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The SARS-CoV-2 virus precipitated the coronavirus 2019 (COVID-19) pandemic, which placed considerable strain on healthcare systems and necessitated immediate and rapid alterations in the delivery of healthcare. In the transplant population, COVID-19 directly impacts an inherently vulnerable population in the setting of immunosuppression and co-morbidities, but also further complicates the clinical evaluation and management of kidney transplant candidates and recipients in a strained healthcare environment being challenged by the pandemic. Many transplant centers around the world saw mortality rate spikes in organ recipients related to COVID-19, and changes in care delivery abound. This review evaluates the care of the kidney transplant patient through all phases of the process including pre-operative evaluations, perioperative care, post-transplantation considerations, and how the global pandemic has changed the way we care for our patients.
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Phosphatidylinositol phosphate kinases (PIPKs) produce lipid signaling molecules and have been attracting increasing attention as drug targets for cancer, neurodegenerative diseases, and viral infection. Given the potential cross-inhibition of kinases and other ATP-utilizing enzymes by ATP-competitive inhibitors, targeting the unique lipid substrate binding site represents a superior strategy for PIPK inhibition. Here, by taking advantage of the nearly identical stereochemistry between myo-inositol and D-galactose, we designed and synthesized a panel of D-galactosyl lysophospholipids, one of which was found to be a selective substrate of phosphatidylinositol 4-phosphate 5-kinase. Derivatization of this compound led to the discovery of a human PIKfyve inhibitor with an apparent IC50 of 6.2â µM, which significantly potentiated the inhibitory effect of Apilimod, an ATP-competitive PIKfyve inhibitor under clinical trials against SARS-CoV-2 infection and amyotrophic lateral sclerosis. Our results provide the proof of concept that D-galactose-based phosphoinositide mimetics can be developed into artificial substrates and new inhibitors of PIPKs.
ABSTRACT
Phosphatidylinositol phosphate kinases (PIPKs) produce lipid signaling molecules and have been attracting increasing attention as drug targets for cancer, neurodegenerative diseases, and viral infection. Given the potential cross-inhibition of kinases and other ATP-utilizing enzymes by ATP-competitive inhibitors, targeting the unique lipid substrate binding site represents a superior strategy for PIPK inhibition. Here, by taking advantage of the nearly identical stereochemistry between myo-inositol and D-galactose, we designed and synthesized a panel of D-galactosyl lysophospholipids, one of which was found to be a selective substrate of phosphatidylinositol 4-phosphate 5-kinase. Derivatization of this compound led to the discovery of a human PIKfyve inhibitor with an apparent IC50 of 6.2â µM, which significantly potentiated the inhibitory effect of Apilimod, an ATP-competitive PIKfyve inhibitor under clinical trials against SARS-CoV-2 infection and amyotrophic lateral sclerosis. Our results provide the proof of concept that D-galactose-based phosphoinositide mimetics can be developed into artificial substrates and new inhibitors of PIPKs.
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OBJECTIVES: To assess total antibody levels against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2) spike protein up to 12 months after Coronavirus Disease (COVID-19) infection in non-vaccinated individuals and the possible predictors of antibody persistence. METHODS: This is the first part of a prospective multi-centre cohort study. PARTICIPANTS: The study included SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) positive and negative participants in South-Eastern Norway from February to December 2020. Possible predictors of SARS-CoV-2 total antibody persistence was assessed. The SARS-CoV-2 total antibody levels against spike protein were measured three to five months after PCR in 391 PCR-positive and 703 PCR-negative participants; 212 PCR-positive participants were included in follow-up measurements at 10 to 12 months. The participants completed a questionnaire including information about symptoms, comorbidities, allergies, body mass index (BMI), and hospitalisation. PRIMARY OUTCOME: The SARS-CoV-2 total antibody levels against spike protein three to five and 10 to 12 months after PCR positive tests. RESULTS: SARS-CoV-2 total antibodies against spike protein were present in 366 (94%) non-vaccinated PCR-positive participants after three to five months, compared with nine (1%) PCR-negative participants. After 10 to 12 months, antibodies were present in 204 (96%) non-vaccinated PCR-positive participants. Of the PCR-positive participants, 369 (94%) were not hospitalised. The mean age of the PCR-positive participants was 48 years (SD 15, range 20-85) and 50% of them were male. BMI ≥ 25 kg/m2 was positively associated with decreased antibody levels (OR 2.34, 95% CI 1.06 to 5.42). Participants with higher age and self-reported initial fever with chills or sweating were less likely to have decreased antibody levels (age: OR 0.97, 95% CI 0.94 to 0.99; fever: OR 0.33, 95% CI 0.13 to 0.75). CONCLUSION: Our results indicate that the level of SARS-CoV-2 total antibodies against spike protein persists for the vast majority of non-vaccinated PCR-positive persons at least 10 to 12 months after mild COVID-19.
