A field epidemiological investigation and emergency response of a confirmed COVID-19 case of a foreign airline cargo service personnel in Shanghai's international airport

Objective: To conduct on-site epidemiological investigation, emergency response, tracing of infection source and analysis of a confirmed COVID-19 case of a foreign airline cargo service staff member in Shanghai's international airport, aiming to provide reference for prevention of imported COVID-19 cases under regular prevention and control of COVID-19.

Impact of COVID-19 control measures on the spread of influenza

Objective: To analyze the effects of respiratory control measures before and after COVID-19 epidemic on influenza virus.

Uncertainty Modeling of a Modified SEIR Epidemic Model for COVID-19.

Based on SEIR (susceptible-exposed-infectious-removed) epidemic model, we propose a modified epidemic mathematical model to describe the spread of the coronavirus disease 2019 (COVID-19) epidemic in Wuhan, China. Using public data, the uncertainty parameters of the proposed model for COVID-19 in Wuhan were calibrated. The uncertainty of the control basic reproduction number was studied with the posterior probability density function of the uncertainty model parameters. The mathematical model was used to inverse deduce the earliest start date of COVID-19 infection in Wuhan with consideration of the lack of information for the initial conditions of the model. The result of the uncertainty analysis of the model is in line with the observed data for COVID-19 in Wuhan, China. The numerical results show that the modified mathematical model could model the spread of COVID-19 epidemics.

Epidemiological investigation of a Coronavirus disease 2019 epidemic and emergency response in Shanghai

Objective: To analyze the epidemiological investigation results and emergency response to a coronavirus disease 2019 (COVID-19) epidemic in Shanghai.

Long-term immune responses in patients with confirmed novel coronavirus disease-2019: a 9-month prospective cohort study in Shanghai, China.

BACKGROUND: The duration of antibodies against SARS-CoV-2 in Covid-19 patients remains uncertain. Longitudinal serological studies are needed to prevent disease and transmission of the virus. METHODS: In 2020, 414 blood samples were tested, obtained from 157 confirmed Covid-19 patients, in a prospective cohort study in Shanghai. RESULTS: The seropositive rate of IgM peaked at 40.5% (17/42) within 1 month after illness onset and then declined. The seropositive rate of IgG was 90.6% (58/64) after 2 months, remained above 85% from 2 to 9 months and was 90.9% (40/44) after 9 months. Generalized estimating equations models suggested that IgM (P < 0.001) but not IgG significantly decreased over time. Age ≥ 40 years (adjusted odds ratio [aOR] 4.531; 95% confidence interval [CI] 1.879-10.932), and cigarette smoking (aOR 0.344; 95% CI 0.124-0.951) were associated with IgG, and age ≥ 40 years (aOR 2.820; 95% CI 1.579-5.036) was associated with IgM. After seroconversion, over 90% and 75.1% of subjects were estimated to remain IgG-positive 220 and 254 days, respectively. Of 1420 self-reported symptoms questionnaires, only 5% reported symptoms 9 months after onset. CONCLUSIONS: In patients with a history of natural infection, anti-SARS-CoV-2 IgG is long-lived, being present for at least 9 months after illness onset. The long duration of natural immunity can mitigate and eliminate Covid-19 and the ongoing pandemic.

Epidemiological and co-infection characteristics of common human coronaviruses in Shanghai, 2015-2020: a retrospective observational study.

The coronavirus disease (COVID-19) pandemic is a major challenge worldwide. However, the epidemic potential of common human coronaviruses (HCoVs) remains unclear. This study aimed to determine the epidemiological and co-infection characteristics of common HCoVs in individuals with influenza-like illness (ILI) and severe acute respiratory infection (SARI). This retrospective, observational, multicentre study used data collected from patients admitted to nine sentinel hospitals with ILI and SARI from January 2015 through December 2020 in Shanghai, China. We prospectively tested patients for a total of 22 respiratory pathogens using multi-real-time polymerase chain reaction. Of the 4541 patients tested, 40.37% (1833/4541) tested positive for respiratory pathogens and 3.59% (163/4541) tested positive for common HCoVs. HCoV infection was more common in the non-endemic season for respiratory pathogens (odds ratio: 2.33, 95% confidence interval: 1.64-3.31). HCoV-OC43 (41.72%, 68/163) was the most common type of HCoV detected. The co-infection rate was 31.29% (51/163) among 163 HCoV-positive cases, with HCoV-229E (53.13%, 17/32), the HCoV type that was most frequently associated with co-infection. Respiratory pathogens responsible for co-infections with HCoVs included parainfluenza virus, rhinovirus/enterovirus, influenza A virus, and adenovirus. Furthermore, we identified one patient co-infected with HCoV-OC43 and HCoV-NL63/HKU1. The prevalence of common HCoVs remains low in ILI/SARI cases, in Shanghai. However, the seasonal pattern of HCoVs may be opposite to that of other respiratory pathogens. Moreover, HCoVs are likely to co-exist with specific respiratory pathogens. The potential role of co-infections with HCoVs and other pathogenic microorganisms in infection and pathogenesis of ILI and SARI warrants further study.

