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1.
Preprint in English | EuropePMC | ID: ppcovidwho-294053

ABSTRACT

The cardiovascular complications of acute COVID-19 are well described;however, a comprehensive characterization of the post-acute cardiovascular manifestations of COVID-19 at one year has not been undertaken. Here we use the US Department of Veterans Affairs national healthcare databases to build a cohort of 151,195 people with COVID-19, 3,670,087 contemporary and 3,656,337 historical controls to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that beyond the first 30 days of infection, people with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disease. The risks and burdens were evident among those who were non-hospitalized during the acute phase of the infection and increased in a graded fashion according to care setting of the acute infection (non-hospitalized, hospitalized, and admitted to intensive care). Taken together, our results provide evidence that risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of people who survived the acute episode of COVID-19 should include attention to cardiovascular health and disease.

2.
Preprint in English | EuropePMC | ID: ppcovidwho-292486

ABSTRACT

The post-acute sequelae of COVID-19 have been described 1 , but whether breakthrough COVID-19 (that is the disease that ensues following vaccine breakthrough SARS-CoV-2 infection) results in post-acute sequelae is not yet clear. Here we use the national healthcare databases of the US Department of Veterans Affairs to characterize 6-month risks of incident post-acute sequelae in people with breakthrough COVID-19 who survived for at least 30 days after diagnosis. We show that compared to people with no evidence of COVID-19, beyond the first 30 days of illness, people with breakthrough COVID-19 exhibit a higher risk of death and broad array of incident post-acute sequelae in the pulmonary system, as well as extrapulmonary sequelae that include cardiovascular disorders, coagulation disorders, gastrointestinal disorders, general disorders (e.g., fatigue), kidney disorders, mental health disorders, metabolic disorders, musculoskeletal disorders, and neurologic disorders. Our analyses by care setting of the acute phase of the disease show that people who were not hospitalized during the first 30 days after diagnosis with breakthrough COVID-19 exhibit a small but not insignificant increase in risk of death and post-acute sequelae;the risks are further increased in people who were hospitalized during the acute phase of the disease. Our comparative approach shows that people with breakthrough COVID-19 exhibit lower risks of death and post-acute sequelae than people with COVID-19 who were not previously vaccinated for it;and in analyses among individuals who were hospitalized during the acute phase of the disease, people with breakthrough COVID-19 exhibit higher risks of death and post-acute sequelae than people with seasonal influenza. Altogether, our findings show increased risks of death and post-acute sequalae in people with breakthrough COVID-19;the risks are evident among those who were not hospitalized during the acute phase of the disease. Our comparative approach provides context for understanding the risks in relation to COVID-19 without prior vaccination and seasonal influenza. The findings will inform the ongoing effort to optimize strategies for prevention of breakthrough SARS-CoV-2 infections and will guide development and optimization of post-acute care pathways for people with breakthrough COVID-19.

3.
Nat Commun ; 12(1): 6571, 2021 11 12.
Article in English | MEDLINE | ID: covidwho-1514413

ABSTRACT

The Post-Acute Sequelae of SARS-CoV-2 infection (PASC) have been characterized; however, the burden of PASC remains unknown. Here we used the healthcare databases of the US Department of Veterans Affairs to build a cohort of 181,384 people with COVID-19 and 4,397,509 non-infected controls and estimated that burden of PASC-defined as the presence of at least one sequela in excess of non-infected controls-was 73.43 (72.10, 74.72) per 1000 persons at 6 months. Burdens of individual sequelae varied by demographic groups (age, race, and sex) but were consistently higher in people with poorer baseline health and in those with more severe acute infection. In sum, the burden of PASC is substantial; PASC is non-monolithic with sequelae that are differentially expressed in various population groups. Collectively, our results may be useful in informing health systems capacity planning and care strategies of people with PASC.

4.
J Am Soc Nephrol ; 32(11): 2851-2862, 2021 11.
Article in English | MEDLINE | ID: covidwho-1394649

ABSTRACT

BACKGROUND: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. METHODS: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. RESULTS: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. CONCLUSIONS: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.


