ABSTRACT
SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.
Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar , Pneumonia , Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
The mutations make uncertain to SARS-CoV-2 disease control and vaccine development. At population-level, single nucleotide polymorphism (SNPs) have displayed mutations for illustrating epidemiology, transmission, and pathogenesis of COVID-19. These mutations are to be expected by the analysis of intra-host level, which presented as intra-host variations (iSNVs). Here, we performed spatio-temporal analysis on iSNVs in 402 clinical samples from 170 patients, and observed an increase of genetic diversity along the day post symptom onset within individual patient and among subpopulations divided by gender, age, illness severity and viral shedding time, suggested a positive selection at intra-host level. The comparison of iSNVs and SNPs displayed that most of nonsynonymous mutations were not fixed suggested a purifying selection. This two-step fitness selection enforced iSNVs containing more nonsynonymous mutations, that highlight the potential characters of SARS-CoV-2 for viral infections and global transmissions.
Subject(s)
COVID-19ABSTRACT
Background: Serosurvalence is crucial in estimating the range of SARS-CoV-2 infections, predicting the possibility of another wave, and decide on a vaccination strategy. To understand the herd immunity after the COVID-19 pandemic, the seroprevalence was measured in 3062 individuals with or without COVID-19. Methods: The levels of SARS-CoV-2 antibody IgM and IgG were measured by the immuno-colloidal gold method.Results: The mean seroprevalence for IgM and IgG in all participants was 2.81% and 7.51%, respectively. The positive rate of IgG was significantly higher in women than in men (P<0.05). The highest positive rate of IgM was observed in 41-60 years of age (3.49%), while the highest seroprevalence for IgG was observed in persons >60 years of age (8.61%). The positive rates of IgM and IgG in the convalescent patients were 31.82% and 77.27%, respectively, which was significantly higher than individuals with suspected syndromes or individuals without any clinical signs (P<0.01). Seroprevalence for IgG in medical staff was markedly higher than those in residents. The seroprevalence in patients with various comorbidity was no significant difference (P>0.05).Conclusions: The low positive rate of the SARS-CoV-2 IgM and NA test indicated that the SARS-CoV-2 outbreak is subsiding after three months, and the possibility of reintroduction of the virus from an unidentified natural reservoir is low. Seroprevalence provides the information for humoral immunity and vaccine in the future.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
Background: Recent studies reported that sex differences in patients with coronavirus disease-2019 (COVID-19). However the predictive value of sex differences in disease severity were less studied by previous scholars. Methods: All adults (≥18 years) diagnosed with COVID-19 and admitted to Beijing Ditan Hospital, Capital Medical University (admission date from January 13 to March 19, 2020) were included in samples. Data analyzed in this study included epidemiological, demographic, comorbidities, initial symptoms and signs, laboratory findings, imaging study, disease severity and in-hospital mortality. Results: A total of 185 inpatients were enrolled in the study, among whom 95 patients are males (51.4%). The mean age of all patients was 41 years. Based on the hospital record, the duration from symptoms initiation to hospital admission was longer for men than that for women. Moreover, the mean BMI of males was relatively higher compared to females (25.45vs22.29, p<.001). In addition, the proportion of male patients with CHD, NAFLD, smoking and drinking history was higher than females. During the hospital stay, compared to female patients, male patients were more prone to develop symptoms such as high fever, cough, and chill. Higher levels of AST, CK, CRP and FIB were also observed in male patients. Following this fact, more patients with abnormal CT activities, severe and critical symptoms were developed in male group than females. However, there was no difference in complications and outcome between two groups. By analyzing data comprehensively, we found out that age (analyzed in quartiles, OR: 1.087; 95% CI: 1.038–1.139; p <.001) and BMI (OR: 1.250; 95% CI: 1.046–1.493; p =.014) could be used to help predict disease severity. Conclusions: In this cohort of hospitalized patients in Beijing, male patients developed more clinical symptoms, obtained more abnormal laboratory test results, and showed higher rates in severity of COVID-19. Other than that, the severity of COVID-19 was positively correlated with age and BMI independently.