Viral mimetic poly(I:C) induces neutrophil extracellular traps via PAD4 to promote inflammation and thrombosis.

Neutrophil extracellular traps (NETs) are extracellular webs of DNA, histones and granular contents that are released by neutrophils to control infections. However, NETs that is not properly regulated can propagate inflammation and thrombosis. It was recognized that viruses can induce NETs. As a synthetic analog of viral double-stranded (ds) RNA, polyinosinic-polycytidylic acid [poly(I:C)] is known to induce inflammation and thrombosis. However, whether and how poly(I:C) modulates NETs remains unclear. Here, we have demonstrated that poly(I:C) induced extracellular DNA traps in human neutrophils in a dose-dependent manner. Further, poly(I:C) or dsRNA virus elevated the levels of myeloperoxidase-DNA complexes and citrullinated histone H3, which are specific markers of NETs, in both neutrophil supernatants and mouse plasma. Interestingly, a potent peptidylarginine deiminase 4 (PAD4) inhibitor, BB-CL-Amidine (BB-CLA) or PAD4 knockdown effectively prevented poly(I:C)-induced NETs formation and release. In addition, BB-CLA abrogated poly(I:C)-triggered neutrophil activation and infiltration, and vascular permeability in lungs. BB-CLA also attenuated poly(I:C)-induced thrombocytopenia in circulation, fibrin deposition and thrombus formation in tissues. Taken together, these results suggest that viral mimetic poly(I:C) may induce NETs-dependent inflammation and thrombosis through PAD4, and that inhibiting PAD4 may become a good strategy to protect against viral infection-caused inflammation/thrombosis-related pathological conditions of diseases.

Urban Hierarchical Open-up Schemes Based on Fine Regional Epidemic Data for the Lockdown in COVID-19

During the COVID-19 outbreaking, China's lock-down measures have played an outstanding role in epidemic prevention;many other countries have followed similar practices. The policy of social alienation and community containment was executed to reduce civic activities, which brings up numerous economic losses. It has become an urgent task for these countries to open-up, while the epidemic has almost under control. However, it still lacks sufficient literature to set appropriate open-up schemes that strike a balance between open-up risk and lock-down cost. Big data collection and analysis, which play an increasingly important role in urban governance, provide a useful tool for solving the problem. This paper explores the influence of open-up granularity on both the open-up risk and the lock-down cost. It proposes an SEIR-CAL model considering the effect of asymptomatic patients based on propagation dynamics, and offered a model to calculate the lock-down cost based on the lock-down population. A simulation experiment is then carried out based on the mass actual data of Wuhan City to explore the influence of open-up granularity. Finally, this paper proposed the evaluation score (ES) to comprehensively measure schemes with different costs and risks. The experiments suggest that when released under the non-epidemic situation, the open-up scheme with the granularity refined to the block has the optimal ES. Results indicated that the fine-grained open-up scheme could significantly reduce the lock-down cost with a relatively low open-up risk increase.

Epidemiological and clinical characteristics of 161 discharged cases with coronavirus disease 2019 in Shanghai, China.

BACKGROUND: In December 2019, the outbreak of coronavirus disease 2019 (COVID-19) began in Wuhan, China, and rapidly spread to other regions. We aimed to further describe the epidemiological and clinical characteristics of discharged COVID-19 cases and evaluate the public health interventions. METHODS: We collected epidemiological and clinical data of all discharged COVID-19 cases as of 17 February 2020 in Shanghai. The key epidemiological distributions were estimated and outcomes were also compared between patients whose illness were before 24 January and those whose illness were after 24 January. RESULTS: Of 161 discharged COVID-19 cases, the median age was 45 years, and 80 (49.7%) cases were male. All of the cases were categorized as clinical moderate type. The most common initial symptoms were fever (85.7%), cough (41.0%), fatigue (19.3%), muscle ache (17.4%), sputum production (14.9%), and there were six asymptomatic cases. 39 (24.2%) cases got infected in Shanghai, and three of them were second-generation cases of Shanghai native cases. The estimated median of the time from onset to first medical visit, admission, disease confirmation, and discharge for 161 cases was 1.0 day (95% CI, 0.6-1.2), 2.0 days (95% CI, 1.5-2.6), 5.2 days (95% CI, 4.6-5.7), 18.1 days (95% CI, 17.4-18.8), respectively. The estimated median of the time from admission to discharge was 14.0 days (95% CI, 13.3-14.6). The time from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. In Cox regression model, the significant independent covariates for the duration of hospitalization were age, the time from onset to admission and the first-level public health emergency response. CONCLUSIONS: Local transmission had occurred in Shanghai in late January 2020. The estimated median of the time from onset to discharge of moderate COVID-19 was 18.1 days in Shanghai. Time intervals from onset to first medical visit, admission and disease confirmation were all shortened after the Shanghai's first-level public health emergency response. Age, the first-level public health emergency response and the time from onset to admission were the impact factors for the duration of hospitalization.

