Moderating Effect of a Cross-Level Social Distancing Policy on the Disparity of COVID-19 Transmission in the United States

Currently, coronavirus disease 2019 (COVID-19) remains a global pandemic, but the prevention and control of the disease in various countries have also entered the normalization stage. To achieve economic recovery and avoid a waste of resources, different regions have developed prevention and control strategies according to their social, economic, and medical conditions and culture. COVID-19 disparities under the interaction of various factors, including interventions, need to be analyzed in advance for effective and precise prevention and control. Considering the United States as the study case, we investigated statistical and spatial disparities based on the impact of the county-level social vulnerability index (SVI) on the COVID-19 infection rate. The county-level COVID-19 infection rate showed very significant heterogeneity between states, where 67% of county-level disparities in COVID-19 infection rates come from differences between states. A hierarchical linear model (HLM) was adopted to examine the moderating effects of state-level social distancing policies on the influence of the county-level SVI on COVID-19 infection rates, considering the variation in data at a unified level and the interaction of various data at different levels. Although previous studies have shown that various social distancing policies inhibit COVID-19 transmission to varying degrees, this study explored the reasons for the disparities in COVID-19 transmission under various policies. For example, we revealed that the state-level restrictions on the internal movement policy significantly attenuate the positive effect of county-level economic vulnerability indicators on COVID-19 infection rates, indirectly inhibiting COVID-19 transmission. We also found that not all regions are suitable for the strictest social distancing policies. We considered the moderating effect of multilevel covariates on the results, allowing us to identify the causes of significant group differences across regions and to tailor measures of varying intensity more easily. This study is also necessary to accomplish targeted preventative measures and to allocate resources.

The dichotomous and incomplete adaptive immunity in COVID-19 (preprint)

The adaptive immunity that protects patients from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not well characterized. In particular, the asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses, but the underlying mechanisms remain unknown; meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is also not well studied. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 49 patients with other disease severity (mild, n=10, moderate, n=32, severe, n=7) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and long-term humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in asymptomatic patients and revealed the strikingly dichotomous and unbalanced humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of COVID-19 vaccines.

Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19 (preprint)

COVID-19 patients exhibit differential disease severity after SARS-CoV-2 infection. It is currently unknown as to the correlation between the magnitude of neutralizing antibody (NAb) responses and the disease severity in COVID-19 patients. In a cohort of 59 recovered patients with disease severity including severe, moderate, mild and asymptomatic, we observed the positive correlation between serum neutralizing capacity and disease severity, in particular, the highest NAb capacity in sera from the patients with severe disease, while a lack of ability of asymptomatic patients to mount competent NAbs. Furthermore, the compositions of NAb subtypes were also different between recovered patients with severe symptoms and with mild-to-moderate symptoms. These results reveal the tremendous heterogeneity of SARS-CoV-2-specific NAb responses and their correlations to disease severity, highlighting the needs of future vaccination in COVID-19 patients recovered from asymptomatic or mild illness.

Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor (preprint)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel corona virus disease (COVID-19). To date, no prophylactic vaccines or approved therapeutic agents are available for preventing and treating this highly transmittable disease. Here we report two monoclonal antibodies (mAbs) cloned from memory B cells of patients recently recovered from COVID-19, and both mAbs specifically bind to the spike (S) protein of SARS-CoV-2, block the binding of receptor binding domain (RBD) of SARS-CoV-2 to human angiotensin converting enzyme 2 (hACE2), and effectively neutralize S protein-pseudotyped virus infection. These human mAbs hold the promise for the prevention and treatment of the ongoing pandemic of COVID-19.