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1.
Clin Infect Dis ; 73(6): e1397-e1401, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1412539

ABSTRACT

Recent case studies have highlighted the fact that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intrahost viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of this risk, the duration of infectiousness, and optimal treatment and prevention strategies in immunocompromised hosts are ill defined. Of additional concern is the widespread use of immunosuppressive medications to treat COVID-19, which may enhance and prolong viral replication in the context of immunodeficiency. We outline the rationale for 4 interrelated approaches to usher in an era of evidence-based medicine for optimal management of immunocompromised patients with COVID-19: multicenter pathogenesis and outcomes studies to relate the risk of severe disease to the type and degree of immunodeficiency, studies to evaluate immunologic responses to SARS-CoV-2 vaccines, studies to evaluate the efficacy of monoclonal antibodies for primary prophylaxis, and clinical trials of novel antiviral agents for the treatment of COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , COVID-19 Vaccines , Humans , Immunocompromised Host , SARS-CoV-2
2.
Transbound Emerg Dis ; 69(3): 1596-1605, 2022 May.
Article in English | MEDLINE | ID: covidwho-1388405

ABSTRACT

Knowledge of the level and duration of protective immunity against SARS-CoV-2 after primary infection is of crucial importance for preventive approaches. Currently, there is a lack of evidence on the persistence of specific antibodies. We investigated the generation and maintenance of neutralizing antibodies of convalescent SARS-CoV-2-afflicted patients over a ten-month period post-primary infection using an immunofluorescence assay, a commercial chemiluminescent immunoassay and an in-house enzyme-linked neutralization assay. We present the successful application of an improved version of the plaque-reduction neutralization assay which can be analysed optometrically to simplify data interpretation. Based on the results of the enzyme-linked neutralization assay, neutralizing antibodies were maintained in 77.4% of convalescent individuals without relevant decay over ten months. Furthermore, a positive correlation between severity of infection and antibody titre was observed. In conclusion, SARS-CoV-2-afflicted individuals have been proven to be able to develop and maintain neutralizing antibodies over a period of ten months after primary infection. Findings suggest long-lasting presumably protective humoral immune responses after wild-type infection.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/veterinary , Immunity, Humoral
3.
Clin Infect Dis ; 73(6): e1397-e1401, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1216639

ABSTRACT

Recent case studies have highlighted the fact that certain immunocompromised individuals are at risk for prolonged SARS-CoV-2 replication, intrahost viral evolution of multiply-mutated variants, and poor clinical outcomes. The immunologic determinants of this risk, the duration of infectiousness, and optimal treatment and prevention strategies in immunocompromised hosts are ill defined. Of additional concern is the widespread use of immunosuppressive medications to treat COVID-19, which may enhance and prolong viral replication in the context of immunodeficiency. We outline the rationale for 4 interrelated approaches to usher in an era of evidence-based medicine for optimal management of immunocompromised patients with COVID-19: multicenter pathogenesis and outcomes studies to relate the risk of severe disease to the type and degree of immunodeficiency, studies to evaluate immunologic responses to SARS-CoV-2 vaccines, studies to evaluate the efficacy of monoclonal antibodies for primary prophylaxis, and clinical trials of novel antiviral agents for the treatment of COVID-19.


Subject(s)
COVID-19 , Antiviral Agents/therapeutic use , COVID-19 Vaccines , Humans , Immunocompromised Host , SARS-CoV-2
4.
Cell Rep Med ; 2(4): 100228, 2021 04 20.
Article in English | MEDLINE | ID: covidwho-1195472

ABSTRACT

Considerable concerns relating to the duration of protective immunity against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) exist, with evidence of antibody titers declining rapidly after infection and reports of reinfection. Here, we monitor the antibody responses against SARS-CoV-2 receptor-binding domain (RBD) for up to 6 months after infection. While antibody titers are maintained, ∼13% of the cohort's neutralizing responses return to background. However, encouragingly, in a selected subset of 13 participants, 12 have detectable RBD-specific memory B cells and these generally are increasing out to 6 months. Furthermore, we are able to generate monoclonal antibodies with SARS-CoV-2 neutralizing capacity from these memory B cells. Overall, our study suggests that the loss of neutralizing antibodies in plasma may be countered by the maintenance of neutralizing capacity in the memory B cell repertoire.


Subject(s)
Antibodies, Neutralizing/blood , COVID-19/pathology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/immunology , Asymptomatic Diseases , COVID-19/immunology , COVID-19/virology , Female , Humans , Limit of Detection , Male , Middle Aged , Neutralization Tests , Protein Domains/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Time Factors , Young Adult
6.
J Perinatol ; 41(5): 952-960, 2021 05.
Article in English | MEDLINE | ID: covidwho-1111968

ABSTRACT

OBJECTIVE: The influence of previous viral symptoms on the level and duration of human milk antibodies reactive to SARS-CoV-2, and common human coronaviruses (HCoVs) was investigated. STUDY DESIGN: Antibodies reactive to S1 and S2 subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E were measured via ELISA in human milk samples collected from March to June 2020 in mothers with and without viral symptoms. RESULTS: The presence of viral symptoms influenced the levels of SARS-CoV-2 S2-reactive SIgA/IgA and tended to influence SARS-CoV-2 S1 SIgA/IgA and S2-reactive SIgM/IgM in human milk but did not relate to IgG. HCoV-229E S1 + S2-reactive SIgA/IgA and SIgM/IgM, as well as HCoV-OC43 S1 + S2-reactive IgG were related to the symptoms. The duration of antibody levels in human milk in mothers with viral symptoms varied between 3 and 4 months post maternal report of viral symptoms. CONCLUSION: Previous viral symptoms and individual mothers may change the antibody cross-reactive levels to SARS-CoV-2 and HCoVs in human milk.


Subject(s)
Antibodies, Viral/analysis , COVID-19/immunology , Milk, Human/chemistry , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Adult , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Coronavirus 229E, Human/immunology , Coronavirus OC43, Human/immunology , Cross Reactions/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin Isotypes/blood , Immunoglobulin Isotypes/immunology , Young Adult
7.
Nat Commun ; 12(1): 897, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1075219

ABSTRACT

The dynamics, duration, and nature of immunity produced during SARS-CoV-2 infection are still unclear. Here, we longitudinally measured virus-neutralising antibody, specific antibodies against the spike (S) protein, receptor-binding domain (RBD), and the nucleoprotein (N) of SARS-CoV-2, as well as T cell responses, in 25 SARS-CoV-2-infected patients up to 121 days post-symptom onset (PSO). All patients seroconvert for IgG against N, S, or RBD, as well as IgM against RBD, and produce neutralising antibodies (NAb) by 14 days PSO, with the peak levels attained by 15-30 days PSO. Anti-SARS-CoV-2 IgG and NAb remain detectable and relatively stable 3-4 months PSO, whereas IgM antibody rapidly decay. Approximately 65% of patients have detectable SARS-CoV-2-specific CD4+ or CD8+ T cell responses 3-4 months PSO. Our results thus provide critical evidence that IgG, NAb, and T cell responses persist in the majority of patients for at least 3-4 months after infection.


Subject(s)
Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/physiology , T-Lymphocytes/immunology , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Immunologic Memory , Interferon-gamma/metabolism , Kinetics , Leukocyte Common Antigens/metabolism , Male , Middle Aged , Phenotype , Receptors, CCR7/metabolism
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