A simplified viral RNA extraction method based on magnetic nanoparticles for fast and high-throughput detection of SARS-CoV-2.

The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19) draws worldwide concerns due to its long incubation period and strong infectivity. Although RT-PCR-based methods are being widely applied for clinical diagnosis, timely and accurate diagnosis towards COVID-19 causing virus, the SARS-CoV-2, is still limited due to labor-intensive and time-consuming operations. Herein, we report a new viral RNA extraction method based on poly-(amino ester) with carboxyl group (PC)-coated magnetic nanoparticles (pcMNPs) for the sensitive detection of SARS-CoV-2. This method combines the lysis and binding steps into one step, and refines multiple washing steps into one step, giving a turnaround time of less than 9 min. Furthermore, the extracted pcMNP-RNA complexes can be directly introduced into subsequent RT-PCR reactions without elution. This simplified viral RNA method could be well adapted in fast manual and automated high-throughput nucleic acids extraction protocols suitable for different scenarios. A high sensitivity down to 100 copies/mL and a linear correlation between 100 and 106 copies/mL of SARS-CoV-2 pseudovirus particles are achieved in both protocols. Benefitting from the simplicity and excellent performances, this new method can dramatically improve the efficiency and reduce operational requirements for the early clinical diagnosis and large-scale SARS-CoV-2 nucleic acid screening.

Neutralizing antibodies and T-cell responses to inactivated SARS-CoV-2 vaccine in COVID-19 convalescents one and a half years after infection.

Vaccines have been considered the most promising solution for ending the coronavirus disease 2019 (COVID-19) pandemic. Information regarding neutralizing antibodies (NAbs) and T-cell immune response in inactivated SARS-CoV-2 vaccine-immunized COVID-19 convalescent patients were either only available for a short time after illness recovered or not available at all (T-cell immunity). We evaluated SARS-CoV-2 NAbs and cellular immune responses to the SARS-CoV-2 inactivated vaccine in convalescent patients who recovered from infection for about one and a half years. We found that compared to before vaccination, SARS-CoV-2 NAbs and specific T-cell responses were significantly boosted by the inactivated vaccine in convalescent patients, which confirmed the pre-existing adaptive immunity in SARS-CoV-2 infected people. We observed that NAbs and IFN-γ-secreting T-cell response elicited by a single vaccine dose in subjects with prior COVID-19 infection were higher than after two doses of vaccine in SARS-CoV-2 naïve subjects. Both humoral and cellular immune responses elicited by one and two doses of inactivated vaccine were comparable in COVID-19-recovered persons. In conclusion, inactivated COVID-19 vaccine induced robust NAbs and T-cell responses to SARS-CoV-2 in COVID-19 convalescent patients and immune responses after one dose were equal to that after receiving two doses, which highlighted that robust humoral and cellular immune response can be reactivated by the inactivated vaccine in SARS-CoV-2 convalescent patients.

Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia.

Our object was to examine how the pre- and post-pandemic COVID-19 impacted the care of acute ST-segment elevation myocardial infarction (STEMI) patients in county hospitals. Using January 20, 2020, as the time point for the control of a unique coronavirus pneumonia epidemic in Jieshou, 272 acute STEMI patients were separated into pre-epidemic (group A, n = 130) and epidemic (group B, n = 142). There were no significant differences between the two groups in terms of mode of arrival, symptom onset-to-first medical contact time, door-to-needle time, door-to-balloon time, maximum hypersensitive cardiac troponin I levels, and in-hospital adverse events (P > 0.05). Emergency percutaneous coronary intervention (PCI) was much less common in group B (57.7%) compared to group A (72.3%) (P = 0.012), and the proportion of reperfusion treatment with thrombolysis was 30.3% in group B compared to 13.1% in group A (P < 0.001). Logistic regression analysis showed that age ≥76 years, admission NT-proBNP levels ≥3,018 pg/ml, and combined cardiogenic shock were independent risk factors for death. Compared with thrombolytic therapy, emergency PCI treatment further reduced the risk of death in STEMI. In conclusion, the county hospitals treated more acute STEMI with thrombolysis during the COVID-19 outbreak.

A nanomaterial targeting the spike protein captures SARS-CoV-2 variants and promotes viral elimination.

