Real-time risk ranking of emerging epidemics based on optimized moving average prediction limit-taking the COVID-19 pandemic as an example.

BACKGROUND: Mathematical models to forecast the risk trend of the COVID-19 pandemic timely are of great significance to control the pandemic, but the requirement of manual operation and many parameters hinders their efficiency and value for application. This study aimed to establish a convenient and prompt one for monitoring emerging infectious diseases online and achieving risk assessment in real time. METHODS: The Optimized Moving Average Prediction Limit (Op-MAPL) algorithm model analysed real-time COVID-19 data online and was validated using the data of the Delta variant in India and the Omicron in the United States. Then, the model was utilized to determine the infection risk level of the Omicron in Shanghai and Beijing. RESULTS: The Op-MAPL model can predict the epidemic peak accurately. The daily risk ranking was stable and predictive, with an average accuracy of 87.85% within next 7 days. Early warning signals were issued for Shanghai and Beijing on February 28 and April 23, 2022, respectively. The two cities were rated as medium-high risk or above from March 27 to April 20 and from April 24 to May 5, indicating that the pandemic had entered a period of rapid increase. After April 21 and May 26, the risk level was downgraded to medium and became stable by the algorithm, indicating that the pandemic had been controlled well and mitigated gradually. CONCLUSIONS: The Op-MAPL relies on nothing but an indicator to assess the risk level of the COVID-19 pandemic with different data sources and granularities. This forward-looking method realizes real-time monitoring and early warning effectively to provide a valuable reference to prevent and control infectious diseases.

Anti-Coronaviral Nanocluster Restrain Infections of SARS-CoV-2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation.

Antivirals that can combat coronaviruses, including SARS-CoV-2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad-spectrum anti-coronavirus efficacy, which is difficult to achieve using a single small-molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS-CoV-2-like coronavirus of pangolin origin, is screened and a surface-functionalized gold nanocluster (TMA-GNC) is identified as the top hit. TMA-GNC inhibits transcription- and replication-competent SARS-CoV-2 virus-like particles and all tested pseudoviruses of SARS-CoV-2 variants. TMA-GNC prevents viral dissemination through destroying membrane integrity physically to enable a virucidal effect, interfering with viral replication by inactivating 3CL protease and priming the innate immune system against coronavirus infection. TMA-GNC exhibits biocompatibility and significantly reduces viral titers, inflammation, and pathological injury in lungs and tracheas of GX_P2V-infected hamsters. TMA-GNC may have a role in controlling the COVID-19 pandemic and inhibiting future emerging coronaviruses or variants.

Induction of Significant Neutralizing Antibodies against SARS-CoV-2 by a Highly Attenuated Pangolin Coronavirus Variant with a 104nt Deletion at the 3'-UTR.

SARS-CoV-2 related coronaviruses (SARS-CoV-2r) from Guangdong and Guangxi pangolins have been implicated in the emergence of SARS-CoV-2 and future pandemics. We previously reported the culture of a SARS-CoV-2r GX_P2V from Guangxi pangolins. Here we report the GX_P2V isolate rapidly adapted to Vero cells by acquiring two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104-nucleotide deletion in the hypervariable region (HVR) of the 3'-terminus untranslated region (3'-UTR). We further report the characterization of the GX_P2V variant (renamed GX_P2V(short_3UTR)) in in vitro and in vivo infection models. In cultured Vero, BGM and Calu-3 cells, GX_P2V(short_3UTR) had similar robust replication kinetics, and consistently produced minimum cell damage. GX_P2V(short_3UTR) infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection in pulmonary, not extrapulmonary, tissues. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V(short_3UTR) is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely partially due to the 104-nt deletion in the HVR in the 3'-UTR. This study furthers our understanding of pangolin coronaviruses pathogenesis and provides novel insights for the design of live attenuated vaccines against SARS-CoV-2.

Bovine lactoferrin inhibits SARS-CoV-2 and SARS-CoV-1 by targeting the RdRp complex and alleviates viral infection in the hamster model.

Breast milk has been found to inhibit coronavirus infection, while the key components and mechanisms are unknown. We aimed to determine the components that contribute to the antiviral effects of breastmilk and explore their potential mechanism. Lactoferrin (Lf) and milk fat globule membrane (MFGM) inhibit SARS-CoV-2 related coronavirus GX_P2V and SARS-CoV-2 trVLP in vitro and block viral entry into cells. We confirmed that bovine lactoferrin (bLf) blocked the binding between human angiotensin-converting enzyme 2 (hACE2) and SARS-CoV-2 spike protein by combining receptor binding domain (RBD). Importantly, bLf inhibited RNA-dependent RNA polymerase (RdRp) activity of both SARS-CoV-2 and SARS-CoV in vitro in the nanomolar range. So far, no biological macromolecules have been reported to inhibit coronavirus RdRp. Our result indicated that bLf plays a major role in inhibiting viral replication rather than viral entry, which has been widely explored. bLf treatment reduced viral load in lungs and tracheae and alleviated pathological damage. Our study provides evidence that bLf prevents SARS-CoV-2 infection by combining SARS-CoV-2 spike protein RBD and inhibiting coronaviruses' RdRp activity, and may be a promising candidate for the treatment of COVID-19. This article is protected by copyright. All rights reserved.

The characteristics and implications of epidemic reports during COVID-19 in the United States.

We summarized the basic practices and characteristics of epidemic reporting during the COVID-19 pandemic in the United States. Based on the analysis of the advantages and disadvantages of epidemic data reporting, we put forward some suggestions that should be used for reference and thus improve the epidemic data reports of infectious diseases.

Multiple organ injury on admission predicts in-hospital mortality in patients with COVID-19.

Multiorgan injury has been implicated in patients with coronavirus disease 2019 (COVID-19). We aim to assess the impact of organ injury (OI) on prognosis according to the number of affected organs at admission. This is a retrospective cohort study of patients with confirmed COVID-19 in Wuhan Third Hospital & Tongren Hospital of Wuhan University from February 17 to March 22, 2020. We classified the patients according to the presence and number of damaged organs (heart, liver, and kidney). The percentage of patients with no, one, two, or three organs affected was 59.75%, 30.46%, 8.07%, and 1.72%, respectively. With the increasing number of OI, there is a tendency of gradual increase regarding the white blood cell counts, neutrophil counts, levels of C-reactive protein (CRP), lactate dehydrogenase, D-dimer, and fibrinogen as well as the incidence of most complications. In a Cox regression model, individuals with OI, old age, and an abnormal level of CRP were at a higher risk of death compared with those without. Patients with three organ injuries had the highest mortality rate (57.9%; hazard ratio [HR] with 95% confidence interval [CI] vs. patients without OI: 22.31 [10.42-47.77], those with two [23.6%; HR = 8.68, 95% CI = 4.58-16.48], one [8.6%; HR = 3.1, 95% CI = 1.7-5.7], or no OI [2.6%]; p < .001). The increasing number of OI was associated with a high risk of mortality in COVID-19 infection.