Pharmacotherapeutic considerations in solid organ transplant patients with COVID-19

Abstract

Introduction: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. While there are presently a few case reports/series on COVID-19 amongst solid organ transplant (SOT) patients, there is no official guideline for the management of SOT patients. Areas covered: The authors discuss the pharmacotherapeutic management of SOT patients during the COVID-19 outbreak and provide their expert perspectives. Expert opinion: Prophylactic reduction of immunosuppression because of fear of COVID-19 is not suggested in SOT patients. With maintenance immunosuppressive regimens, corticosteroids can be continued during COVID-19. Continuing other immunosuppressive drugs with lowest effective dose/ blood concentration is suggested for patients with mild to moderate COVID-19. Discontinuation of antimetabolites and perhaps inhibitors of mammalian target of rapamycin (mTOR) is suggested in moderate to severe COVID-19. Calcineurin inhibitors (CNIs) may be continued or substituted for mTOR inhibitors with lowest therapeutic concentrations in moderate to severe COVID-19. If continued in patients with COVID-19, therapeutic drug monitoring of CNIs/mTOR inhibitors and appropriate dose reduction is recommended in co-administration with protease inhibitors, hydroxychloroquine/chloroquine, or interleukin (IL)-1/IL-6 receptor antagonists. Complete blood count monitoring is recommended in patients who continue taking antimetabolites or mTOR inhibitors. Dose modification/ avoidance should be considered for chloroquine, atazanavir, oseltamivir, ribavirin, anakinra, and Janus associated kinase inhibitors in patients with organ function impairment.

The effect of immunosuppressants on the prognosis of SARS-CoV-2 infection

“…[3][4][5] Patients receiving immunosuppressant therapies for conditions including inflammatory diseases and solid organ transplantation are susceptible to intercurrent viral and bacterial infections, 6,7 and although evidence is lacking regarding their effect on COVID-19, expert groups concerned that immunosuppression may worsen the prognosis have advised withholding or reducing immunosuppressants during intercurrent COVID-19. [8][9][10] Immunosuppressants differ in their mechanisms of action and may therefore have differing effects on the disease course of COVID-19, and effects may vary with the severity of disease, and timing in the disease course. Certain immunosuppressants may have beneficial effects in COVID-19 by regulating the elevated inflammatory response associated with severe disease.…”

“…Severe cases are predominantly characterised by viral pneumonia and may feature multi-organ inflammatory involvement, including elevated pro-inflammatory cytokines such as interleukins IL-6 and IL-8, and tumour necrosis factor (TNF) [ 3 – 5 ]. Patients receiving immunosuppressant therapies for conditions including inflammatory diseases and solid organ transplantation are susceptible to intercurrent viral and bacterial infections [ 6 , 7 ], and although evidence is lacking regarding their effect on COVID-19, expert groups concerned that immunosuppression may worsen the prognosis have advised withholding or reducing immunosuppressants during intercurrent COVID-19 [ 8 – 10 ].…”

Solid organ transplantations and COVID-19 disease

“…Checking the hemogram is suggested in cases using antimetabolite drugs or mTOR inhibitors. Drug dose adjustment/evasion should be contemplated for chloroquine, atazanavir, oseltamivir, ribavirin, anakinra, and Janus associated kinase (Jak) inhibitors in cases with organ dysfunctions[ 36 ].…”

Pharmacotherapeutic approach toward urological medications and vaccination during COVID-19: a narrative review

“… 59 On the contrary, reducing the dose of cyclosporine is also necessary in the concomitant use of hydroxychloroquine. 60 …”