The global emergency caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can only be solved with effective and widespread preventive and therapeutic strategies, and both are still insufficient. Here, we describe an ultrathin two-dimensional CuInP2S6 (CIPS) nanosheet as a new agent against SARS-CoV-2 infection. CIPS exhibits an extremely high and selective binding capacity (dissociation constant (KD) < 1 pM) for the receptor binding domain of the spike protein of wild-type SARS-CoV-2 and its variants of concern, including Delta and Omicron, inhibiting virus entry and infection in angiotensin converting enzyme 2 (ACE2)-bearing cells, human airway epithelial organoids and human ACE2-transgenic mice. On association with CIPS, the virus is quickly phagocytosed and eliminated by macrophages, suggesting that CIPS could be successfully used to capture and facilitate virus elimination by the host. Thus, we propose CIPS as a promising nanodrug for future safe and effective anti-SARS-CoV-2 therapy, and as a decontamination agent and surface-coating material to reduce SARS-CoV-2 infectivity.

Neutralizing antibodies and cellular immune response after two doses of inactivated SARS-CoV-2 vaccine in China.

BACKGROUND: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine. METHODS: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China. RESULTS: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type. CONCLUSION: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

Cancer incidence and mortality in Australia from 2020 to 2044 and an exploratory analysis of the potential effect of treatment delays during the COVID-19 pandemic: a statistical modelling study.

BACKGROUND: Long-term projections of cancer incidence and mortality estimate the future burden of cancer in a population, and can be of great use in informing the planning of health services and the management of resources. We aimed to estimate incidence and mortality rates and numbers of new cases and deaths up until 2044 for all cancers combined and for 21 individual cancer types in Australia. We also illustrate the potential effect of treatment delays due to the COVID-19 pandemic on future colorectal cancer mortality rates. METHODS: In this statistical modelling study, cancer incidence and mortality rates in Australia from 2020 to 2044 were projected based on data up to 2017 and 2019, respectively. Cigarette smoking exposure (1945-2019), participation rates in the breast cancer screening programme (1996-2019), and prostate-specific antigen testing rates (1994-2020) were included where relevant. The baseline projection model using an age-period-cohort model or generalised linear model for each cancer type was selected based on model fit statistics and validation with pre-COVID-19 observed data. To assess the impact of treatment delays during the COVID-19 pandemic on colorectal cancer mortality, we obtained data on incidence, survival, prevalence, and cancer treatment for colorectal cancer from different authorities. The relative risks of death due to system-caused treatment delays were derived from a published systematic review. Numbers of excess colorectal cancer deaths were estimated using the relative risk of death per week of treatment delay and different durations of delay under a number of hypothetical scenarios. FINDINGS: Projections indicate that in the absence of the COVID-19 pandemic effects, the age-standardised incidence rate for all cancers combined for males would decline over 2020-44, and for females the incidence rate would be relatively stable in Australia. The mortality rates for all cancers combined for both males and females are expected to continuously decline during 2020-44. The total number of new cases are projected to increase by 47·4% (95% uncertainty interval [UI] 35·2-61·3) for males, from 380 306 in 2015-19 to 560 744 (95% UI 514 244-613 356) in 2040-44, and by 54·4% (95% UI 40·2-70·5) for females, from 313 263 in 2015-19 to 483 527 (95% UI 439 069-534 090) in 2040-44. The number of cancer deaths are projected to increase by 36·4% (95% UI 15·3-63·9) for males, from 132 440 in 2015-19 to 180 663 (95% UI 152 719-217 126) in 2040-44, and by 36·6% (95% UI 15·8-64·1) for females, from 102 103 in 2015-19 to 139 482 (95% UI 118 186-167 527) in 2040-44, due to population ageing and growth. The example COVID-19 pandemic scenario of a 6-month health-care system disruption with 16-week treatment delays for colorectal cancer patients could result in 460 (95% UI 338-595) additional deaths and 437 (95% UI 314-570) deaths occurring earlier than expected in 2020-44. INTERPRETATION: These projections can inform health service planning for cancer care and treatment in Australia. Despite the continuous decline in cancer mortality rates, and the decline or plateau in incidence rates, our projections suggest an overall 51% increase in the number of new cancer cases and a 36% increase in the number of cancer deaths over the 25-year projection period. This means that continued efforts to increase screening uptake and to control risk factors, including smoking exposure, obesity, physical inactivity, alcohol use, and infections, must remain public health priorities. FUNDING: Partly funded by Cancer Council Australia.

