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1.
Healthcare (Basel) ; 9(11)2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488530

ABSTRACT

Concerns over the coronavirus disease 2019 (COVID-19) pandemic and control measures have affected the routine outpatient visits of individuals with comorbidities and their mental well-being. From October 2019 to August 2020, this cross-sectional study enrolled 135 patients who sought medical attention at a medical center in Taiwan. This period covered the early (October to December 2019), peak (January to April 2020), and late (May to August 2020) periods of the COVID-19 outbreak in Taiwan. The demographic data, social support data, activities of daily living (ADL), resilience scale scores, and mental well-being scale scores of the participants were compared. There were no statistically significant differences in the participation rate, demographic data, and social support data between the three periods. The correlation analysis confirmed significant negative relationships between the number of COVID-19 cases and outpatient department visits per month (r = -0.764, p < 0.001), emergency department visits per month (r = -0.023, p < 0.001), ADL (r = -0.257, p = 0.03), resilience scale (r = -0.390, p < 0.001), and mental well-being scale (r = -0.475, p < 0.001). In conclusion, the severity of the COVID-19 outbreak in Taiwan was associated with declines in the ADL, mental well-being, and resilience of patients who sought medical attention.

2.
Front Nutr ; 8: 649422, 2021.
Article in English | MEDLINE | ID: covidwho-1485085

ABSTRACT

Introduction: As coronavirus Disease 2019 (COVID-19) has evolved into a global pandemic, increasing numbers of reports have linked obesity to more severe COVID-19 illness and death. However, almost all the studies focused on an increased risk of mortality or intensive care unit (ICU) admission among hospitalized obese patients with COVID-19. Is obesity also associated with the incidence of acute lung injury (ALI) in the patients with COVID-19? How about underweight patients? The answer is lacking. Therefore, our following research will answer the above two questions. Methods: We collected and analyzed epidemiologic, demographic, clinical, and laboratory data from 193 confirmed cases of COVID-19 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, between January 1, 2020, and March 13, 2020. They were followed up until April 15, 2020. Underweight was defined by body mass index (BMI) lower than 18.5 kg/m2, normal weight by 18.5-23.9 kg/m2, overweight by 24.0-27.9 kg/m2, and obesity as ≥28 kg/m2. Results: Among these patients, 5.70% were underweight, 58.03% were normal weight, 27.98% were overweight, and 8.29% were obese. Underweight patients were more likely to have a headache (P = 0.029). Obese patients were more likely than other groups to experience a decline in lymphocyte counts (P = 0.038), an increase in C-reactive protein (CRP; P = 0.023), bilateral multiple mottling, and ground glass opacity in the lungs (P = 0.007). Besides, the proportion of patients receiving human immunoglobulin + systematic corticosteroids treatment is the highest among the obese group compared with other BMI groups. After adjusting for potential confounders, underweight patients had a 6.483-fold higher (P = 0.012), and obese patients showed a 5.965-fold higher odds for developing ALI than normal-weight patients (P = 0.022). In addition, underweight patients were 3.255 times more likely than normal-weight patients to develop secondary infections (P = 0.041). Conclusions: Our study showed that both underweight and obese patients with COVID-19 tend to develop ALI compared with normal-weight patients. Underweight patients were more likely to develop a secondary infection than other patients.

5.
J Virol ; 95(17): e0074721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1356909

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase , Interferon-beta , Promoter Regions, Genetic , SARS-CoV-2 , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , HEK293 Cells , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon-beta/antagonists & inhibitors , Interferon-beta/biosynthesis , Interferon-beta/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
6.
J Virol ; 95(17): e0074721, 2021 08 10.
Article in English | MEDLINE | ID: covidwho-1350002

ABSTRACT

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.


Subject(s)
Coronavirus RNA-Dependent RNA Polymerase , Interferon-beta , Promoter Regions, Genetic , SARS-CoV-2 , Coronavirus RNA-Dependent RNA Polymerase/genetics , Coronavirus RNA-Dependent RNA Polymerase/metabolism , HEK293 Cells , Humans , Interferon Regulatory Factor-3/genetics , Interferon Regulatory Factor-3/metabolism , Interferon-beta/antagonists & inhibitors , Interferon-beta/biosynthesis , Interferon-beta/genetics , NF-kappa B/genetics , NF-kappa B/metabolism , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , SARS-CoV-2/genetics , SARS-CoV-2/metabolism
7.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907

ABSTRACT

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Subject(s)
COVID-19/pathology , Lung/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/virology , China , Cohort Studies , Critical Illness , Female , Fibrosis , Hospitalization , Humans , Kidney/pathology , Kidney/virology , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/pathology , Male , Middle Aged , RNA, Viral/metabolism , SARS-CoV-2/genetics , Spleen/pathology , Spleen/virology , Trachea/pathology , Trachea/virology
8.
Microbiol Spectr ; 9(1): e0016921, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1270881

ABSTRACT

Nonstructural protein 1 (Nsp1) of severe acute respiratory syndrome coronaviruses (SARS-CoVs) is an important pathogenic factor that inhibits host protein translation by means of its C terminus. However, its N-terminal function remains elusive. Here, we determined the crystal structure of the N terminus (amino acids [aa] 11 to 125) of SARS-CoV-2 Nsp1 at a 1.25-Å resolution. Further functional assays showed that the N terminus of SARS-CoVs Nsp1 alone loses the ability to colocalize with ribosomes and inhibit protein translation. The C terminus of Nsp1 can colocalize with ribosomes, but its protein translation inhibition ability is significantly weakened. Interestingly, fusing the C terminus of Nsp1 with enhanced green fluorescent protein (EGFP) or other proteins in place of its N terminus restored the protein translation inhibitory ability to a level equivalent to that of full-length Nsp1. Thus, our results suggest that the N terminus of Nsp1 is able to stabilize the binding of the Nsp1 C terminus to ribosomes and act as a nonspecific barrier to block the mRNA channel, thus abrogating host mRNA translation.


Subject(s)
SARS-CoV-2/genetics , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , COVID-19 , Crystallography, X-Ray , HEK293 Cells , Humans , Protein Biosynthesis , Protein Conformation , Protein Domains , RNA, Messenger , Sequence Analysis, Protein , Viral Nonstructural Proteins/metabolism
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