Ischemia-induced intestinal de-epithelization and consequent cholangitis lenta after usage of extracorporeal membrane oxygenation in COVID-19 patients: an autopsy series.

Since its discovery in late 2019, severe acute respiratory syndrome coronavirus 2 has spread around the world, causing millions of deaths due to coronavirus disease 2019 (COVID-19). Numerous clinical and post-mortem investigations of COVID-19 cases have found myriad clinical and pathological manifestations of the disease. In this report, we present three autopsy cases in which, despite weaning from extracorporeal membrane oxygenation (ECMO), extensive intestinal epithelial shedding, probably due to ischemia, was followed by massive watery diarrhea and the spread of infection via the portal vein due to bacterial translocation, which resulted in cholangitis lenta. Thrombophilia was attributed to ECMO usage and COVID-19-related vascular endothelial damage. These cases provide instructive findings showing that the loss of the intestinal barrier may be the underlying cause of severe watery diarrhea and liver failure in COVID-19 patients, especially with ECMO usage.

Correlation between the hysteresis of the pressure-volume curve and the recruitment-to-inflation ratio in patients with coronavirus disease 2019.

BACKGROUND: Since the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure-volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown. METHODS: We analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs). RESULTS: The median R/I ratio was 0.90 [interquartile range (IQR), 0.70-1.15] and median NMD was 41.0 [IQR, 37.1-44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (- 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively). CONCLUSIONS: NMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

COVID-19-associated disseminated mucormycosis: An autopsy case report.

BACKGROUND: Reports of mucormycosis, an infectious disease that commonly affects immunocompromised individuals, have increased during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Disseminated mucormycosis associated with COVID-19 is rare but fatal and is characterized by an aggressive clinical course and delayed diagnosis. Our report documents a case of disseminated mucormycosis after COVID-19 infection. This is a rare pathological autopsy report on COVID-19-associated mucormycosis. CASE SUMMARY: A 58-year-old man was transferred to our hospital with severe COVID-19 pneumonia. During treatment for acute respiratory distress syndrome, he developed intra-abdominal bleeding that required a right hemicolectomy and ileostomy for hemostasis. The ileostoma and surgical wound developed necrosis followed by sepsis and multi-organ failure, which led to death. An autopsy revealed multiple thrombi associated with Rhizopus oryzae infection, which led to the necrosis of multiple infected organs. CONCLUSION: Early suspicion and diagnosis followed by treatment are keys to better outcomes of mucormycosis in patients with severe COVID-19.

Pneumomediastinum as patient self‐inflicted lung injury in patients with acute respiratory distress syndrome due to COVID‐19: a case series

Background In patients with coronavirus disease (COVID‐19) due to severe acute respiratory syndrome coronavirus 2 infection, pneumomediastinum has been increasingly reported in cases of noninvasive oxygen therapy, including high‐flow nasal cannula, and invasive mechanical ventilation. However, its pathogenesis is still not understood. Case Presentation We report two cases of pneumomediastinum in acute respiratory distress syndrome (ARDS) caused by COVID‐19. In both cases, control of spontaneous breathing with neuromuscular blocking agents resulted in resolution of pneumoperitoneum. Conclusion The improvement of pneumomediastinum with control of spontaneous breathing suggested patient self‐inflicted lung injury as a possible mechanism in this case series. In ARDS cases with pneumomediastinum, in addition to controlling plateau pressure with conventional lung protective ventilation, spontaneous breathing should be controlled if the patient’s inspiratory effort is suspected to be strong. Time‐series of radiographic results of a 67‐year‐old man with acute respiratory distress syndrome caused by COVID‐19 with pneumomediastinum. (A) Chest X‐ray 2 days before admission to the ICU showing pneumomediastinum (denoted by white arrows). (C) CT on the day of ICU admission after intubation showing pneumomediastinum with air tracking along the sheath of pulmonary vasculature, indicating the Macklin effect (denoted by white arrow). (D) CT on ICU day 4 showing improvement in pneumomediastinum by controlling spontaneous breathing.

Pneumomediastinum as patient self-inflicted lung injury in patients with acute respiratory distress syndrome due to COVID-19: a case series.

