COVID-19 is a public health emergency, and kidney transplant recipients have a significant chance of contracting a severe illness as a result. The present study was conducted to compare RTRs and non-RTRs infected with COVID-19, with a special focus on clinical symptoms, imaging characteristics, disease severity, and outcomes during the Omicron epidemic.
The most prevalent comorbidity among patients with kidney disease was hypertension. No significant correlation existed between HTN and RTRs. The Benoteman et al. cohort study revealed that hypertension was the most prevalent comorbidity among RTRs infected with COVID-19, and a Turkish study identified hypertension and diabetes as the most prevalent comorbidities among patients with kidney disease (25–27). Due to the underlying disease, routine use of steroids and CNIs, and lower glomerular filtration rate (GFR), these results were anticipated.
However, the results of our study did not show this. In accordance with symptoms reported in immunocompromised patients in a recent systematic review (28), fever, cough, and chills were found to be the most common clinical manifestations of RTRs in our study. In some other studies, however, fever was less common among RTRs (29). According to a recent study, solid organ transplant recipients exhibited greater dyspnea than the general population; likewise, in our study, dyspnea was higher in RTRs than in the control group (28). The cytokine release syndrome (CRS), which has been proposed as a destructive mechanism in COVID-19, can cause lung inflammation. Consequently, preventing or reducing cytokine release will reduce organ damage (30).
We found a significant difference between the two study groups in terms of gastrointestinal symptoms. Recent research (31) revealed that diarrhea is a common clinical manifestation of SARS-CoV-2 infection in RTRs, with a prevalence significantly higher than that of the general population. It is hypothesized that immunosuppressive agents exacerbate gastrointestinal (GI) symptoms, making them more prevalent in RTRs infected with COVID-19 than in the general population (31); however, in other studies, GI symptoms were a less common symptom among RTRs (32).
RTRs may be more susceptible to infection due to their immunosuppression and burden of comorbidities, including diabetes, HTN, and cardiovascular disease. Although the definitive effect of immunosuppression on host immune response is unknown yet, it has been speculated that chronic immunosuppression may play a role as a protector against hyper-inflammatory response and cytokine storm severity in RTRs with COVID-19 (33); thus the possibility of subsequent respiratory damage resulting from elevated cytokines would be mitigated.
Because of this, it is assumed that infection with COVID-19 might not result in worse consequences in patients under immunosuppression agents chronically. Additionally, the protective role of chronic use of CNIs has been suggested in COVID-19-infected patients (34).
On the other hand, being on chronic immunosuppression, especially at the first phase of infection, has been thought to increase morbidity and mortality owing to the altered immune system during the early episode of SARS-CoV-2 infection, during which a strong response is required to overcome viral replication and disease progression; moreover, immunosuppression puts individuals at higher risk of secondary infections (33, 35). In our study, we aimed to minimize the negative effects of CNIs and antimetabolites on the clinical course of viral pneumonia by either decreasing the dosage of CNIs or discontinuing them together, and we did so based on the severity of illness in each patient at the time of hospitalization (33).
However, in our study, despite a remarkable dose reduction of IS medications through the admission period, none of the KTRs experienced allograft rejection, as none of them developed progressive kidney failure and renal replacement therapy requirements and gradually recovered without antirejection t. The simultaneous increase of corticosteroids to stress dose in the context of decreasing or discontinuing CNIs and antimetabolites may have modulated the absence of rejection. Patients who had to stop CNIs due to a severe infection have also been hypothesized to benefit from anti-inflammatory drugs' protective effect against rejection (36). It is important; case-by-case immunosuppressive management should be evaluated for each KTR infected with COVID-19.
