Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine as a heterologous booster

To overcome the increased risk of SARS-CoV-2 reinfection or post-vaccination infection caused by the Omicron variant, Omicron-specific vaccines were considered a potential strategy. We reported the increased magnitude and breadth of antibody response against VOCs elicited by post-vaccination Delta and Omicron infection, compared to WT infection without vaccination. Then, in mouse models, three doses of Omicron-RBD immunization elicited comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, a heterologous Omicron-RBD booster following two doses of WT-RBD immunization increased the NAb titers against Omicron by 9 folds than the homologous WT-RBD booster. Moreover, it retains neutralization against both WT and current VOCs. Results suggest that Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs and that SARS-CoV-2 vaccines including two or more virus lineages might improve the NAb response. Graphical

Multi-site validation of an amplicon-based sequencing approach for human monkeypox virus (preprint)

The 2022 multi-country monkeypox outbreak concurrent with the ongoing COVID-19 pandemic has further highlighted the need for genomic surveillance and pathogen whole genome sequencing. While metagenomic sequencing approaches have been used to sequence many of the early human monkeypox virus infections, these methods are resource intensive and require samples with high viral DNA concentrations. Given the atypical clinical presentation of cases associated with the current outbreak and uncertainty regarding viral load across both the course of infection and anatomical body sites, there is an urgent need for a more sensitive and broadly applicable sequencing approach. Amplicon-based sequencing (PrimalSeq) was initially developed for sequencing of Zika virus, and later adapted as the main sequencing approach for SARS-CoV-2. Here, we used PrimalScheme to develop a primer scheme for human monkeypox virus that can be used with many sequencing and bioinformatics pipelines implemented during the COVID-19 pandemic. We sequenced clinical samples that tested presumptive positive for monkeypox virus with amplicon-based and metagenomic sequencing approaches. Upon comparison, we found notably higher genome coverage across the virus genome, particularly in higher PCR cycle threshold (lower DNA titer) samples, with minimal amplicon drop-outs, in using the amplicon-based sequencing approach. By sending out primer pool aliquots to laboratories across the United States and internationally, we validated the primer scheme in 12 public health laboratories with their established Illumina or Oxford Nanopore Technologies sequencing workflows and with different sample types across a range of Ct values. Our findings suggest that amplicon-based sequencing increases the success rate across a wider range of viral DNA concentrations, with the PCR Ct value threshold at which laboratories were able to achieve 80% genome coverage at 10X ranging between Ct 25-33. Therefore, it increases the number of samples where near-complete genomes can be generated and it provides a cost-effective and widely applicable alternative to metagenomics for continued human monkeypox virus genomic surveillance. Importantly, we show that the human monkeypox virus primer scheme can be used with currently implemented amplicon-based SARS-CoV-2 sequencing workflows, with minimal change to the protocol.

Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against Omicron (preprint)

The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the antibodies' epitopes and genotypes. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of one class of antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments show that such antibodies can effectively inhibit the immune escape of Omicron. Cryo-EM results show that this class of antibodies utilizes a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. At the same time, it also provides guidance and insights for developing Omicron antibodies and vaccines.

Mental health crisis in healthcare providers in the COVID-19 pandemic: a cross-sectional facility-based survey

ObjectivesDuring a pandemic, healthcare providers experience increased mental and physical burden. Burnout can lead to treatment errors, patient mortality, increased suicidal ideation and substance abuse as well as medical malpractice suits among medical staff. This study aimed to investigate the occurrence of burnout, acute stress disorder, anxiety disorder and depressive disorder among healthcare providers at the third month of the COVID-19 pandemic.DesignA cross-sectional facility-based survey.SettingHospitals around the country with different levels of care.ParticipantsA total of 1795 respondents, including 360 men and 1435 women who participated in the survey.Primary outcome measuresBurnout was assessed using the Physician Work Life Study. A score of ≥3 implied burnout.ResultsOf the 1795 respondents, 723 (40.3%) reported burnout, and 669 (37.3%) cared for patients with COVID-19. Anxiety levels were mild in 185 (10.3%) respondents, moderate in 209 (11.6%) and severe in 1401 (78.1%). The mean Center for Epidemiologic Studies Depression Scale-10 score was 9.5±6.3, and 817 (45.5%) respondents were classified as having depression. Factors associated with burnout were working in acute and critical care (ACC) divisions (adjusted OR (aOR)=1.84, 95% CI 1.20 to 3.39, p=0.019), caring for patients with COVID-19 (aOR=3.90, 95% CI 1.14 to 13.37, p=0.031) and having depressive disorder (aOR=9.44, 95% CI 7.44 to 11.97, p<0.001).ConclusionsPhysicians and nurses are vulnerable to burnout during a pandemic, especially those working in ACC divisions. Anxiety disorder, depressive disorder and care of patients with COVID-19 may be factors that influence the occurrence of burnout among healthcare providers.

