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1.
Cell Host Microbe ; 28(4): 499-501, 2020 10 07.
Article in English | MEDLINE | ID: covidwho-838112

ABSTRACT

In this issue of Cell Host & Microbe, Nielsen and colleagues sequence antibody repertoires of patients with severe COVID-19 to reveal potentially convergent features on the background of a larger, polyclonal response. Their findings suggest that, as databases improve, it may be possible to monitor virus-specific B cells after infection or vaccination using antibody sequencing.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome , Antibodies, Viral , Antibody Formation , B-Lymphocytes , Betacoronavirus , Humans , Immunoglobulin G
2.
J Infect Dis ; 222(8): 1265-1269, 2020 09 14.
Article in English | MEDLINE | ID: covidwho-811305

ABSTRACT

We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Antibodies, Viral/blood , Antibody Formation , Betacoronavirus/isolation & purification , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Neutralization Tests , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Severity of Illness Index
3.
Evid Based Dent ; 21(3): 82-83, 2020 09.
Article in English | MEDLINE | ID: covidwho-796120

ABSTRACT

Basic health and infection control measures are the main methods of protection against COVID-19. Patients are well informed about how practitioners should be conducting themselves, however, they may lose trust in clinicians who fail to demonstrate, and promote those same basic prevention measures. The broader COVID-19 strategy has included the rapid development and deployment of swabs and antibody tests. Flaws in testing fail to offer assurances due to false negatives while even true positives cannot guarantee future immunity as there is uncertainty regarding long-term antibody response. An understanding of human factors and an appreciation of the limitations of available tests could offer healthcare staff mechanisms to encourage safety.


Subject(s)
Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections , Pandemics , Pneumonia, Viral/epidemiology , Antibody Formation , Coronavirus Infections/diagnosis , Humans
4.
Adv Rheumatol ; 60(1): 50, 2020 09 22.
Article in English | MEDLINE | ID: covidwho-781570

ABSTRACT

The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Pneumonia, Viral/immunology , Respiratory Distress Syndrome, Adult/immunology , Age Factors , Animals , Antibody Formation , Betacoronavirus/pathogenicity , Blood Coagulation Disorders/etiology , Comorbidity , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Humans , Immunity, Innate , Inflammation/immunology , Lung/pathology , Lymphopenia/immunology , Mice , Middle East Respiratory Syndrome Coronavirus/immunology , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Risk Factors , Severe Acute Respiratory Syndrome/immunology , Severity of Illness Index , Sex Factors , Virus Internalization
7.
Tidsskr Nor Laegeforen ; 140(11)2020 08 18.
Article in English, Norwegian | MEDLINE | ID: covidwho-724631

ABSTRACT

BACKGROUND: Robust serological assays for SARS-CoV-2 are essential for determining prior infection and the suitability of donated convalescent plasma for plasma therapy. We compared two in-house and three commercial serological assays in a family cohort with SARS-CoV-2-infected members. CASE PRESENTATION: Three individuals in a family of five developed COVID-19 confirmed by PCR, following a trip abroad. Three to four weeks after the onset of symptoms, three commercial ELISAs and an in-house immunofluorescence test demonstrated antibodies to SARS-CoV-2. An in-house neutralisation test also demonstrated neutralising antibodies. INTERPRETATION: The in-house assays and one commercial assay gave congruent results, which were also consistent with the initial PCR and/or clinical evaluation, indicating prior infection in three of the five family members. The other commercial assays indicated possible infection in a fourth family member, but this result was likely due to cross-reactivity. The neutralising antibodies suggest complete or partial immunity against reinfection.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Antibodies, Neutralizing/immunology , Betacoronavirus , Enzyme-Linked Immunosorbent Assay , Family Health , Fluorescent Antibody Technique , Humans , Neutralization Tests , Pandemics , Serologic Tests
8.
EBioMedicine ; 59: 102940, 2020 09.
Article in English | MEDLINE | ID: covidwho-714054
10.
Endocrinology ; 161(9)2020 09 01.
Article in English | MEDLINE | ID: covidwho-690822

