<b><i>Objective:</i></b> We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. <b><i>Methods:</i></b> We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. <b><i>Results:</i></b> In the severe COVID-19 patients, 60% (95% CI = 56–64%) were male, 25% (95% CI = 21–29%) were over 65 years old, 34% (95% CI = 24–44%) were obese, and 55% (95% CI = 41–70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25–44%), diabetes (20%, 95% CI = 15–25%), and cardiovascular disease (CVD; 12%, 95% CI = 9–16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82–92%), decreased lymphocyte count (68%, 58–77%), and increased lactate dehydrogenase (69%, 95% CI = 57–81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24–63%) and increase in aspartate aminotransferase (47%, 95% CI = 38–56%), alanine aminotransferase (28%, 95% CI = 16–39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13–45%), and serum Cr (SCr; 10%, 95% CI = 5–15%). <b><i>Conclusion:</i></b> The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.

The anisotropy that normally exists in the myocardium may be either enhanced in peri-infarction zones by loss of lateral cell connections or reduced by redistribution of gap junctions. To test how the degree of anisotropy affects the development of ectopic focal activity, we carried out computer simulations in which a model of an ectopic focus is incorporated as the central element of a two-dimensional sheet of ventricular cells. At low values of intercellular coupling conductance (G c ), the focus region is spontaneously active, but the limited intercellular current flow inhibits propagation. At high G c , automaticity is suppressed by the loading effects of the surrounding cells. At intermediate G c , the ectopic activity may propagate into the sheet. In the case of isotropic coupling, the minimum size of the focus region for propagation to occur (in terms of number of collaborating cells within the focus) is as small as approximately ten cells, and this number decreases with increasing anisotropy. Thus, the presence of anisotropy facilitates the development of ectopic focal activity. We conclude that the remodeling that occurs in peri-infarction zones may create a substrate that either facilitates (enhanced anisotropy) or inhibits (reduced anisotropy) the development of cardiac arrhythmias associated with ectopic focal activity.

Tachycardias can be produced when focal activity at ectopic locations in either the atria or the ventricles propagates into the surrounding quiescent myocardium. Isolated rabbit atrioventricular nodal cells were coupled by an electronic circuit to a real-time simulation of an array of cell models. We investigated the critical size of an automatic focus for the activation of two-dimensional arrays made up of either ventricular or atrial model cells. Over a range of coupling conductances for the arrays, the critical size of the focus cell group for successful propagation was smaller for activation of an atrial versus a ventricular array. Failure of activation of the arrays at smaller focus sizes was due to the inhibition of pacing of the nodal cells. At low levels of coupling conductance, the ventricular arrays required larger sizes of the focus due to failure of propagation even when the focus was spontaneously active. The major differences between activation of the atrial and ventricular arrays is due to the higher membrane resistance (lower inward rectifier current) of the atrial cells.

We have extended our "coupling clamp" technique, in which we couple a real cell to a real-time simulation of a model cell, to now incorporate a real cardiac cell as the central element of a two-dimensional sheet of model cells, in which the coupling conductances may be different in the x and y directions and a specific region of lack of coupling conductance may serve as a resistive barrier. We stimulated the real cell in the central location and determined the critical size of the real cell for successful activation of the entire sheet. We found that this critical size was decreased when anisotropy was present compared with the isotropic case and was further decreased when the central site of stimulation was close to the resistive barrier. The heart normally has some degree of anisotropy, and it has been shown that the remodeling that occurs in peri-infarction zones produces a particular loss of lateral connections compared with end-to-end connections among heart cells. We propose that the normal existence of anisotropy and enhancement of the degree of anisotropy both by loss of lateral gap junctions and the development of resistive barriers may play a facilitating role in the development of ectopic foci that may lead to cardiac arrhythmias.