ABSTRACT
Background Wastewater surveillance provides real-time, cost-effective monitoring of SARS-CoV-2 transmission. We developed the first city-level wastewater warning system in mainland China, located in Shenzhen. Our study aimed to reveal cryptic transmissions under the "dynamic COVID-zero" policy and characterize the dynamics of the infected population and variant prevalence, and then guide the allocation of medical resources during the transition to "opening up" in China. Methods In this population-based study, a total of 1,204 COVID-19 cases were enrolled to evaluate the contribution of Omicron variant-specific faecal shedding rates in wastewater. After that, wastewater samples from up to 334 sites distributed in communities and port areas in two districts of Shenzhen covering 1.74 million people were tested daily to evaluate the sensitivity and specificity of this approach and were validated against daily SARS-CoV-2 screening. After the public health policy was switched to "opening up" in December 7, 2022, we conducted wastewater surveillance at wastewater treatment plants and pump stations covering 3.55 million people to estimate infected populations using model prediction and detect the relative abundance of SARS-CoV-2 lineages using wastewater sequencing. Findings In total, 82.4% of SARS-CoV-2 Omicron cases tested positive for faecal viral RNA within the first four days after the diagnosis, which was far more than the proportion of the ancestral variant. A total of 27,759 wastewater samples were detected from July 26 to November 30 in 2022, showing a sensitivity of 73.8% and a specificity of 99.8%. We further found that wastewater surveillance played roles in providing early warnings and revealing cryptic transmissions in two communities. Based on the above results, we employed a prediction model to monitor the daily number of infected individuals in Shenzhen during the transition to "opening up" in China, with over 80% of the population infected in both Futian District and Nanshan District. Notably, the prediction of the daily number of hospital admission was consistent with the actual number. Further sequencing revealed that the Omicron subvariant BA.5.2.48 accounted for the most abundant SARS-CoV-2 RNA in wastewater, and BF.7.14 and BA.5.2.49 ranked second and third, respectively, which was consistent with the clinical sequencing. Interpretation This study provides a scalable solution for wastewater surveillance of SARS-CoV-2 to provide real-time monitoring of the new variants, infected populations and facilitate the precise prediction of hospital admission. This novel framework could be a One Health system for the surveillance of other infectious and emerging pathogens with faecal shedding and antibiotic resistance genes in the future. Funding Sanming Project of Medicine in Shenzhen, Shenzhen Key Medical Discipline Construction Fund.
Subject(s)
COVID-19ABSTRACT
In order to couple the training and dispatch tasks of emergency rescue, and to improve the work efficiency of emergency rescue personnel, an optimization model for the integration of training ＆ assignment of emergency rescuers was established, which took maximizing the overall time satisfaction and minimizing the total cost of training ＆ assignment as the objective function.Taking COVID-19 epidemic as the research background, the simulation and solving were conducted by using the Lingo software.The results showed that the short-term training could effectively improve the rescue capability of emergency rescuers, and meet the requirements of emergency rescue time and rescue tasks of the disaster-affected sites.
ABSTRACT
Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400[~]480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with [≥] 50% decrease in MN titers when comparing the available peak and current MN titers ([≥] 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.
Subject(s)
COVID-19ABSTRACT
Abstract Background SARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed. Methods Epidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines. Results 40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. Conclusion COVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.
