key: cord-0835116-jrwdhmst
authors: Passarelli, V. C.; Perosa, A.; Luna, L.; Conte, D.; Nascimento, O.; Ota-Arakaki, J.; Bellei, N.
title: Cirrhosis and COVID-19: a fatal case of viral peritonitis and disseminated infection
date: 2020-06-29
journal: nan
DOI: 10.1101/2020.06.25.20139998
sha: ad1509cb9584784fe27efdfe720f7b669d9642c7
doc_id: 835116
cord_uid: jrwdhmst

Pathogenesis and clinical presentation of Coronavirus Disease-19 outside the respiratory tract remain to be understood, especially in the immunocompromised. We report an unique case of cirrhosis decompensation with ascites and unprecedented evidence of SARS Coronavirus-2 peritonitis and disseminated infection, demonstrated by viral RNA detection in peritoneal fluid, as well as in blood serum, nasopharyngeal and stool specimens.

Introduction SARS Coronavirus-2 affects primarily upper and lower respiratory tract, but detection in different clinical specimens has raised important insights about its kinetics and pathogenesis 1 .

However, virus' replication in other body sites and pathogenetic details still remain to be understood 2 , although endothelial injury with intracellular virus as well as immune system dysregulation have been described 3, 4 .

In that respect, immunocompromising conditions, such as cirrhosis. can present with even more severe consequences 5 when combined with dysfunctions observed in COVID-19.

We report an unique case of cirrhosis decompensation with ascites and evidence of viral peritonitis and disseminated infection in a kidney transplant patient, demonstrated by viral RNA detection in peritoneal fluid, as well as in blood serum, nasopharyngeal and stool specimens.

A 75-year-old white male with a history of hypertension and a kidney transplantation in 2017 presented in the emergency department on May 18th, 2020, five days following the onset of dry cough and progressive dyspnea, without fever or other respiratory or gastrointestinal tract symptoms. He was on immunossupressive therapy with 4 mg tacrolimus and 5 mg prednisone.

Physical examination at admission revealed an axillary temperature of 37.1ºC, blood pressure of 160/90 mmHg, heart rate of 104 per minute, respiratory rate of 25 breaths per minute and oxygen saturation of 92% while breathing ambient air. Abdominal examination demonstrated mild ascites with collateral circulation.

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The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint He was diagnosed in 2018 with liver cirrhosis, portal hypertension and thrombosis, without a conclusive aetiology, but denied any prior decompensation. His previous serologies were negative for HIV, Hepatitis C, Syphilis, Schistosomiasis and he had an spontaneous cure of Hepatitis B with undetectable viral load.

Initial laboratory findings showed normal white cell count but severe lymphopenia (162 per mm³) as well as other cirrhosis dysfunctions such as thrombocytopenia, increased international normalized ratio (INR) and hypoalbuminemia. Creatinine was 1.5 times its baseline value (2.4 mg/dl), procalcitonin was elevated at 3.92 ng/dl and d-dimer was above 20 µg/mL (maximum test detection). Additional laboratory exams may be seen on Table 1 .

Chest computed tomography scan showed bilateral ground glass opacities with some areas of consolidation and specimens from his nasopharyngeal swab were positive for COVID-19 on Real Time Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR).

Supplementary oxygen (O2) with a nasal cannula was administered at 2 L/min and his pulse oximetry went up to 97% and he was started on ceftriaxone and clarithromycin.

Tacrolimus was suspended and prednisone dose was increased to 30 mg daily.

On day 2 of hospitalization (day 8 of illness) his breathing pattern worsened, as he needed an increase in nasal oxygen flow to 6 L/min, and so did his ascites, which then made his abdomen tense and painful. A diagnostic and therapeutic abdominal paracentesis was performed and 2 litres of citrine yellow ascitic fluid were subsequently removed. Laboratory analysis showed a total cell count of 133 per mm³ (macrophages: 60%, mesotelyocytes: 24% and lymphocytes: 16%) and a serum-ascites albumin gradient value of 2. RT-PCR for COVID-19 in peritoneal fluid was positive, as well as in his serum and fecal samples (table 2) . A rapid serological test performed on day 10 of symptoms was positive for IgM and IgG antibodies.

