key: cord-0804717-jg2ebz08
authors: Rajendra, Akhil; Gokarn, Anant; Mirgh, Sumeet; Ravind, Rahul; Singh, Anuj; Goli, Vasu Babu; Punatar, Sachin; Chichra, Akanksha; Tembhare, Prashant; Patkar, Nikhil; Bhat, Vivek; Chavan, Preeti; Trivedi, Bhakti; Joshi, Amit; Khattry, Navin
title: SARS-CoV2 Infection in Hematopoietic Stem Cell Transplant recipients: A Case Series from a Tertiary Cancer Centre in India
date: 2021-05-13
journal: Indian J Hematol Blood Transfus
DOI: 10.1007/s12288-021-01443-8
sha: 71434e1d3bba83d6c57fc49c9c9d5d307a781f4a
doc_id: 804717
cord_uid: jg2ebz08

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immunosuppressants. Tocilizumab was used for severe COVID-19, as per physician discretion. Nasopharyngeal swab was repeated every 2 weeks till negativity and antibodies to SARS-CoV-2 were tested after 2 weeks of initial RTPCR positivity and then 2 weekly.

We found that 5 of these 6 patients required prolonged time to clear the viral infection, with median time to RTPCR negativity of 31 days (Table 1) . Three patients (patient A, C and D) developed neutralising IgG antibodies (IgG) to SARS-CoV-2 at 83 days, 22 days and 31 days post infection respectively. However, Patient C who developed antibodies at day 22, continued to remain persistently RTPCR positive for SARS-CoV-2 (Table 1) . At a median follow-up of 40 days, all patients in our cohort are alive.

With emerging evidence, treatment options in COVID-19 are becoming clearer. However, there is no standard of care for immunocompromised patients, especially post HCT recipients.

In a phase II randomized trial, triplet combination consisting of oral LPV/r (400 mg/100 mg) and RBV 400 mg twice daily (14 days) along with IFN b1b was compared with LPV/r alone. Along with significantly improved clinical response, the triplet combination resulted in early nasopharyngeal negativity [3] . Amongst the 6 patients in our series, 3 received triplet antivirals, and showed rapid defervesence with clinical improvement. However, in contrast to Hung et al. [3] , the time to negative nasopharyngeal swab was longer in our patients who received this combination. Production of excessive cytokines results in severe inflammatory responses in the lung resulting in severe COVID-19 manifestations and use of Tocilizumab, has been found to abrogate this inflammation [4] . In patient A, Tocilizumab was used twice in view of impending respiratory failure on third day and fifth day of infection resulting in rapid clinical benefit and radiological response. Thus, this case series highlights that use of antivirals (triplet antivirals and Remdesivir) and tocilizumab results in favorable outcome in post HCT patients with COVID-19 infection.

We recorded the immune kinetics of our allogeneic HCT patients during the course of illness (Fig. 1) . In the early phases of infection, there was a decrease in the Absolute NK Cell, CD3, CD4 and CD8. By Day 8-15 there was a rise in these parameters. The graph pattern of patient E is in stark contrast to those of patients A and C. All the T-cell subsets and NK-cells appear to have stabilized, likely because this patient was diagnosed in late stages of the infection.

With the FDA authorizing the use of remdesivir, a more tolerated drug with better outcomes, for the treatment of moderate and severe COVID-19 infection, the place of triplet combination of LPV/r, RBV and IFN b1b in the therapeutic armamentarium is not clear, nevertheless, it still remains an alternative, if remdesivir is unavailable.

Severe COVID-19 in a patient with chronic graftversus-host disease after hematopoietic stem cell transplant successfully treated with ruxolitinib

Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: a single center study of 100 patients in