Identification of serum metabolites enhancing inflammatory responses in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

The clinical efficacy and safety research of Lianhuaqingwen (LHQW) in treatment of COVID-19: A systematic review and meta-analysis

Background : Although vaccines have been launched, COVID-19 has not been effectively curbed, and the number of infections is increasing. Compared with western medicine, Traditional Chinese Medicine has made some achievements in the treatment of COVID-19, which should be paid attention to and play a greater role. As a classical Chinese medicine prescription for treating pestilence, Lianhuaqingwen (LHQW) has gone to many countries with the Chinese medical team to participate in the local fight against the epidemic, which has been widely recognized. Methods : We searched MEDLINE, EMBASE, AMED, Chchrane Central Register of Controlled Trials (CENTRAL), PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Information Database (VIP), Chinese Biomedical Literature Database (CBM), and Wanfang Database from inception up to November 24, 2021, which formed the basis for evidence used to formulate recommendations. Sixteen randomized controlled trials (RCTs) involving 1896 patients were enrolled. LHQW is a traditional Chinese medicine compound preparation, which contains 13 traditional Chinese medicine (TCM) components. Two dosage formulations of LHQW were included: granule and capsule. The most commonly used dosage formulation was granule (15/17, 88.24 %), followed by capsule (2/17, 11.76 %). Conclusion : This systematic review and Meta analysis suggested that, in the treatment of COVID-19, LHQW Capsule (Granule) could not only significantly improve the fever symptoms, shorten the fever time, but also reduce the cough and fatigue symptoms, improve the clinical efficiency, improve the lung CT, significantly reduce the number of patients with mild to severe diseases, and have certain anti-inflammatory effect. And there is no server adverse events which support the safety of LHQW Capsule (Granule) for the treatment of COVID-19. As a classic formula of TCM, LHQW Capsule (Granule) could be used as potential candidates for COVID-19 in this battle.

Management strategies for dermatomyositis during the coronavirus disease 2019 outbreak.

In late 2019, the coronavirus disease 2019 (COVID-19) broke out in Wuhan and then spread over China, which greatly affected the medical practices and health care systems. With most of the hospital's outpatient services closed, the routine clinical diagnosis and treatment for patients with dermatomyositis has been disturbed. We conducted telephone follow-up for 52 patients to know the changes in the condition and the continuation of drug therapy and to ensure the continuity, safety, and effectiveness of the treatment of patients with dermatomyositis during COVID-19.

Measuring imported case risk of COVID-19 from inbound international flights --- A case study on China.

With COVID-19 spreading around the world, many countries are exposed to the imported case risk from inbound international flights. Several governments issued restrictions on inbound flights to mitigate such risk. But with the pandemic controlled in many countries, some decide to reopen the economy by relaxing the international air travel bans. As the virus has still been prevailing in many regions, this relaxation raises the alarm to import overseas cases and results in the revival of local pandemic. This study proposes a risk index to measure one country's imported case risk from inbound international flights. The index combines both daily dynamic international air connectivity data and the updated global COVID-19 data. It can measure the risk at the country, province and even specific route level. The proposed index was applied to China, which is the first country to experience and control COVID-19 pandemic while later becoming exposed to high imported case risk after the epidemic centers switched to Europe and the US afterward. The calculated risk indexes for each Chinese province or region show both spatial and temporal patterns from January to April 2020. It is found that China's strict restriction on inbound flights since March 26 was very effective to cut the imported case risk by half than doing nothing. But the overall index level kept rising because of the deteriorating pandemic conditions around the world. Hong Kong and Taiwan are the regions facing the highest imported case risk due to their superior international air connectivity and looser restriction on inbound flights. Shandong Province had the highest risk in February and early March due to its well-developed air connectivity with South Korea and Japan when the pandemic peaked in these two countries. Since mid-March, the imported case risk from Europe and the US dramatically increased. Last, we discuss policy implications for the relevant stakeholders to use our index to dynamically adjust the international air travel restrictions. This risk index can also be applied to other contexts and countries to relax restrictions on particular low-risk routes while still restricting the high-risk ones. This would balance the essential air travels need and the requirement to minimize the imported case risk.