COVIDpro: Database for Mining Protein Dysregulation in Patients with COVID-19.

The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 still has limited treatment options. Our understanding of the molecular dysregulations that occur in response to infection remains incomplete. We developed a web application COVIDpro (https://www.guomics.com/covidPro/) that includes proteomics data obtained from 41 original studies conducted in 32 hospitals worldwide, involving 3077 patients and covering 19 types of clinical specimens, predominantly plasma and serum. The data set encompasses 53 protein expression matrices, comprising a total of 5434 samples and 14,403 unique proteins. We identified a panel of proteins that exhibit significant dysregulation, enabling the classification of COVID-19 patients into severe and non-severe disease categories. The proteomic signatures achieved promising results in distinguishing severe cases, with a mean area under the curve of 0.87 and accuracy of 0.80 across five independent test sets. COVIDpro serves as a valuable resource for testing hypotheses and exploring potential targets for novel treatments in COVID-19 patients.

Clonorchis sinensis Reinfection Rate and Reinfection Determinants: A Prospective Cohort Study in Hengxian County, Guangxi, China.

BACKGROUND: To understand Clonorchis sinensis reinfection and the determinants of reinfection in endemic areas is important in establishment of control measures. METHODS: A prospective cohort study was implemented in Hengxian County, Guangxi, China. Individuals with C. sinensis infection were completely treated, and those cured were enrolled as study subjects and followed up for 3, 6, and 12 months. The reinfection frequency and incidence were calculated, and a multivariable Cox proportional hazard model was constructed to capture reinfection determinants. RESULTS: Among 635 enrolled subjects, 436 (68.7%) completed follow-up. Of these, 177 (40.6%) were reinfected; 133 (75.1%) were reinfected once, 41 (23.2%) twice, and 3 (1.7%) three times. The incidence of reinfection was 64.0 per 100 person-years. Men (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.14-2.44), those with underlying diseases (aHR, 1.41; 95% CI, 1.02-1.95), and those with moderate- or heavy-intensity infections (aHR, 1.45; 95% CI, 1.14-1.85) had increasing reinfection probabilities. CONCLUSIONS: C. sinensis reinfection is high in endemic areas. Men and high-intensity infection are important determinants of reinfection. Repeated chemotherapy is necessary to control reinfection and its associated morbidities, especially in high-risk individuals. In addition, behavioral education is advised to decrease overall reinfection in endemic areas.

Extensive disseminated cysticercosis: a case report in Yunnan province, China.

BACKGROUND: Cysticercosis is spreading all over the world and it is a major health problem in most countries of Latin America, Africa, and Asia. Extensive disseminated cysticercosis is relatively rare and fewer than 120 case have been reported in the worldwide. We reported a rare case of extensive disseminated cysticercosis in Yunan province, China. CASE PRESENTATION: A rare case of extensive disseminated cysticercosis, in a 61-year-old male Chinese was detected from Yunnan province in 2018. Clinical and etiological examination was performed, as well as the epidemiological investigation. CONCLUSION: The life cycle of T. solium in the area where the case came from is complete. We expect this case could raise the attentions to the control of Taenia solium infection and subsequent cysticercosis there.

A case of chromoblastomycosis by Fonsecaea nubica indicating a possible insect route of transmission.

A first auricular case of chromoblastomycosis due to Fonsecaea nubica is reported in a 42-year-old Chinese male. He presented a slightly verrucous, erythematous plaque on his right auricle which had gradually extended over a 10-year period, and the patient reported a history of dog flea sting before onset of the lesions. Diagnosis was based on histopathological and mycological examination of clinical samples, which revealed muriform cells. Identification of the aetiological agent was assessed by morphological characteristics and confirmed at species level by sequencing of the rDNA internal transcribed spacer (ITS). The patient showed marked clinical improvement after 3 months combination therapy with itraconazole and terbinafine. The possible mode of transmission of auricular chromoblastomycosis is discussed.

[Gaps in Clonorchiasis Control in China].

