Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution.

The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution, we show that the ACE can be selectively inhibited by ACE2 to prevent cleavage of angiotensin I, even when the concentration of ACE is more than 30-fold higher than that of ACE2. We also show that the activity of ACE2 for cleaving angiotensin peptides is clearly suppressed by the spike protein of SARS-CoV-2. This leads to the relaxation of ACE and the increased probability of accumulation of the principal effector angiotensin II. The spike protein of the SARS-CoV-2 Delta variant is demonstrated to have a much greater impact on the crosstalk than the wild type.

Impacts of the COVID-19 Pandemic on Anxiety and Depressive Symptoms in Pregnant Women and Related Perinatal Outcomes.

To evaluate the impacts of the COVID-19 pandemic on anxiety and depression symptoms in pregnant women and their relationship with pregnancy outcomes, 1087 pregnant women completed online questionnaires. Anxiety symptoms were measured using the Self-Rating Anxiety Scale (SAS). Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS), and the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Univariate analysis and logistic regression analysis were used to determine the association between depression and anxiety symptoms, participants' characteristics, and pregnancy outcomes. Of the 986 pregnant women who were included in this study, the rates of anxiety symptoms and depressive tendencies were 13.4% and 18.3%, respectively. Sleep disorder ((Adjusted odds ratio, AOR = 4.166; 95% confidence interval, CI: 2.797−6.205), time spent paying attention to the epidemic per day (≥1 h/d AOR = 1.568; 95% CI: 1.052−2.338), and the time spent with their spouses (Increase AOR = 0.629; 95% CI: 0.409−0.967) were associated with the risk of anxiety. Sleep disorder (AOR = 3.839; 95% CI: 2.718−5.432) and educational level (bachelor's degree or above AOR = 1.833; 95% CI: 1.004−3.345) were associated with the risk of depression. Psychological status was not correlated with the pregnancy outcomes (p > 0.05). Anxiety and depression symptoms were common among pregnant women during the COVID-19 pandemic. Special attention should be paid to manage their risk factors.

Diagnostic value of determination of plasma CRP, PCT and IL-6 levels in patients with COVID-19

The article's objective was to assess the clinical diagnostic utility of plasma levels of CRP, PCT, and IL-6 in individuals with COVID-19 both alone and in combination. Results showed that according to the ROC curve, PCT and CRP were highly valuable in the diagnosis of COVID-19, and CRP was most valuable in the evaluation of patients with severe and critical COVID-19. The combined detection of the three indexes might increase the evaluation's effectiveness. When evaluating COVID-19 patients who were in severe condition, IL-6 demonstrated a strong predictive value. Therefore, combining the three indicators may increase the diagnostic efficiency and provide crucial reference values for the clinical diagnosis and treatment of COVID-19. CRP, PCT, and IL-6 levels may be potential biomarkers for the diagnosis of COVID-19 and can be used to determine the severity of COVID-19.

SARS-CoV-2 Antibody Seroprevalence in Wuhan, China, from 23 April to 24 May 2020.

The outbreak of coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019. To investigate the prevalence of COVID-19 in Wuhan, we conducted serologic tests on 35,326 individuals from four different communities to estimate cumulative incidence of infection. Our results showed that 1,332 individuals (3.77%) showed positive COVID-19 antibody (either IgM or IgG). Males had a lower positivity rate than females (3.02% versus 4.52%). The antibody positivity rates showed a clear trend of increase according to patients' ages and varied among different communities. The results indicate that public health interventions may play important roles in the control of COVID-19.IMPORTANCE Coronavirus disease 2019 (COVID-19) was first detected in December 2019 in Wuhan, China. Afterwards, a number of public health interventions were implemented, including lock-down, face mask ordinances, and social distancing. Studies that rely on viral RNA testing of symptomatic patients have shown that these multifaceted interventions contributed to the control of the COVID-19 outbreak in Wuhan and delayed the epidemic's progression. However, these estimates of confirmed cases may miss large numbers of asymptomatic patients and recovered symptomatic patients who were not tested. To investigate the prevalence of COVID-19 in Wuhan, we conducted serologic tests on 35,326 individuals to estimate the cumulative incidence of infection. The results suggest that public health interventions may play important roles in the control of COVID-19.