COVID-19 and liver dysfunction: What nutritionists need to know.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field. Patients with COVID-19 usually have respiratory symptoms. However, liver dysfunction is not an uncommon presentation. Additionally, the degree of liver dysfunction is associated with the severity and prognosis of COVID-19. Prevention, diagnosis, and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19, especially in those with liver dysfunction. Recently, a large number of studies have reported that nutrition therapy measures, including natural dietary supplements, vitamins, minerals and trace elements, and probiotics, might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant, antiviral, anti-inflammatory, and positive immunomodulatory effects. This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction, nutritional and metabolic characteristics, nutritional status assessment, and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

SARS-CoV-2 Delta Variant in Jingmen City, Hubei Province, China, 2021: Children Susceptible and Vaccination Breakthrough Infection.

Background: The delta variant (B.1.617.2) of SARS-CoV-2 was the dominant viral strain causing COVID-19 in China, 2021. We reported a SARS-CoV-2 delta variant outbreak in Jingmen City, Hubei Province, China. Methods: The data of epidemiological, clinical, laboratorial, and vaccination of COVID-19 cases were collected through field investigation and analyzed. Results: During the outbreak from 4 to 20 August 2021, 58 cases of the SARS-CoV-2 delta variant (B.1.617.2) were identified with 15 (25.9%) asymptomatic and 43 (74.1%) symptomatic (mild and moderate) patients. The mean serial interval was 2.6 days (standard deviation: 2.0, 95% CI: 1.9-3.6). The median age of the patients was 39 years (ranging from 1 to 60 years) with the high proportion in children (19.0%). The secondary attack rate was 9.8% higher from parents to their children (<18 years) (46.2%, 95% CI: 14.8-77.5%) than that between spouses (36.4%, 95% CI: 14.5-58.2%), but no significant difference was observed (p > 0.05). Approximately half (27; 46.6%) of cases were vaccine breakthrough infections. In vaccine breakthrough cases (fully vaccinated), viral loads decreased 1.9-3.4-folds (p < 0.05), duration of viral shedding shortened 5 days (p < 0.05), and the risk of becoming symptomatic from asymptomatic decreased 33% (95% CI: 5-53%) (aged ≥12 years) than those in unvaccinated infections. Conclusions: Children are highly susceptible to the SARS-CoV-2 delta variant in the COVID-19 outbreak in Jingmen City in 2021. Inactivated vaccine derived from wide-type strain can effectively reduce the viral load, duration of viral shedding, and clinical severity in vaccine breakthrough cases. Our study indicates that protective measures that include full vaccination against COVID-19, especially in children, should be strengthened.

Potential role of vitamin D in patients with diabetes, dyslipidaemia, and COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 has become a worldwide public health crisis. Studies have demonstrated that diabetes and dyslipidaemia are common comorbidities and could be high-risk factors for severe COVID-19. Vitamin D, a group of fat-soluble compounds responsible for intestinal absorption of calcium, magnesium, and phosphate, has been widely used as a dietary supplement for the prevention and treatment of numerous diseases, including infectious and non-infectious diseases, due to its high cost-effectiveness; safety; tolerability; and anti-thrombotic, anti-inflammatory, antiviral, and immunomodulatory properties. In this letter to the editor, we mainly discuss the potential role of vitamin D in patients with diabetes, dyslipidaemia, and COVID-19.

Neutralizing Antibodies and Cellular Immune Responses Against SARS-CoV-2 Sustained One and a Half Years After Natural Infection.