Subject(s)
COVID-19ABSTRACT
Background SARS-CoV-2 could infect people at all ages, and the viral shedding and immunological features of children COVID-19 patients were analyzed.Methods Epidemiological information and clinical data were collected from 35 children patients. Viral RNAs in respiratory and fecal samples were detected. Plasma of 11 patients were collected and measured for 48 cytokines.Results 40% (14/35) of the children COVID-19 patients showed asymptomatic infections, while pneumonia shown by CT scan occurred in most of the cases (32/35, 91.43%). Elevated LDH, AST, CRP, neutropenia, leukopenia, lymphopenia and thrombocytopenia occurred in some cases, and CD4 and CD8 counts were normal. A total of 22 cytokines were significantly higher than the healthy control, and IP-10, IFN-α2 of them in children were significantly lower than the adult patients. Meanwhile, MCP-3, HGF, MIP-1α, and IL-1ra were similar or lower than healthy control, while significantly lower than adult patients. Viral RNAs were detected as early as the first day after illness onset (d.a.o) in both the respiratory and fecal samples. Viral RNAs decreased as the disease progression and mostly became negative in respiratory samples within 18 d.a.o, while maintained relatively stable during the disease progression and still detectable in some cases during 36~42 d.a.o. Conclusion COVID-19 in children was mild, and asymptomatic infection was common. Immune responses were relatively normal in children COVID-19 patients. Cytokine storm also occurred in children patients, while much weaker than adult patients. Positive rate of viral RNAs in fecal samples was high, and profile of viral shedding were different between respiratory and gastrointestinal tract.
Subject(s)
Thrombocytopenia , Pneumonia , Leukopenia , Neutropenia , COVID-19 , LymphopeniaABSTRACT
Wuhan has the highest number of deaths and mortality from COVID-19 in China to date, but the reason remains unknown. Here we compared patients with COVID-19 with a history of traveling in Wuhan with those who did not travel in Wuhan in the early stage of pandemic with respect to a series of clinical characteristics and laboratory parameters. We observed that patients who had traveled in Wuhan had an increased rate of severe disease and longer viral duration along with fewer CD4+ and CD8+ T cells, although there was no significant difference in viral load between the two groups.
Subject(s)
COVID-19 , DiseaseABSTRACT
Background: This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes. Methods: 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data. Results: Levels of ALT, AST, cTnI, Cr, PT, APTT and D-DIC of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-DIC and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective. Conclusions: There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients’ multiple organ function damage could be predicted and used as guidance of treatment.
Subject(s)
Pneumonia , COVID-19ABSTRACT
Background: This study aims to analyze the changes and significance of organ function indices in patients with severe Coronavirus Disease 2019 (COVID-19) pneumonia for prediction of major organ damages and guiding treatment schemes.Methods: 63 patients with severe COVID-19 pneumonia were selected as the severe group and 73 patients with mild syndromes were selected as the mild group. SAS9.4 software was used for statistical analysis of the data.Results: Levels of ALT, AST, cTnI, Cr, PT, APTT and D-DIC of the severe group were significantly higher while PLT was lower than those of the mild group. The data of all quantitative variables were converted into categorical variables. Significantly higher levels of AST, ALB, D-DIC and higher proportion of bilateral lung involvement were observed from the severe group comparing to those in the mild group, while the difference in the other indices between the two groups was insignificant in statistical perspective.Discussion: There are significant differences in the levels of multiple organ function indices between the severe group and the mild group of patients with COVID-19 pneumonia infection. Through examining the relevant indices, conditions of patients’ multiple organ function damage could be predicted and used as guidance of treatment.
Subject(s)
Pneumonia , COVID-19ABSTRACT
BackgroundThe novel coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, Hubei, China since Dec 2019 and cases of infection have been continuously reported in various countries. It is now clear that the COVID-19 coronavirus is transmissible from human to human. Nucleic acid detection is considered as the gold standard for the diagnosis of COVID-19. In this case report, we describe our experience in detection of COVID-19 from a confirmed patient using nucleic acid test of bronchoalveolar-lavage fluid (BALF) samples but not nasopharyngeal swabs.Case presentationWe present a case of severely ill COVID-19 infected 46-year-old man with fever, coughing and chest tightness. We performed viral detection using his BALF samples and imaging method (CT) for confirmation. The patient received combination of interferonalfa-1b and ribavirin, lopinavir and ritonavir for antiviral treatment at different stages. Other medication was also given to him in combination for anti-inflammation, intestinal microbial regulation, phlegm elimination, liver protection and pulmonary fibrosis prevention purposes. We provided oxygen supply to him using BIPAP ventilator and high-flow humidification oxygen therapy instrument to facilitate respiration. The patient was cured and discharged.ConclusionThis case report described an effective supportive medication scheme to treat COVID-19 infected patient and emphasized the necessity of detection of the viral genome using BALF samples and its significance in the diagnosis and prognosis of the disease.