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COVID-19 , SARS-CoV-2 , Adult , Aged , Aged, 80 and over , Antibodies, Viral , Cohort Studies , Female , Humans , Male , Middle Aged , Norway , Prospective Studies , Spike Glycoprotein, Coronavirus , Young AdultABSTRACT
The booster vaccination of COVID-19 is being implemented in most parts of the world. This study used behavioral psychology to investigate the predictors of parents' intentions regarding the COVID-19 booster vaccination for their children. This is a cross-sectional study with a self-designed questionnaire based on two behavioral theories-protective motivation theory (PMT) and theory of planned behavior (TPB). A stratified multi-stage sampling procedure was conducted in Nanjing, China, and multivariable regression analyses were applied to examine the parents' intentions. The intention rate was 87.3%. The response efficacy (ORa = 2.238, 95% CI: 1.360-3.682) and response cost (ORa = 0.484, 95% CI: 0.319-0.732) in the PMT, were significant psychological predictors of parents' intentions, and so were the attitude (ORa = 2.619, 95% CI: 1.480-4.636) and behavioral control (ORa = 3.743, 95% CI: 2.165-6.471) in the TPB. The findings of crucial independent predictors in the PMT and TPB constructs inform the evidence-based formulation and implementation of strategies for booster vaccination in children.
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COVID-19 , Intention , COVID-19/epidemiology , COVID-19/prevention & control , Child , China , Cross-Sectional Studies , Humans , Surveys and Questionnaires , VaccinationSubject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Antibodies, Viral , Colostrum , Enzyme-Linked Immunosorbent Assay , Female , Milk , Pregnancy , SwineABSTRACT
Background: Smartphone-based online education gained popularity during and after the COVID-19 pandemic. Although recent studies have highlighted the association between problematic smartphone use (PSU) and mental health symptoms, the potential role of online learning in this relationship remains unclear. This study aimed to analyze the relationships between higher education modes, PSU, and related psychological symptoms in university students. Methods: A total of 1,629 Chinese university students from five provinces completed a web-based questionnaire survey between March 2020 and October 2021. Demographic characteristics and learning conditions were recorded. All participants completed the Smartphone Addiction Scale-Short Version, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Athens Insomnia Scale. Multiple regressions models and stratified analyses were used to examine the association between online education mode, PSU, and symptoms of depression, anxiety, and insomnia. Results: The prevalence of PSU was 58.5%. Students who relied primarily on online learning had a higher prevalence of depressive symptoms (29.95% vs. 22.24%), anxiety symptoms (25.13% vs. 18.91%), and insomnia symptoms (75.89% vs. 70.27%) than those who relied on traditional face-to-face learning (Ps < 0.05). After adjusting for covariates, subjects with PSU were more likely to report depressive symptoms (AdjOR = 3.14, 95% CI = 2.26-4.37), anxiety symptoms (AdjOR = 3.73, 95% CI = 2.13-4.59), and insomnia symptoms (AdjOR = 2.96, 95% CI = 2.23-3.92) than those without PSU. Furthermore, the associations of PSU with depressive symptoms (OR = 4.66 vs. 2.33, P for interaction = 0.015) and anxiety symptoms (OR = 6.05 vs. 2.94, P for interaction = 0.021) were more pronounced in the online learning group. Conclusion: Our study provides preliminary evidence that Chinese university students have serious smartphone addiction problems, which are associated with depressive, anxiety, and insomnia symptoms. Online learning is found to exacerbate PSU and mental health problems. Our findings provide valuable information for targeted psychological interventions in the post-COVID-19 era.
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COVID-19 , Education, Distance , Sleep Initiation and Maintenance Disorders , COVID-19/epidemiology , China/epidemiology , Humans , Internet Addiction Disorder/epidemiology , Pandemics , Sleep Initiation and Maintenance Disorders/epidemiology , Students/psychologyABSTRACT
We were interested in reading an article published by Wang et al. [...].