Background: COVID-19 has caused more than 2.6 billion infections and several million deaths since its outbreak 2 years ago. We know very little about the long-term cellular immune responses and the kinetics of neutralizing antibodies (NAbs) to SARS-CoV-2 because it has emerged only recently in the human population. Methods: We collected blood samples from individuals who were from the first wave of the COVID-19 epidemic in Wuhan between December 30, 2019, and February 24, 2020. We analyzed NAbs to SARS-CoV-2 using pseudoviruses and IgG antibodies to SARS-CoV-2 spike (S) and nucleocapsid (N) protein using enzyme-linked immunosorbent assay in patients' sera and determined SARS-CoV-2-specific T-cell responses of patients with ELISpot assays. Results: We found that 91.9% (57/62) and 88.9% (40/45) of COVID-19 patients had NAbs against SARS-CoV-2 in a year (10-11 months) and one and a half years (17-18 months), respectively, after the onset of illness, indicating that NAbs against SARS-CoV-2 waned slowly and possibly persisted over a long period time. Over 80% of patients had IgG antibodies to SARS-CoV-2 S and N protein one and a half years after illness onset. Most patients also had robust memory T-cell responses against SARS-CoV-2 one and a half years after the illness. Among the patients, 95.6% (43/45) had an IFN-γ-secreting T-cell response and 93.8% (15/16) had an IL-2-secreting T-cell response. The T-cell responses to SARS-CoV-2 were positively correlated with antibodies (including neutralizing antibodies and IgG antibodies to S and N protein) in COVID-19 patients. Eighty percent (4/5) of neutralizing antibody-negative patients also had SARS-CoV-2-specific T-cell response. After long-term infection, protective immunity was independent of disease severity, sex, and age. Conclusions: We concluded that SARS-CoV-2 infection elicited a robust and persistent neutralizing antibody and memory T-cell response in COVID-19 patients, indicating that these sustained immune responses, among most SARS-CoV-2-infected people, may play a crucial role in protection against reinfection.

Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus.

Coronavirus disease 2019 (COVID-19) raises the issue of how hypoxia destroys normal physiological function and host immunity against pathogens. However, there are few or no comprehensive omics studies on this effect. From an evolutionary perspective, animals living in complex and changeable marine environments might develop signaling pathways to address bacterial threats under hypoxia. In this study, the ancient genomic model animal Takifugu obscurus and widespread Vibrio parahaemolyticus were utilized to study the effect. T. obscurus was challenged by V. parahaemolyticus or (and) exposed to hypoxia. The effects of hypoxia and infection were identified, and a theoretical model of the host critical signaling pathway in response to hypoxia and infection was defined by methods of comparative metabolomics and proteomics on the entire liver. The changing trends of some differential metabolites and proteins under hypoxia, infection or double stressors were consistent. The model includes transforming growth factor-ß1 (TGF-ß1), hypoxia-inducible factor-1α (HIF-1α), and epidermal growth factor (EGF) signaling pathways, and the consistent changing trends indicated that the host liver tended toward cell proliferation. Hypoxia and infection caused tissue damage and fibrosis in the portal area of the liver, which may be related to TGF-ß1 signal transduction. We propose that LRG (leucine-rich alpha-2-glycoprotein) is widely involved in the transition of the TGF-ß1/Smad signaling pathway in response to hypoxia and pathogenic infection in vertebrates as a conserved molecule.

Fine particulate matter air pollution and under-5 children mortality in China: A national time-stratified case-crossover study.

BACKGROUND: Under-5 mortality rate is an important indicator in Millennium Development Goals and Sustainable Development Goals. To date, no nationally representative studies have examined the effects of fine particulate matter (PM2.5) air pollution on under-5 mortality. OBJECTIVE: To investigate the association of short-term exposure to PM2.5 with under-5 mortality from total and specific causes in China. METHODS: We used the national Maternal and Child Health Surveillance System to identify under-5 mortality cases during the study period of 2009 to 2019. We adopted a time-stratified case-crossover study design at the individual level to capture the effect of short-term exposure to daily PM2.5 on under-5 mortality, using conditional logistic regression models. RESULTS: A total of 61,464 under-5 mortality cases were included. A 10 µg/m3 increase in concentrations of PM2.5 on lag 0-1 d was significantly associated with a 1.15% (95%confidence interval: 0.65%, 1.65%) increase in under-5 mortality. Mortality from diarrhea, pneumonia, digestive diseases, and preterm birth were significantly associated with exposure to PM2.5. The effect estimates were larger for neonatal mortality (<28 days), female children, and in warm seasons. We observed steeper slopes in lower ranges (<50 µg/m3) of the concentration-response curve between PM2.5 and under-5 mortality, and positive associations remained below the 24-h PM2.5 concentration limit recommended by WHO Air Quality Guidelines and China Air Quality Standards. CONCLUSIONS: This nationwide case-crossover study in China demonstrated that acute exposure to PM2.5 may significantly increase the risk of under-5 mortality, with larger effects for neonates, female children, and during warm seasons. Relevant control strategies are needed to remove this roadblock to achieving under-5 mortality targets in developing countries.