Subject(s)
COVID-19/complications , Kidney Diseases/epidemiology , Kidney Diseases/virology , Veterans/statistics & numerical data , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Cohort Studies , Critical Care , Female , Glomerular Filtration Rate , Hospitalization , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , United States
6.
BMJ Open ; 11(8): e047369, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1360561

ABSTRACT

OBJECTIVES: To investigate the temporal trends of 30-day mortality and hospitalisation in US Veterans with COVID-19 and 30-day mortality in hospitalised veterans with COVID-19 and to decompose the contribution of changes in the underlying characteristics of affected populations to these temporal changes. DESIGN: Observational cohort study. SETTING: US Department of Veterans Affairs. PARTICIPANTS: 49 238 US veterans with a positive COVID-19 test between 20 March 2020 and 19 September 2020; and 9428 US veterans hospitalised with a positive COVID-19 test during the same period. OUTCOME MEASURES: 30-day mortality rate and hospitalisation rate. RESULTS: Between 20 March 2020 and 19 September 2020 and in COVID-19 positive individuals, 30-day mortality rate dropped by 9.2% from 13.6% to 4.4%; hospitalisation rate dropped by 16.8% from 33.8% to 17.0%. In hospitalised COVID-19 individuals, 30-day mortality rate dropped by 12.7% from 23.5% to 10.8%. Among COVID-19 positive individuals, decomposition analyses suggested that changes in demographic, health and contextual characteristics, COVID-19 testing capacity, and hospital occupancy rates accounted for 40.2% and 33.3% of the decline in 30-day mortality and hospitalisation, respectively. Changes in the underlying characteristics of hospitalised COVID-19 individuals accounted for 29.9% of the decline in 30-day mortality. CONCLUSION: Between March and September 2020, changes in demographic and health characteristics of people infected with COVID-19 contributed measurably to the substantial decline in 30-day mortality and hospitalisation.


Subject(s)
COVID-19 , Veterans , COVID-19 Testing , Cohort Studies , Hospitalization , Humans , SARS-CoV-2 , United States/epidemiology
7.
Nature ; 594(7862): 259-264, 2021 06.
Article in English | MEDLINE | ID: covidwho-1275936

ABSTRACT

The acute clinical manifestations of COVID-19 have been well characterized1,2, but the post-acute sequelae of this disease have not been comprehensively described. Here we use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequelae-including diagnoses, medication use and laboratory abnormalities-in patients with COVID-19 who survived for at least 30 days after diagnosis. We show that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Our high-dimensional approach identifies incident sequelae in the respiratory system, as well as several other sequelae that include nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain and anaemia. We show increased incident use of several therapeutic agents-including pain medications (opioids and non-opioids) as well as antidepressant, anxiolytic, antihypertensive and oral hypoglycaemic agents-as well as evidence of laboratory abnormalities in several organ systems. Our analysis of an array of prespecified outcomes reveals a risk gradient that increases according to the severity of the acute COVID-19 infection (that is, whether patients were not hospitalized, hospitalized or admitted to intensive care). Our findings show that a substantial burden of health loss that spans pulmonary and several extrapulmonary organ systems is experienced by patients who survive after the acute phase of COVID-19. These results will help to inform health system planning and the development of multidisciplinary care strategies to reduce chronic health loss among individuals with COVID-19.


Subject(s)
COVID-19/complications , SARS-CoV-2/pathogenicity , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/physiopathology , COVID-19/psychology , Cohort Studies , Databases, Factual , Datasets as Topic , Electronic Health Records , Female , Hospitalization/statistics & numerical data , Humans , Influenza, Human/diagnosis , Influenza, Human/drug therapy , Influenza, Human/physiopathology , Male , Outpatients/psychology , Outpatients/statistics & numerical data , Risk , Time Factors , United States , United States Department of Veterans Affairs
8.
Front Public Health ; 9: 671400, 2021.
Article in English | MEDLINE | ID: covidwho-1256411

