Lessons learned from the mechanisms of posttraumatic inflammation extrapolated to the inflammatory response in COVID-19: a review

Abstract

Up to 20% of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) patients develop severe inflammatory complications with diffuse pulmonary inflammation, reflecting acute respiratory distress syndrome (ARDS). A similar clinical profile occurs in severe trauma cases. This review compares pathophysiological and therapeutic principles of severely injured trauma patients and severe coronavirus disease 2019 (COVID-19). The development of sequential organ failure in trauma parallels deterioration seen in severe COVID-19. Based on established pathophysiological models in the field of trauma, two complementary pathways of disease progression into severe COVID-19 have been identified. Furthermore, the transition from local contained disease into systemic and remote inflammation has been addressed. More specifically, the traumatology concept of sequential insults ('hits') resulting in immune dysregulation, is applied to COVID-19 disease progression modelling. Finally, similarities in post-insult humoral and cellular immune responses to severe trauma and severe COVID-19 are described. To minimize additional 'hits' to COVID-19 patients, we suggest postponing all elective surgery in endemic areas. Based on traumatology experience, we propose that immunoprotective protocols including lung protective ventilation, optimal thrombosis prophylaxis, secondary infection prevention and calculated antibiotic therapy are likely also beneficial in the treatment of SARS-CoV-2 infections. Finally, rising SARS-CoV-2 infection and mortality rates mandate exploration of out-of-the box treatment concepts, including experimental therapies designed for trauma care.

Different characteristics of critical COVID-19 and thinking of treatment strategies in non-elderly and elderly severe adult patients

“…The first stage is the asymptomatic stage with virus incubation; this stage then transitions to the second stage, the direct toxicity and inflammatory activation of the lung, leading to aggravation of respiratory symptoms. In the third stage, patients experience multisystem damage and loss of regulatory control of proinflammatory cytokine production, causing a cytokine storm and hyperinflammatory state, which develop a strong and lethal inflammatory response [11] , [12] , [13] , [14] .…”

COVID Convalescence—A Boon or Bane in Cardiac Surgery?: A “Second Hit” Hypothesis

“…The contained inflammation in the primary disease (first hit) can be exacerbated by stimuli of mechanical ventilation, infection, stasis, thrombosis, bleeding, ischemia, hypoxia, blood transfusions, transfusion-related acute lung injury (TRALI) (second hit) and cause a second uncontrolled inflammatory cascade culminating in a multiple organ dysfunction syndromes. 9 In such scenarios, avoiding the second hit by reducing inflammation with lung-protective strategies, thrombo-prophylaxis, early prone ventilation in the postoperative period, anti-fibrinolytic therapy and peripheral vascular screening are evolving concepts. 9 In the current clinical setting with the presence of IgG antibodies for SARS-CoV-2 and two preoperative negative RT-PCR, we postulated a convalescent phase of a recent past COVID-19 asymptomatic disease in our patient.…”

“…9 In such scenarios, avoiding the second hit by reducing inflammation with lung-protective strategies, thrombo-prophylaxis, early prone ventilation in the postoperative period, anti-fibrinolytic therapy and peripheral vascular screening are evolving concepts. 9 In the current clinical setting with the presence of IgG antibodies for SARS-CoV-2 and two preoperative negative RT-PCR, we postulated a convalescent phase of a recent past COVID-19 asymptomatic disease in our patient. RT-PCR continues to be the gold standard for diagnosing COVID-19 to date.…”

“… 9 In such scenarios, avoiding the second hit by reducing inflammation with lung-protective strategies, thrombo-prophylaxis, early prone ventilation in the postoperative period, anti-fibrinolytic therapy and peripheral vascular screening are evolving concepts. 9 …”

“…The first episode of desaturation and hypoxemia was possibly an exacerbated inflammation due to mechanical ventilation (second hit) potentiated by altered hemodynamics during the verticalization of heart, MR, worsening diastolic function, increased PCWP, and subsequent pulmonary venous congestion. 9 The pulmonary Micro CLOTS pathophysiology evolved extensively during the case with the lowest recorded PaO 2 :FiO 2 ratio of 70mmHg. Cardiac dysfunction secondary to residual COVID-19 is speculative unless preoperative CMRI defines myocardial inflammation.…”