Clonorchiasis is currently the most important food-borne parasitic disease in China. In this review, gaps in the control of clonorchiasis in China are explored through problem tree analysis. From the perspective of disease control, clonorchiasis hyper-endemicity is associated with the implicit disease burden, incomplete epidemiological map, unclear epidemiological determinants, and a lack of surveillance and report system. Thus, studies are needed to overcome these problems, to promote clonorchiasis control and elimination in China.

Inducible nitric oxide synthase response and associated cytokine gene expression in the spleen of mice infected with Clonorchis sinensis.

Clonorchis sinensis is a food-borne parasite that induces a permanent increase of nitrosation in the body upon infection. The spleen is an important secondary lymphoid organ for the regulation of immune responses locally and in the whole body. However, the functions and mechanisms of the spleen in nitric oxide (NO) responses after C. sinensis infection remain unknown. In this study, BALB/c mice were infected with 20, 40, and 80 C. sinensis metacercariae to simulate mild, moderate, and severe infections, respectively. We examined the expression of inducible nitric oxide synthase (iNOS) in the spleen and the relevant cytokine transcription in splenocytes from the mice infected with different amounts of metacercariae. The iNOS of the mice infected with 80 metacercariae was expressed in the spleen as early as 10 days post-infection (dpi) and gradually increased until 90 dpi. The iNOS expression in the mice infected with 40 metacercariae was detected only at 45 and 90 dpi, but not in the mice infected with 20 metacercariae. The level of interferon (IFN)-γ messenger RNA (mRNA) transcription in splenocytes significantly increased at 10 and 20 dpi (P < 0.05) in response to mild/moderate infection but gradually decreased to normal levels after 45 dpi. The level of IL-12p35 mRNA transcription did not change at 10 and 20 dpi but significantly decreased after 45 dpi under moderate/severe infection (P < 0.05/0.01/0.001). The level of IL-18 mRNA transcription significantly increased at 10 dpi (P < 0.05/0.01) but significantly decreased after 20 dpi (P < 0.05/0.01/0.001). These results suggest that spleen is an important organ for iNOS/NO responses, which correspond to the severity of C. sinensis infection, but cannot be attributed to the expression of the Th1 cytokines.

Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis.

The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.

[Effect of Excretory-secretory Products of Clonorchis sinensis on Nitric Oxide Production and NF-κB Activation in RAW264.7 Mouse Macrophages].

OBJECTIVE: To study the role of excretory-secretory products (ESPs) from Clonorchis sinensis in the production of nitric oxide (NO) and the activation of nuclear transcription factor kappa B (NF-κB) in the macrophages of RAW264.7 mouse. METHODS: 20 µg/ml of C. sinensis EPSs, the organic solvent extracts of EPSs (ESP-ex), and 0.1 µg/ml of lipopolysaccharide from Salmonella minnesota (LPS-SM) were used as stimulators in co-culture with RAW264.7 mouse macrophages as experimental groups. The Hank's balanced salt solution (HBSS) served as control. At the same time the RAW264.7 macrophages were stimulated with EPSs, ESP-ex, and LPS-SM, and then added 0.3 mmol/L of SMT, a specific inhibitor of iNOS as the interference groups. After co-culture for 18 days, the concentrations of NO2- in the culture supernatants were detected with Griess regents, and the activation of NF-κB was determined by transfection with a NF-κB-inducible reporter plasmid, pNiFty2-SEAP. The activities of secreted embryonic alkaline phosphatase (SEAP) in culture supernatants were quantified by using HEK-Blue™ detection medium and expressed as the value of optical density at 620 nm (A620 value). The intercellular activities of SEAP were determined by microscopic observation. RESULTS: After stimulation with both ESPs-ex and LPS-SM, the concentrations of NO2- in culture supernatants were (14.30 ± 1.62) and (14.10 ± 2.17) µmol/L, respectively, which were significantly higher than that of the control [(7.70 ± 0.95) µmol/L] (P < 0.05), and significantly decreased to (8.97 ± 0.81) and (4.96 ± 1.36) µmol/L after adding SMT, respectively (P < 0.05). However, the concentration of NO2- in ESPs stimulation group [(4.06 ± 0.62) µmol/L] was lower than that of the control (P < 0.05), and almost unchanged [(3.99 ± 0.87) µmol/L] after adding SMT (P > 0.05). SEAP activity in ESP group (0.836 ± 0.005) was significantly higher than that of the control [(0.097 ± 0.009) µmol/L] (P < 0.05). A strong blue color reaction was observed in cells of ESP group. SEAP activity of ESPs-ex and LPS groups [(0.112 ± 0.004), (0.116 ± 0.009) µmol/L] was slightly higher than that of the control (P > 0.05), and blue color reaction was observed in some cells. CONCLUSION: ESPs from C. sinensis can stimulate NF-κB activation in RAW264.7 cells. The water-soluble components of ESPs can inhibit the NO production, while ESPs-ex and LPS-SM can promote the NO production.

