Alterations in smell or taste in individuals infected with SARS-CoV-2 during periods of Omicron variant dominance.

OBJECTIVES: To characterize the prevalence, severity, correlation with initial symptoms, and role of vaccination in patients with COVID-19 with smell or taste alterations (STAs). METHODS: We conducted an observational study of patients infected with SARS-CoV-2 Omicron admitted to three hospitals between May 17 and June 16, 2022. The olfactory and gustatory functions were evaluated using the taste and smell survey and the numerical visual analog scale at two time points. RESULTS: The T1 and T2 time point assessments were completed by 688 and 385 participants, respectively. The prevalence of STAs at two time points was 41.3% vs 42.6%. Furthermore, no difference existed in the severity distribution of taste and smell survey, smell, or taste visual analog scale scores between the groups. Patients with initial symptoms of headache (P = 0.03) and muscle pain (P = 0.04) were more likely to develop STAs, whereas higher education; three-dose vaccination; no symptoms yet; or initial symptoms of cough, throat discomfort, and fever demonstrated protective effects, and the results were statistically significant. CONCLUSION: The prevalence of STAs did not decrease significantly during the Omicron dominance, but the severity was reduced, and vaccination demonstrated a protective effect. In addition, the findings suggest that the presence of STAs is likely to be an important indicator of viral invasion of the nervous system.

Establishment of Quality Evaluation Method for Yinqiao Powder: A Herbal Formula against COVID-19 in China.

Yinqiao powder, with significant anti-inflammatory and antiviral effects, is a classical formula for the treatment of febrile diseases in China. During the SARS period in 2003, Yinqiao powder showed a good antipyretic effect. It also plays a major role in the treatment for COVID-19 in China. Although there are many studies on the chemical compositions and pharmacological effects of Yinqiao powder, there are few studies on the quality standard system of it. In our study, a systematic quality evaluation method of Yinqiao powder combining HPLC fingerprint with quantitative analysis of multi-components by single marker (QAMS) based on network pharmacology and UPLC-Q-Exactive-Orbitrap-MS was established for the first time. In the UPLC-Q-Exactive-Orbitrap-MS experiment, a total of 53 compounds were identified in the extract solution of Yinqiao powder. In addition, 33 blood components were characterized, 23 of which were prototypes. The results of network pharmacology analysis showed that Yinqiao powder may inhibit inflammatory responses by suppressing IL-6, CXCL2, TNFα, NF-κB, etc., in the treatment of COVID-19. The HPLC fingerprint analysis of Yinqiao powder was conducted at 237 nm and 29 characteristic peaks were matched, 11 of which were identified. Forsythoside A was selected as the internal standard reference and double-wavelength (237 nm and 327 nm) was established in QAMS experiment. The repeatability was well under different conditions, and the results measured by QAMS were consisted with that of the external standard method (ESM), indicating that the QAMS method was reliable and accurate. The quality evaluation method of Yinqiao powder would be helpful to evaluate the intrinsic quality of Yinqiao powder more comprehensively, which is conducive to improve the quality standard of Yinqiao powder and provide a beneficial guarantee for the clinical treatment of COVID-19.

Small-molecule screening identifies Syk kinase inhibition and rutaecarpine as modulators of macrophage training and SARS-CoV-2 infection.

Biologically active small molecules can impart modulatory effects, in some cases providing extended long-term memory. In a screen of biologically active small molecules for regulators of tumor necrosis factor (TNF) induction, we identify several compounds with the ability to induce training effects on human macrophages. Rutaecarpine shows acute and long-term modulation, enhancing lipopolysaccharide (LPS)-induced pro-inflammatory cytokine secretion and relieving LPS tolerance in human macrophages. Rutaecarpine inhibits ß-glucan-induced H3K4Me3 marks at the promoters of several pro-inflammatory cytokines, highlighting the potential of this molecule to modulate chromosomal topology. Syk kinase inhibitor (SYKi IV), another screen hit, promotes an enhanced response to LPS similar to that previously reported for ß-glucan-induced training. Macrophages trained with SYKi IV show a high degree of resistance to influenza A, multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and OC43 coronavirus infection, highlighting a potential application of this molecule and other SYKis as prophylactic treatments for viral susceptibility.