Issue Cover

The cover image is based on the Original Article Clinical characteristics of COVID‐19 patients with hepatitis B virus infection — a retrospective study by Rui Liu et al., https://doi.org/10.1111/liv.14774.

Clinical characteristics of COVID-19 patients with hepatitis B virus infection - a retrospective study.

BACKGROUND & AIMS: The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic. Although COVID-19 is caused by infection in the respiratory tract, extrapulmonary manifestations including dysregulation of the immune system and hepatic injury have been observed. Given the high prevalence of hepatitis B virus (HBV) infection in China, we sought to study the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HBV coinfection in patients. METHODS: Blood samples of 50 SARS-CoV-2 and HBV coinfected patients, 56 SARS-CoV-2 mono-infected patients, 57 HBeAg-negative chronic HBV patient controls and 57 healthy controls admitted to Renmin Hospital of Wuhan University were collected in this study. Complete blood count and serum biochemistry panels including markers indicative of liver functions were performed. Cytokines including IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 were evaluated. T cell, B cell and NK cell counts were measured using flow cytometry. RESULTS: SARS-CoV-2 and HBV coinfection did not significantly affect the outcome of the COVID-19. However, at the onset of COVID-19, SARS-CoV-2 and HBV coinfected patients showed more severe monocytopenia and thrombocytopenia as well as more disturbed hepatic function in albumin production and lipid metabolism. Most of the disarrangement could be reversed after recovery from COVID-19. CONCLUSIONS: While chronic HBV infection did not predispose COVID-19 patients to more severe outcomes, our data suggest SARS-CoV-2 and HBV coinfection poses a higher extent of dysregulation of host functions at the onset of COVID-19. Thus, caution needs to be taken with the management of SARS-CoV-2 and HBV coinfected patients.

Descriptive, Retrospective Study of the Clinical Characteristics of Asymptomatic COVID-19 Patients.

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread around the world. Persons with asymptomatic disease exhibit viral shedding, resulting in transmission, which presents disease control challenges. However, the clinical characteristics of these asymptomatic individuals remain elusive. We collected samples of 25 asymptomatic and 27 symptomatic COVID-19 patients. Viral titers of throat swabs were determined by quantitative reverse transcription-PCR (qRT-PCR). COVID-19 IgG and IgM were examined. Complete blood counts were determined, and serum biochemistry panels were performed. Cytokines, including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), IL-4, IL-6, and IL-10 were evaluated. T cell, B cell, and NK cell counts were measured using flow cytometry. Although similar viral loads were detected, asymptomatic patients had significantly faster virus turnover than symptomatic patients. Additionally, asymptomatic patients had higher counts of lymphocytes, T cells, B cells, and NK cells. While liver damage was observed in symptomatic patients, as indicated by elevated liver enzymes and decreased liver-synthesized proteins in the blood, asymptomatic patients showed normal liver measurements. Lactate dehydrogenase, a COVID-19 risk factor, was significantly lower in asymptomatic patients. These results suggest that asymptomatic COVID-19 patients had normal clinical indicators and faster viral clearance than symptomatic patients. Lymphocytes may play a role in their asymptomatic phenotype. Since asymptomatic patients may be a greater risk of virus transmission than symptomatic patients, public health interventions and a broader range of testing may be necessary for the control of COVID-19.IMPORTANCE Asymptomatic transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a potential problem for pandemic control through public health strategies. Our results demonstrate that asymptomatic COVID-19 patients have better outcomes than symptomatic patients. This may have been due to more active cellular immune responses and normal liver function. Since asymptomatic patients have no clinical symptoms which can easily prevent timely diagnosis and treatment, they may cause a greater risk of virus transmission than symptomatic patients, which poses a major challenge to infection control. Evidence suggests that nonpharmaceutical public health interventions, like social distancing and face mask ordinances, play important roles in the control of COVID-19. Looking forward, it may be necessary to proceed cautiously while reopening businesses in areas of epidemicity to prevent potential waves of COVID-19 in the future.

