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1.
Clin Infect Dis ; 73(12): 2155-2162, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1592795

ABSTRACT

BACKGROUND: Assessing the duration of immunity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a first priority to gauge the degree of protection following infection. Such knowledge is lacking, especially in the general population. Here, we studied changes in immunoglobulin isotype seropositivity and immunoglobulin G (IgG) binding strength of SARS-CoV-2-specific serum antibodies up to 7 months following onset of symptoms in a nationwide sample. METHODS: Participants from a prospective representative serological study in the Netherlands were included based on IgG seroconversion to the spike S1 protein of SARS-CoV-2 (N = 353), with up to 3 consecutive serum samples per seroconverted participant (N = 738). Immunoglobulin M (IgM), immunoglobulin A (IgA), and IgG antibody concentrations to S1, and increase in IgG avidity in relation to time since onset of disease symptoms, were determined. RESULTS: While SARS-CoV-2-specific IgM and IgA antibodies declined rapidly after the first month after disease onset, specific IgG was still present in 92% (95% confidence interval [CI], 89%-95%) of the participants after 7 months. The estimated 2-fold decrease of IgG antibodies was 158 days (95% CI, 136-189 days). Concentrations were sustained better in persons reporting significant symptoms compared to asymptomatic persons or those with mild upper respiratory complaints only. Similarly, avidity of IgG antibodies for symptomatic persons showed a steeper increase over time compared with persons with mild or no symptoms (P = .022). CONCLUSIONS: SARS-CoV-2-specific IgG antibodies persist and show increasing avidity over time, indicative of underlying immune maturation. These data support development of immune memory against SARS-CoV-2, providing insight into protection of the general unvaccinated part of the population. CLINICAL TRIALS REGISTRATION: NL8473 (the Dutch trial registry).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Netherlands/epidemiology , Prospective Studies
2.
Ann Intern Med ; 174(6): 811-821, 2021 06.
Article in English | MEDLINE | ID: covidwho-1456489

ABSTRACT

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear. LIMITATIONS: Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy. CONCLUSION: Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).


Subject(s)
Antibodies, Viral/blood , Antibody Formation , COVID-19/immunology , Pneumonia, Viral/immunology , SARS-CoV-2/immunology , Antibody Specificity/immunology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Pneumonia, Viral/virology , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
3.
Mol Psychiatry ; 27(1): 34-37, 2022 01.
Article in English | MEDLINE | ID: covidwho-1275900

ABSTRACT

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called "post-COVID syndrome" or "long-COVID" [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.


Subject(s)
Blood Component Removal , COVID-19 , Fatigue Syndrome, Chronic , COVID-19/complications , Fatigue Syndrome, Chronic/diagnosis , Fatigue Syndrome, Chronic/drug therapy , Humans , SARS-CoV-2
4.
Int J Infect Dis ; 109: 17-23, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1267698

ABSTRACT

BACKGROUND: The distribution and nature of symptoms among SARS-CoV-2 infected individuals need to be clarified. METHODS: Between May and August 2020, 11 138 healthcare and administrative personnel from Central Denmark Region were tested for SARS-CoV-2 antibodies and subsequently completed a questionnaire. Symptom prevalence and overall duration for symptoms persisting for more than 30 days were calculated. Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% CIs. RESULTS: In total, 447 (4%) of the participants were SARS-CoV-2-seropositive. Loss of sense of smell and taste was reported by 50% of seropositives compared with 3% of seronegatives. Additionally, seropositives more frequently reported fever, dyspnoea, muscle or joint ache, fatigue, cough, headache and sore throat, and they were more likely to report symptoms persisting for more than 30 days. In adjusted models, they had a higher risk of reporting symptoms, with the strongest association observed for loss of sense of taste and smell (OR = 35.6; 95% CI: 28.6-44.3). CONCLUSION: In this large study, SARS-CoV-2-seropositive participants reported COVID-19-associated symptoms more frequently than those who were seronegative, especially loss of sense of taste and smell. Overall, their symptoms were also more likely to persist for more than 30 days.


Subject(s)
COVID-19 , SARS-CoV-2 , Administrative Personnel , Delivery of Health Care , Denmark/epidemiology , Humans
5.
Front Immunol ; 12: 640093, 2021.
Article in English | MEDLINE | ID: covidwho-1133915

ABSTRACT

COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.


