Prolonged shedding of SARS COV-2 in an asymptomatic patient– a case report

Abstract

Background- There have been few reports of asymptomatic SARS-CoV2 patients who have shed viruses for unusually prolonged period. These cases are generally identified during contact tracing of positive SARS-CoV2 patients and remain a stumbling block for control of transmission and spread of SARS-CoV2 viral infection. We are reporting a similar case of asymptomatic SARS-CoV2 carriage in respiratory secretions of a patient for two months. Materials and methods- The present case study discusses about an asymptomatic young male patient who was tested positive for SARS-CoV2 after a recent travel. His nasopharyngeal samples showed consistent positivity for SARS-CoV2 from June 2021 till August 2021 when tested by Real Time RT PCR and the Ct values always remained less than 25. His clinical investigations were within normal limits except for high D-dimer levels and his HIV serology was negative during initial work up. He received second dose of COVID vaccine during quarantine period. Upon six months follow up of the patient, it was learned that he died of HIV infection in March 2022. Discussion and conclusions- The persistence of SARS-CoV2 could be attributed to either COVID vaccination taken during quarantine period or may be due to HIV infection which might have been missed during the window period. This report suggests that there is high risk for silent spread of SARS-CoV2 by asymptomatic persons, thus it would be imperative to include such asymptomatic patients too for dynamic surveillance.

Comments to Author

Presented for review was a case report titled 'Prolonged shedding of SARS-CoV-2 in an asymptomatic patient - a case report.' Kaur et al detail a case report comprising of a single asymptomatic infection in a young male that had recently travelled. The case report concludes with the demise of the patient due to their HIV status. It concludes that there is high risk of silent spread of SARS-CoV-2. The results presented in this manuscript are limited to one table. The entire report is based around 7x RT-qPCR results from one patient over a 62 day period therefore I do not believe there is enough data to warrant the claims made downstream of the results. The manuscript is written as a case report and follows the standardised layout one would typically associate with a case report. It starts with a very short introduction, with about a third of this giving a summary of the report, thus providing little room for a full introduction to the matter at hand. This is followed by the report itself which presents the patient in question and gives some basic health information. The report then loosely follows the testing timeline which ultimately ends in the demise of the patient. Finally, there is the discussion and conclusion from the data presented. The literature and discussion regarding the case report is tenuous at best to the data presented. Whilst some points in the discussion are valid (E.G., RT-qPCR not being able to differentiate between viable/non-viable infectious virus), there is not enough information in the data and/or methodology to make the claims in the report. Whilst case reports regarding asymptomatic transmission of SARS-CoV-2 are of importance to the field, there are too many inconsistencies in the presented case report as it currently stands. I do not believe there is sufficient data to justify the discussion points and conclusions of the report. I have collated my comments regarding below (in no particular order): 1 - Inconsistency in nomenclature of SARS-CoV-2. The authors start with SARS-CoV-2 but then they have used SARS CoV-2, SARS-CoV2, SARS-CoV 2, SARS CoV2, SARS-CoV-2 and COVID-19 interchangeably. Whilst this might seem like pedantry, COVID-19 is the disease caused by SARS-CoV-2 (the latter is used line 80). 2 - Patient reported to hospital in March 2023 for 6-month follow-up (line 82) but died in March 2022 (line 88). I will give the benefit of doubt to the authors that it is a typo but date inconsistencies in a case report should not happen. 3 - Authors have suggested that the patient had HIV originally, but the test came up negative. They mention false negative HIV tests but do not actually elude to any studies regarding false negativity. HIV false negative rates are reported at a median rate of 0.4 % (Johnson et al [2017] PMID:28872271). This would suggest that the chance of a false negative being given as incredibly slim. 4 - Linked to point 3 above, the patient died of AIDS by the time of a 6-month follow up due to a recently diagnosed HIV infection. Generally, it takes an average of 10-15 years from initial HIV infection to develop into AIDS without medical intervention. Therefore, short of genetic defect in the patient or much more advanced HIV infection than initially thought, this further decreases the chance of the patient being HIV negative at initial presentation. Basically, is the patients HIV status relevant to the findings from the data or not as this is confusing. If it is important, there should be data regarding this. 5 - Table 1. What were the Ct values of the 'negative tests' reported on 16/08/2021 and 18/08/2021? Were they 'undetermined' or below the threshold to class as positive? No information on which SARS-CoV-2 test was used or the machines used to run the tests. What were the designated Ct value cut-offs for determining if a sample was positive or negative? Were there controls used? 6 - The authors mention two of the positive samples were randomly selected and sent for sequencing. Which ones? Were they consecutive time points? And if the viral sequences are present, are they the same exact sequence? Whilst I appreciate that they were randomly selected, more information is needed as to which samples were known to have been sequenced. More work could be done here on this data to back up some of these claims and it would add some more substance to the manuscript as a whole. For example, if positive swab 1 and 5 were sent (2 months gap in tests) for sequencing, was it the exact same virus at both time points? This is much more pertinent when further into the report, it is established the patient broke home quarantine to get a 2nd vaccine dose (between these time points). That raises the potential that the person was re-infected due to coming into contact with an infected person whilst heading to/from the vaccine appointment thus giving rise to a second infection. 7 - The authors concluded that asymptomatic transmission is a significant problem with regards to community transmission. This is something that has been speculated about since the beginning of the pandemic (as evidence by Ref 4 listed in the references of the case report). I am unsure how the report of a positive patient under supposed home quarantine rules links to asymptomatic transmission, short of community testing immediate contacts of the patient to provide some evidence of this occurring in this instance. 8 - Whilst I am not a clinician, elevated D-dimer levels are indicative of a blot clotting issue and can be caused by viral infection (amongst other things). Several studies have been published regarding the correlation between D-dimer levels and COVID-19 severity (Li et al [2020], PMID: 32420615). I would think that this is actually important in this particular case and whilst the patient was not showing any clinical manifestation, their vital signs would suggest otherwise in this instance.

Please rate the quality of the presentation and structure of the manuscript

Very poor

To what extent are the conclusions supported by the data?

Not at all

Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?

Is there a potential financial or other conflict of interest between yourself and the author(s)?

If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?

Yes

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Prolonged shedding of SARS COV-2 in an asymptomatic patient– a case report

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