Analysis of adjunctive serological detection to nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection diagnosis.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. METHODS: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. RESULTS: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. CONCLUSION: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets.

Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors.

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

Decreased T cell populations contribute to the increased severity of COVID-19.

BACKGROUND: We observe changes of the main lymphocyte subsets (CD16+CD56、CD19、CD3、CD4、and CD8) in COVID-19-infected patients and explore whether the changes are associated with disease severity. METHODS: One-hundred and fifty-four cases of COVID-19-infected patients were selected and divided into 3 groups (moderate group, severe group and critical group). The flow cytometry assay was performed to examine the numbers of lymphocyte subsets. RESULTS: CD3+, CD4+ and CD8 + T lymphocyte subsets were decreased in COVID-19-infected patients. Compared with the moderate group and the sever group, CD3+, CD4+ and CD8+ T cells in the critical group decreased greatly (P < 0.001, P = 0.005 or P = 0.001). CONCLUSIONS: Reduced CD3+, CD4+, CD8+ T lymphocyte counts may reflect the severity of the COVID-19. Monitoring T cell changes has important implications for the diagnosis and treatment of severe patients who may become critically ill.

The value of urine biochemical parameters in the prediction of the severity of coronavirus disease 2019.

Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.

Analysis of heart injury laboratory parameters in 273 COVID-19 patients in one hospital in Wuhan, China.

An outbreak of severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) epidemic spreads rapidly worldwide. SARS-CoV-2 infection caused mildly to seriously and fatally respiratory, enteric, cardiovascular, and neurological diseases. In this study, we detected and analyzed the main laboratory indicators related to heart injury, creatine kinase isoenzyme-MB (CK-MB), myohemoglobin (MYO), cardiac troponin I (ultra-TnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP), in 273 patients with COVID-19 and investigated the correlation between heart injury and severity of the disease. It was found that higher concentration in venous blood of CK-MB, MYO, ultra-TnI, and NT-proBNP were associated with the severity and case fatality rate of COVID-19. Careful monitoring of the myocardiac enzyme profiles is of great importance in reducing the complications and mortality in patients with COVID-19.

Prominent changes in blood coagulation of patients with SARS-CoV-2 infection.

Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.

Positive rate of RT-PCR detection of SARS-CoV-2 infection in 4880 cases from one hospital in Wuhan, China, from Jan to Feb 2020.

BACKGROUND: There's an outbreak of a novel coronavirus (SARS-CoV-2) infection since December 2019, first in China, and currently with more than 80 thousand confirmed infection globally in 29 countries till March 2, 2020. Identification, isolation and caring for patients early are essential to limit human-to-human transmission including reducing secondary infections among close contacts and health care workers, preventing transmission amplification events. The RT-PCR detection of viral nucleic acid test (NAT) was one of the most quickly established laboratory diagnosis method in a novel viral pandemic, just as in this COVID-19 outbreak. METHODS: 4880 cases that had respiratory infection symptoms or close contact with COVID-19 patients in hospital in Wuhan, China, were tested for SARS-CoV-2 infection by use of quantitative RT-PCR (qRT-PCR) on samples from the respiratory tract. Positive rates were calculated in groups divided by genders or ages. RESULTS: The positive rate was about 38% for the total 4880 specimens. Male and older population had a significant higher positive rates. However, 57% was positive among the specimens from the Fever Clinics. Binary logistic regression analysis showed that age, not gender, was the risk factor for SARS-CoV-2 infection in fever clinics. CONCLUSIONS: Therefore, we concluded that viral NAT played an important role in identifying SARS-CoV-2 infection.