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The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint On day 4, he required intubation as his respiratory status worsened further (PaO2/FiO2 ratio: 110). His ventilation parameters improved in the following days but his renal dysfunction did not and he was started on hemodialysis. The patient died on day 16 due to a refractory septic shock.

Nasal and oropharyngeal swabs were collected and stored in 2 mL of sterile Ringer's lactate solution prior to RNA extraction with QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany), following manufacturer's instructions. Virus screening was carried out with AgPath-ID One-Step RT-PCR Reagents on 20 µL of total reaction volume. SARS-CoV-2 detection was performed with oligonucleotides described by the Centers for Disease Control and Prevention (CDC). Serum was collected in a serum separator tube and then centrifuged according to CDC guidelines. Feces and ascitic fluid were collected with sterile specimen containers and all three specimens tested for SARS-CoV-2 at the same protocol. Rapid serological test was performed with serum sample following manufacturer's instructions (Zhuhai Livzon Diagnostics).

This case report was approved by Local Ethics Committee.

Specimens from nasopharyngeal swab obtained on day 5 of patient's illness were positive for SARS-Cov-2 (table 2). Low cycle threshold (Ct) values (14-15) suggest high levels of virus.

Peritoneal fluid from day 7 was also positive (Ct, 34-38), serum samples collected on day 9 and . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint 6 10 were positive for both SARS-CoV-2 (Ct, 31-32) and IgM/IgG antibodies, respectively. Stool collected on day 10 was positive as well (Ct, 25-26).

A great variety of clinical features have been attributed to coronavirus disease including cough and dyspnea², which were similar to the ones reported by this patient. Pneumonia is the most common feature on severe disease² and, sometimes, it can lead to multi-organ disease syndrome, including heart, kidney and liver dysfunctions 4 . One possible explanation for that is endothelial injury associated with intracelular viruses, previously described in lung autopsy reports³, which also appears to incite a high rate of thrombotic events 6 .We assume this could partially explain further aggravation of a previous portal vein thrombosis observed with this patient, which would justify the worsening of his ascites. Moreover, we also hypothesize direct viral damage had a potential role on his initial clinical presentation, which could be considered a viral peritonitis, as SARS CoV-2 RNA was detected in his ascitic fluid. Interestingly, reports on cirrhotic patients with COVID-19 show a high rate of decompensation with ascites 5 , but this is the first report of such finding.

Furthermore, viral detection in blood samples from immunocompetent patients suggests systemic infection is sometimes possible 1 and, since solid-organ transplant patients on immunosuppressive therapy have impaired T cell immunity, higher rates of replication would be expected 8 . Therefore we hypothesize a combination of a potentially systemic infection and immunosuppression in addition to cirrhosis' immune dysfunction 5 could have contributed to a disseminated infection in this patient. In spite of that, he presented with seemingly adequate . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint humoral immune response as he was able to produce IgM and IgG antibodies by day 10 of symptoms onset, which is consonant with previous literature 9, 10 .

Unfortunately, other dysfunctions observed with COVID-19² prolonged hospitalization and led to complications which were fatal to this patient..

This unprecedented case report adds new information on COVID-19 pathogenesis and highlights the need for more research about viral dynamics as well as clinical outcomes, especially in patients with end-stage liver disease.

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The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 29, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint

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This research received support from the Coordination for the Improvement of Higher Education Personnel (CAPES) and the National Council for Scientific and Technological Development (CNPq).Authors declare no conflict of interest.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)The copyright holder for this preprint this version posted June 29, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted June 29, 2020. . https://doi.org/10.1101/2020.06.25.20139998 doi: medRxiv preprint