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Antibodies, Viral , Deltacoronavirus , Animals , Enzyme-Linked Immunosorbent Assay , SwineSubject(s)
Blood Pressure , COVID-19/mortality , COVID-19/physiopathology , Critical Illness/mortality , Aged , China , Female , Humans , Kaplan-Meier Estimate , Length of Stay , Male , Middle Aged , Retrospective Studies , Survival AnalysisABSTRACT
BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.
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Amides/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Pyrazines/therapeutic use , SARS-CoV-2/drug effects , Adult , Aged , Aged, 80 and over , Amides/administration & dosage , Amides/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/diagnostic imaging , COVID-19/pathology , COVID-19/therapy , Drug Therapy, Combination , Female , Humans , Interleukin-6/blood , Kaplan-Meier Estimate , Lung/diagnostic imaging , Lung/pathology , Male , Middle Aged , Models, Immunological , Pyrazines/administration & dosage , Pyrazines/adverse effects , Receptors, Interleukin-6/antagonists & inhibitors , Respiration, Artificial/statistics & numerical data , Sample Size , Treatment OutcomeABSTRACT
ABSTRACT: Since December 2019, an outbreak of COVID-19 sweeping the world. Understanding the clinical and SARS-CoV-2 dynamic changes of mild and ordinary patients of COVID-19, so as to provide basis for the prevention and control of COVID-19.On February 1st, 2020, 16 SARS-CoV-2 RNA positive patients diagnosed in the same site in Beijing. The patients symptoms, signs, medication, and SARS-CoV-2 results were recorded.Of the 16 patients, 12 were female. Although they were infected at the same time in the same workplace, their clinical processes were very different and can be roughly divided into three different types: persistent sputum positive, persistent stool positive and persistent both positive. In 7 patients with mild clinical manifestations, the median days of SARS-CoV-2 RNA negative conversion in sputum samples were significantly later than those with obvious lung injury (27 days [range: 18 to 36]; 17 days, [range 6 to 25], P = .021). The negative conversion of SARS-CoV-2 RNA in stool was significant later than in sputum.There were various clinical manifestations after SARS-CoV-2 infection, even if they were infected by the same source of infection in the same place. The presence of SARS-CoV-2 virus RNA in stool samples was longer than that in respiratory tract.
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COVID-19/epidemiology , Disease Outbreaks , Occupational Exposure , Pneumonia, Viral/epidemiology , Workplace , Adult , COVID-19 Testing , China/epidemiology , Feces/virology , Female , Humans , Male , Pneumonia, Viral/virology , RNA, Viral/analysis , SARS-CoV-2 , Sputum/virologyABSTRACT
BACKGROUND: The novel COVID-19 disease has spread worldwide, resulting in a new pandemic. The Chinese government implemented strong intervention measures in the early stage of the epidemic, including strict travel bans and social distancing policies. Prioritizing the analysis of different contributing factors to outbreak outcomes is important for the precise prevention and control of infectious diseases. We proposed a novel framework for resolving this issue and applied it to data from China. OBJECTIVE: This study aimed to systematically identify national-level and city-level contributing factors to the control of COVID-19 in China. METHODS: Daily COVID-19 case data and related multidimensional data, including travel-related, medical, socioeconomic, environmental, and influenza-like illness factors, from 343 cities in China were collected. A correlation analysis and interpretable machine learning algorithm were used to evaluate the quantitative contribution of factors to new cases and COVID-19 growth rates during the epidemic period (ie, January 17 to February 29, 2020). RESULTS: Many factors correlated with the spread of COVID-19 in China. Travel-related population movement was the main contributing factor for new cases and COVID-19 growth rates in China, and its contributions were as high as 77% and 41%, respectively. There was a clear lag effect for travel-related factors (previous vs current week: new cases, 45% vs 32%; COVID-19 growth rates, 21% vs 20%). Travel from non-Wuhan regions was the single factor with the most significant impact on COVID-19 growth rates (contribution: new cases, 12%; COVID-19 growth rate, 26%), and its contribution could not be ignored. City flow, a measure of outbreak control strength, contributed 16% and 7% to new cases and COVID-19 growth rates, respectively. Socioeconomic factors also played important roles in COVID-19 growth rates in China (contribution, 28%). Other factors, including medical, environmental, and influenza-like illness factors, also contributed to new cases and COVID-19 growth rates in China. Based on our analysis of individual cities, compared to Beijing, population flow from Wuhan and internal flow within Wenzhou were driving factors for increasing the number of new cases in Wenzhou. For Chongqing, the main contributing factor for new cases was population flow from Hubei, beyond Wuhan. The high COVID-19 growth rates in Wenzhou were driven by population-related factors. CONCLUSIONS: Many factors contributed to the COVID-19 outbreak outcomes in China. The differential effects of various factors, including specific city-level factors, emphasize the importance of precise, targeted strategies for controlling the COVID-19 outbreak and future infectious disease outbreaks.
