SARS-CoV-2 Envelope protein triggers depression and dysosmia via TLR2 mediated neuroinflammation (preprint)

Background: Depression and dysosmia have been regarded as the main neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that SARS-CoV-2 envelope protein served as a pro-inflammatory factor as sensed by Toll like receptor 2 (TLR2), suggesting the viral infection independent pathological feature of E protein. In this study, we aim to determine the role of E protein in depression, dysosmia and associated neuroinflammation in central nervous system (CNS). Methods: Depression and olfactory function were observed in both female and male mice as receiving intracisternal injection of envelope protein. Immunohistochemistry was applied in conjunction with RT-PCR to assess the glial activation, blood-brain barrier status and mediators synthesis in cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein related depression and dysosmia. Results: Intracisternal injection of envelope protein evoked depression and dysosmia in both female and male mice. Immunohistochemistry suggested that envelope protein upregulated IBA1 and GFAP in cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-beta, TNF-alpha, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-beta, IL-6 and CCL2 were upregulated in olfactory bulb. Furtherly, inhibiting microglia, but not astrocyte, alleviated depression and dysosmia induced by envelope protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression and dysosmia induced by envelope protein. Conclusions: Our study demonstrates that envelope protein could directly induce depression and dysosmia together with obvious neuroinflammation in CNS. TLR2 mediated depression and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.

Research progress on the mutation of SARS-CoV-2

At the end of December 2019,an outbreak of pneumonia caused by SARS-CoV-2 occurred in Wuhan, Hubei Province. So far, the epidemic caused by the virus is still circulating globally, infecting more than 180 million people in total. With the continuous spread of SARS-CoV-2 among populations, its genome has continued to mutate, from the first discovery of D614G mutation of the S protein in SARS-CoV-2 to Alpha, Beta, Gamma, Delta listed as concerns by the World Health Organization and some other variants of interest. The continuous emergence of new variants has aroused widespread public concern. Therefore, this article will briefly summarize the genome structure and function of SARS-CoV-2, some of the characteristics of the main international variants, the protection results of SARS-CoV-2 vaccines against the variants, and the vaccine strategies to deal with SARS-CoV-2 mutations.

Guided release of a breath (GRAB) – bringing urea breath test (UBT) to the doorstep

BackgroundUrea Breath Tests (UBTs) are common non-invasive tests performed in hospitals under the guidance of trained technicians. However, COVID-19 has reduced access to within-hospital UBTs. Self-conducted UBT (SUBT) at home has been suggested as an alternative. This study aims to compare the efficacy of SUBT with written compared to video instructions.MethodsThe study was divided into 3 parts. In Part 1, consecutive first-time UBT patients were randomized to receive either written or video instructions. In Part 2, the original video was enhanced. For Parts 1 and 2, a competency score of 1-5 based on the assessment of the 5 key steps was determined by a trained observer. Having reviewed the steps for breath collection in the first 2 parts, we went on to Part 3 to determine if breath collection with these steps would be successful. A further enhanced instructional video was created and successful collection of breath was recorded based on detection of sufficient recovered C-13 in the breath bag for the baseline test.ResultsIn total, 129 patients were recruited for the study. Patients excluded for this study included those who had visual or hearing impairment, cognitive impairment and those who did not understand English as our instructional materials were in English. For Part 1, 20 patients were randomised into written (n=10) and original video (n=10) groups. There was numerical improvement but no statistically significant difference in median scores for written and video instructions (2 vs 4, p=0.055). A further 10 patients were recruited for Part 2, the enhanced video group. Median scores were statistically improved for enhanced video compared to written (5 vs 2, p=0.043). In Part 3, 99 patients were recruited. Barring machine fault, all the UBTs were successful without repeating the breath test.ConclusionsAn enhanced instructional video is highly successful at enabling SUBT. This can improve the safety of patients and operators by allowing UBTs to be conducted at home, while maintaining accuracy. This would reduce the time that patients spend in the hospital and reduce exposure to potential COVID infections.