Most SARS-COV-2 infection in children with intact immune response is mild. However, severe infection can rarely occur14. The difference in diseases severity between adult and pediatric might be related to more robust innate immune response and higher levels of interleukin- 17 and Interferon gamma in children15. Immunocompromised patients are always at a higher risk of contracting severe viral and bacterial infections. Understanding the host immune response of transplant adult and children to SARS-COV-2 is evolving but remains unclear.
Herein, we reported our experience in using serological testing as screening and confirmatory tool for COVID-19 patients. Of the 72 pediatric kidney transplant patient’s cohort who underwent serological testing, the prevalence of COVID-19 based on two positive serological tests for SARS-COV-2 IgG was 11.1% (8 0f 72). In our series all patients with positive serology including the one who tested positive for PCR and did not seroconvert were either asymptomatic or had mild symptoms not requiring hospital admission. None of them developed pneumonia or required oxygen supplementation. Our findings are consistent with what is reported so far.
After reviewing the current literature about SARS-COV-2 infection in pediatric and adult transplant population, we found no clear evidence that transplantation increases the risk of ICU admission and mortality. It is well known that early adaptive humoral response with the development of neutralizing anti-viral antibodies is an important mechanism in eliminating viral replication16. Our patients demonstrated high titer against Spike proteins (which correlate with neutralizing antibodies) suggesting that the adaptive humoral response is the dominating response in PKT, and it is sufficiently intact to overcome severe disease. However, such finding needs to be confirmed by larger studies. Moreover, there is growing evidence from multiple case series showing that immunosuppressants medications might have a beneficial effect. Bush et al. have reported a case of pediatric kidney transplant recipient who had a mild course of the disease despite being on immunosuppressant medications12. In a series of 200 pediatric liver transplant patient in a big transplant center in Italy, they reported 3 cases of covid-19 none of them had severe pneumonia or severe course17. This observation has led the author to conclude that immunosuppressant medications might have protective role. In one adult liver transplant study of 111 long term (> 10 years) stable liver transplant patients, three died because of severe COVID-19 pneumonia. Worth mentioning all of them had other risk factors associated with more sever course of COVID-19 like ( male > 65 years, hypertension, DM, and hyperlipidemia) other than being immunocompromised18. They were also on very low doses immunosuppressant, making it difficult to be blamed. On the other hand, there are some case series from the adult transplant population showing high mortality rate (28%) compared to the general population19.
Furthermore, it has been shown in a systematic review of 16 articles including children and adult with cancer, kidney, heart, liver and immunodeficiency patients that immunocompromise patients has similar and sometimes more favorable outcome when compared with general population. However this favorable outcome was not observed in cancer patients20
In our study, serological testing identified five patients with COVID-19 who otherwise would have been missed because of false negative PCR results or because of silent disease. Although none of those five patients had severe symptoms or complications that required hospital attention, identifying them helped us better understand the full clinical spectrum of the disease in this vulnerable group. Now we learned that asymptomatic COVID-19 is not uncommon in the PKT population. Identifying positive cases could also help in contact tracing and reduce disease spread. Moreover, we realize the stigma associated with COVID-19 in our community which led them to not reach out to us when their children developed symptoms. This will make us more vigilant in assessing our transplant patients during admission and out-patient clinic visits when we fully operate.
Out of the four patients with documented positive PCR, 75% seroconverted with relatively high antibody titers. Two patients had readings above the detectable upper limits of the test (> 400 AU/ml). Although these levels are very high, yet, no one really know how these levels translate into protection from the virus. These findings were unexpected as we already know that transplant patients who developed infection have blunted immune response and low rate of seroconversion when compared to regular population 21. More interestingly, all those patients who mount vigorous immune response to COVID-19 were still positive at median time of 75 days (IQR ,69–83). One patient (Case 2) was still positive for SARS-cov-2 IgG at 120 days. More Interestingly, most parent’s antibodies titers taking around the same time as their children were significantly lower than their children except in one patient. These findings are in contrast to what have been reported by Pierce et al. were they show that serum neutralizing SARS-COV-2 IgG antibodies were higher in adults when compared to children15
Important to note that, despite no major modifications was made on the immunosuppressant medication for all PCR positive patients except for one patient (Case 3) in whom MMF dose was reduced by half for one week. All patient but one, developed humoral immune response to COVI-D19. Two adult kidney transplant patients reported to have seroconversion between day 19–23 days after reduction of immunosuppressants 22. There was also a documented seroconversion in another two adult kidney transplant patients who developed SARS-COV-2 antibodies at 30 days post infection23 Moreover, study done by Hartzell et al. reported 100% seroconversion in 16 SARS-COV-2 positive adult kidney transplant patients24. Furthermore, Choi et al. have also reported 100% seroconversion rate in 5 adult KTR25 .Most of the current transplant guidelines suggest reduction or complete withdrawal of immunosuppressant. However, this suggestions was challenged by multiple studies that showed the ability of CNI to inhibit in vitro viral replication of SARS-COV-2 infection independent of its immunosuppressants effects 26. Furthermore, cyclosporine was successfully used to treat cases secondary hemophagocytic lymphohistocytosis ( HLH) that overlaps with the cytokine- release storm which seems to be the leading cause of mortality in COVID-19 infection27
To the best of our knowledge, our study is the first study to report a relatively high seroprevalnce of COVID-19 in PKT population. And it is the first study to test the humoral immunes response to SARS-COV-2 infection using quantitative serological assay that correlate with neutralization antibodies in this population. However, as all pediatric kidney transplant studies we are limited by the small samples size especially in this highly protected group. Moreover, results cannot be generalized to all PKT patients as majority of the patients enrolled were more than one year post transplants and on low maintenance immunosuppressants. Immuneassays used were IgG based, so acute infection could have been missed. Important to mention, all samples obtained were from Saudi children who might have different immunological background that can affect the immunoassays performance characteristics. For all these mentioned reasons, further larger studies with wider geographical presentation, and longer duration of antibodies titer follow up are needed.