Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the fundamental physiological and immunological processes underlying the clinical manifestations of COVID-19 is vital for the identification and rational design of effective therapies. Here, we provide an overview of the pathophysiology of SARS-CoV-2 infection. We describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. From nascent reports describing SARS-CoV-2, we make inferences on the basis of the parallel pathophysiological and immunological features of the other human coronaviruses targeting the lower respiratory tract - severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, we highlight the implications of these approaches for potential therapeutic interventions that target viral infection and/or immunoregulation.

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The trinity of COVID-19: immunity, inflammation and intervention.

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

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Extrapulmonary manifestations of COVID-19.

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study.

COVID-19 pathophysiology: A review.

The COVID-19 pandemic has shown a markedly low proportion of cases among children1–4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12–31%) of infections in 10- to 19-year-olds, rising to 69% (57–82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures—such as many low-income countries—the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic. A new epidemiological study shows reduced susceptibility to SARS-CoV-2 and decreased risk of developing severe symptoms in people aged younger than 20 years, suggesting that children have limited contribution to spread of COVID-19.

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Age-dependent effects in the transmission and control of COVID-19 epidemics.

OBJECTIVE: To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China. METHODS: Nationwide case series of 2135 pediatric patients with COVID-19 reported to the Chinese Center for Disease Control and Prevention from January 16, 2020, to February 8, 2020, were included. The epidemic curves were constructed by key dates of disease onset and case diagnosis. Onset-to-diagnosis curves were constructed by fitting a log-normal distribution to data on both onset and diagnosis dates. RESULTS: There were 728 (34.1%) laboratory-confirmed cases and 1407 (65.9%) suspected cases. The median age of all patients was 7 years (interquartile range: 2–13 years), and 1208 case patients (56.6%) were boys. More than 90% of all patients had asymptomatic, mild, or moderate cases. The median time from illness onset to diagnoses was 2 days (range: 0–42 days). There was a rapid increase of disease at the early stage of the epidemic, and then there was a gradual and steady decrease. The disease rapidly spread from Hubei province to surrounding provinces over time. More children were infected in Hubei province than any other province. CONCLUSIONS: Children of all ages appeared susceptible to COVID-19, and there was no significant sex difference. Although clinical manifestations of children’s COVID-19 cases were generally less severe than those of adult patients, young children, particularly infants, were vulnerable to infection. The distribution of children’s COVID-19 cases varied with time and space, and most of the cases were concentrated in Hubei province and surrounding areas. Furthermore, this study provides strong evidence of human-to-human transmission.

https://pediatrics.aappublications.org/content/pediatrics/early/2020/03/16/peds.2020-0702.1.full.pdf

Epidemiology of COVID-19 Among Children in China.

Abstract Pulmonary tuberculosis (PTB) is a major health issue in Northwest China. Most previous studies on the spatiotemporal patterns of PTB considered all PTB cases as a whole; they did not distinguish notified bacteriologically positive PTB (BP-PTB) and notified bacteriologically negative PTB (BN-PTB). Thus, the spatiotemporal characteristics of notified BP-PTB and BN-PTB are still unclear. A retrospective county-level spatial epidemiological study (2011–2018) was conducted in Shaanxi, Northwest China. In total, 44,894 BP-PTB cases were notified, with an average annual incidence rate of 14.80 per 100,000 persons between 2011 and 2018. Global Moran’s I values for notified BP-PTB ranged from 0.19 to 0.49 ( P &lt; 0.001). Anselin’s local Moran’s I analysis showed that the high–high (HH) cluster for notified BP-PTB incidence was mainly located in the southernmost region. The primary spatiotemporal cluster for notified BP-PTB ( LLR = 612.52, RR = 1.77, P &lt; 0.001) occurred in the central region of the Guanzhong Plain in 2011. In total, 116,447 BN-PTB cases were notified, with an average annual incidence rate of 38.38 per 100,000 persons between 2011 and 2018. Global Moran’s I values for notified BN-PTB ranged from 0.39 to 0.69 (P &lt; 0.001). The HH clusters of notified BN-PTB were mainly located in the north between 2011 and 2014 and in the south after 2015. The primary spatiotemporal cluster for notified BN-PTB ( LLR = 1084.59, RR = 1.85, P &lt; 0.001) occurred in the mountainous areas of the southernmost region from 2014 to 2017. Spatiotemporal clustering of BP-PTB and BN-PTB was detected in the poverty-stricken mountainous areas of Shaanxi, Northwest China. Our study provides evidence for intensifying PTB control activities in these geographical clusters. 

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Distribution of bacteriologically positive and bacteriologically negative pulmonary tuberculosis in Northwest China: spatiotemporal analysis

Thyroid cancer (TC) is the fastest growing cancer in China and has lots of influencing factors which can be intervened to reduce its incidence. In this article, we aimed to identify the risk factors of TC. The regional TC data in 2016 were obtained from the China Cancer Registry Annual Report published by the National Cancer Center (NCC). Univariate correlation analysis and generalized linear Poisson regression analysis were used to determine risk factors for morbidity of TC from the provincial and prefecture levels. High urbanization rate (UR) (RR = 1.109, 95%CI: 1.084, 1.135), high GDP per capita (PGDP) (RR = 1.013, 95%CI: 1.007, 1.018), high aquatic products (RR = 1.047, 95%CI: 1.020, 1.075) and dry and fresh fruit consumption (RR = 1.024, 95%CI: 1.007, 1.040) can increase TC incidence. Therefore, high PGDP, high UR, high aquatic products and dry and fresh fruit consumption were all risk factors for TC incidence. Our results may be helpful for providing analytical ideas and methodological references for the regionalized prevention and control of TC in a targeted manner.

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Xin Qi

Papers

Epidemiology of COVID-19 Among Children in China.

Distribution of bacteriologically positive and bacteriologically negative pulmonary tuberculosis in Northwest China: spatiotemporal analysis

Risk Analysis of Thyroid Cancer in China: A Spatial Analysis

Spatial pattern and environmental drivers of breast cancer incidence in Chinese women