Clinical features of Omicron variant infection in 445 patients with coronavirus 19 disease.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can mutate frequently and many new strains have emerged thus far. The clinical and epidemiological characteristics differ with each dominant strain. OBJECTIVES: Obtain an understanding of the clinical characteristics of patients infected with the Omicron variants of the SARS CoV-2. DESIGN: Retrospective cohort SETTINGS: Teaching hospital in China. PATIENTS AND METHODS: Data on sociodemography, signs/symptoms, hospital stay, viral shedding period, comorbidities, treatment options and final outcome were retrieved from hospital electronic medical record. We collected nasopharyngeal samples, laboratory data, and clinical data from patients admitted to the hospital with SARS CoV-2. MAIN OUTCOME MEASURES: Clinical characteristics of the patients infected with Omicron variant of SARS CoV-2. SAMPLE SIZE: 445 patients RESULTS: The median age was 43.0 years with a range from 2 to 75 years. Two-thirds of the participants were male and one-third were female. Almost half of the participants (51.9%) had no symptoms, whereas 48.1% had at least one symptom. Of symptomatic patients, 26.7% had mild symptoms and 21.3% had moderate symptoms. No patients were admitted with severe or critical symptoms. All patients discharged from the hospital after complete recovery without any serious complications or death. The most common symptom was cough followed by sore throat and fever. Less common symptoms were having sputum, stuffy nose, and muscle pain. Rare symptoms were weakness, headache, diarrhea, hemoptysis and nausea/vomiting. CONCLUSIONS: All patients had mild to moderate symptoms. Shortness of breath was not a common symptom among the study group. No patients needed invasive oxygen therapy in this cohort. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.

Rational design of multivalent biosensor surfaces to enhance viral particle capture.

Viral particles bind to receptors through multivalent protein interactions. Such high avidity interactions on sensor surfaces are less studied. In this work, three polyelectrolytes that can form biosensing surfaces with different interfacial characteristics in probe density and spatial arrangement were designed. Quartz crystal microbalance, interferometry and atomic force microscopy were used to study their surface density and binding behaviors with proteins and virus particles. A multivalent adsorption kinetic model was developed to estimate the number of bonds from the viral particles bound to the polyelectrolyte surfaces. Experimental results show that the heterogeneous 3D surface with jagged forest-like structure enhances the virus capture ability by maximizing the multivalent interactions. As a proof of concept, specific coronavirus detection was achieved in spiked swab samples. These results indicate the importance of both probe density and their spatial arrangement on the sensing performance, which could be used as a guideline for rational biosensing surface design.

Parainfluenza virus 5 is a next-generation vaccine vector for human infectious pathogens.

Parainfluenza virus 5 (PIV5) is a negative-sense, single-stranded RNA virus that can infect humans and many species of animals. Infection in these reservoir hosts is generally asymptomatic and has few safety concerns. Emerging evidence has shown that PIV5 is a promising vector for developing vaccines against human infectious diseases caused by coronaviruses, influenza, respiratory syncytial virus, rabies, HIV, or bacteria. In this review, we summarize recent progress and highlight the advantages and strategies of PIV5 as a vaccine vector to improve future vaccine design and application for clinical trials.

Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analog inhibitors.

Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here, we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5' end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analog inhibitors can be bonded to nsp9 and fit into a previously unknown "Nuc-pocket" in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an "induce-and-lock" mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs but also provide a strategy to design antiviral drugs.