Subject(s)
COVID-19 , CoughABSTRACT
Background: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or Kaletra plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown.Methods: This is a retrospective cohort study of 123 laboratory-confirmed COVID-19 patients between Jan.13 2020 and Apr. 23. All patients received standard supportive care and regular clinical monitoring, patients were assigned to standard care group (n=12), interferon alfa-2b group (n=44), and combination Kaletra plus interferon alfa-2b group (n=67) according to their therapies. The primary endpoint for this study was the duration of oxygen-support requirement and virus clearance time. The associations of therapies with these outcomes were assessed by Cox proportional hazards regression. Results: Baseline clinical and laboratory characteristics were similar among 3 groups (p＞0.05). There was no significant association of Kaletra /interferon alfa-2b with faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% CI, 0.45–1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI, 0.32–1.11]; P = 0.10 in Kaletra plus interferon alfa-2b group). The duration of oxygen-support requirement in therapy groups similarly showed no significant association. There were no differences among 3 groups in the incidence of adverse events (p＞0.05).Conclusions: In patients with confirmed SARS-CoV-2 infection, no benefit was observed with interferon alfa-2b and Kaletra plus interferon alfa-2b treatment beyond standard care. Further trials in appropriately randomized design may contribute to validate the effective role and safety profile of the test drugs.
Subject(s)
COVID-19ABSTRACT
Background A pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on-going. Clinical characters of afebrile cases infected with SARS-CoV-2 remain poorly understood and informations are limited on the duration of SARS-CoV-2 viral positivity.Methods We performed a single-center retrospective study of 143 patients with SARS-CoV-2 infection in Beijing Ditan Hospital, Capital Medical University from January 26 to April 15, 2020. Differences were compared among patients with/without fever. Risk factors for the duration of SARS-CoV-2 viral positivity were evaluated.Results A total of 143 patients with positive SARS-CoV-2 test were enrolled, including 38 afebrile patients and 105 febrile patients. On admission, a total of 40 (28%) patients had leukopenia, 44 (30.8%) had lymphopenia and 8 (5.6%) had thrombocytopenia. 78 patients (54.5%) had decreased T lymphocytes and 105 patients (73.4%) had decreased CD4+T lymphocytes. Compared with febrile cases, afebrile patients had a significantly higher white blood cell count (P = 0.02), total lymphocytes (P < 0.01), platelet count (P < 0.01), T lymphocytes (P < 0.01) and CD8+ T lymphocytes (P = 0.02). The median SARS-CoV-2 viral positivity duration of these 143 patients was 14 days (IQR, 10-30 days) and for febrile and afebrile group were 13 days (IQR, 10-29 days) and 20 days (IQR, 11-31 days) respectively. Multivariate Cox regression results showed that the fever [hazard ratio (HR) = 0.49, P < 0.01]and higher count of platelet (HR = 5.47, P = 0.02) were the predominant risk factor for the SARS-CoV-2 viral positivity duration.Conclusion The SARS-CoV-2 virial positivity duration of the afebrile group was significantly longer than that in the febrile group. Fever and a higher count of platelet were the independent protective factors for a shorter SARS-CoV-2 RNA positivity duration.
Subject(s)
Thrombocytopenia , Leukopenia , Fever , COVID-19 , LymphopeniaABSTRACT
ObjectiveTo investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. MethodsWe retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), 2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). ResultThe levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). Whats more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. ConclusionThe coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.
Subject(s)
COVID-19ABSTRACT
【Background】Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown.【Methods】 This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild and severe groups. We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined.【Results】 56.2% of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% cases the level of ALT, AST or TBil ≤ 3 fold of the upper normal range. The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (p<0.05).The percentage of the patients with both elevated ALT and AST was 12.7% in mild cases vs. 46.2% in severe cases (p = 0.001). 34.6% severe group patients started to have abnormal ALT after admission，and 73.4% of all patients had normal ALT before discharge.【Conclusion】Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN，but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.
Subject(s)
Coronavirus Infections , Chemical and Drug Induced Liver Injury , COVID-19ABSTRACT
Since SARS-CoV-2 infection was first identified in December 2019, it spread rapidly and a global pandemic of COVID-19 has occurred. ACE2, the receptor for entry into the target cells by SARS-CoV-2, was found to abundantly express in testes, including spermatogonia, Leydig and Sertoli cells. However, there is no clinical evidence about whether SARS-CoV-2 infection can affect male gonadal function so far. In this study, we compared the sex-related hormones between 81 reproductive-aged men with SARS-CoV-2 infection and 100 age-matched healthy men, and found that serum luteinizing hormone (LH) was significantly increased, but the ratio of testosterone (T) to LH and the ratio of follicle stimulating hormone (FSH) to LH were dramatically decreased in males with COVID-19. Besides, multivariable regression analysis indicated that c-reactive protein (CRP) level was significantly associated with serum T:LH ratio in COVID-19 patients. This study provides the first direct evidence about the influence of medical condition of COVID-19 on male sex hormones, alerting more attention to gonadal function evaluation among patients recovered from SARS-CoV-2 infection, especially the reproductive-aged men.