Implications of Sex Difference in CT Scan Findings and Outcome of                     Patients with COVID-19 Pneumonia

Moradi, Behnaz; Kazemi, Mohammad Ali; Gity, Masoumeh; Hashemi, Hassan; Davari-tanha, Fateme; Chavoshi, Mohammadreza; Rouzrokh, Pouria; Kolahdouzan, Kasra

doi:10.1148/ryct.2020200248

Cited by 22 publications

(17 citation statements)

References 22 publications

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“…Our total lung volume data (without positive pressure) is consistent with prior published data about lung volumes in hamsters [ 21 , 45 ] and thus validates this technique. Moreover, similar to what has been reported in patients with COVID-19 [ 9 , 34 ], male hamsters had worse pulmonary disease compared to females.…”

Section: Discussionsupporting

confidence: 87%

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection

et al. 2021

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Purpose Molecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with 124 I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection. Procedures Pulmonary 124 I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues. Results Infected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals ( P < 0.01). Increased 124 I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary 124 I-iodo-DPA-713 PET activity was noted in male versus female hamsters ( P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues ( P = 0.02). Conclusion 124 I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, 124 I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19. Supplementary Information The online version contains supplementary material available at 10.1007/s11307-021-01638-5.

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Section: Discussionsupporting

confidence: 87%

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection

et al. 2021

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“…1C ). As reported in COVID-19 patients who underwent CT ( 27 , 28 ), there was significantly more disease in the lungs of male hamsters than in female hamsters ( P < 0.05) ( Fig. 1D ).…”

Section: Resultssupporting

confidence: 76%

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model

Dhakal

Ruiz-Bedoya

Zhou

et al. 2021

mBio

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“…Volumes of interest (VOIs) were drawn to capture total and diseased (pneumonic) lung volumes (Figure 1C). As reported in COVID-19 patients who underwent CT (27,28), there was significantly more disease in the lung of male versus female hamsters (p<0.05) (Figure 1D). These results indicate that infected male hamsters developed more severe disease, including more extensive lung injury, than females.…”

Section: Males Experience Greater Morbidity Than Females Following Sars-cov-2 Infection Which Cannot Be Reversed By Estradiol (E2) Treatmsupporting

confidence: 77%

Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model

Dhakal

Ruiz-Bedoya

Zhou

et al. 2021

Preprint

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In the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males compared with females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8-10 weeks of age) were inoculated intranasally with 105 TCID50 of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developing more extensive pneumonia as noted on chest computed tomography, and recovering more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including IFNb and TNFa, were comparable between the sexes. However, during the recovery phase of infection, females mounted two-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole inactivated SARS-CoV-2 and mutant S-RBDs, as well as virus neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2 associated sex differences seen in the human population.

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Implications of Sex Difference in CT Scan Findings and Outcome of Patients with COVID-19 Pneumonia

Cited by 22 publications

References 22 publications

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model

Sex differences in lung imaging and SARS-CoV-2 antibody responses in a COVID-19 golden Syrian hamster model

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