key: cord-0980712-lvx9iv8s
authors: Elhence, Anshuman; Mahapatra, Soumya Jagannath; Vajpai, Tanmay; Garg, Pramod Kumar
title: Acute pancreatitis and nosocomial COVID-19: Cause specific host responses may determine lung injury
date: 2020-08-19
journal: Pancreatology
DOI: 10.1016/j.pan.2020.08.008
sha: c0e823f8947f0702e0fcd6cdeafdf10d09710308
doc_id: 980712
cord_uid: lvx9iv8s

BACKGROUND: /ObjectivesCoronavirus disease 2019 (COVID-19) presents with myriad extra-pulmonary manifestation and a high mortality in patients with comorbidities. Its effect on patients with pre-existing severe acute pancreatitis is not known. METHODS: We hereby, present 3 cases with severe acute pancreatitis with persistent respiratory failure who acquired nosocomial COVID-19 during their hospital stay after recovery from respiratory failure. Their clinical course is highlighted which might reflect on pathophysiology of organ dysfunction. RESULTS: None of the 3 patients with severe acute pancreatitis who developed nosocomial COVID-19 redeveloped respiratory failure suggestive of severe COVID-19 despite having recently recovered from pancreatitis induced acute hypoxemic respiratory failure. Only one patient had SARS-CoV2 induced moderate pneumonia. CONCLUSION: These cases highlight that host responses and mechanisms of lung injury might be different in severe pancreatitis and COVID-19.

Acute pancreatitis (AP) may lead to organ dysfunction most commonly respiratory failure with a high mortality.(1) During the COVID-19 pandemic, hospitalized patients are at risk of cross-infection with SARS-CoV-2 which has a tropism for angiotensin converting enzyme 2 (ACE2) receptors having high expression on the pulmonary alveolar epithelial cells and endothelial cells. (2, 3) COVID-19 leads to a high mortality in patients with comorbidities. (4) What clinical course does COVID-19 run in patients with severe pancreatitis and does it differ from those with virus induced AP is unknown. We present a case-series of 5 patients of whom 3 with severe acute pancreatitis and respiratory failure acquired nosocomial COVID-19 while recovering from AP.

Their clinical course highlights specific host responses leading to distinct pathophysiological mechanisms in different disease states affecting a common organ i.e. lung in the present context.

Our hospital has created separate facilities for non-COVID and COVID-19 patients. As a policy, all patients are tested before admission and re-tested during hospitalization on suspicion of SARS-CoV2 infection and managed in the appropriate facility. We collected the data of all hospitalized patients with AP who subsequently acquired nosocomial COVID 19 and patients who presented to dedicated COVID-19 facilities with features of AP from 1 st April till 30 th June 2020. The severity of acute pancreatitis was graded according to revised Atlanta classification. (5) The clinical severity of COVID-19 was defined according to the Indian Ministry of Health and Family Welfare (MOHFW) criteria as follows-mild disease as patients with only upper respiratory tract symptoms without any signs of breathlessness and hypoxia; moderate severity as the presence of pneumonia with the respiratory rate (RR) between 24-30/minute and SpO 2 between 90-94% on room air while the severe disease was defined by the presence of pneumonia with RR >30/minute or SpO 2 <90% on room air or severe respiratory distress.(6)

Of a total of 22 patients with AP admitted to non-COVID inpatient ward, 3 patients with severe AP (Table) developed nosocomial COVID-19 infection. In addition,2 patients presenting as AP had COVID-19 infection at diagnosis. J o u r n a l P r e -p r o o f Case 1:A31-year-old female patient with biliary pancreatitis presented to us on the day 12 of her illness after previous hospitalization elsewhere (Table) . She had respiratory failure at admission with a PaO 2 /FiO 2 of 250 and was started on non-invasive ventilation (NIV) which improved in next few days. She developed a large peripancreatic collection in the lesser sac and extending to left paracolic gutters and a percutaneous drain was placed in view of sepsis. Drain output showed intestinal contents and communication with bowel was suspected.

