Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given the scale of the worldwide infections, the long-term recovery and the integrative health-care in the nearest future, it is critical to understand the cellular and molecular mechanisms as well as possible predictors of the longitudinal post-COVID-19 responses in convalescent individuals. The immune system and T cell alterations are proposed as drivers of post-acute COVID syndrome. However, despite the number of studies on COVID-19, many of them addressed only the severe convalescents or the short-term responses. Here, we performed longitudinal studies of mild, moderate and severe COVID-19-convalescent patients, at two time points (3 and 6 months from the infection), to assess the dynamics of T cells immune landscape, integrated with patients-reported symptoms. We show that alterations among T cell subsets exhibit different, severity- and time-dependent dynamics, that in severe convalescents result in a polarization towards an exhausted/senescent state of CD4+ and CD8+ T cells and perturbances in CD4+ Tregs. In particular, CD8+ T cells exhibit a high proportion of CD57+ terminal effector cells, together with significant decrease of naïve cell population, augmented granzyme B and IFN-γ production and unresolved inflammation 6 months after infection. Mild convalescents showed increased naïve, and decreased central memory and effector memory CD4+ Treg subsets. Patients from all severity groups can be predisposed to the long COVID symptoms, and fatigue and cognitive dysfunctions are not necessarily related to exhausted/senescent state and T cell dysfunctions, as well as unresolved inflammation that was found only in severe convalescents. In conclusion, the post-COVID-19 functional remodeling of T cells could be seen as a two-step process, leading to distinct convalescent immune states at 6 months after infection. Our data imply that attenuation of the functional polarization together with blocking granzyme B and IFN-γ in CD8+ cells might influence post-COVID alterations in severe convalescents. However, either the search for long COVID predictors or any treatment to prevent PACS and further complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe COVID-19.

No abstract

Background: The manual lymphatic drainage in lymphedema has proved to be successful; however, this method cannot be applied to millions of patients around the world. The only solution is to offer inexpensive, easily accessible mechanical devices for pneumatic compression (IPC). These devices should be designed on parameters of edema fluid hydromechanics. Recent data point to high pressures and long time of compression. Aim: To validate the effects of 3 years daily high pressure, long inflation time IPC therapy in terms of decrease of limb circumference/volume, tissue elasticity, histological changes, and incidental complications. Methods: A group of 18 patients with unilateral leg lymphedema stage II to IV was treated for a period of 3 years using an 8-chamber sleeve, sequential inflation of chambers to 100-120 mmHg for 50 sec (total 400 sec). Limb circumference and tissue tonicity were measured at monthly intervals. Correlation between decrease in calf and thigh circumference and increase in elasticity was done. Results: The treatment revealed durable permanent decrease of limb circumference and increased elasticity of tissues. The improvement was most expressed in the calf above the ankle and mid-calf. No complications as thigh ring or chronic genital edema were observed. There was no direct correlation between the decrease in limb circumference and increase in elasticity, most likely due to different mass of fibrous tissue. Conclusions: IPC takes over the permanently missing function of the obliterated lymphatics by squeezing edema tissue fluid to the regions with normal lymphatic drainage. The limb circumference is decreased or at least does not further increase, elasticity of tissue is increased and maintained. No complications in limb tissues were observed. The long-term, high pressure IPC, long inflation timed therapy can be safely be recommended to patients with lower limb lymphedema.