Background: In patients with coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 infection, pneumomediastinum has been increasingly reported in cases of noninvasive oxygen therapy, including high-flow nasal cannula, and invasive mechanical ventilation. However, its pathogenesis is still not understood. Case Presentation: We report two cases of pneumomediastinum in acute respiratory distress syndrome (ARDS) caused by COVID-19. In both cases, control of spontaneous breathing with neuromuscular blocking agents resulted in resolution of pneumoperitoneum. Conclusion: The improvement of pneumomediastinum with control of spontaneous breathing suggested patient self-inflicted lung injury as a possible mechanism in this case series. In ARDS cases with pneumomediastinum, in addition to controlling plateau pressure with conventional lung protective ventilation, spontaneous breathing should be controlled if the patient's inspiratory effort is suspected to be strong.

Continuous renal replacement therapy using a cellulose triacetate hemofilter for severe coronavirus disease.

Background: In patients with severe coronavirus disease (COVID-19), the use of acrylonitrile hemofilters can reduce cytokine concentrations. However, acrylonitrile hemofilters can easily coagulate, and the effect of hemofilters on improvement in patient prognosis remains unclear. Therefore, we aimed to investigate the changes in serum cytokine concentrations, alleviation of organ damage, and improvement in patient prognosis with continuous renal replacement therapy (CRRT) using a cellulose triacetate (CTA) filter with excellent anticoagulation property in patients with severe COVID-19. Methods: This was a retrospective, single-center study conducted by the Advanced Critical Care Center in Sapporo Medical University Hospital, Japan. Seven patients with severe COVID-19 between March 01 and June 30, 2020, were included. The patients were under mechanical ventilation and received continuous blood purification therapy with a CTA filter. We summarized the CRRT status and patient prognosis and measured their serum cytokine (interleukin [IL]-1ß, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, and interferon-γ) and serum marker levels, before and after CRRT. In addition, we evaluated the changes in their respiratory status, hemodynamics, and organ dysfunction scores. The average age of the patients was 61.5 years, and five patients were male. Extracorporeal membrane oxygenation was used in five patients. The treatment outcome included three deaths. Results: The median CRRT duration was 7 days. The hemofilter was replaced once a day. After CRRT, the IL-6 concentration decreased from 393 to 85 pg/mL (p = 0.016), the Krebs von den Lungen-6 concentration decreased from 554 to 350 U/mL, and the PaO2/FiO2 ratio increased significantly from 90 to 248, and therefore, oxygenation improved. In addition, the norepinephrine dose and lactate level decreased, and the circulation tended to improve; however, the renal function and Sequential Organ Failure Assessment score did not change. Conclusions: The serum IL-6 level decreased, and the respiratory status improved upon CRRT using a CTA filter in patients with severe COVID-19.

Impaired tryptophan metabolism in the gastrointestinal tract of patients with critical coronavirus disease 2019.

Introduction: Coronavirus disease 2019 (COVID-19) is still causing a global pandemic. But the mechanism of COVID-19 severity is not well elucidated. Materials and methods: We conducted two single-center observational studies of patients with COVID-19. In the first study, the enrolled patients were distinguished based on critical vs. non-critical COVID-19. We collected blood samples from the patients at admission to measure markers related to inflammation and thrombosis and stool samples to analyze the fecal microbiome, metabolome, and calprotectin level. In the second study, we collected ileum and colon tissue samples from patients with critical COVID-19 who required colonoscopy due to severe gastrointestinal symptoms and analyzed mucosal gene expression. Results: A total of 19 blood samples and 10 stool samples were collected. Interleukin (IL)-6 was the only serum inflammatory marker with significantly higher levels in the critical group than in the non-critical group. The fecal calprotectin level in the critical group was significantly higher than that in the non-critical group (P = 0.03), regardless of the presence of gastrointestinal symptoms. Stool metabolomic analysis showed that the level of indole-3-propionic acid, a ligand for aryl hydrocarbon receptor (AhR), was markedly decreased in the critical group compared to that in the non-critical group (P = 0.01). The expression of genes involved in tryptophan metabolism, including ACE2, AHR, CARD9, and IL22, was downregulated in the ileum of critical COVID-19 patients who required a colonoscopy. Discussion: Critical COVID-19 patients have gastrointestinal inflammation potentially caused by impaired tryptophan metabolism in the small intestine due to decreased expression of genes involved in tryptophan metabolism.

Disseminated mucormycosis in a patient with severe COVID-19 on venovenous extracorporeal membrane oxygenation: A case report.

Background: Since the global outbreak of coronavirus disease 2019 (COVID-19), there have been several reports of mucormycosis as a secondary complication. However, the disseminated type of mucormycosis is extremely rare. Case: A 58-year-old male patient with COVID-19 started receiving venovenous extracorporeal membrane oxygenation because of severe respiratory failure. During hospitalization, intra-abdominal hemorrhage occurred and an emergency laparotomy was performed. Subsequently, the patient suffered septic shock, and part of the small intestines and the abdominal wall became necrotic. Finally, the patient died. At autopsy, he was diagnosed with disseminated mucormycosis. Conclusion: Disseminated mucormycosis should be considered in patients with COVID-19 with refractory sepsis unresponsive to broad-spectrum antimicrobial therapy.