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COVID-19/epidemiology , Disease Outbreaks/statistics & numerical data , China/epidemiology , Factor Analysis, Statistical , HumansABSTRACT
The 2003 SARS pandemic heralded the return of quarantine as a vital part of twenty-first century public health practice. Over the last two decades, MERS, Ebola, and other emerging infectious diseases each posed unique challenges for applying quarantine ethics lessons learned from the 2003 SARS-CoV-1 outbreak. In an increasingly interdependent and connected global world, the use of quarantine to contain the spread of SARS-CoV-2, or COVID-19, similarly poses new and unexpected ethical challenges. In this essay, we look beyond standard debates about the ethics of quarantine and state power to explore a key quarantine principle, Reciprocity, and how it is being negotiated by healthcare workers, volunteers, and citizens in the context of the Wuhan, China, quarantine. We analyze Reciprocity through the lens of two Wuhan case studies: (1) healthcare workers, particularly nurses, who are simultaneously essential workers and quarantined citizens, asked by their hospital administration to shave their heads because adequate PPE was not available, and (2) citizen-to-citizen mutual aid societies attempting to fill gaps in essential supplies left unfilled by the state. We analyze social media and video-blogs from Wuhan, on the platforms of Douyin and Sina Weibo, to understand how people define and respond to ethical and legal obligations in the wake of COVID-19. It is no surprise that quarantine principles from the 2003 SARS outbreak are inadequate for COVID-19 and that both infectious disease outbreak responses and ethics must adapt to the virtual age. We offer ideas to strengthen and clarify Reciprocal obligations for the state, hospital administrators, and citizens as the globe prepares for the next wave of COVID-19 circulating now.
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Since December 2019, coronavirus disease (COVID-19) has rapidly swept the world. So far, more than 30 million people have been infected and nearly one million have died. Although the world is still in the stage of COVID-19 pandemic, the treatment of new cases and critically ill patients is the focus of the current work. However, COVID-19 patients lead to pulmonary fibrosis, such a serious threat to the prognosis of complications were also worthy of our attention. First of all, we proposed the possible mechanism of pulmonary fibrosis caused by SARS-CoV-2, based on the published data of COVID-19 ((i) Direct evidence: pulmonary fibrosis was found in autopsy and pulmonary puncture pathology. (ii) Indirect evidence: increased levels of fibrosis-related cytokines[transforming growth factor [TGF]- ß, tumor necrosis factor [TNF]- α, interleukin [IL]-6, etc] in peripheral blood of severe patients.) What is more, we summarized the role of three fibrosis-related signaling pathways (TGF- ß signal pathway, WNT signal pathway and YAP/TAZ signal pathway) in pulmonary fibrosis. Finally, we suggested the therapeutic value of two drugs (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis in COVID-19-induced pulmonary fibrosis.