Impact of COVID-19 on Supply Chains: A Hybrid Trade Credit Policy

The COVID-19 pandemic has affected all sectors of the world's economy and society. Firms need to have disaster recovery and business sustainability plans and to be able to generate profits in order to develop. Trade credit may be a good way for firms to free up cash flow and finance short-term growth. Extensions of payment will provide firms with low-cost loans under the COVID-19 credit guarantee scheme. Implementation of hybrid trade credit activities has been shown to improve the financial crisis of many firms, and the effects are particularly evident within two-echelon supply chains. An economic order quantity (EOQ) model is derived under conditions of deteriorating items, an upstream full trade credit or cash discount, and downstream partial trade credit in a supply chain. A computer program is developed to provide a numerical solution and a numerical example is used to show the solution's form and verify that the solution gives the minimum total cost per unit time.

Infectivity rate of COVID-19 following close contact with COVID-19 cases in Quzhou

Objective: To determine the infectivity rate following close contact with confirmed COVID-19 cases in Quzhou from January to September 2020, and to provide reference for pandemic control and prevention.

Study on the performance condition and impact mechanism of tourism system vulnerability under the impact of COVID-19: analysis of tourism data of the Chinese Spring Festival holiday in 2020

In order to study the impact degree of tourism system of the Spring Festival holiday in China under the impact of the COVID-19, this article establishes the concept and theory of performance vulnerability of a system by using the concept of vulnerability in the measurement of the effect degree of a system under the impact of disturbance factors. Combined with AHP and compositive evaluation method, we set up a vulnerability evaluation index system of tourism system to measure the index of performance vulnerability of the tourism system and its subsystems under the impact of the COVID-19, and discuss the impact mechanism model of the COVID-19 on the tourism system during the Spring Festival. The research shows that: the index of performance vulnerability of the tourism system in Spring Festival holiday is 0.6560, which reaches high vulnerability;the index of tourist market system is 0.7250, which reaches high vulnerability;the index of transportation system is 0.6930, which reaches high vulnerability;the index of central tourism enterprise system is 0.8714, which reaches severe vulnerability;the index of destination system is 0.8024, which reaches severe vulnerability;The index of support system is 0.1368, which reaches slight vulnerability.

Biomarkers Linked with Dynamic Changes of Renal Function in Asymptomatic and Mildly Symptomatic COVID-19 Patients.

The catastrophic coronavirus disease 2019 (COVID-19) pandemic is currently a critical global issue. One well-known complication of COVID-19 in severe cases is acute kidney injury, but no research has given a description of its impact on the kidney in patients with mild symptoms. We explore the renal function changes in mild COVID-19 patients. This retrospective, single-center study included 27 participants with laboratory-detected severe acute respiratory syndrome coronavirus two (SARS-CoV-2) infection who were admitted to the Tri-Service General Hospital from 4 February to 26 May 2020 and analyzed their clinical features, radiological findings, and laboratory data. Data collected upon admission and discharge showed a median estimated glomerular filtration rate (eGFR) of 106.7 mL/min/1.732 m2 and 112.2 mL/min/1.732 m2, respectively, with a p-value of 0.044. A correlation between renal function and the severity of infection was also found and was statistically significant upon admission. Patients with a lower lymphocyte count or higher C-reactive protein, neutrophil count, and neutrophil-to-lymphocyte ratio presented with a decreased eGFR during their early infection phase. The biomarkers (CRP and NLR) may be linked with dynamic changes of renal function in COVID-19 patients who are asymptomatic or have mild symptoms.