Subject(s)
Antibody-Dependent Enhancement , COVID-19/immunology , Mast Cells/immunology , Middle East Respiratory Syndrome Coronavirus/physiology , Phagocytes/immunology , SARS-CoV-2/physiology , Systemic Inflammatory Response Syndrome/immunology , Animals , Antibodies, Viral/metabolism , COVID-19/transmission , Child , Cross Reactions , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Models, Immunological , Pregnancy , Receptors, Fc/metabolism , Risk , T-Lymphocytes/immunology
6.
Transl Res ; 232: 60-74, 2021 06.
Article in English | MEDLINE | ID: covidwho-1081356

ABSTRACT

COVID-19 patients elicit strong responses to the nucleocapsid (N) protein of SARS-CoV-2 but binding antibodies are also detected in prepandemic individuals, indicating potential crossreactivity with common cold human coronaviruses (HCoV) and questioning its utility in seroprevalence studies. We investigated the immunogenicity of the full-length and shorter fragments of the SARS-CoV-2 N protein, and the crossreactivity of antibodies with HCoV. We identified a C-terminus region in SARS-CoV2 N of minimal sequence homology with HCoV that was more specific for SARS-CoV-2 and highly immunogenic. IgGs to the full-length SARS-CoV-2 N also recognized N229E N, and IgGs to HKU1 N recognized SARS-CoV-2 N. Crossreactivity with SARS-CoV-2 was stronger for alpha- rather than beta-HCoV despite having less sequence identity, revealing the importance of conformational recognition. Higher preexisting IgG to OC43 N correlated with lower IgG to SARS-CoV-2 N in rRT-PCR negative individuals, reflecting less exposure and indicating a potential protective association. Antibodies to SARS-CoV-2 N were higher in patients with more severe and longer duration of symptoms and in females. IgGs remained stable for at least 3 months, while IgAs and IgMs declined faster. In conclusion, N protein is a primary target of SARS-CoV-2-specific and HCoV crossreactive antibodies, both of which may affect the acquisition of immunity to COVID-19.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Cross Reactions , Female , Humans , Immunoglobulin G/immunology , Male , Rhinovirus/immunology , Seroepidemiologic Studies
7.
Eur J Neurol ; 28(10): 3537-3539, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1015539

ABSTRACT

INTRODUCTION: Since the onset of the novel coronavirus pandemic, several neurological complications secondary to SARS-CoV-2 infection have been reported, affecting central nervous system, peripheral nervous system and neuromuscular junction. CASE REPORT: We present the case of a 77-year-old man who developed bulbar myasthenia gravis (MG) eight weeks after SARS-CoV-2 infection. The search for serum antibodies against the acetylcholine receptor and the muscle-specific tyrosine kinase (MuSK), performed by radioimmunoassay (RIA), and the search of low-density lipoprotein receptor-related protein 4 antibodies, performed by immunohistochemistry, resulted negative, while anti-MuSK antibodies were detected by cell-based assay (CBA). The patient was treated with pyridostigmine (60 mg four times a day) with unsatisfactory clinical response, followed by immunosuppressive therapy (azathioprine 1.5 mg/kg/day) with improvement of MG symptoms after two months of treatment. DISCUSSION: Several viral diseases have been described as associated with the onset of MG, although the underlying mechanisms are not yet fully understood. Similarly, a growing number of scientific reports suggest a correlation between SARS-CoV-2 infection and autoimmune diseases. The interest of our case lies in the timing of the MG onset (after 2 months from infection), together with the unusual late onset of anti-MuSK MG. These elements suggest that coronavirus infection may act as a trigger of the disease. We confirm the importance of CBA in the serological diagnosis of RIA-negative MG.


