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Viruses ; 14(2)2022 01 24.
Article in English | MEDLINE | ID: covidwho-1650825


We explored the molecular evolution of the spike gene after the administration of anti-spike monoclonal antibodies in patients with mild or moderate forms of COVID-19. Four out of the 13 patients acquired a mutation during follow-up; two mutations (G1204E and E406G) appeared as a mixture without clinical impact, while the Q493R mutation emerged in two patients (one receiving bamlanivimab and one receiving bamlanivimab/etesevimab) with fatal outcomes. Careful virological monitoring of patients treated with mAbs should be performed, especially in immunosuppressed patients.

Antibodies, Monoclonal/therapeutic use , COVID-19/therapy , Evolution, Molecular , Immune Evasion , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/immunology , Drug Combinations , Female , Humans , Immunotherapy/statistics & numerical data , Male , Middle Aged , Spike Glycoprotein, Coronavirus/immunology
J Immunother Cancer ; 9(6)2021 06.
Article in English | MEDLINE | ID: covidwho-1266400


SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.

COVID-19 , Drug Repositioning , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Immunotherapy , COVID-19/epidemiology , COVID-19/immunology , COVID-19/therapy , Comorbidity , Drug Repositioning/methods , Drug Repositioning/statistics & numerical data , HIV Infections/epidemiology , HIV Infections/immunology , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/statistics & numerical data , Humans , Immunocompromised Host/physiology , Immunotherapy/adverse effects , Immunotherapy/methods , Immunotherapy/statistics & numerical data , Mortality , Pandemics , Prognosis , Rheumatic Diseases/epidemiology , SARS-CoV-2/physiology , Transplant Recipients/statistics & numerical data