The acceptance to heterologous booster vaccination of COVID-19 vaccine among HCWs and targeted population: A cross-sectional study in central China

Background There are few studies reported on the acceptance of heterologous booster vaccination for the COVID-19 vaccine among healthcare workers (HCWs) and the general population. We aimed to address that gap and explore determinant factors of acceptance of the heterologous booster vaccination. Methods We conducted a cross-sectional study to examine the prevalence and determinant factors of the acceptance of heterologous booster vaccination for the COVID-19 vaccine among HCWs and the targeted population. Results A total of 364 HCWs and 1,898 targeted populations were investigated in our study. 76.4% HCWs would recommend heterologous booster vaccination to their patients and 59.8% targeted population endorsed a clear willingness to receive this strategy. Compared with the adenoviral vector vaccine (AD5-nCOV), recombinant protein vaccine (ZF2001) was more preferred by HCWs (79.1%) and the targeted population (72.0%) as a heterologous booster vaccine. HCWs who did not work in the vaccination clinics were more likely to recommend heterologous booster vaccination (OR = 3.3, CI: 1.5–7.3). The targeted population aged 18–59 years (OR = 1.5, 95% CI:1.1–2.3), had a positive attitude toward COVID-19 vaccination (OR = 3.8, 95% CI: 1.7–8.6), had confidence in the safety of COVID-19 vaccines (OR = 6.6, 95% CI: 4.2–10.2), followed the recommendation of HCWs (OR = 33.6, 95% CI: 22.0–51.2), took initiative in collecting booster shots information (OR = 2.1, 95% CI: 1.5–3.0), and were familiar with the heterologous strategy (OR = 1.9, 95% CI: 1.1–3.1) were more likely to choose heterologous booster vaccination. The history of side effects of inactivated COVID-19 vaccine was a negative factor in choosing heterologous booster vaccination (OR = 0.4, 95% CI: 0.4–1.0). Conclusions The heterologous booster vaccination strategy on the COVID-19 vaccine could be widely accepted among HCWs, whereas its acceptance among targeted population was only moderate. Public authorities should make efforts to communicate the public about the effectiveness and safety of the heterologous booster vaccination which could help increase their willingness to get vaccinated.

Crucial control measures to contain China's first Delta variant outbreak.

The SARS-CoV-2 B.1.617.2 (Delta) variant flared up in late May in Guangzhou, China. Transmission characteristics of Delta variant were analysed for 153 confirmed cases and two complete transmission chains with seven generations were fully presented. A rapid transmission occurred in five generations within 10 days. The basic reproduction number (R0) was 3.60 (95% confidence interval: 2.50-5.30). After redefining the concept of close contact, the proportion of confirmed cases discovered from close contacts increased from 43% to 100%. With the usage of a yellow health code, the potential exposed individuals were self-motivated to take a nucleic acid test and regained public access with a negative testing result. Facing the massive requirement of screening, novel facilities like makeshift inflatable laboratories were promptly set up as a vital supplement and 17 cases were found, with 1 pre-symptomatic. The dynamic adjustment of these three interventions resulted in the decline of Rt from 5.00 to 1.00 within 9 days. By breaking the transmission chain and eliminating the transmission source through extending the scope of the close-contact tracing, health-code usage and mass testing, the Guangzhou Delta epidemic was effectively contained.

Transcriptomic Signatures of Airway Epithelium Infected With SARS-CoV-2: A Balance Between Anti-infection and Virus Load.

COVID-19 pneumonia requires effective medical therapies. However, it is a challenge to find therapeutic drugs that not only inhibit viral replication, but also inhibit the accompanying cytokine storm and maintain an appropriate immune response. In this study, the effects of SARS-CoV-2 on gene expression in lung epithelial cells from patients with COVID-19 were systematically evaluated with bioinformatics analysis methods. Transcriptome expression specific to bystander (exposed but uninfected) and infected cells were found, and the vital pathways were identified by conducting differentially expressed gene analysis regarding the relationship between gene signatures of COVID-19 infection and disease severity. We found that a high viral load did not necessarily imply a low response of epithelial cells or a poor disease convalescence. The ability to distinguish the role of virus-correlated genes facilitates the development of potential new medicines and therapies for COVID-19 infection.