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COVID-19/complications , Indoles/therapeutic use , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/etiology , Pyridones/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , COVID-19/metabolism , COVID-19/pathology , Humans , Lung/pathology , Patient Discharge , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Severity of Illness Index , Signal TransductionABSTRACT
Background: Emerging evidence shows that coronavirus disease 2019 (COVID-19) is commonly complicated by coagulopathy, and venous thromboembolism (VTE) is considered to be a potential cause of unexplained death. Information on the incidence of VTE in COVID-19 patients, however, remains unclear. Method: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platforms were searched to identify studies with data of VTE occurrence in hospitalized COVID-19 patients. Pooled incidence and relative risks (RRs) of VTE were estimated by a random-effects model. Variations were examined based on clinical manifestations of VTE (pulmonary embolism-PE and deep vein thrombosis-DVT), disease severity (severe patients and non-severe patients), and rate of pharmacologic thromboprophylaxis (≥60 and <60%). Sensitivity analyses were conducted to strengthen the robustness of results. Meta-regression was performed to explore the risk factors associated with VTE in COVID-19 patients. Results: A total of 17 studies involving 1,913 hospitalized COVID-19 patients were included. The pooled incidence of VTE was 25% (95% CI, 19-31%; I 2, 95.7%), with a significant difference between the incidence of PE (19%; 95% CI, 13-25%; I 2, 93.2%) and DVT (7%; 95% CI, 4-10%; I 2, 88.3%; P interaction < 0.001). Higher incidence was observed in severe COVID-19 patients (35%; 95 CI%, 25-44%; I 2, 92.4%) than that in non-severe patients (6%; 95 CI%, 3-10%; I 2, 62.2%; P interaction < 0.001). The high rate of pharmacologic thromboprophylaxis in COVID-19 patients (≥60%) was associated with a lower incidence of VTE compared with the low pharmacologic thromboprophylaxis rate (<60%) (19 vs. 40%; P interaction = 0.052). Severe patients had a 3.76-fold increased risk of VTE compared with non-severe patients (RR, 4.76; 95% CI, 2.66-8.50; I 2, 47.0%). Sensitivity analyses confirmed the robustness of the primacy results. Conclusions: This meta-analysis revealed that the estimated VTE incidence was 25% in hospitalized COVID-19 patients. Higher incidence of VTE was observed in COVID-19 patients with a severe condition or with a low rate of pharmacologic thromboprophylaxis. Assessment of VTE risk is strongly recommended in COVID-19 patients, and effective measures of thromboprophylaxis should be taken in a timely manner for patients with high risk of VTE.
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INTRODUCTION: To report about the successful outbreak containment of COVID-19 in Shantou, one of the prefectural cities of Guangdong province in the mainland China. METHODOLOGY: All patients confirmed as having COVID-19 between 23 January and 25 March 2020 by RT-PCR assay in the clinical lab of Shantou CDC were included and divided into three groups based on the source of identification: hospital diagnosis, contact tracing, and community screening. Collected data was analyzed and compared among these three groups. RESULTS: A total of 25 COVID-19 cases were identified in Shantou. The first case was identified on 14 January 2020 at one of two COVID-19 dedicated hospitals in Shantou. The majority of the cases were either imported from Wuhan or linked to Wuhan/Hubei. The median lag time for diagnosis (i.e., the time between symptom onset and case confirmation) was 2 days (IQR, 2.0-4.0) for all cases, 9 days (IQR, 7.0-10.0) for the cases diagnosed in hospitals, 2 days (IQR, 1.5-2.0) for the cases in contact tracing, and 4 days (IQR, 2.5-4.5) for cases in community screening, with a significantly longer diagnosis lag time in hospitals (p = 0.003). Multivariate linear regression models showed larger family size and severe cases as the significant predictor for increasing number of close contacts. CONCLUSIONS: The current pandemic appears to exist for an uncertain period. The early containment measures applied in Shantou, a city with insufficient healthcare resources for COVID-19, seems to be appropriate for cities or areas with similar profiles.
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Betacoronavirus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Adult , Aged , COVID-19 , COVID-19 Testing , China/epidemiology , Clinical Laboratory Techniques , Contact Tracing , Coronavirus Infections/diagnosis , Disease Outbreaks/prevention & control , Family , Female , Humans , Male , Middle Aged , Pneumonia, Viral/diagnosis , SARS-CoV-2 , Socioeconomic FactorsABSTRACT
BACKGROUND: In the context of the COVID-19 outbreak of worldwide, we aim to analyze the laboratory risk factors of in-hospital death in patients with severe COVID-19. METHODS: All ≥18-year-old patients with confirmed severe COVID-19 admitted to Tongji Hospital (Wuhan, China) from February 3 to February 20, 2020, were retrospectively enrolled and followed up until March 20, 2020. Epidemiological, clinical, laboratory, and treatment data were collected and explored the risk factors associated with in-hospital death. RESULTS: A total of 73 severe patients were enrolled in the study, of whom 20 (27%) patients died in hospital during the average 28 days of follow-up period. The median age of non-survivors was significantly older than survivors (69 [64-76.5] years vs 64 [56-71.3] years, P = .033) and 15 (75%) patients were males. The laboratory abnormalities of non-survivors mainly presented in serious inflammation response and multiple organ failure, with high levels of cytokines and deranged coagulation parameters. Multivariable regression showed that neutrophil count greater than 4.47 × 109 /L (OR, 58.35; 95%CI: 2.16-1571.69; P = .016), hypersensitivity C-reactive protein greater than 86.7 mg/L (OR, 14.90; 95%CI: 1.29-171.10; P = .030), creatine kinase greater than 101 U/L (OR, 161.62; 95%CI: 6.45-4045.20; P = .002), and blood urea nitrogen greater than 6.7 mmol/L (OR, 11.18; 95%CI: 1.36-91.62; P = .024) were risk factors for in-hospital death. CONCLUSION: The risk factors of neutrophil count, hypersensitivity C-reactive protein, creatine kinase, and blood urea nitrogen could help clinicians to early identify COVID-19 severe patients with poor outcomes on admission. Virus direct attack and cytokine storm play a major role in the death of COVID-19.