Subject(s)
COVID-19 , Myasthenia Gravis , Aged , Autoantibodies , Humans , Male , Myasthenia Gravis/drug therapy , Receptors, Cholinergic , SARS-CoV-2 , Tyrosine
8.
Arch Dis Child ; 106(7): 680-686, 2021 07.
Article in English | MEDLINE | ID: covidwho-919185

ABSTRACT

BACKGROUND: Studies based on molecular testing of oral/nasal swabs underestimate SARS-CoV-2 infection due to issues with test sensitivity, test timing and selection bias. The objective of this study was to report the presence of SARS-CoV-2 antibodies, consistent with previous infection. DESIGN: This multicentre observational cohort study, conducted between 16 April to 3 July 2020 at 5 UK sites, recruited children of healthcare workers, aged 2-15 years. Participants provided blood samples for SARS-CoV-2 antibody testing and data were gathered regarding unwell contacts and symptoms. RESULTS: 1007 participants were enrolled, and 992 were included in the final analysis. The median age of participants was 10·1 years. There were 68 (6.9%) participants with positive SARS-CoV-2 antibody tests indicative of previous SARS-CoV-2 infection. Of these, 34/68 (50%) reported no symptoms prior to testing. The presence of antibodies and the mean antibody titre was not influenced by age. Following multivariable analysis four independent variables were identified as significantly associated with SARS-CoV-2 seropositivity: known infected household contact OR=10.9 (95% CI 6.1 to 19.6); fatigue OR=16.8 (95% CI 5.5 to 51.9); gastrointestinal symptoms OR=6.6 (95% CI 3.0 to 13.8); and changes in sense of smell or taste OR=10.0 (95% CI 2.4 to 11.4). DISCUSSION: Children demonstrated similar antibody titres in response to SARS-CoV-2 irrespective of age. Fatigue, gastrointestinal symptoms and changes in sense of smell or taste were the symptoms most strongly associated with SARS-CoV-2 antibody positivity. TRIAL REGISTRATION NUMBER: NCT0434740.


Subject(s)
Antibodies, Viral/blood , COVID-19 , Gastrointestinal Diseases , Olfaction Disorders , SARS-CoV-2 , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/methods , COVID-19 Serological Testing/statistics & numerical data , Child , Female , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/virology , Humans , Male , Olfaction Disorders/diagnosis , Olfaction Disorders/virology , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Seroepidemiologic Studies , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , United Kingdom/epidemiology
9.
Pediatr Transplant ; 25(5): e13880, 2021 08.
Article in English | MEDLINE | ID: covidwho-796050

ABSTRACT

We describe the successful pediatric liver transplant for unresectable hepatoblastoma in a 4-year-old male with COVID-19 prior to transplant. The first negative NP swab was documented 1 month after initial diagnosis, when SARS-CoV-2 antibodies were also detected. The patient was actively listed for liver transplant after completing four blocks of a SIOPEL-4 based regimen due to his PRETEXT IV disease which remained unresectable. Following three additional negative NP swabs and resolution of symptoms for 4 weeks, he underwent a whole-organ pediatric liver transplant. COVID-19 positivity determined via NP swab SARS-CoV-2 real-time RT-PCR (Hologic Aptima SARS-CoV-2 RT-PCR assay). IgG and IgM total SARS- CoV-2 antibodies detected by Ortho Clinical Diagnostics VITROS® Immunodiagnostics Products Anti-SARS-CoV-2 Test. Patient received standard prednisone and tacrolimus-based immunosuppression without induction therapy following transplant. Post-transplant course was remarkable for neutropenia and thrombocytopenia, with discharge home on post-transplant day #11. Surveillance tests have remained negative with persistent SARS-CoV-2 IgG antibodies at 6 weeks after transplant. We describe one of the earliest, if not the first case of liver transplant following recent recovery from COVID-19 in a pediatric patient with a lethal malignant liver tumor. A better understanding of how to balance the risk profile of transplant in the setting of COVID-19 with disease progression if transplant is not performed is needed. We followed existing ASTS guidelines to document clearance of the viral infection and resolution of symptoms before transplant. This case highlights that pediatric liver transplantation can be safely performed upon clearance of COVID-19.


Subject(s)
COVID-19/therapy , Hepatoblastoma/surgery , Liver Neoplasms/surgery , Liver Transplantation/methods , COVID-19/complications , COVID-19 Testing , Child, Preschool , Disease Progression , Hepatoblastoma/complications , Humans , Immunoglobulin G , Immunoglobulin M , Immunosuppression Therapy , Immunosuppressive Agents/administration & dosage , Liver Neoplasms/complications , Male , Neutropenia/complications , Prednisone/administration & dosage , Tacrolimus/administration & dosage , Thrombocytopenia/complications , Treatment Outcome
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