RESUMO
Patients who died from COVID-19 often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV-2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples from patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. Our systems biology approach offers a possible explanation for increased COVID-19 severity in patients with certain comorbidities.
Assuntos
Infecções por Coronavirus/epidemiologia , Pulmão/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Enzima de Conversão de Angiotensina 2 , COVID-19 , Estudos de Casos e Controles , Transtornos Cerebrovasculares/epidemiologia , Transtornos Cerebrovasculares/genética , Comorbidade , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/genética , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/genética , Epigenômica , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/genética , Masculino , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/enzimologia , Pneumonia Viral/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Índice de Gravidade de Doença , Biologia de Sistemas , TranscriptomaRESUMO
The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.
