key: cord-0771234-bpklkpyu authors: Jamir, Imtiakum; Lohia, Pankaj; Pande, Rajesh Kumar; Setia, Rasika; Singhal, Amit Kumar; Chaudhary, Abhideep title: Convalescent plasma therapy and remdesivir duo successfully salvaged an early liver transplant recipient with severe COVID-19 pneumonia date: 2020-11-30 journal: Ann Hepatobiliary Pancreat Surg DOI: 10.14701/ahbps.2020.24.4.526 sha: d3bf0e84ef06427e0c0315eef1de5e374a50e517 doc_id: 771234 cord_uid: bpklkpyu The impact and clinical spectrum of COVID-19 infection in liver transplant recipients/solid organ transplants are being unveiled during this recent pandemic. The clinical experience of use of current antiviral drugs and immunomodulators are sparse in solid organ transplantation. We present the clinical course of a 49-year-old male recipient who underwent living donor liver transplant for recurrent gastrointestinal bleed and contracted severe COVID-19 pneumonia during the third postoperative week. Herein we report the successful management of severe COVID-19 pneumonia using convalescent plasma therapy and remdesivir. Recipient’s clinical deterioration was halted after three consecutive convalescent plasma transfusions with improvement in hypoxia and inflammatory markers (interleukin-6 and C-reactive protein). The use of convalescent plasma therapy along with remdesivir may be an ideal combination in the management of severe COVID-19 pneumonia in solid organ transplant recipients. India ranked third globally in COVID-19 cases as of July 2020. 1 We rebooted our logistics and reconstructed our protocols to prevent the risk of COVID-19 illness as per national and international transplant society guidelines. 2, 3 The early report of COVID-19 related perioperative mortality of a liver transplant recipient from China highlights the severity of illness which one can encounter. 4 Currently multiple clinical and randomized trials are underway to find effective combination therapy in severe COVID-19 illness. The use of antiviral drugs and immunotherapy in transplant settings are limited to case reports. 5, 6 Herein we report a case of severe COVID-19 pneumonia in an early post liver transplant recipient managed with a combination of convalescent plasma therapy (CPT) and remdesivir. A 49-year-old obese (BMI-33.9) Indian male, known case of ethanol related decompensated liver cirrhosis with recurrent life threatening variceal bleeds, mild ascites and jaundice (CTP score −9, Child: B, MELD Na: 17) was referred to us for liver transplant. He had no previous history of hypertension, diabetes, or asthma. His 45-year-old wife was evaluated for donation as per our unit protocol. The first nasopharyngeal swab for COVID-19 reverse transcriptase polymerase chain reaction (RT-PCR) test Fig. 1 ). The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) showed a rising trend in the 2 nd post-operative week and methylprednisolone pulse therapy was given to which he responded well ( Fig. 1) . A percutaneous liver biopsy was not performed in view high-flow nasal cannula oxygen therapy (Fig. 2 ). On day 3 of fever (POD22) he became increasingly tachypnoeic (respiratory rate-37/min) and chest x-ray showed patchy parenchymal bilateral opacities (Fig. 3) . He was pre-emptively shifted to intensive care isolation We decided against administration of tocilizumab, as thrombocytopenia continued to persist in the late post-operative weeks ( Table 1) . As our hospital was gradually gaining experience in treating sick COVID-19 patients As per patient's request to be in home quarantine, he was discharged on 6 th August 2020. He is doing well presently and is being followed up telephonically. Recently it has been used by another centre to treat a COVID-19 pneumonia infected liver transplant recipient. 6 Elucidating the safety profile of tocilizumab, the drug company stated that it could cause transaminitis with a rare risk of liver failure requiring liver transplant. 12 Also tocilizumab being an IL-6 inhibitor may interfere with early graft regeneration as IL-6 plays an important role in liver regeneration. 13 In view of our patient having thrombocytopaenia with recovering transaminitis and the fear of potential hepatotoxicity, we decided against the use of tocilizumab and considered the use of other available immunotherapies. We had to make a choice between using intravenous immunoglobins or CPT in our patient. Intravenous immunoglobulins are pooled human plasma which lack the specific antibodies against COVID-19 virus. 14 CPT has multipronged antiviral immunomodulatory effects-direct neutralization and entry of virus into host cells, antibody dependent cellular cytotoxicity and phagocytosis, complement action and other passenger proteins such as anti-inflammatory cytokines, defensin, pentraxins and the undefined protein from convalescent plasma donors. 15 Convalescent plasma has been successfully used to treat infectious epidemic outbreaks for patients with SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome), and 2009 H1N1 influenza viruses. 16 The CPT has been shown to reduce mortality rate and length of hospitalization from Wuhan. 17 The literature is not clear on the dosage and duration of CPT. We transfused two aliquots of convalescent plasma in our recipient however as he did not show much improvement an additional third aliquot was given to which he responded well. 7 Though the use of plasma therapy in solid organ transplant is anecdotal, CPT with no potential interactions with immunosuppressants and not affecting hepatic and renal functions will form an important armamentarium in the management of COVID-19 illness in SOT recipients. 18 Preliminary reports have suggested that remdesivir as a sole antiviral may not be sufficient to prevent CRS. 19 Hence we used the combination of CPT and remdesivir The CPT and remdesivir duo can prove to be a perfect combination to salvage liver transplant recipients with severe COVID-19 pneumonia. WHO coronavirus disease (COVID-19) dashboard. 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The authors of this manuscript have no conflicts of interest to disclose.