Evidence for residual SARS-CoV-2 in glioblastoma tissue of a convalescent patient.

Since coronavirus disease 2019 (COVID-19) swept all over the world, several studies have shown the susceptibility of a patient with cancer to COVID-19. In this case, the removed glioblastoma multiforme (GBM)-adjacent (GBM-A), GBM-peritumor and GBM-central (GBM-C) tissues from a convalescent patient of COVID-19, who also suffered from glioblastoma meanwhile, together with GBM-A and GBM tissues from a patient without COVID-19 history as negative controls, were used for RNA ISH, electron microscopy observing and immunohistochemical staining of ACE2 and the virus antigen (N protein). The results of RNA ISH, electron microscopy observing showed that SARS-CoV-2 directly infects some cells within human GBM tissues and SARS-CoV-2 in GBM-C tissue still exists even when it is cleared elsewhere. Immunohistochemical staining of ACE2 and N protein showed that the expressions of ACE2 are significantly higher in specimens, including GBM-C tissue from COVID-19 patient than other types of tissue. The unique phenomenon suggests that the surgical protection level should be upgraded even if the patient is in a convalescent period and the pharyngeal swab tests show negative results. Furthermore, more attention should be paid to confirm whether the shelter-like phenomenon happens in other malignancies due to the similar microenvironment and high expression of ACE2 in some malignancies.

Analytical sensitivity comparison of 14 conventional and three rapid RT-PCR assays for SARS-CoV-2 detection.

Recent reports have compared the analytical sensitivities of some SARS-CoV-2 RT-PCR assays, but differences in the viral materials used for these evaluations made comprehensive conclusions difficult. We carried out a direct comparison of the analytical sensitivities of 14 conventional and three rapid RT-PCR assays for the detection of SARS-CoV-2. The comparison was performed utilizing a certified reference material for SARS-CoV-2 RNA that was serially two-fold diluted in RNA storage solution. Our results show that the analytical sensitivities of the 17 assays varied within an 8-fold range (100-800 copies/mL). Moreover, a trend with some rapid assays yielding slightly higher analytical sensitivities (2- to 4-fold) compared with conventional assays was observed. We conclude that most of the RT-PCR assays can be used for routine COVID-19 diagnosis, but some assays with the poorest analytical sensitivities may lead to false-negative results when used to identify asymptomatic individuals who can carry a low viral load but still be infectious. These findings should be kept in mind when selecting high-sensitivity and rapid assays.

Plasma metabolomic and lipidomic alterations associated with COVID-19.

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Infection Prevention and Control Strategies for the Peri-Operative Period of Emergency Surgery during the Coronavirus Disease 2019 Outbreak in a Neurosurgery Department in Wuhan, China.

Objective: In December 2019, a novel coronavirus infectious disease, coronavirus disease 2019 (COVID-19), began to appear in China. Wuhan, Hubei Province, is the origin and core location of the epidemic. Neurosurgeons were faced with the challenge of balancing treatment of patients with life-threatening conditions and preventing the cross-transmission of the virus. Methods: A series of infection prevention and control strategies was adopted for the peri-operative period of emergency surgeries in our department. These strategies include protective measures for the emergency department (ED) and measures for the peri-operative period of emergency surgery. The propensity score matching (PSM) was used to match COVID-19-related patients with patients before the epidemic. Length of wait time in the ED and duration of operation were compared. Results: From January 23, 2020 to March 18, 2020, we performed emergency surgery for 19 patients who were either COVID-19-related or COVID-19-suspected. None of the medical staff involved in the surgeries developed viral infection, and no peri-operative virus transmission occurred in our hospital. After the PSM, 32 patients were included in the epidemic group and the pre-epidemic group (16 patients in each group). The duration of wait time in the ED of the former group was longer than that of the latter group (z = -3.000; p = 0.003). During the epidemic, the duration of a craniotomy was longer than before the epidemic (z = -2.253; p = 0.024), and there was no difference in the duration of interventional surgery (z = -0.314; p = 0.753). Conclusion: We believe that our experience can provide a useful reference for other surgeons facing the same challenges and as a lesson for similar infectious diseases that may occur in the future.