METHODS: A cross-sectional randomized study was conducted in Moscow region from March to May 2020. Two groups were examined for EBV-markers: hospital patients (n = 95) treated for SARS-CoV-2 infection and blood donors (n = 92). RESULTS: With equal EBV prevalence the detection of active infection markers in donors (10.9%) was noticeably lower than in SARS-CoV-2 patients (80%). Significant differences in this indicator were also found when patients from subgroups with interstitial pneumonia with the presence (96.6%) and absence (97.2%) of SARS-CoV-2 in the nasopharyngeal smear were compared with the subgroup of patients with mild COVID-19 (43.3%). The average IgG VCA and IgG EBNA positivity coefficients in donor group were higher than in patient group (p < 0.05). Patients with active EBV infection markers were significantly more likely to have pneumonia, exceeding the reference values of ALT and the relative number of monocytes (odds ratio - 23.6; 3.5; 9.7, respectively). DISCUSSION: The present study examined the incidence and analyzed epidemiological features of active EBV infection in patients with COVID-19. CONCLUSION: A significantly higher rate of detection of active EBV infection markers in hospital patients indicates a combined participation SARS-CoV-2 and EBV in the development of interstitial pneumonia. Low levels of specific IgG EBV serve as predictors of EBV reactivation. Exceeding the reference values of ALT and the relative number of monocytes in patients should serve as a reason for examination for active EBV infection markers.


Subject(s)
COVID-19/metabolism , Epstein-Barr Virus Infections/metabolism , Herpesvirus 4, Human/metabolism , SARS-CoV-2/metabolism , Virus Activation , Adolescent , Adult , COVID-19/epidemiology , COVID-19/pathology , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/pathology , Female , Humans , Male , Middle Aged
13.
Transplantation ; 105(1): 206-211, 2021 01 01.
Article in English | MEDLINE | ID: covidwho-1226601

ABSTRACT

BACKGROUND: There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined. METHODS: We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury. RESULTS: Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype. CONCLUSIONS: In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.


Subject(s)
Apolipoprotein L1/genetics , COVID-19/complications , Glomerulosclerosis, Focal Segmental/etiology , Kidney Transplantation/adverse effects , SARS-CoV-2 , Tissue Donors , Humans , Kidney/pathology , Male , Middle Aged
14.
Clin Epidemiol Glob Health ; 11: 100763, 2021.
Article in English | MEDLINE | ID: covidwho-1225163

ABSTRACT

BACKGROUND: Recent evidence suggested that the higher titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody from convalescent plasma donors contributed to the clinical improvement in coronavirus disease 2019 (COVID-19) patients. However, the titers of anti-SARS-CoV-2 antibodies varied in each individual, and the precise factors that might govern such variation have not been elucidated. OBJECTIVES: To assess the factors associated with high titers of anti-SARS-CoV-2 antibody among COVID-19 convalescent plasma (CCP) donors. METHODS: A cross-sectional study was conducted in Saiful Anwar General Hospital, Malang, Indonesia. Information of interest including demographic characteristics, clinical symptoms, comorbidities, laboratory findings, and the titers of anti-SARS-CoV-2 antibody among COVID-19 CCP donors were collected. The correlation was assessed using multiple logistic regression. RESULTS: A total of 50 COVID-19 CCP donors with the titers of anti-SARS-CoV-2 antibody of more than 1:320 and 33 donors with the titers of less than 1:320 were analyzed. Our analysis revealed that CCP donors with history of cough, fever, dyspnea, and pneumonia significantly had higher titers of anti-SARS-CoV-2 antibody compared to asymptomatic donors. Moreover, CCP donors with elevated levels of eosinophils and immature granulocytes and low levels of albumins had higher levels of anti-SARS-CoV-2 antibody. The titer of antibody was not affected by comorbidities of donors. CONCLUSIONS: CPP donors who had experience of symptomatic COVID-19 with high eosinophils level, high immature granulocytes and low albumin level have higher titers of anti-SARS-COV-2 antibody than those who experienced asymptomatic COVID-19. Our current findings may be used as the additional baseline criteria for selecting the donors of CCP for the management of COVID-19.

