Characteristics and containment of the outbreak caused by the SARS-CoV-2 Omicron variants in Shanghai, China: a retrospective study

Objective: The study aimed to describe the characteristics and containment of the Omicron variants in Shanghai compared with the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in China. Methods: We summarized the data retrieved from the Shanghai Municipal Health Commission from January to June 2022 and the National Health Commission of the People's Republic of China from March 2020 to August 2021. Epidemiological analysis was utilized to describe the differences among SARS-CoV-2 variants and the infection situation in the outbreaks in China. Results: The Omicron variants had the characteristics of high insidiousness, rapid transmission, high infectivity, and short incubation period, which were consistent with the characteristics of outbreaks caused by Omicron in other regions in China and abroad. There were 568978 asymptomatic infections in Shanghai from Feburary 26 to June 30, 2022, accounting for 90.73% of the SARS-CoV-2 infections in this outbreak wave. It's significantly different from a total of 23277 SARS-CoV-2 infections in China between March 31, 2020 and August 8, 2021, of which 41.97% of the cases were asymptomatic infections. Conclusions: Compared with previous outbreaks emerged in China, the Omicron outbreak in Shanghai was characterized by multiple point dissemination, wide coverage, a large number of close contacts of confirmed infections and asymptomatic carriers, and difficult source tracing. The lessons from Shanghai's response to Omicron showed that the dynamic zero-COVID policy is still the most suitable response to the virus which can quickly find the infections and curb the transmission route.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Impact of COVID-19-related regulatory changes on nationwide access to buprenorphine: An interrupted time series design.

Background: The impact of COVID-19-related healthcare changes on access to buprenorphine (BUP) nationwide in the US is unknown. Methods: We conducted an interrupted time series with the IQVIA LRx database. The study timeline included BUP prescriptions from 52 weeks before (2/23/19-2/21/20) to 52 weeks after (4/4/20-4/2/21) the initial pandemic period (2/22/20-4/3/20). Segmented regression estimated relative changes in total milligrams (MG) of BUP available per week nationwide at 1, 26, and 52 weeks post-initial-pandemic. We evaluated treatment disruptions in previously stable patients, defined as ≥6 months of BUP prescriptions. Results: A total of 31 617 849 prescriptions were included. Total MG BUP dispensed increased at 1 and 26 weeks and then returned to baseline trends at 52 weeks post-initial pandemic period (4.1% [95% CI: 3.7,4.5], 2.1% [1.5,2.6], 0.1% [-0.6,0.9]). Stably-treated patients saw a decrease in 7-, 14-, and 28-day treatment disruptions at 52 weeks post-initial-pandemic period (-21.6% [-25.6,-17.7]; -10.8% [-16.3,-5.3]; -27.3% [-33.0,-21.6]). Men retained an increase in MG BUP compared to women at 52 weeks (0.7% [0.01,1.4] versus -0.6% [-1.5,0.2]). Younger age groups (18-29 years and 30-39 years) had a decrease in MG BUP at 52 weeks compared to expected baseline trend (-16.6 [-24.2, -9.0]; -1.6 [-3.0, -0.1). Patients with Medicaid demonstrated an increase in MG BUP at 52 weeks (8.3% [6.3,10.3]). MG BUP prescribed by APP prescribing increased by over 140 000 mg per week prior to the pandemic and continued to increase. Conclusions: Regulatory changes around buprenorphine prescribing facilitated patient access to buprenorphine during the pandemic.

A novel rumor detection with multi-objective loss functions in online social networks.

COVID-19 quickly swept across the world, causing the consequent infodemic represented by the rumors that have brought immeasurable losses to the world. It is imminent to achieve rumor detection as quickly and accurately as possible. However, the existing methods either focus on the accuracy of rumor detection or set a fixed threshold to attain early detection that unfortunately cannot adapt to various rumors. In this paper, we focus on textual rumors in online social networks and propose a novel rumor detection method. We treat the detection time, accuracy and stability as the three training objectives, and continuously adjust and optimize this objective instead of using a fixed value during the entire training process, thereby enhancing its adaptability and universality. To improve the efficiency, we design a sliding interval to intercept the required data rather than using the entire sequence data. To solve the problem of hyperparameter selection brought by integration of multiple optimization objectives, a convex optimization method is utilized to avoid the huge computational cost of enumerations. Extensive experimental results demonstrate the effectiveness of the proposed method. Compared with state-of-art counterparts in three different datasets, the recognition accuracy is increased by an average of 7%, and the stability is improved by an average of 50%.

Characterization of SARS-CoV-2 and host entry factors distribution in a COVID-19 autopsy series.