ABSTRACT

Severe outcomes and death from the novel coronavirus disease 2019 (COVID-19) appear to be characterized by an exaggerated immune response with hypercytokinemia leading to inflammatory infiltration of the lungs and acute respiratory distress syndrome. Risk of severe COVID-19 outcomes is consistently lower in women than men worldwide, suggesting that female biological sex is instrumental in protection. This mini-review discusses the immunomodulatory and anti-inflammatory actions of high physiological concentrations of the steroids 17ß-estradiol (E2) and progesterone (P4). We review how E2 and P4 favor a state of decreased innate immune inflammatory response while enhancing immune tolerance and antibody production. We discuss how the combination of E2 and P4 may improve the immune dysregulation that leads to the COVID-19 cytokine storm. It is intended to stimulate novel consideration of the biological forces that are protective in women compared to men, and to therapeutically harness these factors to mitigate COVID-19 morbidity and mortality.


Subject(s)
Coronavirus Infections/immunology , Estradiol/immunology , Immunomodulation/immunology , Pneumonia, Viral/immunology , Progesterone/immunology , Antibody Formation/immunology , Betacoronavirus , Contraceptives, Oral, Hormonal/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Drug Repositioning , Estradiol/therapeutic use , Estrogen Replacement Therapy , Estrogens/therapeutic use , Female , Humans , Immune Tolerance/immunology , Immunity, Innate/immunology , Male , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Pneumonia, Viral/physiopathology , Pregnancy , Pregnancy Complications, Infectious/immunology , Progesterone/therapeutic use , Progestins/therapeutic use , Selective Estrogen Receptor Modulators/therapeutic use , Severity of Illness Index , Sex Factors
11.
J Infect Dis ; 222(8): 1265-1269, 2020 09 14.
Article in English | MEDLINE | ID: covidwho-684599

ABSTRACT

We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Antibodies, Viral/blood , Antibody Formation , Betacoronavirus/isolation & purification , Cohort Studies , Coronavirus Infections/blood , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Neutralization Tests , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Severity of Illness Index
12.
Sci Transl Med ; 12(555)2020 08 05.
Article in English | MEDLINE | ID: covidwho-655207

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is having a deleterious impact on health services and the global economy, highlighting the urgent need for an effective vaccine. Such a vaccine would need to rapidly confer protection after one or two doses and would need to be manufactured using components suitable for scale up. Here, we developed an Alphavirus-derived replicon RNA vaccine candidate, repRNA-CoV2S, encoding the SARS-CoV-2 spike (S) protein. The RNA replicons were formulated with lipid inorganic nanoparticles (LIONs) that were designed to enhance vaccine stability, delivery, and immunogenicity. We show that a single intramuscular injection of the LION/repRNA-CoV2S vaccine in mice elicited robust production of anti-SARS-CoV-2 S protein IgG antibody isotypes indicative of a type 1 T helper cell response. A prime/boost regimen induced potent T cell responses in mice including antigen-specific responses in the lung and spleen. Prime-only immunization of aged (17 months old) mice induced smaller immune responses compared to young mice, but this difference was abrogated by booster immunization. In nonhuman primates, prime-only immunization in one intramuscular injection site or prime/boost immunizations in five intramuscular injection sites elicited modest T cell responses and robust antibody responses. The antibody responses persisted for at least 70 days and neutralized SARS-CoV-2 at titers comparable to those in human serum samples collected from individuals convalescing from COVID-19. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection against SARS-CoV-2 infection.


