SARS CoV‐2 related microvascular damage and symptoms during and after COVID‐19: Consequences of capillary transit‐time changes, tissue hypoxia and inflammation

Abstract

Corona virus disease 2019 (COVID‐19) causes symptoms from multiple organs after infection by severe acute respiratory syndrome corona virus 2 (SARS CoV‐2). They range from early, low blood oxygen levels (hypoxemia) without breathlessness (“silent hypoxia”), delirium, rashes, and loss of smell (anosmia), to persisting chest pain, muscle weakness and ‐pain, fatigue, confusion, memory problems and difficulty to concentrate (“brain fog”), mood changes, and unexpected onset of hypertension or diabetes. SARS CoV‐2 affects the microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation. Similar to other instances of critical illness, COVID‐19 is also associated with elevated cytokine levels in the systemic circulation. This review examines how capillary damage and inflammation may contribute to these acute and persisting COVID‐19 symptoms by interfering with blood and tissue oxygenation and with brain function. Undetectable by current diagnostic methods, capillary flow disturbances limit oxygen diffusion exchange in lungs and tissue and may therefore cause hypoxemia and tissue hypoxia. The review analyzes the combined effects of COVID‐19‐related capillary damage, pre‐existing microvascular changes, and upstream vascular tone on tissue oxygenation in key organs. It identifies a vicious cycle, as infection‐ and hypoxia‐related inflammation cause capillary function to deteriorate, which in turn accelerates hypoxia‐related inflammation and tissue damage. Finally, the review addresses the effects of low oxygen and high cytokine levels in brain tissue on neurotransmitter synthesis and mood. Methods to assess capillary functions in human organs and therapeutic means to protect capillary functions and stimulate capillary bed repair may prove important for the individualized management of COVID‐19 patients and targeted rehabilitation strategies.

“Post-COVID syndrome”: The focus is on musculoskeletal pain

“…При критическом течении заболевания в качестве крайней степени поражения мышечной ткани описан рабдомиолиз, сопровождающийся тяжелой интоксикацией и быстрым развитием ОПН. Последствиями перенесенного COVID-19 являются рассеянный фиброз мышечной ткани, мышечная атрофия, а также нарушения нейротрасмиттерных процессов [23,24].…”

Post COVID-19 Syndrome (“Long COVID”) and Diabetes: Challenges in Diagnosis and Management

“…Pathophysiologically, post COVID-19 syndrome is not a single clinical entity but a conglomeration of symptoms and signs due to multiple biological factors, which need more research. Commonly understood factors include organ damage, persistently dysregulated inflammatory and immune responses, and unrecognised microvascular thrombosis and endotheliitis [ 9 ]. Many other factors have been hypothesised; persistent tissue reservoirs of SARS-CoV-2, re-activation of other viruses, brainstem and/or vagus nerve dysfunctions and activation of autoimmunity due to molecular mimicry between pathogen and host proteins [ 10 ].…”

“…Interestingly, capillary dysfunction {capillary cell swelling and damage (endotheliitis), microthrombosis, pericyte damage, scarring etc.} has been hypothesised to cause multiple symptoms of PCS including fatigue, brain fog, and memory problems [ 9 ]. Theoretically, severe capillary damage can cause renal and other organ failures, a particularly worrying scenario in patients with diabetes [ 9 ].…”

“…has been hypothesised to cause multiple symptoms of PCS including fatigue, brain fog, and memory problems [ 9 ]. Theoretically, severe capillary damage can cause renal and other organ failures, a particularly worrying scenario in patients with diabetes [ 9 ].…”

Isolated “puffy hands” following COVID-19: clue to a long-term capillary leakage syndrome?

“…The pathophysiology of PACS has not been clarified, but findings from acute COVID-19 patients provide interesting clues to a potential mechanism. Capillary dysfunction and microvascular damage have been shown in acute COVID-19 patients [3], with increased permeability and subsequent leakage [4]. Further, acro-ischaemic lesions were found to be common during the course of SARS-CoV-2 infection [5], and signs of endothelial activation have been histologically described in acral lesions obtained from COVID-19 patients [6].…”