ABSTRACT
OBJECTIVES: To evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness. PATIENTS AND METHODS: We evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients). RESULTS: The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log10 copies/mL before administration to 4.3 log10 copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients. CONCLUSION: Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological , COVID-19 , Evolution, Molecular , SARS-CoV-2/genetics , Viral Load , Antibodies, Monoclonal, Humanized , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral , Antineoplastic Agents, Immunological/therapeutic use , COVID-19/therapy , Humans , Mutation , Quasispecies , Selection, GeneticABSTRACT
(1) Background: COVID-19 has become a global pandemic and older patients present higher mortality rates. However, studies on the characteristics of this population set are limited. The objective of this study is to describe clinical characteristics and outcomes of older patients hospitalized with COVID-19. (2) Methods: This retrospective cohort study was conducted from March to May 2020 and took place in three acute geriatric wards in France. Older patients hospitalized for COVID-19 infections were included. We collected clinical, radiological, and laboratory outcomes. (3) Results: Ninety-four patients were hospitalized and included in the final analysis. Mean age was 85.5 years and 55% were female. Sixty-four (68%) patients were confirmed COVID-19 cases and 30 (32%) were probable. A majority of patients were dependent (77%), 45% were malnourished, and the mean number of comorbidities was high in accordance with the CIRS-G score (12.3 ± 25.6). The leading causes of hospitalization were fever (30%), dyspnea (28%), and geriatric syndromes (falls, delirium, malaise) (18%). Upon follow-up, 32% presented acute respiratory failure and 30% a geriatric complication. Frailty and geriatric characteristics were not correlated with mortality. Acute respiratory failure (p = 0.03) and lymphopenia (p = 0.02) were significantly associated with mortality. (4) Conclusions: Among older patients hospitalized with COVID-19, clinical presentations were frequently atypical and complications occurred frequently. Frailty and geriatric characteristics were not correlated with mortality.
ABSTRACT
(1) Background: COVID-19 has become a global pandemic and older patients present higher mortality rates. However, studies on the characteristics of this population set are limited. The objective of this study is to describe clinical characteristics and outcomes of older patients hospitalized with COVID-19. (2) Methods: This retrospective cohort study was conducted from March to May 2020 and took place in three acute geriatric wards in France. Older patients hospitalized for COVID-19 infections were included. We collected clinical, radiological, and laboratory outcomes. (3) Results: Ninety-four patients were hospitalized and included in the final analysis. Mean age was 85.5 years and 55% were female. Sixty-four (68%) patients were confirmed COVID-19 cases and 30 (32%) were probable. A majority of patients were dependent (77%), 45% were malnourished, and the mean number of comorbidities was high in accordance with the CIRS-G score (12.3 ±25.6). The leading causes of hospitalization were fever (30%), dyspnea (28%), and geriatric syndromes (falls, delirium, malaise) (18%). Upon follow-up, 32% presented acute respiratory failure and 30% a geriatric complication. Frailty and geriatric characteristics were not correlated with mortality. Acute respiratory failure (p = 0.03) and lymphopenia (p = 0.02) were significantly associated with mortality. (4) Conclusions: Among older patients hospitalized with COVID-19, clinical presentations were frequently atypical and complications occurred frequently. Frailty and geriatric characteristics were not correlated with mortality.