[SWOT Analysis of the National Survey on Current Status of Major Human Parasitic Diseases in China].

The National Survey on Current Status of Major Human Parasitic Diseases in China has been carried out since 2014 under the organization of the National Health and Family Planning Commission of the People's Republic of China. The National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (NIPD, China CDC) provided technical support and was responsible for quality control in this survey. This study used SWOT method to analyze the strengths, weaknesses, opportunities and threats that were encountered by he NIPD, China CDC during the completion of the survey. Accordingly, working strategies were proposed to facilitate the future field work.

Increasing prevalence and intensity of foodborne clonorchiasis, Hengxian County, China, 1989-2011.

During 1989-2011, three parasitic disease surveys were conducted in Hengxian County, China, where soil-transmitted helminthiases and foodborne clonorchiasis are endemic. We compared the data and found that the prevalence of helminthiases decreased and the prevalence and intensity of clonorchiasis increased over time, especially among men. Clonorchiasis control/intervention measures are urgently needed in this area.

[From recognition to practice: The 140th anniversary of the discovery of Clonorchis sinensis].

It has been the 140th anniversary since the discovery of Clonorchis sinensis, of which adult worms were found by McConnell in an oversea Chinese in Calcutta, India, September of 1874. Then, Japanese scholar Kobayashi proved that freshwater fish served as the second intermediate hosts in 1910, while another Japanese parasitologist Muto found that the first intermediate hosts were freshwater snails in 1918. However, the perniciousness has not been recognized until recently. C. sinensis infection was classified as definite carcinogen (group 1) in cholangiocarcinoma in 2009 by the International Agency for Research on Cancer, WHO, and listed as one of the 17 diseases in WHO's first report on neglected tropical diseases in 2010, while its disease burden was published on line in an international journal in 2011. Nevertheless, our awareness on and practices in the control of clonorchiasis still lag behind the reality. Great efforts on research and control of clonorchiasis are especially required in China, since China takes the biggest share in global disease burden of clonorchiasis.

[Identification of Clonorchis sinensis metacercariae based on PCR targeting ribosomal DNA ITS regions and COX1 gene].

OBJECTIVE: To identify Clonorchis sinensis metacercariae using PCR targeting ribosomal DNA ITS region and COX1 gene. METHODS: Pseudorasbora parva were collected from Hengxian County of Guangxi at the end of May 2013. Single metacercaria of C. sinensis and other trematodes were separated from muscle tissue of P. parva by digestion method. Primers targeting ribosomal DNA ITS region and COX1 gene of C. sinensis were designed for PCR and the universal primers were used as control. The sensitivity and specificity of the PCR detection were analyzed. RESULTS: C. sinensis metacercariae at different stages were identified by PCR. DNA from single C. sinensis metacercaria was detected by PCR targeting ribosomal DNA ITS region and COX1 gene. The specific amplicans have sizes of 437/549, 156/249 and 195/166 bp, respectively. The ratio of the two positive numbers in PCR with universal primers and specific primers targeting C. sinensis ribosomal DNA ITS1 and ITS2 regions was 0.905 and 0.952, respectively. The target gene fragments were amplified by PCR using COX1 gene-specific primers. The PCR with specific primers did not show any non-specific amplification. However, the PCR with universal primers targeting ribosomal DNA ITS regions performed serious non-specific amplification. CONCLUSION: C. sinensis metacercariae at different stages are identified by morphological observation and PCR method. Species-specific primers targeting ribosomal DNA ITS region show higher sensitivity and specificity than the universal primers. PCR targeting COX1 gene shows similar sensitivity and specificity to PCR with specific primers targeting ribosomal DNA ITS regions.

