Challenging management of severe chronic disorders in acute pandemic situation: Chronic liver disease under COVID-19 pandemic as the proof-of-principle model to orchestrate the measures in 3PM context

Abstract

Chronic liver disease management is a comprehensive approach requiring multi-professional expertise and well-orchestrated healthcare measures thoroughly organized by responsible medical units. Contextually, the corresponding multi-faceted chain of healthcare events is likely to be severely disturbed or even temporarily broken under the force majeure conditions such as global pandemics. Consequently, the chronic liver disease is highly representative for the management of any severe chronic disorder under lasting pandemics with unprecedented numbers of acutely diseased persons who, together with the chronically sick patient cohorts, have to be treated using the given capacity of healthcare systems with their limited resources. Current study aimed at exploring potentially negative impacts of the SARS CoV-2 outbreak on the quality of the advanced chronic liver disease (ACLD) management considering two well-classified parameters, namely, (1) the continuity of the patient registrations and (2) the level of mortality rates, comparing pre-COVID-19 statistics with these under the current pandemic in Slovak Republic. Altogether 1091 registrations to cirrhosis registry (with 60.8% versus 39.2% males to females ratio) were included with a median age of 57 years for patients under consideration. Already within the very first 3 months of the pandemic outbreak in Slovakia (lockdown declared from March 16, 2020, until May 20, 2020), the continuity of the patient registrations has been broken followed by significantly increased ACLD-related death rates. During this period of time, the total number of new registrations decreased by about 60% (15 registrations in 2020 versus 38 in 2018 and 38 in 2019). Corresponding mortality increased by about 52% (23 deaths in 2020 versus 10 in 2018 and 12 in 2019). Based on these results and in line with the framework of 3PM guidelines, the pandemic priority pathways (PPP) are strongly recommended for maintaining tertiary care uninterrupted. For the evidence-based implementation of PPP, creation of predictive algorithms and individualized care strategy tailored to the patient is essential. Resulting classification of measures is summarized as follows: The Green PPP Line is reserved for prioritized (urgent and comprehensive) treatment of patients at highest risk to die from ACLD (tertiary care) as compared to the risk from possible COVID-19 infection. The Orange PPP Line considers patients at middle risk of adverse outcomes from ACLD with re-addressing them to the secondary care. As further deterioration of ACLD is still probable, pro-active management is ascertained with tertiary center serving as the 24/7 telemedicine consultation hub for a secondary facility (on a physician-physician level). The Red PPP Line is related to the patients at low risk to die from ACLD, re-addressing them to the primary care. Since patients with stable chronic liver diseases without advanced fibrosis are at trivial inherent risk, they should be kept out of the healthcare setting as far as possible by the telemedical (patient-nurse or patient- physician) measurements. The assigned priority has to be monitored and re-evaluated individually—in intervals based on the baseline prognostic score such as MELD. The approach is conform with principles of predictive, preventive and personalized medicine (PPPM / 3PM) and demonstrates a potential of great clinical utility for an optimal management of any severe chronic disorder (cardiovascular, neurological and cancer) under lasting pandemics.

Modeling SARS-CoV-2 spike/ACE2 protein–protein interactions for predicting the binding affinity of new spike variants for ACE2, and novel ACE2 structurally related human protein targets, for COVID-19 handling in the 3PM context

“…Once obtained this multi-subunit complexes, the entire protein complexes can be relaxed by using molecular dynamics [ 109 , 110 ] for the following estimation of the interaction energies at the ACE2/spike protein interface. The possibility to relax and study the entire trimeric spike protein interacting with ACE2 (and/or antibodies) [ 7 ] might allow to predict more efficiently the aggressiveness of future VoC and/or their abilities in escaping vaccine induced antibodies and this would help in obtaining better predictions in the context of personalized medicine [ 15 , 16 , 111 – 113 ]. In addition, results of the analyses performed on the entire spike protein interacting with ACE2 and/or antibodies would also allow to design more efficient antibodies which will target specific portions of the spike RBD for preventing ACE2 binding, without creating at the same time undesired clashes in protein structure with different chains of the same spike trimeric protein.…”

“…Furthermore, we would recommend using our webservice for the estimation of the interaction energies at the spike RBD/ACE2 protein–protein interface, for each RBD/ACE2 combination, as sequenced from patients, would allow creating a list of the RBD/ACE2 protein complexes sorted by increasing interaction energy and the corresponding degree of disease severity for each known variant combination. The interaction energy parameter, function of the disease severity for each patient, synergically with other established priority parameters [ 111 , 119 ], might be used for training our pipeline to provide more and more accurate predictions about future variants transmissibility, virulence and disease severity. The early recognition of more transmissible/virulent variants would also help in assigning priority and personalized treatments to future patients, based on the specific RBD/ACE2 variants sequenced from the infected patients, by overcoming most of the contradictory results of the currently employed in vitro assays.…”

Sleep quality and COVID-19 outcomes: the evidence-based lessons in the framework of predictive, preventive and personalised (3P) medicine

“…Taking into account multi-faceted anti-inflammatory and anti-mitochondriopathic effects of melatonin, melatonin treatment is strongly recommended as an essential pillar of the anti-COVID-19 protection for the shift workers, COVID-19-affected individuals and patients suffering from chronic non-communicable disorders under the viral pandemic conditions [89][90][91].…”

Personalization of medical treatments in oncology: time for rethinking the disease concept to improve individual outcomes

“…In simple words, we actually lack the minimal facts needed to support the hope that genetics can be a key to realizing that vision. This statement implies we should orchestrate a stratified and multilevel diagnostic and treatment approach [123].…”