SARS-CoV-2 ORF3a Induces Incomplete Autophagy via the Unfolded Protein Response.

In the past year and a half, SARS-CoV-2 has caused 240 million confirmed cases and 5 million deaths worldwide. Autophagy is a conserved process that either promotes or inhibits viral infections. Although coronaviruses are known to utilize the transport of autophagy-dependent vesicles for the viral life cycle, the underlying autophagy-inducing mechanisms remain largely unexplored. Using several autophagy-deficient cell lines and autophagy inhibitors, we demonstrated that SARS-CoV-2 ORF3a was able to induce incomplete autophagy in a FIP200/Beclin-1-dependent manner. Moreover, ORF3a was involved in the induction of the UPR (unfolded protein response), while the IRE1 and ATF6 pathways, but not the PERK pathway, were responsible for mediating the ORF3a-induced autophagy. These results identify the role of the UPR pathway in the ORF3a-induced classical autophagy process, which may provide us with a better understanding of SARS-CoV-2 and suggest new therapeutic modalities in the treatment of COVID-19.

A water-soluble membrane for SARS-CoV-2 viral nucleic acid sampling and detection.

This communication describes a novel water-soluble membrane prepared from chitosan intended for SARS-CoV-2 viral nucleic acid collection and detection. The CSH membrane formed from nanofibers shows promising potential in the quantitative determination of the SARS-CoV-2 viral nucleic acids at a concentration of 102 copies per L in air. The sponge-like structure which allows gas to pass through for collection of viral nucleic acids potentially provides simple, fast, and reliable sampling as well as detection of various types of airborne viruses.

A COVID-19 Outbreak Emerging in a Food Processing Company - Harbin City, Heilongjiang Province, China, January-February 2021.

What is already known about this topic? The coronavirus disease 2019 (COVID-19) epidemic in China had been effectively controlled for several months, but as the ambient temperature dropped, large gathering-initiated epidemics occurred in northern China, including Hebei, Liaoning, and Jilin provinces. What is added by this report? A sudden epidemic emerged in Wangkui County, Suihua City, Heilongjiang Province, on January 9, 2021. An asymptomatically-infected resident of Harbin City returned from Suihua and triggered a large-scale outbreak in the Zhengda Food Processing Company in Harbin, Heilongjiang. The epidemic was associated with widespread community transmission inside and outside the company, eventually leading to 260 persons being infected (87.8% of 296 patients in Harbin). What are the implications for public health practice? This study demonstrates the importance of screening for infections in the COVID-19 prevention and control system, shares experiences identifying and managing asymptomatic infections, and recommends food processing enterprises like the Zhengda Company to improve preventative measures. Our evidence-based epidemiological analyses provide methods for finding high-risk settings and evaluating epidemic situations when many asymptomatic patients are identified in a short period of time.

A Tuberculosis Outbreak During the COVID-19 Pandemic - Hubei Province, China, 2020.

What is already known about topic? Multidrug-resistant tuberculosis (MDR-TB) has become a growing threat to public health. There were few reports about family-to-school MDR-TB outbreaks in China, especially during the coronavirus disease 2019 (COVID-19) pandemic. What is added by this report? A tuberculosis (TB) outbreak happened in Hubei Province during the COVID-19 pandemic. The transmission chain was probably from a father （MDR-TB case）with retreated TB history to his daughter, who then spread TB to her classmates. What are the implications for public health practice? We should enhance TB control both in schools and households, including strengthening TB/MDR-TB detection, health education, and ventilation. The TB contact screening cannot only be limited to outside school settings and should be conducted in the school when a TB student is absent from school for 2 or 3 months, or even longer especially during the COVID-19 pandemic.