Phospho-Tyr705 of STAT3 is a therapeutic target for sepsis through regulating inflammation and coagulation

BACKGROUND: Sepsis is an infection-induced aggressive and life-threatening organ dysfunction with high morbidity and mortality worldwide. Infection-associated inflammation and coagulation promote the progression of adverse outcomes in sepsis. Here, we report that phospho-Tyr705 of STAT3 (pY-STAT3), not total STAT3, contributes to systemic inflammation and coagulopathy in sepsis. METHODS: Cecal ligation and puncture (CLP)-induced septic mice were treated with BP-1-102, Napabucasin, or vehicle control respectively and then assessed for systemic inflammation, coagulation response, lung function and survival. Human pulmonary microvascular endothelial cells (HPMECs) and Raw264.7 cells were exposed to lipopolysaccharide (LPS) with pharmacological or genetic inhibition of pY-STAT3. Cells were assessed for inflammatory and coagulant factor expression, cell function and signaling. RESULTS: Pharmacological inhibition of pY-STAT3 expression by BP-1-102 reduced the proinflammatory factors, suppressed coagulation activation, attenuated lung injury, alleviated vascular leakage and improved the survival rate in septic mice. Pharmacological or genetic inhibition of pY-STAT3 diminished LPS-induced cytokine production in macrophages and protected pulmonary endothelial cells via the IL-6/JAK2/STAT3, NF-κB and MAPK signaling pathways. Moreover, the increase in procoagulant indicators induced by sepsis such as tissue factor (TF), the thrombin-antithrombin complex (TAT) and D-Dimer were down-regulated by pY-STAT3 inhibition. CONCLUSIONS: Our results revealed a therapeutic role of pY-STAT3 in modulating the inflammatory response and defective coagulation during sepsis. Video Abstract.

Aggressive Quarantine Measures Reduce the High Morbidity of COVID-19 in Patients on Maintenance Hemodialysis and Medical Staff of Hemodialysis Facilities in Wuhan, China.

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Medical staff of dialysis facilities without sufficient biosecurity protection are susceptible once exposed to asymptomatic coronavirus disease 2019 (COVID-19) patients. This study evaluated the epidemiological characteristics of COVID-19 in all MHD patients and medical staff of dialysis facilities in Wuhan, China. METHODS: We collected COVID-19 morbidity and mortality data from MHD patients and medical staff from 52 hemodialysis centers in Wuhan. Then, we analyzed the symptoms and signs of patients and staff in our hospital (Tongji Hospital in Wuhan), and chest CT, SARS-CoV-2 nucleic acid detection and laboratory tests were performed. After aggressive quarantine of the COVID-19 patients, we followed up on the prognosis of them. RESULTS: We analyzed the hemodialysis data from Wuhan and found that 10% of MHD patients and 6.0% of medical staff were suspected of COVID-19. Further detection of SARS-CoV-2 nucleic acid showed that 1.7% of MHD patients and 2.9% of medical staff were confirmed as having COVID-19. In our facility, 18.9% (46/244) of patients and 9.5% (6/63) of medical staff were suspected of COVID-19. Among them, 2.9% (7/244) of MHD patients and 4.8% (3/63) of medical staff tested positive for SARS-CoV-2 were confirmed as having COVID-19. Interestingly, 87.0% of MHD patients suspected of COVID-19 did not have obvious symptoms, but the CT screening showed features of viral pneumonia. There were no significant differences in symptoms, CT findings, comorbidity and laboratory findings of SARS-CoV-2 nucleic-acid-positive and -negative patients. We followed up these patients and found that 57 patients with COVID-19 died (COVID-19 mortality 8.9%). Two patients from our dialysis center with COVID-19 (mortality 4.3%) died. No new infections occurred in our dialysis center after aggressive quarantine was initiated. CONCLUSIONS: The SARS-CoV-2 infection rates in MHD patients and medical staff in dialysis facilities were both high in Wuhan. Frequent chest CT and SARS-CoV-2 nucleic acid detection were needed to screen COVID-19 patients in dialysis facilities. Through the lessons of this experience on the aggressive diagnosis and quarantine measures of COVID-19 patients, we hope medical staff avoid more infections in serious epidemic areas.