The relationship between daytime napping and glycemic control in people with type 2 diabetes.

Aim: To examine the association between napping characteristics and glycemic control in people with type 2 diabetes. Design: This study used a cross-sectional design. Methods: A convenience sample of people with type 2 diabetes (N=226) were included. Glycemic control was indicated by HbA1c which was measured by A1C Now®+. Napping characteristics including napping frequency, duration, timing, and type were measured by validated questionnaires. Other variables, such as insomnia, cognitive impairment, and depression were measured by the Insomnia Severity Index, Montreal Cognitive Assessment, and Patient Health Questionnaire-9, respectively. Multivariate linear regression analyses were performed. Results: The sample consisted of 122 women (54.0%), with a median age of 67 years. Their median HbA1c was 6.8%. No significant relationship was found between napping frequency and HbA1c. Among nappers, after controlling for covariates, long napping duration (≥60 min) and morning napping were both associated with poorer glycemic control. Compared with appetitive napping, restorative napping was associated with better glycemic control. Conclusion: Daytime napping (e.g., duration and type) is an important modifiable factor for glycemic control in people with type 2 diabetes. This study provides new insights into the relationship between napping and glucose management among people with diabetes.

[Research priorities for the control and elimination of major helminthiases].

In 2009, the Disease Reference Group on Helminth Infections (DRG4) was established by the Special Programme for Research and Training in Tropical Diseases (TDR) to comprehensively review recent advances, identify gaps and rank priorities in helminthiases research towards control and elimination. Six major human helminthiases are targeted, namely onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiasis and cysticercosis/taeniasis. Systematic reports made by the DRG4 from such aspects as the impact of helminthiases, control and elimination, interventions, diagnostics, social-ecology and health systems, modeling, basic research and capacity building in research was published in PLoS Neglected Tropical Diseases in 2012. Generalized introduction is presented here and further analysis of its influence on the research of the major helminthiases in China is done.

[Enterobius vermicularis infection status among children in 9 provinces/autonomous regions/municipalities of China].

OBJECTIVE: To investigate the infection status of Enterobius vermicularis among children in 9 Provinces/Autonomous regions/Municipalities (P/A/M) of China, and analyze its risk factors. METHOD: From April to December 2011, one provincial capital (prefecture-level city) and one county (city, district) were chosen as investigation spots from Guangdong, Guangxi, Hainan, Chongqing, Sichuan, Zhejiang, Fujian, Anhui and Guizhou, respectively. Children aged 2 to 12 were examined by using adhesive cellophane anal swab with round-bottom tube. Information of children's family condition, health behavior and school environment were collected by questionnairing. RESULTS: 14 964 children were examined, and 14 582 qualified questionnaires were collected. The total prevalence was 17.8% (2 659/14 964). Of the 9 P/A/M, the prevalence was highest in Hainan Province (51.1%, 869/1 701) and lowest in Anhui Province (0.8%, 13/1 589). The prevalence in urban areas (7.3%, 552/7 581) was lower than that of rural areas (28.5%, 2 107/7 383) (chi2 = 1156.73, P < 0.01). The highest prevalence in urban and rural areas was found in Haikou City(38.0%, 322/847) and Wanning City (64.1%, 547/854) of Hainan Province. The prevalence rate in males and females was 17.4% (1 410/8 128) and 18.3% (1249/6 834), respectively (chi2 = 2.192, P > 0.05). The highest prevalence in males (61.2%, 300/490) and females (67.9%, 247/364) was found in children of Wanning City. Multivariate logistic regression analysis showed that residence, education level of parents, occupation of parents, nail biting, types of classroom ground and type of boarding were the risk factors on E. vermicularis infection. CONCLUSION: The prevalence of enterobiasis in children is still high in many areas of China, and the prevention and control measures should be taken according to the risk factors.