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Coronavirus Infections , Pandemics , Pneumonia, Viral , Aged , Betacoronavirus , C-Reactive Protein/analysis , COVID-19 , COVID-19 Testing , China , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Creatine Kinase/blood , Critical Illness , Cytokine Release Syndrome , Female , Hospitalization , Humans , Leukocyte Count , Male , Middle Aged , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness IndexABSTRACT
Background: A novel enveloped RNA beta coronavirus, Corona Virus Disease 2019 (COVID-19) caused severe and even fetal pneumonia in China and other countries from December 2019. Early detection of severe patients with COVID-19 is of great significance to shorten the disease course and reduce mortality. Methods: We assembled a retrospective cohort of 80 patients (including 56 mild and 24 severe) with COVID-19 infection treated at Beijing You'an Hospital. We used univariable and multivariable logistic regression analyses to select the risk factors of severe and even fetal pneumonia and build scoring system for prediction, which was validated later on in a group of 22 COVID-19 patients. Results: Age, white blood cell count, neutrophil, glomerular filtration rate, and myoglobin were selected by multivariate analysis as candidates of scoring system for prediction of disease severity in COVID-19. The scoring system was applied to calculate the predictive value and found that the percentage of ICU admission (20%, 6/30) and ventilation (16.7%, 5/30) in patients with high risk was much higher than those (2%, 1/50; 2%, 1/50) in patients with low risk (p = 0.009; p = 0.026). The AUC of scoring system was 0.906, sensitivity of prediction is 70.8%, and the specificity is 89.3%. According to scoring system, the probability of patients in high risk group developing severe disease was 20.24 times than that in low risk group. Conclusions: The possibility of severity in COVID-19 infection predicted by scoring system could help patients to receiving different therapy strategies at a very early stage. Topic: COVID-19, severe and fetal pneumonia, logistic regression, scoring system, prediction.
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Coronavirus Infections/epidemiology , Coronavirus Infections/pathology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/pathology , Severity of Illness Index , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , China , Comorbidity , Disease Progression , Female , Glomerular Filtration Rate/physiology , Humans , Leukocyte Count , Male , Middle Aged , Myoglobin/analysis , Neutrophil Infiltration/immunology , Neutrophils/immunology , Pandemics , Prognosis , Retrospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: Identifying immune correlates of COVID-19 disease severity is an urgent need for clinical management, vaccine evaluation, and drug development. Here, we present a temporal analysis of key immune mediators, cytokines, and chemokines in blood of hospitalized COVID-19 patients from serial sampling and follow-up over 4 weeks. METHODS: A total of 71 patients with laboratory-confirmed COVID-19 admitted to Beijing You'an Hospital in China with either mild (53 patients) or severe (18 patients) disease were enrolled with 18 healthy volunteers. We measured 34 immune mediators, cytokines, and chemokines in peripheral blood every 4-7 days over 1 month per patient using a bioplex multiplex immunoassay. RESULTS: We found that the chemokine RANTES (CCL5) was significantly elevated, from an early stage of the infection, in patients with mild but not severe disease. We also found that early production of inhibitory mediators including IL-10 and IL-1RA were significantly associated with disease severity, and a combination of CCL5, IL-1 receptor antagonist (IL-1RA), and IL-10 at week 1 may predict patient outcomes. The majority of cytokines that are known to be associated with the cytokine storm in virus infections such as IL-6 and IFN-γ were only significantly elevated in the late stage of severe COVID-19 illness. TNF-α and GM-CSF showed no significant differences between severe and mild cases. CONCLUSION: Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.