Subject(s)
Alphavirus/genetics , Antibodies, Neutralizing/immunology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , RNA, Viral/genetics , Replicon/genetics , T-Lymphocytes/immunology , Viral Vaccines/immunology , Animals , Antibody Formation/immunology , Coronavirus Infections/prevention & control , Inorganic Chemicals/chemistry , Lipids/chemistry , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nanoparticles/chemistry , Pandemics , Primates
13.
Science ; 369(6507): 1119-1123, 2020 08 28.
Article in English | MEDLINE | ID: covidwho-654485

ABSTRACT

Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti-SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53-neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)-binding site. This binding mode limits the IGHV3-53 antibodies to short complementarity-determining region H3 loops but accommodates light-chain diversity. These IGHV3-53 antibodies show minimal affinity maturation and high potency, which is promising for vaccine design. Knowledge of these structural motifs and binding mode should facilitate the design of antigens that elicit this type of neutralizing response.


Subject(s)
Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Antibody Formation , Betacoronavirus/immunology , Complementarity Determining Regions/chemistry , Coronavirus Infections/prevention & control , Immunoglobulin Heavy Chains/chemistry , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Binding Sites , Complementarity Determining Regions/genetics , Complementarity Determining Regions/immunology , Coronavirus Infections/genetics , Coronavirus Infections/immunology , Crystallography, X-Ray , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Pneumonia, Viral/immunology , Protein Domains , Viral Vaccines/chemistry , Viral Vaccines/genetics , Viral Vaccines/immunology
14.
Rev Col Bras Cir ; 47: e20202634, 2020.
Article in Portuguese, English | MEDLINE | ID: covidwho-646964

ABSTRACT

SARS-CoV-2 is a novel virus which has proven to be highly contagious. Specific viral dynamics and immune response to the virus are yet to be fully defined and determining the sensitivity and specificity of the available testing methods is still a work in progress. This study examines the published information on the testing methods, and finds that yield of COVID-19 tests changes with specimen types and with time through course of illness. We propose a sequential battery of testing consisting of an epidemiologic survey, RT-PCR tests, serologic tests and chest CT on surgical candidates which may increase the negative predictive value, and facilitate surgical procedures.


Subject(s)
Coronavirus Infections/diagnosis , Elective Surgical Procedures , Pneumonia, Viral/diagnosis , Antibody Formation , Betacoronavirus , Clinical Laboratory Techniques , Coronavirus Infections/immunology , Humans , Pandemics , Pneumonia, Viral/immunology , Predictive Value of Tests , Virus Shedding
15.
Am J Clin Pathol ; 154(4): 459-465, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-646825

ABSTRACT

OBJECTIVES: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)-based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method. RESULTS: All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. CONCLUSIONS: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population.


Subject(s)
Antibodies, Viral/blood , Betacoronavirus/immunology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Immunoglobulin G/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Severity of Illness Index , Antibody Formation , Biomarkers/blood , Case-Control Studies , Coronavirus Infections/blood , Cross Reactions , Cross-Sectional Studies , Humans , Immunoglobulin M/blood , Pandemics , Pneumonia, Viral/blood , Sensitivity and Specificity
16.
BMC Infect Dis ; 20(1): 500, 2020 Jul 11.
Article in English | MEDLINE | ID: covidwho-640102

ABSTRACT

BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Adult , Antibody Formation , Antiviral Agents/therapeutic use , B-Lymphocytes/immunology , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Hospitals , Humans , Immunity, Humoral , Indoles/therapeutic use , Male , Nucleotidyltransferases/genetics , Pandemics , Patient Discharge , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Recurrence , Ventilators, Mechanical
19.
J Clin Invest ; 130(10): 5112-5114, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-635709

ABSTRACT

Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and the antibody responses of 23 individuals with COVID-19 experiencing mild and severe disease. The researchers found that (a) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset, (b) SARS-CoV-2 persisted longer in those with severe disease, and (c) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome , Antibodies, Viral , Antibody Formation , Betacoronavirus , Coronavirus Infections/therapy , Humans , Immunization, Passive , Kinetics , Viral Load
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