A mechanism for SARS-CoV-2 RNA capping and its inhibition by nucleotide analogue inhibitors

Decoration of cap on viral RNA plays essential roles in SARS-CoV-2 proliferation. Here we report a mechanism for SARS-CoV-2 RNA capping and document structural details at atomic resolution. The NiRAN domain in polymerase catalyzes the covalent link of RNA 5’ end to the first residue of nsp9 (termed as RNAylation), thus being an intermediate to form cap core (GpppA) with GTP catalyzed again by NiRAN. We also reveal that triphosphorylated nucleotide analogue inhibitors can be bonded to nsp9 and fit into a previously unknown ‘Nuc-pocket’ in NiRAN, thus inhibiting nsp9 RNAylation and formation of GpppA. S-loop (residues 50-KTN-52) in NiRAN presents a remarkable conformational shift observed in RTC bound with sofosbuvir monophosphate, reasoning an ‘induce-and-lock’ mechanism to design inhibitors. These findings not only improve the understanding of SARS-CoV-2 RNA capping and the mode of action of NAIs, but also provide a strategy to design antiviral drugs. Graphical Structural analyses reveal how proteins from SARS-CoV-2 cooperate and use GTP to form the cap on viral mRNA, and how this process is interrupted by nucleotide analogues that serve as antiviral drugs.

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.

A Supported Lipid Bilayer-Based Lab-on-a-Chip Biosensor for the Rapid Electrical Screening of Coronavirus Drugs.

With the rapid spread and multigeneration variation of coronavirus, rapid drug development has become imperative. A major obstacle to addressing this issue is adequately constructing the cell membrane at the molecular level, which enables in vitro observation of the cell response to virus and drug molecules quantitatively, shortening the drug experiment cycle. Herein, we propose a rapid and label-free supported lipid bilayer-based lab-on-a-chip biosensor for the screening of effective inhibition drugs. An extended gate electrode was prepared and functionalized by an angiotensin-converting enzyme II (ACE2) receptor-incorporated supported lipid bilayer (SLB). Such an integrated system can convert the interactions of targets and membrane receptors into real-time charge signals. The platform can simulate the cell membrane microenvironment in vitro and accurately capture the interaction signal between the target and the cell membrane with minimized interference, thus observing the drug action pathway quantitatively and realizing drug screening effectively. Due to these label-free, low-cost, convenient, and integrated advantages, it is a suitable candidate method for the rapid drug screening for the early treatment and prevention of worldwide spread of coronavirus.

The association of intensity and duration of non-pharmacological interventions and implementation of vaccination with COVID-19 infection, death, and excess mortality: Natural experiment in 22 European countries.

BACKGROUND: Critical questions remain regarding the need for intensity to continue NPIs as the public was vaccinated. We evaluated the association of intensity and duration of non-pharmaceutical interventions (NPIs) and vaccines with COVID-19 infection, death, and excess mortality in Europe. METHODS: Data comes from Our Word in Data. We included 22 European countries from January 20, 2020, to May 30, 2021. The time-varying constrained distribution lag model was used in each country to estimate the impact of different intensities and duration of NPIs on COVID-19 control, considering vaccination coverage. Country-specific effects were pooled through meta-analysis. RESULTS: This study found that high-intensity and long-duration of NPIs showed a positive main effect on reducing infection in the absence of vaccines, especially in the intensity above the 80th percentile and lasted for 7 days (RR = 0.93, 95% CI: 0.89-0.98). However, the adverse effect on excess mortality also increased with the duration and intensity. Specifically, it was associated with an increase of 44.16% (RR = 1.44, 95% CI: 1.27-1.64) in the excess mortality under the strict intervention (the intensity above the 80th percentile and lasted for 21 days). As the vaccine rollouts, the inhibition of the strict intervention on cases growth rate was increased (RR dropped from 0.95 to 0.87). Simultaneously, vaccination also alleviated the negative impact of the strict intervention on excess mortality (RR decreased from 1.44 to 1.25). Besides, maintaining the strict intervention appeared to more reduce the cases, as well as avoids more overall burden of death compared with weak intervention. CONCLUSIONS: Our study highlights the importance of continued high-intensity NPIs in low vaccine coverage. Lifting of NPIs in insufficient vaccination coverage may cause increased infections and death burden. Policymakers should coordinate the intensity and duration of NPIs and allocate medical resources reasonably with widespread vaccination.

Three elderly asymptomatic SARS-CoV-2 infected patients in ICU.