Three infection clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19), Shanghai, China, January to February 2020.

We report three clusters related with potential pre-symptomatic transmission of coronavirus disease (COVID-19) between January and February 2020 in Shanghai, China. Investigators interviewed suspected COVID-19 cases to collect epidemiological information, including demographic characteristics, illness onset, hospital visits, close contacts, activities' trajectories between 14 days before illness onset and isolation, and exposure histories. Respiratory specimens of suspected cases were collected and tested for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) assay. The interval between the onset of illness in the primary case and the last contact of the secondary case with the primary case in our report was 1 to 7 days. In Cluster 1 (five cases), illness onset in the five secondary cases was 2 to 5 days after the last contact with the primary case. In Cluster 2 (five cases) and Cluster 3 (four cases), the illness onset in secondary cases occurred prior to or on the same day as the onset in the primary cases. The study provides empirical evidence for transmission of COVID-19 during the incubation period and indicates that pre-symptomatic person-to-person transmission can occur following sufficient exposure to confirmed COVID-19 cases. The potential pre-symptomatic person-to-person transmission puts forward higher requirements for prevention and control measures.

Clusters of 2019 coronavirus disease (COVID-19) cases in Chinese tour groups.

International travel may facilitate the spread of the novel coronavirus disease (COVID-19). The study describes clusters of COVID-19 cases within Chinese tour groups travelling in Europe January 16-28. We compared characteristics of cases and non-cases to determine transmission dynamics. The index case travelled from Wuhan, China, to Europe on 16 January 2020, and to Shanghai, China, on 27 January 2020, within a tour group (group A). Tour groups with the same outbound flight (group B) or the same tourism venue (group D) and all Chinese passengers on the inbound flight (group C) were investigated. The outbreak involved 11 confirmed cases, 10 suspected cases and six tourists who remained healthy. Group A, involving seven confirmed cases and six suspected cases, consisted of familial transmission followed by propagative transmission. There was less pathogenicity with propagative transmission than with familial transmission. Disease was transmitted in shared outbound flights, shopping venues within Europe and inbound flight back to China. The novel coronavirus caused clustered cases of COVID-19 in tour groups. When tourism and travel opens up, governments will need to improve screening at airports and consider increased surveillance of tour groups-particularly those with older tour members.

Pre-symptomatic transmission of novel coronavirus in community settings.

We used contact tracing to document how COVID-19 was transmitted across 5 generations involving 10 cases, starting with an individual who became ill on January 27. We calculated the incubation period of the cases as the interval between infection and development of symptoms. The median incubation period was 6.0 days (interquartile range, 3.5-9.5 days). The last two generations were infected in public places, 3 and 4 days prior to the onset of illness in their infectors. Both had certain underlying conditions and comorbidity. Further identification of how individuals transmit prior to being symptomatic will have important consequences.

Epidemiological and clinical characteristics of 333 confirmed cases with coronavirus disease 2019 in Shanghai, China.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease first identified in Wuhan City, Hubei Province, China. As of 19 February 2020, there had been 333 confirmed cases reported in Shanghai, China. This study elaborates on the epidemiological and clinical characteristics of COVID-19 based on a descriptive study of the 333 patients infected with COVID-19 in Shanghai for the purpose of probing into this new disease and providing reference. Among the 333 confirmed cases in Shanghai, 172 (51.7%) were males and 161 (48.3%) were females, with a median age of 50 years. 299 (89.8%) cases presented mild symptoms. 139 (41.7%) and 111 (33.3%) cases were infected in Wuhan and Shanghai, respectively. 148 (44.4%) cases once had contact with confirmed cases before onset, while 103 (30.9%) cases had never contacted confirmed cases but they had a sojourn history in Wuhan. The onset date of the first case in Shanghai was 28 December, with the peak appearing on 27 January. The median incubation period of COVID-19 was estimated to be 7.2 days. 207 (62.2%) cases had fever symptoms at the onset, whereas 273 (82.0%) cases experienced fever before hospitalization. 56 (18.6%) adults experienced a decrease in white blood cell and 84 (42.9%) had increased C-reactive protein after onset. Elderly, male and heart disease history were risk factors for severe or critical pneumonia. These findings suggest that most cases experienced fever symptoms and had mild pneumonia. Strengthening the health management of elderly men, especially those with underlying diseases, may help reduce the incidence of severe and critical pneumonia. Time intervals from onset to visit, hospitalization and diagnosis confirmed were all shortened after Shanghai's first-level public health emergency response. Shanghai's experience proves that COVID-19 can be controlled well in megacities.