Assessing the spatial distribution of and inequality in 15-minute PCR test site accessibility in Beijing and Guangzhou, China.

China has been planning to construct SARS-CoV-2 antigen testing sites within a 15-min walk in most major cities to timely identify asymptomatic cases and stop the transmission of COVID-19. However, little is known about the spatial distribution of 15-min accessibility to PCR test sites. In this study, we analyze the spatial distribution of and inequality in 15-min accessibility to PCR test sites in two major Chinese cities (Beijing and Guangzhou) based on the cumulative-opportunity model. The results indicate that the current distribution of 15-min accessibility to PCR test sites is satisfactory when normal commuting is not disrupted. However, disruptions of normal commuting (e.g., due to work-from-home restrictions) can negatively influence 15-min accessibility to PCR test sites and increase its inequality. Our study provides policymakers with up-to-date knowledge about the spatial distribution of 15-min accessibility to PCR test sites, identifies the disadvantaged neighborhoods in terms of test site accessibility, and highlights the changes in accessibility and inequality because of travel disruptions.

Risk assessment of novel coronavirus COVID-19 outbreaks in the border areas of southwest China.

This study aimed to assess the risk of coronavirus disease 2019 in the border areas of southwest China, so as to provide guidance to targeted prevention and control measures in the border areas of different risk levels. We assessed the dependence of the risk of an outbreak in the southwest China from imported cases on key parameters such as the cumulative number of infectious diseases in the border area of southwest China in the past 3 years; the connectivity of the neighboring countries with China's Southwest border, including baseline travel numbers, travel frequencies, the effect of travel restrictions, and the length of borders with neighboring countries; the cumulative number of close contacts of coronavirus disease 2019 patients; (iv) the population density in border areas; the efficacy of control measures in border areas; experts estimated risks in border areas based on experience and then given a score; Spearman correlation and Logistic regression models were used to analyze the associated factors of novel coronavirus. According to the correlation of various factors, we assigned values to each parameter, calculated the risk score of each county, and then divided each county into high, medium, and low risk according to the sick score and took different control measure according to different risk levels. Finally, the total risk level was evaluated according to the Harvard disease risk index model. The number of infectious diseases in the past 3 years, travel numbers, travel frequencies, experts estimated risk score, effect of travel restrictions, and the number of close contacts were associated with the incidence of new coronary pneumonia. It is concluded that bilateral transportation convenience is a risk factor for new coronary pneumonia, (odds ratio = 9.23, 95% confidence interval, 1.99-42.73); the number of observers is a risk factor for new coronary pneumonia (odds ratio = 1.04, 95% confidence interval, 1.00-1.08). We found that in countries with travel numbers, travel frequencies, and experts' estimated risk scores were the influencing factors of novel coronavirus. The effect of travel restrictions and the cumulative number of close contacts of the case are risk factors for novel coronavirus.

Plasma Proteomics of COVID-19 Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics (preprint)

Cardiovascular complications are common in COVID-19 and strongly associated with disease severity and mortality. However, the mechanisms driving cardiac injury and failure in COVID-19 are largely unknown. We performed plasma proteomics on 80 COVID-19 patients and controls, grouped according to disease severity and cardiac involvement. Findings were validated in 305 independent COVID-19 patients and investigated in an animal model. Here we show that senescence-associated secretory proteins, markers of biological aging, strongly associate with disease severity and cardiac involvement even in age-matched cohorts. FSTL3, an indicator of Activin/TGFβ signaling, was the most significantly upregulated protein associated with the heart failure biomarker, NTproBNP (β = 0.4;padj=4.6x10− 7), while ADAMTS13, a vWF-cleaving protease whose loss-of-function causes microvascular thrombosis, was the most downregulated protein associated with myocardial injury (β=-0.4;padj=8x10− 7). Mendelian randomization supported a causal role for ADAMTS13 in myocardial injury. These data provide important new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

Single-cell landscape of immunological responses in COVID-19 patients (preprint)

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.