In the context of the corona pandemic, the question arises whether and with which diagnostic possibilities the safety of corneal transplants can be increased. For this reason, MCH routinely tests a pooled nasopharyngeal/conjunctival swab for SARS-CoV-2 using qRT-PCR in all tissue donors post-mortem.
In the present case, the weakly positive PCR signal from the pre-mortem smear suggested that the donor's infection with SARS-CoV-2 had already largely subsided. The donor probably had no or only mild symptoms, since both the medical history taken at the hospital and by the tissue establishment were unremarkable. Due to the borderline CT value of the positive pre-mortem test, the negative result of the post-mortem test is not unexpected. The respective CT values of the individual tests [Tab.1] correspond to the data described in the literature [2]. A false positive result is therefore excluded. Re-examination of the pre-mortem swab specimens was not possible due to a lack of reserves.
To date, over 50 donors have been tested by post-mortem nasopharyngeal/conjunctival swab and all results have been negative. This could be due to the fact that all potential donors are subject to a strict risk assessment and that the general infection rate in the donor region is very low. In the DGFG network, this is the only case in which a SARS-CoV-2 infection has been detected.
The risk of viral infection via tissue transplantation cannot be assessed yet. The suitability of existing tests for post-mortem analysis is unclear. However, initial studies on COVID-19-dead patients showed that SARS-CoV-2 can be detected in cornea and conjunctiva, although with comparably lower virus RNA concentrations [3]. Analyses of the infectivity of PCR-positive samples showed that virus growth from samples with a CT value >24 and >8 days after onset of symptoms was not successful [4]. Analyses of the correlation between viral load and the ability to cultivate the viruses in cell culture as a measure of infectivity can be used to derive threshold values above which there is very little or no infectivity. The Robert Koch Institute has recommended that a control examination should be initiated to assess further measures if the CT value exceeds 30 [5]. Currently, it must be assumed that transmission of the virus via transplanted tissue such as the cornea is potentially possible. Based on the anamnesis, symptomatic patients are not available as tissue donors, so that patients in the pre-symptomatic phase and symptom-free patients remain as risk groups. To what extent these patients represent a risk of transmission is not yet clear. Therefore, it would be important for recipient protection to know whether a donor is infected with SARS-CoV-2.
This case clearly shows the diagnostic gap in the test methods used, since with largely identical methods the virus could not be detected 45 h after the first test. First indications suggest that in a SARS-CoV-2 infection specific antibodies are only detected after seroconversion from day 7 to 14. The IgA-positive but IgG-negative serum result indicates an acute or recent infection with SARS-CoV-2. The detection of antibodies alone is therefore not recommended for acute diagnosis. It is not yet clear over what period of time SARS-CoV-2 specific IgM, IgA and IgG antibodies are detected, especially since viral RNA may still be detectable in the nasopharynx despite cured COVID19 disease. In comparative studies of infected patients with mild vs. severe symptoms, IgA antibodies were not detected until 8 days after the onset of symptoms in mildly progressing SARS-CoV-2 infections, with a correlation between the intensity of the symptoms and the onset of detection [6]. In cases with weak symptoms, IgG antibody detection may be absent or delayed.
The case presented in this paper illustrates the following facts:
In the case of a asymptomatic patient, the importance of routine clinical swabbing at patient admission is clearly demonstrated, as the right test must be performed at the right time [7]. With the presented case, no statement can be made whether the post-mortem swab test is suitable for testing for SARS-CoV-2. There is no valid proof that this method can reliably detect post-mortem infection with SARS-CoV-2. Whether a proposed test of the extracted cornea or culture medium by qRT-PCR [8] would be suitable for SARS-CoV-2 detection requires further analysis.