ABSTRACT

The prevalence and related factors of mental health impact among medical staffs who experienced the second wave of the COVID-19 pandemic in China is unknown. Therefore, this survey was conducted to investigate the prevalence and related factors of depressive, anxiety, acute stress, and insomnia symptoms in medical staffs in Kashi, Xinjiang, China during the second wave of the COVID-19 pandemic. A cross-sectional online survey was conducted among medical staffs working in First People's Hospital of Kashi, Xinjiang. The questionnaire collected demographic data and self-design questions related to the COVID-19 pandemic. The Impact of Events Scale-6, the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder Scale-7, the Perceived Social Support Scale, the Chinese Big Five Personality Inventory-15, and the Trait Coping Style Questionnaire were used to measure psychological symptoms or characteristics. Binary logistic regression was carried out to examine the associations between socio-demographic factors and symptoms of depression, anxiety, stress, and insomnia. In total, data from 123 participants were finally included, among which the prevalence rate of depressive, anxiety, acute stress, and insomnia symptoms is 60.2, 49.6, 43.1, and 41.1%, respectively. The regression model revealed that minority ethnicity, being worried about infection, spending more time on following pandemic information, and neurotic personality were positively associated with the mental health symptoms, while extraversion personality, higher education level, and better social support were negatively associated. In our study, the prevalence of mental health impact was high among medical staffs in Kashi, China who experienced the second wave of the COVID-19 pandemic. Several factors were found to be associated with mental health conditions. These findings could help identify medical staffs at risk for mental health problems and be helpful for making precise mental health intervention policies during the resurgence. Our study may pave way for more research into Xinjiang during the COVID-19 pandemic.


Subject(s)
COVID-19 , Sleep Initiation and Maintenance Disorders , Anxiety/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Medical Staff , Pandemics , Prevalence , SARS-CoV-2 , Sleep Initiation and Maintenance Disorders/epidemiology
9.
Environ Int ; 154: 106564, 2021 09.
Article in English | MEDLINE | ID: covidwho-1174221

ABSTRACT

BACKGROUND: Ecologic analyses suggest that living in areas with higher levels of ambient fine particulate matter air pollution (PM2.5) is associated with higher risk of adverse COVID-19 outcomes. Studies accounting for individual-level health characteristics are lacking. METHODS: We leveraged the breadth and depth of the US Department of Veterans Affairs national healthcare databases and built a national cohort of 169,102 COVID-19 positive United States Veterans, enrolled between March 2, 2020 and January 31, 2021, and followed them through February 15, 2021. Annual average 2018 PM2.5 exposure, at an approximately 1 km2 resolution, was linked with residential street address at the year prior to COVID-19 positive test. COVID-19 hospitalization was defined as first hospital admission between 7 days prior to, and 15 days after, the first COVID-19 positive date. Adjusted Poisson regression assessed the association of PM2.5 with risk of hospitalization. RESULTS: There were 25,422 (15.0%) hospitalizations; 5,448 (11.9%), 5,056 (13.0%), 7,159 (16.1%), and 7,759 (19.4%) were in the lowest to highest PM2.5 quartile, respectively. In models adjusted for State, demographic and behavioral factors, contextual characteristics, and characteristics of the pandemic a one interquartile range increase in PM2.5 (1.9 µg/m3) was associated with a 10% (95% CI: 8%-12%) increase in risk of hospitalization. The association of PM2.5 and risk of hospitalization among COVID-19 individuals was present in each wave of the pandemic. Models of non-linear exposure-response suggested increased risk at PM2.5 concentrations below the national standard 12 µg/m3. Formal effect modification analyses suggested higher risk of hospitalization associated with PM2.5 in Black people compared to White people (p = 0.045), and in those living in socioeconomically disadvantaged neighborhoods (p < 0.001). CONCLUSIONS: Exposure to higher levels of PM2.5 was associated with increased risk of hospitalization among COVID-19 infected individuals. The risk was evident at PM2.5 levels below the regulatory standards. The analysis identified those of Black race and those living in disadvantaged neighborhoods as population groups that may be more susceptible to the untoward effect of PM2.5 on risk of hospitalization in the setting of COVID-19.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Cohort Studies , Environmental Exposure/analysis , Hospitalization , Humans , Particulate Matter/adverse effects , Particulate Matter/analysis , SARS-CoV-2 , United States/epidemiology
10.
World Allergy Organ J ; 14(3): 100521, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1078226