Two cases of multisystem inflammatory syndrome in adults after improvement in severe acute respiratory distress syndrome due to coronavirus disease 2019.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a postacute coronavirus disease 2019 (COVID-19) syndrome occurring weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although this hyperinflammatory syndrome causes significant morbidity, mortality is low. Reports of MIS-A following acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection have rarely been reported. We describe two cases of MIS-A that developed after recovery from critical acute COVID-19. CASE PRESENTATION: We present two cases of MIS-A. In both cases, approximately 4 weeks after the onset of COVID-19, the patients developed gastrointestinal disorders, complicated by other organ damage, and died. CONCLUSION: ARDS and MIS-A can occur in a patient with COVID-19 at different times of onset. Clinicians should consider MIS-A when unexplained multisystemic abnormalities are noted after the treatment of ARDS due to COVID-19.

Extensive mucosal sloughing of the small intestine and colon in a patient with severe COVID-19.

Patients with coronavirus disease 2019 (COVID-19) primarily cause respiratory symptoms. However, gastrointestinal (GI) symptoms can also occur. The endoscopic characteristics of the GI tract in COVID-19 patients remain unclear. We herein report a 62-year-old male with severe COVID-19 who needed multidisciplinary treatment, including extracorporeal membrane oxygenation (ECMO). Despite the improvement in his respiratory status, GI bleeding developed. Capsule endoscopy and colonoscopy revealed extensive mucosal sloughing in the lower intestinal tract. Additionally, we performed a comprehensive analysis of the mRNA expression levels of various proinflammatory cytokines in the intestinal mucosal tissues. The results suggested a significant elevation of IL-6, which could be involved in the pathophysiology of the GI involvement in COVID-19. Further investigation with more clinical data, including endoscopic findings and molecular analyses, will contribute to a comprehensive understanding of COVID-19-associated GI injury.

A 48-Year-Old Previously Healthy Man Presenting with Acute Respiratory Distress Syndrome (ARDS), Negative Tests for SARS-CoV-2, and Positive Serology for Parainfluenza Virus Type 3 (PIV-3).

BACKGROUND Human parainfluenza viruses (PIVs) belong to the Paramyxoviridae family. PIVs cause lower respiratory tract infections in children and the elderly. In addition, severe pneumonia due to PIVs has been reported in immunocompromised adults. However, no reports have described PIV infections leading to acute respiratory distress syndrome (ARDS) in immunocompetent hosts. CASE REPORT A 48-year-old otherwise healthy man was transported to our hospital due to worsening dyspnea. On arrival, strong effortful breathing was observed and results of arterial blood gas analysis revealed severe hypoxia. On the basis of the clinical presentation, we intubated the patient for mechanical ventilation. However, mechanical ventilation provided inadequate oxygenation. Finally, veno-venous extracorporeal membrane oxygenation was initiated. Pneumonia was considered to be a cause of the ARDS, based on the patient's history and blood examination. Repeated reverse transcription-polymerase chain reaction tests for the novel coronavirus were performed, and endotracheal aspirate specimens were cultured for bacteria and fungus; however, the results were all negative. On day 2, the PIV-3-specific antibody titer was elevated. Two weeks later, the PIV-3-specific antibody titer had increased 4-fold. On the basis of these results, we diagnosed pneumonia induced by PIV-3 infection. CONCLUSIONS ARDS can occur because of severe pneumonia induced by PIV-3. In cases of unexplained severe pneumonia or ARDS, PIV infection should be included in the differential diagnosis.

Bilateral phrenic nerve block as an effective means of controlling inspiratory efforts in a COVID-19 patient.

Bilateral continuous phrenic nerve block effectively regulates refractory persistent, strong inspiratory effort in a patient with coronavirus disease (COVID-19). A 73-year-old man with acute respiratory distress syndrome (ARDS) due to COVID-19 was admitted to the intensive care unit (ICU). Use of neuromuscular blocking agents (NMBAs) was stopped due to uncontrollable strong inspiratory efforts and worsened lung injury. We performed bilateral continuous phrenic nerve block, which suppressed inspiratory efforts, resulting in lung injury improvement. A bilateral continuous phrenic nerve block is a viable alternative to control refractory strong inspiratory effort leading to lung injury in cases with prolonged NMBA use.