Sewage Treatment Project Design of Wuhan Huoshenshan and Leishenshan Hospitals

The Huoshenshan hospital and Leishenshan hospital are special infectious diseases hospitals that were designed to focus on the treatment of patients infected by new Coronavirus pneumonia( COVID-19). The design of sewage treatment system was "pre-disinfection contact tank + septic tank + lifting pump station( including crushed grille) + regulating tank + MBBR biochemical tank +coagulation sedimentation tank + contact disinfection tank ". MBBR process could achieve efficient removal of pollutants in sewage at low temperature. Two-stage disinfection process guaranteed 100% virus elimination. At the same time,HDPE membrane was laid under the sewage station according to the landfill standard to ensure the full collection,disinfection and discharge of rainwater and sewage. The sludge was collected and transported as hazardous waste after disinfection and dehydration. The waste gas was collected,deodorized and disinfected in a unified way,so as to realize the full collection and treatment of rainwater,sewage,sludge and waste gas. At present,the operations of the sewage stations of Huoshenshan and Leishenshan hospitals had kept stable,and the relevant effluent indexes met the design requirements. COD concentration was stable below 50 mg/L,ammonia nitrogen was stable below 2 mg/L,residual chlorine was stable near 13 mg/L. Therefore,the pollutant removal and disinfection effect were stable during the whole operation.

Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2 (preprint)

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies.  Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.    

Border Quarantine Measures and Achievement of COVID-19 Control in Taiwan

Since December 21, 2019, on-board inspection had been implemented on direct flights from Wuhan, China, marking the beginning of boarder quarantine challenges in respond to COVID-19 pandemic. In line with the development of the international epidemic, the Central Epidemic Command Center gradually expanded entry restrictions and post-entry quarantine requirements. Since March 19, 2020, all foreign nationals had been prohibited from entering Taiwan. Passengers eligible for entry were required to undergo home quarantine for 14 days. Upon arrival, passengers were required to declare their symptoms and travel history, and to receive fever screening and health assessment. Throat swab specimens were collected from those who presented symptoms at the airport or in the hospital, and then these passengers stayed in a centralized quarantine facility to wait for testing results. In addition, aiming at reducing risks originated from crowds and frequent movement, only aircrafts from five airports in China were allowed to enter Taiwan. Also, all connecting flights were suspended, and cruises and cross-strait passenger liners were banned from calling at ports of Taiwan. For front-line officers at ports of entry, health monitoring and protection guidelines were developed to protect their safety. In order to ensure safety and security of air and sea transport, the competent authorities in charge of transportation have established an epidemic prevention and management mechanism for air and sea transport respectively. Over 184,000 home quarantine notices had been issued by border quarantine authorities. More than 80% of the inbound travelers completed the declaration via Entry Quarantine System, greatly improving timeliness and accuracy of information required for further epidemic prevention and control in community. With on-board quarantine and health surveillance system for entry, not only the first confirmed case in Taiwan, but also more than one-third of imported cases were detected through border quarantine, sparing more capacity for domestic response and preparedness for medical resources and medical systems and therefore alleviating pressure on epidemic prevention and control in the community. Despite continuous and serious epidemic and significant challenges ahead, Taiwan keeps on implementing various quarantine measures in accordance with the principle of ＂strict risk control at border ＂ to comprehensively protect border security.

COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms (preprint)

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.

Clinical characteristics of 276 hospitalized patients with coronavirus disease 2019 in Zengdu District, Hubei Province: A single-center descriptive study (preprint)

Background: We aimed to report the epidemiological and clinical characteristics of hospitalized patients with coronavirus disease-19 (COVID-19) in Zengdu District, Hubei Province, China.Methods Epidemiological,clinical features, laboratory findings, radiologic manifestations, and clinical outcomes of 276 patients in Zengdu hospital were analyzed. Clinical outcomes were followed up to March 13, 2020.Results All hospitalized COVID-19 patients, 276 (median age: 51.0 years), were enrolled, including 262 non-severe and 14 severe patients. The proportion of patients aged over 60 years was higher in the severe group (78.6%) than in the non-severe group (18.7%, p 

A COVID-19 patient with multiple negative results for PCR assays outside Wuhan, China: a case report (preprint)

Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a public health emergency of major international concern. Real-time RT-PCR assays are recommended for diagnosis of COVID-19. Here we report a rare case of COVID-19 with multiple negative results for PCR assays outside Wuhan, China. Case presentation: A 32-year old male was admitted to our hospital because of 6 days of unexplained fever on January 29, 2020. He had come from Wuhan city 10 days before admission. 5 days before admission, no abnormality was noted in laboratory test, chest radiography, and nasopharyngeal swab test for the SARS-CoV-2 nucleic acid. The patient was treated with ibuprofen for alleviating fever. On admission, chest computed tomography showed multiple ground-glass opacities in right lower lung field. COVID-19 was suspected. 3 times of nasopharyngeal swab specimens were collected after admission. However, none of the specimens were positive. The patient was confirmed with COVID-19 after fifth SARS-CoV-2 nucleic acid test. He was treated with lopinavir/ritonavir, recombinant human interferon alfa-2b inhalation, methylprednisolone. After 18 days of treatment, he was discharged with improved symptoms, lung lesions and negative results of nasopharyngeal swab. Conclusion: This case reminds clinician that a patient with high clinical suspicion of COVID-19 but multiple negative RT-PCR result should not be taken out of isolation. A combination of patient’s exposure history, clinical manifestations, laboratory tests, and typical imaging findings plays a vital role in making preliminary diagnosis and guide early isolation and treatment. Repeat swab tests are helpful in diagnosis for this kind of patients. 

High resolution computed tomography for the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia: a study from multiple medical centers in western China (preprint)

Objective: To evaluate the role of high-resolution computed tomography (HRCT) in the diagnosis of 2019 novel coronavirus (2019-nCoV) pneumonia and to provide experience in the early detection and diagnosis of 2019-nCoV pneumonia. Methods: 72 patients confirmed to be infected with 2019-nCoV from multiple medical centers in western China were retrospectively analyzed, including epidemiologic characteristics, clinical manifestations, laboratory findings and HRCT chest features. Results: All patients had lung parenchymal abnormalities on HRCT scans, which were mostly multifocal in both lungs and asymmetric in all patients, and were mostly in the peripheral or subpleural lung regions in 52 patients (72.22%), in the central lung regions in sixteen (22.22%), and in both lungs, with "white lung "manifestations in four (5.56%). Subpleural multifocal consolidation was predominant abnormality in 38 patients (52.78%). Ground-glass opacity was seen in 34 patients (47.22%). Interlobular septal thickening was found in 18patients, of which eight had only generally mild thickening with no zonal predominance. Reticulation was seen in 8 patients (11.11%), in all of whom it was mild and randomly distributed. In addition, both lungs of 28 patients had two or three CT imaging features. Out of these 72 patients, 36 were diagnosed as early stage, 32 patients as progressive stage and 4 patient as severe stage pneumonia. Moreover, the diagnostic accuracy of HRCT features combined with epidemiological history was not significantly different from the detection of viral nucleic acid (all P >0.05). Conclusion: The HRCT features of 2019-nCoV pneumonia are characteristic to a certain degree, which when combined with epidemiological history yield high clinical value in the early detection and diagnosis of 2019-nCoV pneumonia.Authors Hong-Wei Li, Li-Hua Zhuo, Gao-Wu Yan contributed equally to this work.

Recommendations for standardized management of CML patients in the core epidemic area of COVID-19(Multi-center survey results in Hubei Province, China) (preprint)