Background: SARS-CoV-2 is a highly contagious virus that causes the disease COVID-19. We have recently reported that androgens regulate the expression of SARS-CoV-2 host entry factors ACE2 and TMPRSS2, and androgen receptor (AR) in lung epithelial cells. We also demonstrated that the transcriptional repression of the AR enhanceosome inhibited SARS-CoV-2 infection in vitro. Methods: To better understand the various sites of SARS-CoV-2 infection, and presence of host entry factors, we extensively characterized the tissue distribution and localization of SARS-CoV-2 virus, viral replication, and host entry factors in various anatomical sites sampled via autopsy. We applied RNA in-situ-hybridization (RNA-ISH), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) approaches. We also assessed histopathological changes in SARS-CoV-2 infected tissues. Results: We detect SARS-CoV-2 virus and viral replication in pulmonary tissues by RNA-ISH and IHC and a variety of non-pulmonary tissues including kidney, heart, liver, spleen, thyroid, lymph node, prostate, uterus, and colon by qRT-PCR. We observe heterogeneity in viral load and viral cytopathic effects among various organ systems, between individuals and within the same patient. In a patient with a history of kidney transplant and under immunosuppressant therapy, we observe an unusually high viral load in lung tissue by RNA-ISH, IHC and qRT-PCR. SARS-CoV-2 virus is also detected in this patent's kidney, liver and uterus. We find ACE2, TMPRSS2 and AR expression to overlap with the infection sites. Conclusions: This study portrays the impact of dispersed SARS-CoV-2 infection in diverse organ systems, thereby facilitating avenues for systematic therapeutic approaches.

An Investigation of a Confirmed Imported Case of COVID-19 Infected Abroad - Qingpu District, Shanghai Municipality, China, November 15, 2020.

SUMMARY: What is already known about this topic? A passenger who was from the United States was taken to the hotel for the required isolation on November 13, 2020. During the quarantine she was diagnosed as the COVID-19 patient on November 15, 2020. Controlling the importation of COVID-19 remains a major challenge.What is added by this report? In this study, an epidemiological investigation was conducted for a confirmed case of COVID-19, including the treatment records in the hospital and 14-day travel trajectory before the onset of disease.What are the implications for public health practice? This study described an epidemiological investigation and management process on an imported case of COVID-19 and analyzed the test results, aiming to provide useful warnings to strengthen the capacity of public health system in response to the importation.

A novel One-pot rapid diagnostic technology for COVID-19.

Novel coronavirus disease (COVID-19) caused by SARS-CoV-2 is an ongoing global pandemic associated with high rates of morbidity and mortality. RT-qPCR has become the diagnostic standard for the testing of SARS-CoV-2 in most countries. COVID-19 diagnosis generally relies upon RT-qPCR-mediated identification of SARS-CoV-2 viral RNA, which is costly, labor-extensive, and requires specialized training and equipment. Herein, we established a novel one-tube rapid diagnostic approach based upon formamide and colorimetric RT-LAMP (One-Pot RT-LAMP) that can be used to diagnose COVID-19 without the extraction of specific viral RNA. The technique could visually detect SARS-CoV-2 within 45 min with a limit of detection of 5 copies per reaction in extracted RNA, and about 7.66 virus copies per µL in viral transport medium. The One-Pot RT-LAMP test showed a high specificity without cross-reactivity with 12 viruses including SARS-CoV, MERS-CoV, and human infectious influenza virus (H1N1/H3N2 of influenza A and B virus, ect. We validated this One-Pot RT-LAMP approach by its successful use for the analysis of 45 clinical nasopharyngeal swab samples, yielding results identical to those of traditional RT-qPCR analyses, while achieving good selectivity and sensitivity relative to a commercial RT-qPCR approach. As such, this One-Pot RT-LAMP technology may be a valid means of conducting high-sensitivity, low-cost and rapid SARS-CoV-2 identification without the extraction of viral RNA.

Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, employs two key host proteins to gain entry and replicate within cells, angiotensin-converting enzyme 2 (ACE2) and the cell surface transmembrane protease serine 2 (TMPRSS2). TMPRSS2 was first characterized as an androgen-regulated gene in the prostate. Supporting a role for sex hormones, males relative to females are disproportionately affected by COVID-19 in terms of mortality and morbidity. Several studies, including one employing a large epidemiological cohort, suggested that blocking androgen signaling is protective against COVID-19. Here, we demonstrate that androgens regulate the expression of ACE2, TMPRSS2, and androgen receptor (AR) in subsets of lung epithelial cells. AR levels are markedly elevated in males relative to females greater than 70 y of age. In males greater than 70 y old, smoking was associated with elevated levels of AR and ACE2 in lung epithelial cells. Transcriptional repression of the AR enhanceosome with AR or bromodomain and extraterminal domain (BET) antagonists inhibited SARS-CoV-2 infection in vitro. Taken together, these studies support further investigation of transcriptional inhibition of critical host factors in the treatment or prevention of COVID-19.

[Retrospective Analysis of Neurological Symptoms of Severe/Critical COVID-19 Patients in Sichuan Province].