Dilemma of physician-mothers faced with an increased home burden and clinical duties in the hospital during the COVID-19 pandemic.

PURPOSE: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world. During the pandemic, physicians in our hospital have had to respond both to the issue of treating the patients and the increasing domestic burden associated with social disruption. The purpose of this study was to assess how much the burden on our doctors, especially female doctors, was increasing. MATERIAL AND METHODS: The Physicians' Career Support Committee in Sapporo Medical University conducted a questionnaire survey. The questionnaire inquired about a wide range of subjects with regard to working style and family life during the first and second waves of the COVID-19 pandemic, and was sent to all medical/dental physicians working in Sapporo Medical University. RESULTS: A total of 266 (42.7%) physicians in our hospital responded to our questionnaire and the data for 264 data were analyzed. The total numbers of males, females, and others, including those who did not want to specify, were 178 (67.4%), 82 (31.0%), and 4 (1.5%), respectively. Among them, 62 (23.5%) and 23 (8.7%) answered that their domestic burden was slightly or markedly increased. The increase in the domestic burden showed a significant difference between genders (p = 0.04). Even after correction for background differences using multivariate analysis, being female (p<0.001), having child dependents (p<0.001), and treating COVID-19 patients (p = 0.03) were significantly related to an increased domestic burden. Regarding family style, 58.1% of the physician-fathers were from two-income families (i.e., families with both parents in employment), and they answered that their partner mainly cared for the children. In contrast, 97.3% of physician-mothers were from two-income families, and 94.6% of the physician-mothers had to take care of children by themselves. CONCLUSION: Physician-mothers are caught in a dilemma between an increased home burden and clinical duties in the hospital, with a significantly higher ratio than physician-fathers during the pandemic. As we showed, female doctors could have not continued their careers and take responsible positions in the same way as male doctors. This is a social risk in the timing of a crisis, such as a pandemic.

Invasive pneumococcal disease affected the fatal outcome in a COVID-19 patient.

A 68-year-old man experienced fever and cough and was referred to a hospital for day 4. He had a positive reverse transcription-polymerase chain reaction result for severe acute respiratory syndrome coronavirus-2. On day 12, his PaO2/FiO2 ratio worsened to 120 and he was transferred to Sapporo Medical University Hospital for treatment using extracorporeal membrane oxygenation. Venous blood cultures were positive for Streptococcus pneumoniae, which were serotype 3, mucoid-type, and penicillin susceptible. Coinfections with coronavirus disease-2019 and invasive pneumococcal disease are rare; however, they are associated with a higher case fatality than either of the conditions manifesting alone.

Tracheostomy in Patients With COVID-19: A Single-center Experience.

BACKGROUND/AIM: Tracheostomy performed on patients with Coronavirus disease 2019 (COVID-19) may lead to the infection of operators and medical staff. To date, there are no established methods of infection control. The aim of this study was to provide helpful and useful information regarding tracheostomy during the COVID-19 pandemic. PATIENTS AND METHODS: We performed a retrospective analysis on 12 patients with severe COVID-19 who were intubated and underwent tracheostomy in our hospital. RESULTS: Percutaneous tracheostomy was performed in eight cases, and open tracheostomy was performed in four cases. Open tracheostomy in the operating room was performed under a negative pressure closed-space system using a surgical drape to prevent aerosolization. CONCLUSION: Our experience suggests that bedside percutaneous tracheostomy may be a useful option in patients with COVID-19. In cases where percutaneous tracheostomy is anticipated to be difficult, open tracheostomy using a negative pressure closure may be useful in preventing aerosolization and reducing the risk of infection of healthcare workers.

Veno-venous extracorporeal membrane oxygenation and prone ventilation for therapeutic management of COVID-19.

BACKGROUND: The efficacy and safety of the combined use of veno-venous extracorporeal membrane oxygenation (ECMO) and prone ventilation are currently not known for coronavirus disease 2019 (COVID-19). CASE PRESENTATION: We report two cases in which the combination of veno-venous ECMO and prone ventilation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia were successfully carried out. Both patients had developed severe respiratory failure due to SARS-CoV-2 pneumonia, thus requiring veno-venous ECMO. Prone ventilation was also administered safely. CONCLUSION: Oxygenation and lung compliance gradually improved during prone ventilation, and both patients were successfully extubated. For patients with severe SARS-CoV-2 pneumonia who require veno-venous ECMO, the use of prone ventilation could be beneficial, and should be considered.