Previous studies on asymptomatic COVID-19 carriers indicated that asymptomatic infections always occurred in people in community or patients in general wards, prone to be young and middle aged people. Limited data are available for asymptomatic infections in critically ill patients in intensive care unit or elderly people. Here we reported three elderly asymptomatic SARS-CoV-2 infected patients in intensive care unit. These three elderly patients had negative CT images and 14 consecutive negative RT-PCR test results, with dynamic changes in IgG-IgM antibody levels without any clinical symptoms, which might be related to their weakened immune responses due to elder age (over 85 years old) and the history of hypertension. Therefore, combining nucleic acid RT-PCR and the IgM-IgG antibody test can provide more accurate SARS-CoV-2 infection diagnosis, especially for elderly asymptomatic patients.

Newly-Diagnosed Diabetes and Sustained Hyperglycemia are Associated with Poorer Outcomes in COVID-19 Inpatients Without Pre-Existing Diabetes.

PURPOSE: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD). PATIENTS AND METHODS: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers. RESULTS: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49-4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21-183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01-0.56; P < 0.001). CONCLUSION: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.

Low vaccination coverage of pneumococcal conjugate vaccines (PCVs) in Shanghai, China: A database analysis based on birth cohorts from 2012 to 2020.

BACKGROUND: Pneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage. METHODS: Vaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed. RESULTS: The total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020. CONCLUSIONS: Despite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.

A cross-sectional study of olfactory and taste disorders among COVID-19 patients in China.

To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.

Predisposing Variations in Fear-Related Brain Networks Prospectively Predict Fearful Feelings during the 2019 Coronavirus (COVID-19) Pandemic.

The novel coronavirus (COVID-19) pandemic has led to a surge in mental distress and fear-related disorders, including posttraumatic stress disorder (PTSD). Fear-related disorders are characterized by dysregulations in fear and the associated neural pathways. In the present study, we examined whether individual variations in the fear neural connectome can predict fear-related symptoms during the COVID-19 pandemic. Using machine learning algorithms and back-propagation artificial neural network (BP-ANN) deep learning algorithms, we demonstrated that the intrinsic neural connectome before the COVID-19 pandemic could predict who would develop high fear-related symptoms at the peak of the COVID-19 pandemic in China (Accuracy rate = 75.00%, Sensitivity rate = 65.83%, Specificity rate = 84.17%). More importantly, prediction models could accurately predict the level of fear-related symptoms during the COVID-19 pandemic by using the prepandemic connectome state, in which the functional connectivity of lvmPFC (left ventromedial prefrontal cortex)-rdlPFC (right dorsolateral), rdACC (right dorsal anterior cingulate cortex)-left insula, lAMY (left amygdala)-lHip (left hippocampus) and lAMY-lsgACC (left subgenual cingulate cortex) was contributed to the robust prediction. The current study capitalized on prepandemic data of the neural connectome of fear to predict participants who would develop high fear-related symptoms in COVID-19 pandemic, suggesting that individual variations in the intrinsic organization of the fear circuits represent a neurofunctional marker that renders subjects vulnerable to experience high levels of fear during the COVID-19 pandemic.

Liver injury in COVID-19: Known and unknown.

Since the first report of the coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, the outbreak of the disease is currently continuously evolving. Previous studies have shown varying degrees of liver damage in patients with COVID-19. However, the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear. This article describes liver injury induced by COVID-19, analyzes its causes, and discusses the treatment and prognosis of liver damage in patients with COVID-19.

An intelligent face mask integrated with high density conductive nanowire array for directly exhaled coronavirus aerosols screening.