In view of persistent systemic inflammatory response syndrome (SIRS) she underwent surgical diversion procedure. Necrosectomy of pancreatic bed was not attempted at that time in view of frozen abdomen ( Figure   1a ). Endoscopic necrosectomy was done through the percutaneous sinus tract postoperatively as reported previously (7). She improved after necrosectomy and was running a stable course when she developed COVID-19 at the time of a mini localized outbreak of COVID-19 in the ward. She had mild illness with upper respiratory tract symptoms and did not develop any respiratory complication due to COVID-19. She improved and was discharged uneventfully.

A 40-year-old male patient with chronic alcoholism presented on 5 th May 2020 on the day 3 of illness.

AP was diagnosed based on clinical features and laboratory investigations (Table) . At presentation, he had acute kidney injury with a serum creatinine of 2.6 mg/dL and grade 2 respiratory failure with a PaO 2 /FiO 2 ratio of Figures 1b & c) requiring intermittent oxygen support but no respiratory failure. He improved with supportive therapy and was discharged.

A 42-year-old man was admitted with us after 10 weeks of onset of acute biliary pancreatitis with infected pancreatic necrosis. He had documented respiratory failure early during the course of his illness within first two weeks of onset for which he had required non-invasive ventilatory support in another hospital. He had not responded to antibiotics and percutaneous catheter drainage (Table) . He underwent two sessions of endoscopic lavage of the infected necrotic collection via percutaneous route at our center and improved. While improving from sepsis, he acquired COVID-19. He also did not develop any respiratory symptoms related to COVID-19 and had a mild disease which improved over 5 days.

facility with upper abdominal pain in June 2020. On evaluation, they had mild cough and infiltrates on chest Xray on day 3 of illness but no fever. Serum amylase levels were elevated (>3 times of upper limit of normal) and an abdominal ultrasound examination showed bulky pancreas with no evidence of gallstones. There was no history of intake of alcohol, trauma, or drug predisposing to AP. Both had normal serum triglycerides and calcium levels. One patient also had concomitant elevation in liver enzymes and renal injury which improved over next 5 days. Both the patients were diagnosed as moderate COVID-19 illness and mild acute pancreatitis.

They improved with conservative management and discharged home over the next 10-14 days.

The most important observation was that despite all 3 patients having had respiratory failure due to acute pancreatitis per se, none developed severe respiratory complication due to COVID-19. The possible explanations could be: (i) These patients had marked systemic inflammation during the initial phase of AP due to a dysregulated immune response leading to organ failure and subsequently developed compensatory antiinflammatory response syndrome, a state of immune exhaustion.(8) Hence, they could not mount a strong inflammatory response to SARS-CoV-2; (ii) The host immune response to a viral infection is fundamentally different from that due to damage-associated molecular patterns (DAMPs) or free fatty acids in AP and its severity may be determined by host genetic predisposition(9); (iii) Another possibility could be that AP primed immune response which might have modulated the inflammatory response to SARS-CoV2; (iv) The pathophysiology of organ failure in COVID-19 might be unrelated to the cytokine storm and could be due to endothelialitis and vascular thrombosis seen in <10% of patients (3); and (v) COVID-19 is mild in ~80% of patients particularly in younger age group. The risk of developing acute respiratory distress syndrome (ARDS)

is age dependent and is 5.36% for patients less than 60 years as compared to 16.91% in those over 60 years (10) .

A larger prospective study evaluating the relationship between age and severity is required to say that patients with acute pancreatitis are at no greater risk than general population for developing ARDS from COVID-19 infection.

Thus, differential pathophysiological mechanisms depending on specific host responses to the inciting injury i.e. DAMPs in acute pancreatitis or virus in COVID-19 may determine the extent of lung involvement regardless of the tropism of the latter. 

Annals for Hospitalists Inpatient Notes -Clinical Pearls-Acute Pancreatitis

Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus

Percutaneous Endoscopic Step-Up Therapy Is an Effective Minimally Invasive Approach for Infected Necrotizing Pancreatitis

Organ Failure Due to Systemic Injury in Acute Pancreatitis

Genomewide Association Study of Severe Covid-19 with Respiratory Failure

Analysis of Epidemiological and Clinical Features in Older Patients With Coronavirus Disease 2019 (COVID-19) Outside Wuhan