SARS-CoV-2 convalescent plasma therapy in pediatric patient after hematopoietic stem cell transplantation

Abstract

Immunocompromised patients, including HSCT recipients, may have a poor prognosis after contracting COVID-19 due to the absence of a pathogen-specific adaptive immune response. One of the possible options for severe COVID-19 treatment may be the transfusion of hyperimmune SARS-CoV-2 convalescent plasma. A 9-month-old girl with juvenile myelomonocytic leukemia received an HSCT from a haploidentical donor. On day +99, during routine virologic monitoring, SARS-CoV-2 was detected without any clinical symptoms. On day +144, the child developed a polysegmental bilateral viral pneumonia with 60 % damage to the lung tissue and confirm a positive SARS-Cov-2 results in throat swab. The patient was treated with tocilizumab and three doses of fresh frozen plasma obtained from a SARS-CoV-2 convalescent patient. Therapy with tocilizumab and three doses of fresh frozen plasma was well tolerated. In spite of full resolution of the lung lesions, complete elimination of SARS-CoV-2 has not been achieved 4 months after the first detection, which is due to persistence of secondary immunodeficiency after HSCT and the lack of reconstitution of the adaptive immune response. This case represents a demonstration of an atypical course of COVID-19 and the delayed development of lung lesions, which was most likely associated with the features of the patient's immune status after HSCT. SARS-CoV-2 convalescent plasma in combination with other therapeutic approaches is one of the possible curative options for this clinical situation.

The use of convalescent plasma for pediatric patients with SARS-CoV-2: A systematic literature review

“…Table 1 presents the characteristics of the studies included in the final review. Three case reports included patients (n = 9) without comorbidity [ [17] , [18] , [19] ]; 5 reported on patients (n = 5) with a comorbid condition: one each with agammaglobulinemia [ 20 ], aplastic anemia and severe pancytopenia [ 21 ], acute lymphoblastic leukemia [ 22 ], trisomy 21 with congenital heart disease [ 23 ], and juvenile myelomonocytic leukemia [ 24 ].

Fig.

…”

“…Clinical conditions at admission before treatment were severe, including pneumonia [ 20 , 22 , 24 ], respiratory failure [ 17 , 18 ], and (multi)organ failure [ 21 , 23 , 19 ]. Among the additional drug treatments administered during hospital stay, the most frequent was remdesivir (n = 5) [ 20 , 22 , 17 , 23 , 19 ].…”

“…Among the additional drug treatments administered during hospital stay, the most frequent was remdesivir (n = 5) [ 20 , 22 , 17 , 23 , 19 ]. Five case reports described the use of CP antibodies against SARS-CoV-2 IgG [ 21 , 17 , 23 , 18 , 24 ], whereas 3 did not [ 20 , 22 , 19 ]. No CPT-related adverse events were reported in 5 studies [ 21 , 17 , 18 , 24 , 22 ], and 3 studies made no mention of adverse events [ 20 , 23 , 19 ].…”

“…Five case reports described the use of CP antibodies against SARS-CoV-2 IgG [ 21 , 17 , 23 , 18 , 24 ], whereas 3 did not [ 20 , 22 , 19 ]. No CPT-related adverse events were reported in 5 studies [ 21 , 17 , 18 , 24 , 22 ], and 3 studies made no mention of adverse events [ 20 , 23 , 19 ]. Patient outcomes were reported as recovery and/or discharge from hospital (n = 6) [ 20 , 22 , 17 , 23 , 19 , 24 ] or as amelioration of markers of SARS-CoV-2 infection [ 21 , 18 ].…”

“… Uneventful complete recovery (47 dys) CP* may be safe and effective treatment option in SARS-CoV-2 infection refractory to remdesivir. Diorio C, et al (Sep 2020) [ 18 ] Case report USA N = 4 patients, 14–18 years old; CD4, CD15, CD17, CD25# None Intubation and ventilation; two required extracorporeal membrane oxygenation RT-PCR*** testing of respiratory tract mucosa Patient CD4 received CP* 2 mL/kg Patients CD15, CD17, CD25 received CP* 4 mL/kg (RBD**-specific antibody titer levels <1:160) Life-threatening COVID-19-associated respiratory disease Donor for patient CD25# had higher SARS-CoV-2 RBD** antibody titers (>1:6000) than donor for other patients; no adverse event CP* may be of greatest benefit early in illness Greene AG, et al (Jun 2020) [ 19 ] Case report USA 11-year-old female None Toxic shock-like syndrome; LV systolic function mildly decreased based on decreased shortening fraction RT-PCR*** positive for SARS-CoV-2 Furosemide, enoxaparin, tocilizumab, CP*, remdesivir, steroids, IVIG Signs of distributive shock, multi-organ injury, systemic inflammation associated with COVID-19 Improved dramatically (24 h) Close follow-up for children presenting with fever lasting 3 dys Balashov D, et al (Nov 2020) [ 24 ] Case report Russia 9-month-old girl Juvenile myelomonocytic leukemia; hematopoietic stem cell transplantation Polysegmental bilateral viral pneumonia with 60 % damage of lung tissue RT-PCR***, throat swab positive for SARS-CoV-2 on day 99 after hematopoietic stem cell transplantation Tocilizumab (10 mg/kg), CP* (10 mL/kg; 3 doses; titers 1:160, 1:160 and 1:80) Secondary immunodeficiency Full resolution of lung lesions; complete elimination SARS-CoV-2 4 mths after first detection CT* well tolerated SARS-CoV-2 CP* in combination with other therapeutic approaches possible curative options Legend...…”