Subject(s)
Infections , Chest Pain , Fever , COVID-19 , Inflammation , Pulmonary Fibrosis , Cerebrospinal Fluid LeakABSTRACT
The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.
Subject(s)
COVID-19ABSTRACT
Summary Background The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. Methods A total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. Findings Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). Interpretation The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.
Subject(s)
COVID-19 , InfectionsABSTRACT
The novel coronavirus SARS-CoV-2, etiological agent of recently named Coronavirus infected disease (COVID-19) by WHO, has caused more than 2, 000 deaths worldwide since its emergency in Wuhan City, Hubei province, China, in December, 2019. The symptoms of COVID-19 varied from modest, mild to acute respiratory distress syndrome (ARDS), and the latter of which is generally associated with deregulated immune cytokine production; however, we currently know little as to the interplay between the extent of clinical symptoms and the compositions of lung immune microenvironment. Here, we comprehensively characterized the lung immune microenvironment with the bronchoalveolar lavage fluid (BALF) from 3 severe and 3 mild COVID-19 patients and 8 previously reported healthy lung controls through single-cell RNA sequence (scRNA-seq) combined with TCR-seq. Our data shows that monocyte-derived FCN1+ macrophages, whereas notFABP4+ alveolar macrophages that represent a predominant macrophage subset in BALF from patients with mild diseases, overwhelm in the severely damaged lungs from patients with ARDS. These cells are highly inflammatory and enormous chemokine producers implicated in cytokine storm. Furthermore, the formation of tissue resident, highly expanded clonal CD8+ T cells in the lung microenvironment of mild symptom patients suggests a robust adaptive immune response connected to a better control of COVID-19. This study first reported the cellular atlas of lung bronchoalveolar immune microenvironment in COVID-19 patients at the single-cell resolution, and unveiled the potential immune mechanisms underlying disease progression and protection in COVID-19.
Subject(s)
Coronavirus Infections , Adenocarcinoma, Bronchiolo-Alveolar , Lung Diseases , Respiratory Distress Syndrome , COVID-19ABSTRACT
Background: The outbreak of novel coronavirus pneumonia (NCP) caused by 2019-nCoV spread rapidly, and elucidation the diagnostic accuracy of different respiratory specimens is crucial for the control and treatment of this diseases. Methods: Respiratory samples including nasal swabs, throat swabs, sputum and bronchoalveolar lavage fluid (BALF) were collected from Guangdong CDC confirmed NCP patients, and viral RNAs were detected using a CFDA approved detection kit. Results were analyzed in combination with sample collection date and clinical information. Finding: Except for BALF, the sputum possessed the highest positive rate (74.4%~88.9%), followed by nasal swabs (53.6%~73.3%) for both severe and mild cases during the first 14 days after illness onset (d.a.o). For samples collected [≥] 15 d.a.o, sputum and nasal swabs still possessed a high positive rate ranging from 42.9%~61.1%. The positive rate of throat swabs collected [≥] 8 d.a.o was low, especially in samples from mild cases. Viral RNAs could be detected in all the lower respiratory tract of severe cases, but not the mild cases. CT scan of cases 02, 07 and 13 showed typical viral pneumonia with ground glass opacity, while no viral RNAs were detected in first three or all the upper respiratory samples. Interpretation: Sputum is most accurate for laboratory diagnosis of NCP, followed by nasal swabs. Detection of viral RNAs in BLAF is necessary for diagnosis and monitoring of viruses in severe cases. CT scan could serve as an important make up for the diagnosis of NCP. Funding National Science and Technology Major Project, Sanming Project of Medicine and China Postdoctoral Science Foundation.