Modeling COVID-19: Forecasting and analyzing the dynamics of the outbreaks in Hubei and Turkey

As the pandemic of Coronavirus Disease 2019 (COVID-19) rages worldwide, accurate modeling of the dynamics thereof is essential. However, since the availability and quality of data vary dramatically from region to region, accurate modeling directly from a global perspective is difficult. Nevertheless, via local data collected by certain regions, it is possible to develop accurate local prediction tools, which may be coupled to develop global models. In this study, we analyze the dynamics of local outbreaks of COVID-19 via a system of ordinary differential equations (ODEs). Utilizing a large amount of data available from the ebbing outbreak in Hubei, China, as a testbed, we predict the trajectory of daily cases, daily deaths, and other features of the Hubei outbreak. Through numerical experiments, we observe the effects of social distancing on the dynamics of the outbreak. Using knowledge gleaned from the Hubei outbreak, we apply our model to analyze the dynamics of the outbreak in Turkey. We provide forecasts for the peak of the outbreak and the daily number of cases and deaths in Turkey, by varying levels of social distancing and the transition rate which is from infected class to confirmed infected class.

The impact of hypoxia on B cells in COVID-19 (preprint)

Prominent early features of COVID-19 include severe, often clinically silent, hypoxia and a pronounced reduction in B cells, the latter important in defence against SARS-CoV-2. This brought to mind the phenotype of mice with VHL-deficient B cells, in which Hypoxia-Inducible Factors are constitutively active, suggesting hypoxia might drive B cell abnormalities in COVID-19. We demonstrated the breadth of early and persistent defects in B cell subsets in moderate/severe COVID-19, including reduced marginal zone-like, memory and transitional B cells, changes we also observed in B cell VHL-deficient mice. This was corroborated by hypoxia-related transcriptional changes in COVID-19 patients, and by similar B cell abnormalities in mice kept in hypoxic conditions, including reduced marginal zone and germinal center B cells. Thus hypoxia might contribute to B cell pathology in COVID-19, and in other hypoxic states. Through this mechanism it may impact on COVID-19 outcome, and be remediable through early oxygen therapy.

Arteritis and Large Vessel Occlusive Strokes in Children After COVID-19 Infection.

We describe 2 previously healthy children who suffered disabling arterial ischemic strokes because of acute intracranial large vessel occlusion within 3 to 4 weeks of coronavirus disease 2019 (COVID-19) infection. Both children presented from communities with high COVID-19 case rates in the Southwest United States. An 8-year-old American Indian girl experienced severe iron deficiency anemia requiring blood transfusion and presented with bilateral middle cerebral artery (MCA) distribution strokes 3 weeks later. She underwent emergent mechanical thrombectomy of the left MCA with successful clot retrieval but experienced reocclusion of that artery 5 hours after intervention. She also had evidence of cerebral arteritis on catheter angiography and vessel wall imaging, and clot pathology revealed recently formed, unorganized platelet- and fibrin-rich thrombus with sparse clusters of erythrocytes, degenerated histiocytes, few eosinophils, and rare neutrophils. A 16-year old African American boy demonstrated evidence of arteritis on brain magnetic resonance angiography and serological markers of cardiac and renal injury accompanied by positive lupus anticoagulant antibodies. The children described in this report express clinical features inconsistent with focal cerebral arteriopathy, including elevated markers of systemic inflammation in both bilateral MCA strokes in one case and multiple organ system dysfunction in the other case. Neither patient fulfilled criteria for multisystem inflammatory syndrome in children, given absence of fever. These cases illustrate that systemic postinfectious arteritis with cerebrovascular involvement may complicate COVID-19 infection in previously healthy school-aged children, and their presentations may overlap but not fulfill criteria for multisystem inflammatory syndrome in children or focal cerebral arteriopathy.

The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres (preprint)

The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included: healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19: 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effector:effector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.

Modeling COVID-19: Forecasting and analyzing the dynamics of the outbreak in Hubei and Turkey (preprint)

As the pandemic of Coronavirus Disease 2019 (COVID-19) rages throughout the world, accurate modeling of the dynamics thereof is essential. However, since the availability and quality of data varies dramatically from region to region, accurate modeling directly from a global perspective is difficult, if not altogether impossible. Nevertheless, via local data collected by certain regions, it is possible to develop accurate local prediction tools, which may be coupled to develop global models. In this study, we analyze the dynamics of local outbreaks of COVID-19 via a coupled system of ordinary differential equations (ODEs). Utilizing the large amount of data available from the ebbing outbreak in Hubei, China as a testbed, we estimate the basic reproductive number, R0 of COVID-19 and predict the total cases, total deaths, and other features of the Hubei outbreak with a high level of accuracy. Through numerical experiments, we observe the effects of quarantine, social distancing, and COVID-19 testing on the dynamics of the outbreak. Using knowledge gleaned from the Hubei outbreak, we apply our model to analyze the dynamics of outbreak in Turkey. We provide forecasts for the peak of the outbreak and the total number of cases/deaths in Turkey, for varying levels of social distancing, quarantine, and COVID-19 testing.