Does COVID-19 cause corneal transplant rejection?

Investigators report a case of acute corneal endothelial graft rejection with the concurrent onset of symptoms associated with COVID-19.

Study design

A 31-year-old female with an ocular history of bilateral keratoconus underwent a penetrating keratoplasty (PK) in the left eye. The patient had an uncomplicated operative and early postoperative course without signs of graft rejection. Three months after surgery, she presented with new-onset pain, redness and worsening vision in the left eye for 2 days. The patient's uncorrected visual acuity in the left eye was finger counting at 1 foot with improvement to 20/250 with pinhole, which was decreased from the previous uncorrected visual acuity of 20/200, and 20/80 with pinhole.

The examination revealed 1+ conjunctival injection, a full-thickness corneal graft with 2+ microcystic and stromal edema, and diffuse keratic precipitates involving only the donor graft. No neovascularization of the host or donor cornea was noted. Otherwise, the examination was stable from previous visits. The patient reported full compliance with the postoperative regimen of prednisolone acetate 1%, with verification from her pharmacy that the medication was repeatedly filled.

Outcomes

The diagnosis of acute endothelial rejection was made, and the patient was administered topical and oral steroids. Five days after the onset of ocular symptoms, the patient tested positive for SARS-CoV-2. Six weeks after the onset of endothelial rejection, the patient had improvement in the keratic precipitates, but persistent corneal edema. Three months after the initial rejection episode, she tested negative for SARS-CoV-2 and subsequently underwent repeat PK. At 1-month postop, the patient's best corrected visual acuity was 20/40 and the graft remained clear without any signs of rejection. Other than subjective fever and dysgeusia beginning the same day as her ocular symptoms, the patient had no other common symptoms of COVID-19 such as shortness of breath, chills, sore throat or cough.

Limitations

There is only one case report documenting an association between acute corneal endothelial graft rejection and COVID-19. Even though the cornea is the most commonly allotransplanted tissue in the United States, graft rejection rates are typically low because of ocular immune privilege. It is unknown if there is a direct cause and effect relationship between infection with SARS-CoV-2 and corneal transplant rejection. However, the patient's postoperative course lacked signs or risk factors for graft rejection such as corneal neovascularization or medication noncompliance.

Clinical significance

The ocular manifestations of COVID-19 are evolving. It is known that SARS-CoV-2 causes other ocular signs and symptoms including conjunctivitis and that the virus has demonstrated transmissibility through ocular secretions. Viral genomic and subgenomic RNA of SARS-CoV-2 were detected in the cornea of patients with COVID-19 viremia. Acute immune and inflammatory dysregulations have been seen in cases of COVID-19 through various mechanisms. It is possible that a pro-inflammatory microenvironment induced by SARS-CoV-2 may compromise corneal ocular immune privilege and increase the patient's susceptibility for acute corneal graft rejection.