ABSTRACT

Objectives: A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is causing the worldwide coronavirus disease 2019 (COVID-19) outbreak with high mortality. A unique finding among COVID-19 patients was a decline of eosinophil levels (eosinopenia). However, results from previous studies on the relationship between eosinopenia and disease severity were inconsistent. The objective of this study is to determine the relationship between eosinopenia and COVID-19 mortality as well as the clinical conditions that could potentially lead to mortality. Methods: One hundred ninety patients diagnosed as moderate, severe, or critical COVID-19 at hospital admission were enrolled. Data collected from patients' medical records on the second day after hospital admission included medical histories, clinical symptoms, chest images of computed tomography (CT), laboratory examinations, and outcomes. Results: Eosinophil levels were significantly lower in patients with critical disease, when compared to those with moderate and severe diseases. After controlled for confounding factors, ie, age, gender, hypertension, coronary heart disease, diabetes, and chronic lung disease, a progressive decline of eosinophil levels was independently associated with mortality. Moreover, eosinophil levels significantly and positively correlated with platelet and D-dimer levels but significantly and inversely correlated with serum levels of urea, creatinine, aspartate aminotransferase, lactate dehydrogenase, and creatine kinase. Conclusions: Eosinopenia, if progressively worsening, indicates that COVID-19 patients may progress to critical disease and have a significantly higher chance of mortality. Additionally, eosinopenia correlates with biomarkers of coagulation disorder and those of tissue damage in kidney, liver, and other tissues.

12.
Clin J Am Soc Nephrol ; 16(1): 14-25, 2020 12 31.
Article in English | MEDLINE | ID: covidwho-926261

ABSTRACT

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with higher risk of AKI. We aimed to describe rates and characterize predictors and health outcomes associated with AKI in a national cohort of US veterans hospitalized with COVID-19. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cohort of 5216 US veterans hospitalized with COVID-19 identified through July 23, 2020, we described changes in serum creatinine and examined predictors of AKI and the associations between AKI, health resource utilization, and death, utilizing logistic regressions. We characterized geographic and temporal variations in AKI rates and estimated variance explained by key variables utilizing Poisson regressions. RESULTS: In total, 1655 (32%) participants had AKI; 961 (58%), 223 (13%), and 270 (16%) met Kidney Disease Improving Global Outcomes definitions of stage 1, 2, and 3 AKI, respectively, and 201 (12%) received KRT. Eight percent of participants had AKI within 1 day of hospitalization, and 47% did not recover to baseline serum creatinine by discharge. Older age, Black race, male gender, obesity, diabetes, hypertension, and lower eGFR were significant predictors of AKI during hospitalization with COVID-19. AKI was associated with higher mechanical ventilation use (odds ratio, 6.46; 95% confidence interval, 5.52 to 7.57) and longer hospital stay (5.56 additional days; 95% confidence interval, 4.78 to 6.34). AKI was also associated with higher risk of death (odds ratio, 6.71; 95% confidence interval, 5.62 to 8.04); this association was stronger in Blacks (P value of interaction <0.001). Hospital-level rates of AKI exhibited substantial geographic variability, ranging from 10% to 56%. Between March and July 2020, AKI rates declined from 40% to 27%; proportions of AKI stage 3 and AKI requiring KRT decreased from 44% to 17%. Both geographic and temporal variabilities were predominately explained by percentages of Blacks (31% and 49%, respectively). CONCLUSIONS: AKI is common during hospitalization with COVID-19 and associated with higher risk of health care resource utilization and death. Nearly half of patients with AKI did not recover to baseline by discharge. Substantial geographic variation and temporal decline in rates and severity of AKI were observed. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_16_CJN09610620_final.mp3.


Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , African Americans/statistics & numerical data , COVID-19/epidemiology , Acute Kidney Injury/physiopathology , Acute Kidney Injury/therapy , Age Factors , Aged , Comorbidity , Creatinine/blood , Diabetes Mellitus/epidemiology , Female , Glomerular Filtration Rate , Humans , Hypertension/epidemiology , Length of Stay/statistics & numerical data , Male , Middle Aged , Obesity/epidemiology , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Risk Factors , SARS-CoV-2 , Sex Factors , Spatio-Temporal Analysis , Survival Rate , United States/epidemiology , Veterans/statistics & numerical data
14.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2287-2290, 2020 May.
Article in Chinese | MEDLINE | ID: covidwho-398792

ABSTRACT

High-quality clinical study on traditional Chinese medicine is of great significance to effectively control new public health emergencies represented by outbreaks of infectious diseases and ensure people's health and safety, but it still faces a series of ethical issues. Based on the seven core values of equity, good deeds, effectiveness, respect for individuals, freedom, reciprocity, and solida-rity proposed in the Guidelines for Management of Ethical Issues in Outbreaks of Infectious Diseases, this article emphasizes the characteristics and laws of clinical studies on traditional Chinese medicine. Main points of ethical review of traditional Chinese medicine were summarized in the aspects of overall concept, syndrome differentiation and treatment, prevention before disease onset, cultural value, and clinical basis. Based on the outbreak of coronavirus disease 2019(COVID-19), we collected relevant registered Chinese medicine clinical studies, summarized the core issues of the ethics review for COVID-19, and further improved the traditional Chinese medicine ethics review system and resources, so as to better serve ethical review and scientific studies in public health emergencies.


Subject(s)
Betacoronavirus , Coronavirus Infections , Ethical Review , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral , COVID-19 , Emergencies , Humans , Public Health , SARS-CoV-2
15.
Zhongguo Zhong Yao Za Zhi ; 45(10): 2291-2295, 2020 May.
Article in Chinese | MEDLINE | ID: covidwho-381585

ABSTRACT

2019 novel coronavirus(2019-nCoV) has occurred for 2 months, and seriously affected the people's health in the world. Therefore, scientific prevention and control strategies and effective intervention measures are the only ways to solve the world problem. In the determination of intervention measures, not only the effectiveness evaluation, but also accessibility, treatment cost, inventory and production capacity and other relevant sociological issues shall be considered, especially in low and middle-income countries and regions. With the introduction of clinical epidemiological experiment design and evidence-based medicine evidence evaluation into the evaluation of curative effect of traditional Chinese medicine(TCM), TCM has officially entered the studies of syndrome regularity of new public health emergencies(such as SARS and influenza) clearly diagnosed by modern medicine for many years, as well as the development of relevant guidelines, consensus and paths. The results of curative effect show that TCM could significantly alleviate symptoms, control disease and tendency, reduce the occurrence of critical illness, and improve the clinical efficacy and the prognosis and quality of life of patients, which fully reflects the consciousness and self-confidence of traditional Chinese medicine workers. For the evidence-based evaluation of TCM intervention in new public health emergencies, the basic principles and general methods of clinical epidemiology and evidence-based medicine shall be followed to obtain high-quality evidence; besides, we shall also fully realize that clinical scientific study is carried out with the epidemic treatment as the primary task. The scientific hypothesis comes from the clinical problems unsolved. The scientific study conclusions aim to give feedbacks to clinical diagnosis and treatment regimens. The core elements of clinical trials are population(P), intervention(I), control(C), outcome(O), which are abbreviated as "PICO". The evaluation of intervention measures for new public health emergencies with traditional Chinese medicine shall have clear study objectives and a high quality, with a correct analysis method as the guarantee of real and reliable results. Then, the selection of patients, the de-finition of intervention measures and control measures, the development of end-point indicators, the clinical quality control under special epidemics, the data verification, and the data analysis methods to be adopted are all characteristics and key points that need special consideration. It is suggested that scientific experimental design, rigorous collection and scientific data analysis shall be conducted to reflect the therapeutic value of traditional Chinese medicine, so that the study results could be adopted and shared, and become the scientific evidence for China and even the global to republish the diagnosis and treatment regimens.


Subject(s)
Betacoronavirus , Coronavirus Infections , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Pandemics , Pneumonia, Viral , COVID-19 , China , Emergencies , Evidence-Based Medicine , Humans , Public Health , Quality of Life , SARS-CoV-2
16.
iScience ; 23(6): 101160, 2020 Jun 26.
Article in English | MEDLINE | ID: covidwho-245505

ABSTRACT

The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a cofactor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidylpeptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those that are bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.

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