The current ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has globally affected the lives of more than one hundred million people. RT-PCR based molecular test is recommended as the gold standard method for diagnosing current infections. However, transportation and processing of the clinical sample for detecting virus require an expert operator and long processing time. Testing device enables on-site virus detection could reduce the sample-to-answer time, which plays a central role in containing the pandemic. In this work, we proposed an intelligent face mask, where a flexible immunosensor based on high density conductive nanowire array, a miniaturized impedance circuit, and wireless communication units were embedded. The sub-100 nm size and the gap between the neighbored nanowires facilitate the locking of nanoscale virus particles by the nanowire arrays and greatly improve the detection efficiency. Such a point-of-care (POC) system was demonstrated for coronavirus 'spike' protein and whole virus aerosol detection in simulated human breath. Detection of viral concentration as low as 7 pfu/mL from the atomized sample of coronavirus aerosol mimic was achieved in only 5 min. The POC systems can be readily applied for preliminary screening of coronavirus infections on-site and may help to understand the COVID-19 progression while a patient is under prescribed therapy.

Molecular Insights into Small‐Molecule Drug Discovery for SARS‐CoV‐2

The mainstream approach to antiviral drugs against COVID‐19 is to focus on key stages of the SARS‐CoV‐2 life cycle. The vast majority of candidates under investigation are repurposed from agents of other indications. Understanding protein–inhibitor interactions at the molecular scale will provide crucial insights for drug discovery to stop this pandemic. In this article, we summarize and analyze the most recent structural data on several viral targets in the presence of promising inhibitors for COVID‐19 in the context of the perspective of modes of action (MOA) to unravel insightful mechanistic features with atomistic resolution. The targets include spike glycoprotein and various host proteases mediating the entry of the virus into the cells, viral chymotrypsin‐ and papain‐like proteases, and RNA‐dependent RNA polymerase. The main purpose of this review is to present detailed MOA analysis to inspire fresh ideas for both de novo drug design and optimization of known scaffolds to combat COVID‐19.

Mental health and preventive behaviour of pregnant women in China during the early phase of the COVID-19 period.

BACKGROUND: The COVID-19 has caused significant toll over the globe. Pregnant women are at risk of infection. The present study examined the frequency of washing hands with soap and wearing face mask when going out, prevalence of depression and anxiety, and identified their associated factors among pregnant women during the early phase of COVID-19 outbreak in China. METHODS: A cross-sectional online survey was conducted between 24 February and 3 March 2020. A total of 15 428 pregnant women who were using maternal health care services in China completed a questionnaire which assessed their socio-demographic and pregnancy-related characteristics, contextual, cognitive and social factors related to COVID-19, frequency of washing hands and wearing face masks, and depression and anxiety. Logistics regression analyses were performed to identify the associated factors of preventive behaviours and mental health. RESULTS: The prevalence of probable anxiety and depression was 28.2% and 43.6% respectively. 19.8% reported always wearing face mask when going out, and 19.1% reported washing hands with soap for more than 10 times per day. Results from logistic regression analyses showed that older age was associated with lower levels of depression and anxiety (OR = 0.42-0.67) and higher frequency of washing hands (OR = 1.57-3.40). Higher level of education level was associated with probable depression (OR = 1.31-1.45) and higher frequency of wearing face mask (OR = 1.50-1.57). After adjusting for significant socio-demographic and pregnancy-related factors, place of residence being locked down (aOR = 1.10-1.11), being quarantined (aOR = 1.42-1.57), personally knowing someone being infected with COVID-19 (aOR = 1.80-1.92), perception that COVID-19 would pose long term physical harm to human (aOR = 1.25-1.28) were associated with higher levels of depression and anxiety, while the perception that the disease will be under control in the coming month was associated with lower levels of depression and anxiety (aOR = 0.59-0.63) and lower tendency of always wearing face mask (aOR = 0.85). Social support was associated with lower levels of depression and anxiety (aOR = 0.86-0,87) and higher frequency of washing hands (aOR = 1.06). CONCLUSIONS: The mental health and preventive behaviours of pregnant women during COVID-19 outbreak was associated with a range of socio-demographic, pregnancy-related, contextual, cognitive and social factors. Interventions to mitigate their mental health problems and to promote preventive behaviours are highly warranted.

Issue Cover

The cover image is based on the Original Article Clinical characteristics of COVID‐19 patients with hepatitis B virus infection — a retrospective study by Rui Liu et al., https://doi.org/10.1111/liv.14774.