Soil-transmitted helminthiasis in mainland China from 2016 to 2020: a population-based study.

Background: Soil-transmitted helminthiasis is epidemic in China and many other countries of the world, and has caused substantial burdens to human health. We conducted successive national monitoring in China from 2016 to 2020 to analyze the prevalence, changing trends, and factors influencing soil-transmitted helminthiasis, which provided a reference for future control strategies. Methods: Soil-transmitted helminth monitoring was carried out in 31 provinces (autonomous regions or municipalities, herein after referred to as "provinces") throughout China. Each province determined the number and location of monitoring sites (counties), and a unified sampling method was employed. At least 1,000 subjects were investigated in each monitoring county. Stool samples were collected and the modified Kato-Katz thick smear method was employed for stool examination. Infection data and the details of factors influencing soil-transmitted helminthiasis from 2016 to 2020 were collected from national monitoring sites. Additional influencing factors such as environment, climate and human activities were obtained from authoritative websites. Prevalence of soil-transmitted helminths was presented by species, province, sex, and age group. ArcGIS software was used to conduct spatial autocorrelation and hotspot analysis on the infection data. A Poisson distribution model and SaTScan software were used to analyze the infection data with retrospective spatiotemporal scan statistics. A database was built by matching village-level infection rate data with influencing factors. Subsequently, machine learning methods, including a Linear Regression (LR), a Random Forest (RF), a Gradient Boosted Machine (GBM), and an Extreme gradient boosting (XGBOOST) model was applied to construct a model to analyze the main influencing factors of soil-transmitted helminthiasis. Findings: The infection rates of soil-transmitted helminths at national monitoring sites from 2016 to 2020 were 2.46% (6,456/262,380), 1.78% (5,293/297,078), 1.29% (4,200/326,207), 1.40% (5,959/424,766), and 0.84% (3,485/415,672), respectively. The infection rate of soil-transmitted helminths in 2020 decreased by 65.85% compared to that in 2016. From 2016 to 2020, the infection rate of soil-transmitted helminthiasis was relatively high in southern and southwestern China, including Hainan, Yunnan, Sichuan, Guizhou, and Chongqing. In general, the infection rate was higher in females than in males, with the highest rate in the population aged 60 years and above, and the lowest in children aged 0-6 years. Global autocorrelation and hotspot analyses revealed spatial aggregation in both the national and local distribution of soil-transmitted helminthiasis in China from 2016 to 2020. The hotspots were concentrated in southwestern China. The spatiotemporal scanning analysis revealed aggregation years from 2016 to 2017 located in southwestern China, including Yunnan, Sichuan, Chongqing, Guizhou and Guangxi. The RF model was the best fit model for the infection rate of soil-transmitted helminths in China. The top six influencing factors of this disease in the model were landform, barefoot farming, isothermality, temperature seasonality, year, and the coverage of sanitary toilets. Interpretation: The overall infection rate of soil-transmitted helminths in China showed a decreasing trend from 2016-2020 due to the implementation of control measures and the economic boom in China. However, there are still areas with high infection rates and the distribution of such areas exhibit spatiotemporal aggregation. As a strategic next step, control measures should be adjusted to local conditions based on the main influencing factors and the prevalence of different sites to aid in the control and elimination of soil-transmitted helminthiasis. Funding: This research was funded by the National Key Research and Development Program of China (Grant Nos. 2021YFC2300800 and 2021YFC2300804) and the National Natural Science Foundation of China (Grant No. 32161143036).