In-hospital mortality, ICU admission, and MV requirements were significantly different between RTRs and non-RTRs, according to our findings. Due to the immune suppression caused by antirejection protocols, RTRs are generally more susceptible to bacterial superinfection. In this group of ICU-admitted patients, a higher mortality rate may have been caused by concurrent superinfection. In addition to a higher burden of comorbidities, single-functioning kidneys, and worse laboratory parameters in these patients, the higher mortality rate in RTRs could be attributed to ineffective immune function during the early phase of infection, when a strong immune response is required to suppress viral replication and overload. In the study we conducted in 2020, the mortality rate and ICU admission rate were 41.6% (10/24) and 50% (12/24), respectively, in RTRs (37). This difference can be due to the experience of the treatment staff, drugs and vaccination. Unlike our study, previous observational studies (27, 32, 38), found no significant difference between RTRs and non-RTRs in terms of mortality and adverse outcomes (death or ICU admission). In our study, severe to critical situations were more detected in patients with kidney disease compared to patients without underlying kidney disease. The most drugs that were used to treat Covid-19 and alleviate its symptoms was Remdesivir, which was prescribed to 97 patients (79.5%). Also, 6 patients (4.9%) received Tocilizumab, 5 patients (4.1%) received Baricitinib, and 2 patients (1.6%) received Everolimus.
whereas, in a recently conducted case-control study, in terms of COVID-19 infection severity, no significant difference was detected between the two groups (32). but, in another case-control study, severe to critical situations were more detected in patients with kidney disease compared to patients without underlying kidney disease (27). Our results showed that among RTRs, AKI was more common than among controls. A recent study (38) also found that the prevalence of AKI in RTRs was substantially higher than in the general population. During the progression of COVID-19 infection, RTRs are predisposed to AKI etiologies like acute rejection, hemodynamic imbalance, volume depletion, medication toxicity, and high fever (39). Thus, complications may arise more frequently in RTRs than in the general population from prerenal azotemia, acute tubular necrosis, or other potential etiologies of AKI. Reasons include immunosuppression, decreased medication tolerance, and a single-functioning kidney (40). both lymphopenia and thrombocytopenia, which are markers of low-grade inflammation, were shown to be much more prevalent in RTRs than in non-RTRs. Consistent with our findings, a recent case-control research found that the prevalence of thrombocytopenia and lymphopenia was much lower in patients without any underlying kidney illness compared to those with RTRs, Chronic kidney disease (CKD), and end-stage renal disease (ESRD) (27). Additionally, immunocompromised organ transplant recipients with COVID-19 were found to frequently have lymphocytopenia (41). RTRs may have lower lymphocyte and platelet counts because of chronic disease and the usage of immunosuppressive agents such as antimetabolites (42). There was no statistically significant difference in C-reactive protein levels between the two groups (27), despite previous case-control studies showing a greater increase in C-reactive protein in RTRs compared with their control group (32).
About 70% of patients in both groups displayed GGO, a highly suggestive pattern of COVID-19 pneumonia, on CT scan, with no statistically significant difference between the two groups. Findings associated with severe to critical clinical conditions (cavity, linear opacity, bronchiectasis, and consolidation alone) were not significantly different between the two groups and were within the same ballpark as those seen in studies of the general population (43, 44).
Among critically ill patients, pleural effusion (23%), an extra pulmonary lesion suggestive of severe inflammation and viral load (43), was usually more common. Another study found that while it was present in all of the RTRs, it was much higher in the control group. Neither group showed statistically significant differences in our investigation. Immunosuppressive drugs may prevent cytokine release, which is thought to cause pleural effusion, explaining why this finding is absent in RTRs. The prevalence of bilateral, peripheral, and basal lesions was statistically higher in the control group. As an additional point, the RTRs had a significantly higher prevalence of unilateral and diffuse lesions, and the ratios did not agree with those found in earlier research (43, 44). The prevalence of pulmonary involvement was higher in the control group as a whole.
There are some limitations to our study. We had a limited number of participants in our study, and we only followed them for a brief period. Secondly, there wasn't enough useful information to go around because our facility doesn't have many registry databases.