Is the outcome of SARS-CoV-2 infection in solid organ transplant recipients really similar to that of the general population?

To the Editor:

We read with great interest “Outcomes of Critically Ill Solid Organ Transplant Patients With COVID-19 in the United States” by Molnar et al¹ and “Clinical Characteristics and Outcomes of COVID-19 in Solid Organ Transplant Recipients: A Case-Control Study” by Chaudhry et al.² The first, matched case–control study compared the outcomes of critically ill Severe Acute Respiratory Virus Syndrome 2 (SARS-CoV-2) infection among solid organ transplant (SOT) recipients and the general population. The latter² was also a case–control study of hospitalized SOT and non-SOT recipients with Coronavirus disease 2019 (COVID-19), comparing outcomes including mortality.

Given the novelty of this virus and the limited number of SOT cases, there remains a paucity of data regarding SARS-COV-2 infection among SOT recipients. The Centers for Disease Control and Prevention have recognized SOT recipients as an increased risk group for severe illness from COVID-19.³ Moreover, it is well known that T cell–mediated immunity, which is an important component of the immune response against any respiratory virus infection, is significantly hampered in SOT recipients.^{4 , 5} Hence, it is thought that the risk of infection with COVID-19 among SOT recipients must be high.

The studies by Molnar and Chaudhry represent great contributions to the field, highlighting data on coinfections from Molnar et al¹ and the use of severity scores (qSOFA and NEWS) by Chaudhry et al.² However, both studies concluded that transplant status is not associated with higher mortality or other related outcomes. We believe it is difficult to derive these conclusions from outcomes solely based on inpatient or intensive care unit (ICU) admissions. That cohort of patients is already at a higher risk for severe illness and mortality. As the authors declared, there are limitations with sample size especially in the study by Chaudhry et al,² in addition to selection and misclassification bias in both. Based on these two studies, we can conclude that once admitted to the hospital or ICU, clinical outcomes of SOT recipients and non-SOT recipients are comparable, but it is still unclear whether SOT recipients behave similar to the general population when accounting for outpatient diagnoses as well. The largest case series reported by Kates et al⁶ showed hospital admission in SOT recipients was 78%, which is high when compared to the general population.⁷ Furthermore, Kates et al, reported mortality rates in critically ill SOT populations comparable to hospitalized general populations, which supports the statement above, but data regarding outpatient infections are still lacking.

Thus, while the above studies^{1 , 2} conclude no difference in overall mortality rates between the two groups, this may primarily be a result of limiting the comparison to patients already at high risk or at a later phase of COVID-19 infection, when outcomes are unlikely to change regardless of the patients classification. In conclusion, we suggest that future studies should analyze the entirety of the COVID-19 cohort (inpatient, outpatient, diagnosed by screening) to significantly reduce any potential selection and misclassification bias. This will also help identify additional risk factors for COVID-19 severity in SOT recipients.