[A cross analysis on the capability of examining helminths: national technique competition for parasitic disease diagnosis in 2011].

OBJECTIVE: To understand the comprehensive capability of helminth detection among professionals at different level of parasitic disease control institutions and promote the overall strength of diagnosis. METHODS: Four professionals from each parasitic diseases control institutions were selected as contestant (age < 45 and at least two contestant from county-level institution). The content of contest included making stool slides with Kato-Katz method (five slides in thirty minutes, a total score of 15 and 9 as passing score) and identification of eleven common helminth eggs with microscopy (ten slides, five minutes per slide, a total score of 60, 36 as passing score). RESULTS: The average score of making slides in 119 contestants from 30 provinces was 11.4, and 119 contestants passed accounted for 93.3%. The average score of film-reading was 22.0, and 20 contestants passed accounted for 16.8%. There were no statistically significant differences between the results in different gender, age (< or = 30, 31-40, > 40), job title (the junior, intermediate, and senior), institution level (provincial, municipal, and county level) (P > 0.05). By Kato-Katz slide-making and film-reading, the scores in contestants from provinces with schistosomiasis control task (12.1 +/- 1.7, 32.1 +/- 11.5, respectively) were better than contestants from other provinces (11.1 +/- 1.8, 18.1 +/- 10.5, respectively). The scores in contestants from western (18.4 +/- 11.4) were lower than those from eastern (25.2 +/- 12.4) and central (24.1 +/- 13.1) for film-reading. CONCLUSION: The overall capability of parasitic disease examination is unbalanced among regions, and evidently there is a need to strengthen the capacity of pathogen detection in the disease control programs.

[A cross analysis on the theoretical testing results on diagnosis of common parasitic diseases: national technique competition China].

OBJECTIVE: To understand the theoretical level among technicians from disease control and prevention institutions on basic knowledge of parasitic disease diagnosis. METHODS: A national competition on basic knowledge of parasitic disease detection was organized in September, 2011, with 119 technicians participating from disease control and prevention institutions at province, prefecture or county level in 30 provinces. Database was constructed with the essential information of participants and scores of testing results. T-test or one-way Anova methods were used to analyze the scores by gender, age, professional title, institutions and places of participants. RESULTS: The scores of the competitors were in the range of 40-93 with an average value of 66.37 +/- 11.80 and a passing rate of 74.95%. No difference was shown by gender, age and professional tide (P > 0.05). Except the knowledge of helminth detection, the score on the knowledge in other aspects was higher among the technicians from provinces with control activities of schistosomiasis and other parasitic infections than those from provinces without the control activities (P < 0.05). The same was true in technicians from areas with or without malaria control activities (P < 0.05). CONCLUSION: The level of basic knowledge on parasite detection is low in general among technicians at the institutions of parasitic disease control, and therefore, training needs to be strengthened.

Epidemiological Profile and Spatial Patterns of Enterobiasis in Children Aged 3-9 Years in China from 2016 to 2020.

(1) Background: Enterobius vermicularis infection causes a significant health burden in children. The infection occurs throughout the country and remains a serious public concern in China. Therefore, it is necessary to know the situation of E. vermicularis infection, to provide a scientific basis for the disease control and the optimum conditions for children's growth. (2) Methods: Descriptive epidemiological analysis was implemented to demonstrate the status and changing trend of E. vermicularis infection from 2016 to 2020, while the spatial distribution characteristics and spatial-temporal clustering were illuminated by spatial autocorrelation analysis and spatio-temporal scanning analysis. (3) Results: The infection of E. vermicularis showed a fluctuating downward trend with a decline of 32.00% in 2020 compared to that in 2016 and was concentrated in central and southern China. There was no significant difference in infection rate between boys and girls, while the high infection rate was presented in 4-, 5- and 6- year-old children. The hotspots and spatial clustering areas were mainly concentrated in southern China. (4) Conclusions: From 2016 to 2020, the infection rate of E. vermicularis in children aged 3 to 9 years in China demonstrated a declining trend, and its distribution showed spatial clustering, mainly in southern China. Therefore, it is necessary to strengthen surveillance and implement control measures in combination with health education and environmental improvement.