Background Since late December 2019, the outbreak of the novel coronavirus disease, COVID-19, that began in Wuhan, has become endemic in China and more than 100 countries and regions in the world. There is no report about the prevalence of COVID-19 in CML patients untill now. We aimed to describe the clinical course, outcomes of CML patients with COVID-19 and prevalence of COVID-19 in CML patients. Methods In this multi-center survey, cross-sectional survey, observational study, the clinical data of CML patients with COVID-19 in each center were collected. Simultaneously, an online survey was conducted for information about the CML patients under the management at each center by asking the CML patients to complete a questionnaire,from February 15, 2020 to February 21, 2020. The questionnaire includes demographic data, place of residence, smoking status, CML diagnosis and treatment, comorbidities, combined medications, epidemiological history, symptoms(fever, cough, shortness of breath, etc) during the epidemic. Additional clinical data was collected on respondents suspected or confirmed to have COVID-19. We described and analyzed the prevalence of COVID-19 in CML patients, and focus on the clinical characteristics and outcomes of COVID-19 patients. Data were compared between the CML patients with optimal response and those with non-optimal response. The primary outcome was prevalence of COVID-19 in CML patients, as of Feb 21, 2020. Secondary outcomes included the history of epidemiology of CML patients, the clinical characteristics and outcomes of CML patients with COVID-19 . Findings Of 392 respondents, 223( 56.9%) were males, and 240( 61.2%) were 50 years or younger. Only 10 patients took drugs irregularly due to the influence of the epidemic because of traffic control, pharmacies unable to operate normally, etc. In the history of epidemiology, there were 4 patients with definite contact with COVID-19, of which 3 were remote contact and 1 was close contact. 12 respondents had fever, cough or shortness of breath during the epidemic, 1 case (common type) was confirmed with COVID-19 and cured after treatment. 1 patient was clinically diagnosed and succumbed. 1 of 299 (0.3%) patients with an optimal response was diagnosed with COVID-19. Of the 50 patients who failed to respond to CML treatment or had a poor response, 1 patient (2%) had a clinical diagnosis of COVID-19. Interpretation While the 392 CML respondents required regular referrals to hospitals, they did not have much contact with COVID-19 patients during the outbreak. Patients who failed to achieved an optimal response to CML therapy appear more likely to have a symptomatic infection with SARS-CoV-2. Older patients with comorbidities are at increased risk of death.

Clinical Characteristics of Patients with 2019 Coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study (preprint)

Background: Since December, 2019, the 2019 Coronavirus disease (COVID-19) from Wuhan, China, has caused worldwide outbreak with more than 200,000 people infected and thousands of deaths. The clinical characteristics of COVID-19 patients in non-Wuhan areas of Hubei province have not been described. Methods: We retrospectively analyzed the clinical characteristics and treatment progress of 91 patients diagnosed with COVID-19 in Jingzhou Central Hospital. Results: Of the 91 patients diagnosed with COVID-19, 30 (33.0%) cases were severe and two (2.2%) patients died. The severe patients tended to be older (50.5 vs 42.0, P=0.049), and have more chronic disease (40% vs 14.75%, P=0.009), compared to mild group. Only 73.6% of the patients were quantitative polymerase chain reaction (qPCR) positive on their first tests, while typical chest computed tomographic (CT) images were obtained for each patient. The most common complaints were cough (75, 82.4%), fever (59, 64.8%), fatigue (35, 38.5%), and diarrhea (14, 15.4%). Non-respiratory injur y was identified by elevated levels of aspartate aminotransferase (18, 19.8%), creatinine (5, 5.5%) and creatine kinase (14, 15.4%) in laboratory tests. In sum, 28 (30.8%) cases suffered non-respiratory injury, including 50% of the critically ill patients and 21.3% of the mild patients. Conclusions: Overall, the mortality rate of patients in Jingzhou is lower than that of Wuhan. Importantly, we discovered liver, kidney, digestive tract and heart injury in COVID-19 cases besides respiratory problems. Combining Chest CT images with qPCR of throat swab samples would improve the accuracy of COVID-19 diagnose.

Research progress in enteroids in porcine enteric coronavirus infection

Porcine enteric coronavirus, an important agent of diarrhea in piglets, primarily infects the villous epithelia of the small intestine, causing substantial economic losses to the pork industry. The lack of an in vitro model that can recapitulate the highly complex physiological properties of the gastrointestinal tract significantly limits the study of the interactions between porcine enteric coronavirus infection and host intestinal epithelium. With the rapid development of stem cell technology, an in vitro model that can mimic diverse cellular nature and complex structure of the intestine-enteroids, has attracted widespread attention. Compared with conventional cell lines, enteroids not only simulate the structure and function of the intestine, but also retain the genetic characteristics of the host. Enteroids would be expected to be an ideal model for studying the interactions of host-enteric pathogens. This article reviews the recent research progress of porcine enteric coronavirus and the applications of enteroids in enteric pathogens research, in order to provide new insights for the future fundamental research of porcine enteric coronavirus.