15.
Nat Cell Biol ; 23(5): 538-551, 2021 05.
Article in English | MEDLINE | ID: covidwho-1223094

ABSTRACT

COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a+ DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c+ DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence.


Subject(s)
Antigen Presentation/genetics , Antigen Presentation/immunology , Antigens, Viral/immunology , Antiviral Agents/immunology , COVID-19/blood , COVID-19/immunology , Dendritic Cells/immunology , Humans , Monocytes/immunology , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods
16.
PLoS One ; 16(4): e0249938, 2021.
Article in English | MEDLINE | ID: covidwho-1206195

ABSTRACT

This study compared the performance of four serology assays for Coronavirus Disease 2019 (COVID-19) and investigated whether COVID-19 disease history correlates with assay performance. Samples were tested at Northshore using the Elecsys Anti-SARS-CoV-2 (Roche Diagnostics), Access SARS-CoV-2 IgG anti-RBD (Beckman Coulter), and LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin) as well as at Genalyte using Maverick Multi-Antigen Serology Panel. The study included one hundred clinical samples collected before December 2019 and ninety-seven samples collected from convalescent plasma donors originally diagnosed with COVID-19 by PCR. COVID-19 disease history was self-reported by the plasma donors. There was no difference in specificity between the assays tested. Clinical sensitivity of these four tests was 98% (Genalyte), 96% (Roche), 92% (DiaSorin), and 87% (Beckman). The only statistically significant differences in clinical sensitivity was between the Beckman assay and both Genalyte and Roche assays. Convalescent plasma donor characteristics and disease symptoms did not correlate with false negative results from the Beckman and DiaSorin assays. All four tests showed high specificity (100%) and varying sensitivities (89-98%). No correlations between disease history and serology results were observed. The Genalyte Multiplex assay showed as good or better sensitivity to three other previously validated assays with FDA Emergency Use Authorizations.


Subject(s)
COVID-19/immunology , COVID-19/therapy , SARS-CoV-2/immunology , Adult , Aged , Antibodies, Viral/immunology , Female , Humans , Immunization, Passive/methods , Immunoglobulin G/immunology , Male , Middle Aged , Plasma/chemistry , Plasma/immunology , SARS-CoV-2/pathogenicity , Sensitivity and Specificity , Serologic Tests/methods
17.
Front Immunol ; 12: 636768, 2021.
Article in English | MEDLINE | ID: covidwho-1156122

ABSTRACT

Understanding the causes of the diverse outcome of COVID-19 pandemic in different geographical locations is important for the worldwide vaccine implementation and pandemic control responses. We analyzed 42 unexposed healthy donors and 28 mild COVID-19 subjects up to 5 months from the recovery for SARS-CoV-2 specific immunological memory. Using HLA class II predicted peptide megapools, we identified SARS-CoV-2 cross-reactive CD4+ T cells in around 66% of the unexposed individuals. Moreover, we found detectable immune memory in mild COVID-19 patients several months after recovery in the crucial arms of protective adaptive immunity; CD4+ T cells and B cells, with a minimal contribution from CD8+ T cells. Interestingly, the persistent immune memory in COVID-19 patients is predominantly targeted towards the Spike glycoprotein of the SARS-CoV-2. This study provides the evidence of both high magnitude pre-existing and persistent immune memory in Indian population. By providing the knowledge on cellular immune responses to SARS-CoV-2, our work has implication for the development and implementation of vaccines against COVID-19.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , COVID-19/immunology , Immunologic Memory , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , B-Lymphocytes/virology , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/virology , COVID-19/blood , COVID-19/diagnosis , COVID-19/virology , Case-Control Studies , Female , Humans , Immunity, Cellular , Male , Middle Aged , Time Factors , Young Adult
18.
Transpl Infect Dis ; 23(4): e13600, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1138250