COVIDpro: Database for mining protein dysregulation in patients with COVID-19.

Background: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still has limited treatment options partially due to our incomplete understanding of the molecular dysregulations of the COVID-19 patients. We aimed to generate a repository and data analysis tools to examine the modulated proteins underlying COVID-19 patients for the discovery of potential therapeutic targets and diagnostic biomarkers. Methods: We built a web server containing proteomic expression data from COVID-19 patients with a toolset for user-friendly data analysis and visualization. The web resource covers expert-curated proteomic data from COVID-19 patients published before May 2022. The data were collected from ProteomeXchange and from select publications via PubMed searches and aggregated into a comprehensive dataset. Protein expression by disease subgroups across projects was compared by examining differentially expressed proteins. We also visualize differentially expressed pathways and proteins. Moreover, circulating proteins that differentiated severe cases were nominated as predictive biomarkers. Findings: We built and maintain a web server COVIDpro ( https://www.guomics.com/covidPro/ ) containing proteomics data generated by 41 original studies from 32 hospitals worldwide, with data from 3077 patients covering 19 types of clinical specimens, the majority from plasma and sera. 53 protein expression matrices were collected, for a total of 5434 samples and 14,403 unique proteins. Our analyses showed that the lipopolysaccharide-binding protein, as identified in the majority of the studies, was highly expressed in the blood samples of patients with severe disease. A panel of significantly dysregulated proteins was identified to separate patients with severe disease from non-severe disease. Classification of severe disease based on these proteomic signatures on five test sets reached a mean AUC of 0.87 and ACC of 0.80. Interpretation: COVIDpro is an online database with an integrated analysis toolkit. It is a unique and valuable resource for testing hypotheses and identifying proteins or pathways that could be targeted by new treatments of COVID-19 patients. Funding: National Key R&D Program of China: Key PDPM technologies (2021YFA1301602, 2021YFA1301601, 2021YFA1301603), Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars (LR19C050001), Hangzhou Agriculture and Society Advancement Program (20190101A04), National Natural Science Foundation of China (81972492) and National Science Fund for Young Scholars (21904107), National Resource for Network Biology (NRNB) from the National Institute of General Medical Sciences (NIGMS-P41 GM103504). Research in context: Evidence before this study: Although an increasing number of therapies against COVID-19 are being developed, they are still insufficient, especially with the rise of new variants of concern. This is partially due to our incomplete understanding of the disease’s mechanisms. As data have been collected worldwide, several questions are now worth addressing via meta-analyses. Most COVID-19 drugs function by targeting or affecting proteins. Effectiveness and resistance to therapeutics can be effectively assessed via protein measurements. Empowered by mass spectrometry-based proteomics, protein expression has been characterized in a variety of patient specimens, including body fluids (e.g., serum, plasma, urea) and tissue (i.e., formalin-fixed and paraffin-embedded (FFPE)). We expert-curated proteomic expression data from COVID-19 patients published before May 2022, from the largest proteomic data repository ProteomeXhange as well as from literature search engines. Using this resource, a COVID-19 proteome meta-analysis could provide useful insights into the mechanisms of the disease and identify new potential drug targets.Added value of this study: We integrated many published datasets from patients with COVID-19 from 11 nations, with over 3000 patients and more than 5434 proteome measurements. We collected these datasets in an online database, and generated a toolbox to easily explore, analyze, and visualize the data. Next, we used the database and its associated toolbox to identify new proteins of diagnostic and therapeutic value for COVID-19 treatment. In particular, we identified a set of significantly dysregulated proteins for distinguishing severe from non-severe patients using serum samples.Implications of all the available evidence: COVIDpro will support the navigation and analysis of patterns of dysregulated proteins in various COVID-19 clinical specimens for identification and verification of protein biomarkers and potential therapeutic targets.