Predicting susceptibility to COVID-19 infection in patients on maintenance hemodialysis by cross-coupling soluble ACE2 concentration with lymphocyte count: an algorithmic approach.

Introduction: Patients on maintenance hemodialysis (MHD) were more vulnerable to and had a higher mortality during the COVID-19 pandemic. As angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine S1 member 2 (TMPRSS2) played crucial roles in viral entry into the human host cells, we therefore investigated in the MHD patients whether their plasma levels were associated with susceptibility to the COVID-19.

Methods: Blood samples were collected from the patients in our then COVID-19 free center immediately upon lifting of the stringent quarantine measures in early December of 2022 and infection situation was observed within the following 2 weeks. Plasma levels of the soluble ACE2 (sACE2), ACE (sACE) and TMPRSS2 (sTMPRSS2) were measured with ELISA method. Data were stepwisely tested for independent effect, relevant role and synergistic action on the susceptibility by multiple logistic regression, receiver operating characteristic curve and multiple dimensionality reduction (MDR) method, respectively.

Results: Among the 174 eligible patients, 95 (54.6%) turned COVID-19 positive with a male to female ratio of 1.57 during the observation period. Comparing with the uninfected, the infected had significantly higher sACE2 and lower sTMPRSS2 levels upon comparable sACE concentration. Besides the sACE2, factors associated with susceptibility were vintage and individual session time of the hemodialysis, smoking and comorbidity of hepatitis, whereas lymphocyte counts showed a tendency (p = 0.052). Patients simultaneously manifesting higher sACE2 level and lower lymphocyte counts had an increased infection risk as confirmed by the MDR method.

Conclusion: By sorting out the susceptible ones expeditiously, this algorithmic approach may help the otherwise vulnerable MHD patients weather over future wave of COVID-19 variants or outbreak of other viral diseases.