OBJECTIVE: To retrospectively analyze the symptoms and characteristics of nervous system damage in severe/critically severe patients with coronavirus disease 2019 (COVID-19) in Sichuan province, with a view to providing basic references for the prevention and treatment of COVID-19. METHODS: A total of 90 patients with severe/critically severe COVID-19 were included, who were diagnosed and treated in COVID-19 designated hospital of Sichuan province from 11 January 2020 to 20 March 2020. Clinical features, test results, treatment options and clinical outcomes were analyzed retrospectively. RESULTS: Of 90 patients, there were 54 males and 36 females, with an average age of (53.90±16.92) years. In addition to the classic symptoms such as fever and/or respiratory symptoms, 53 patients also had various degrees of neurologic manifestations, including 33 cases of fatigue, 21 muscle soreness, 12 dizziness, 8 headaches, 3 mental disorders, and 1 consciousness disorders and 1 case of neck pain. Compared with the patients without neurologic manifestations, those with neurologic manifestations took a longer time from admission to diagnosis of COVID-19 ( P<0.05), and received more antifungal treatment ( P<0.05). CONCLUSIONS: Neurological symptoms are not uncommon in severe/critically severe patients with COVID-19, and it's relatively difficult in the treatment. It should be paid attention in order to avoid misdiagnosis.

Fecal viral shedding in COVID-19 patients: Clinical significance, viral load dynamics and survival analysis.

BACKGROUND: To investigate the clinical significance, viral shedding duration and viral load dynamics of positive fecal SARS-CoV-2 signals in COVID-19. METHODS: COVID-19 patients were included. SARS-CoV-2 RNA was tested in stool and respiratory specimens until two sequential negative results were obtained. Clinical, laboratory and imaging data were recorded. RESULTS: Of the 69 COVID-19 patients, 20 (28.99 %) had positive fecal viral tests who were younger, had lower C-reactive protein (CRP) and fibrinogen (FIB) levels on admission (all P < 0.05), and showed more improvement and less progression on chest CT during recovery. The median duration of positive viral signals was significantly longer in stool samples than in respiratory samples (P < 0.05). In spite of the negative oropharyngeal swabs, eleven patients were tested positive for viral RNA in stool specimens, with their fecal SARS-CoV-2 RNA Ct (cycle threshold) values reaching 25-27. 6 of these 11 patients' Ct values rebounded. CONCLUSION: SARS-CoV-2 RNA in stool specimens was associated with a milder condition and better recovery of chest CT results while the median duration of SARS-CoV-2 RNA persistence was significantly longer in fecal samples than in oropharyngeal swabs. The fecal viral load easily reached a high level and rebounded even though respiratory signals became negative.

Development and Clinical Application of a Rapid and Sensitive Loop-Mediated Isothermal Amplification Test for SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak urgently necessitates sensitive and convenient COVID-19 diagnostics for the containment and timely treatment of patients. We aimed to develop and validate a novel reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay to detect SARS-CoV-2. Patients with suspected COVID-19 and close contacts were recruited from two hospitals between 26 January and 8 April 2020. Respiratory samples were collected and tested using RT-LAMP, and the results were compared with those obtained by reverse transcription-quantitative PCR (RT-qPCR). Samples yielding inconsistent results between these two methods were subjected to next-generation sequencing for confirmation. RT-LAMP was also applied to an asymptomatic COVID-19 carrier and patients with other respiratory viral infections. Samples were collected from a cohort of 129 cases (329 nasopharyngeal swabs) and an independent cohort of 76 patients (152 nasopharyngeal swabs and sputum samples). The RT-LAMP assay was validated to be accurate (overall sensitivity and specificity of 88.89% and 99.00%, respectively) and diagnostically useful (positive and negative likelihood ratios of 88.89 and 0.11, respectively). RT-LAMP showed increased sensitivity (88.89% versus 81.48%) and high consistency (kappa, 0.92) compared to those of RT-qPCR for SARS-CoV-2 screening while requiring only constant-temperature heating and visual inspection. The time required for RT-LAMP was less than 1 h from sample preparation to the result. In addition, RT-LAMP was feasible for use with asymptomatic patients and did not cross-react with other respiratory pathogens. The developed RT-LAMP assay offers rapid, sensitive, and straightforward detection of SARS-CoV-2 infection and may aid the expansion of COVID-19 testing in the public domain and hospitals.IMPORTANCE We developed a visual and rapid reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the S gene for SARS-CoV-2 infection. The strength of our study was that we validated the RT-LAMP assay using 481 clinical respiratory samples from two prospective cohorts of suspected COVID-19 patients and on the serial samples from an asymptomatic carrier. The developed RT-LAMP approach showed an increased sensitivity (88.89%) and high consistency (kappa, 0.92) compared with those of reverse transcription-quantitative PCR (RT-qPCR) for SARS-CoV-2 screening while requiring only constant-temperature heating and visual inspection, facilitating SARS-CoV-2 screening in well-equipped labs as well as in the field. The time required for RT-LAMP was less than 1 h from sample preparation to the result (more than 2 h for RT-qPCR). This study showed that the RT-LAMP assay was a simple, rapid, and sensitive approach for SARS-CoV-2 infection and can facilitate COVID-19 diagnosis, especially in resource-poor settings.

Longitudinal Association Between Markers of Liver Injury and Mortality in COVID-19 in China.

BACKGROUND AND AIMS: Coronavirus disease 2019 (COVID-19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID-19 pneumonia in Hubei Province. APPROACH AND RESULTS: We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non-severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender. CONCLUSION: The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID-19-associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.