ABSTRACT

INTRODUCTION: Hospital do Rim is a high-volume kidney transplant (KT) center located in São Paulo, a city with 12.2 million inhabitants. Over the last 18 years, we performed 11 436 KT, 70% of which from deceased donors. To mitigate the effects of reduction in the number of transplants on the waiting list, sequential measures were implemented when COVID-19 was declared pandemic. METHODS: The first step was to provide SARS-COV-2 RT-PCR testing for all symptomatic employees and patients and the compulsory use of personal protective equipment in the hospital facilities. Living donor KT were postponed, and all deceased donors and recipients were tested before the transplantation. The immunosuppressive protocols were maintained, and telehealth strategies were developed. RESULTS: Among the 1013 employees, there were 214 cases of COVID-19, nine required ward hospitalization, and no deaths occurred. In 26%, the probable source of contamination was occupational. From the first patient diagnosed with COVID-19 in 03/20/2020 till 10/21/2020, 523 deceased KT were performed, a 21% increase compared with 2019, with no confirmed donor-derived SARS-CoV-2 infection. Four patients were transplanted with a positive pretransplant SARS-CoV-2 test, but none of them developed the disease. Overall, of 11 875 KT followed in our center, 674 developed COVID-19. Among the hospitalized, 53% required mechanical ventilation, and 45% required hemodialysis. Their overall mortality rate was 27.5%. CONCLUSION: This experience shows the challenges that transplant centers faced as the pandemic unfolded and illustrates the effectiveness of the sequential measures implemented to provide a safe environment for transplantation.


Subject(s)
COVID-19 , Kidney Transplantation , Brazil , Humans , Kidney Transplantation/adverse effects , Pandemics , SARS-CoV-2
19.
J Clin Invest ; 131(3)2021 02 01.
Article in English | MEDLINE | ID: covidwho-1124908

ABSTRACT

BACKGROUNDSARS-CoV-2-specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2-neutralizing antibodies (nAbs) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood.METHODSPotential convalescent plasma donors with virologically documented SARS-CoV-2 infection were tested for serum IgG against SARS-CoV-2 spike protein S1 domain and against nucleoprotein (NP), and for nAb.RESULTSAmong 250 consecutive persons, including 27 (11%) requiring hospitalization, who were studied a median of 67 days since symptom onset, 97% were seropositive on 1 or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titers included older age (adjusted OR [AOR] 1.03 per year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. nAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range 77-120) apart (P < 0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses.CONCLUSIONnAb titers correlated with COVID-19 severity, age, and sex. SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels declined, and a small proportion of convalescent individuals lacked adaptive immune responses.FUNDINGThe project was supported by the Frederick National Laboratory for Cancer Research with support from the NIAID under contract number 75N91019D00024, and was supported by the Fred Hutchinson Joel Meyers Endowment, Fast-Grants, a New Investigator award from the American Society for Transplantation and Cellular Therapy, and NIH contracts 75N93019C0063, 75N91019D00024, and HHSN272201800013C, and NIH grants T32-AI118690, T32-AI007044, K08-AI119142, and K23-AI140918.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Blood Donors , COVID-19/therapy , Immunoglobulin G , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunization, Passive , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
20.
Commun Biol ; 4(1): 267, 2021 02 24.
Article in English | MEDLINE | ID: covidwho-1101684

ABSTRACT

Millions of individuals who have recovered from SARS-CoV-2 infection may be eligible to participate in convalescent plasma donor programs, yet the optimal window for donating high neutralizing titer convalescent plasma for COVID-19 immunotherapy remains unknown. Here we studied the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers (VN) in 175 convalescent donors longitudinally sampled for up to 142 days post onset of symptoms (DPO). We observed robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 that persist, in the aggregate, for at least 100 DPO. However, there is a notable decline in VN titers ≥160 for convalescent plasma therapy, starting 60 DPO. The results also show that individuals 30 years of age or younger have significantly lower VN, IgG and IgM antibody titers than those in the older age groups; and individuals with greater disease severity also have significantly higher IgM and IgG antibody titers. Taken together, these findings define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Donors , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Age Factors , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/therapy , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Longitudinal Studies , Male , Middle Aged , Severity of Illness Index , Time Factors , Young Adult
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