As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen continues to spread the world over, public health authorities have had to resort to containment strategies such as case detection and isolation, contact tracing and quarantine. These depend on the use of detection techniques, primarily based on finding viral antigens or genetic material in test samples.
A new study released as a preprint on the medRxiv* server throws cold water on this notion, however, by demonstrating that in a set of asymptomatic cases, less than a tenth actually had evidence of SARS-CoV-2 infection. This finding has serious implications for the practices mentioned above, since they may be neither justifiable nor cost-effective as means to break the chain of viral transmission.
The gold standard for SARS-CoV-2 detection at present is the use of reverse transcriptase polymerase chain reaction (RT PCR) to pick up the presence of viral ribonucleic acid (RNA). In this case, RNA is both the viral genetic material and the mediator of transcription of viral products.
A positive PCR test is taken as proof of acute infection, which is by definition transmissible. Thus, the next step is to isolate the individual after a single positive test is returned. In addition, all contacts of this so-called case are identified so that they can be put into quarantine for a predefined number of days, watching for evidence of infection, either clinical signs and symptoms, or a positive PCR test.
How was the study done?
The current study reports data from a unique program implemented for the protection of top soccer players and staff following the lockdown in Germany. The aim was to enable the matches of the German Bundesliga and Bundesliga 2 to proceed within a closed stadium.
In order to establish this, PCR testing was performed on nasopharyngeal and/or oropharyngeal swabs twice a week. If a test came back positive, some teams voluntarily opted to retest the individual, though this practice was never promoted by the program managers.
Interesting series of results
Of about 1,700 staff and players who underwent regular screening, there were 98 positive tests between September 13, 2020, and January 14, 2021. The current paper focuses on 11 positive results which came from asymptomatic cases.
In all 11, only one test came back positive, with a string of negative PCR tests thereafter. The positive test was associated with a low cycle threshold, the median being 36. This indicates a low viral load.
What does this pattern mean?
The researchers sought to understand the meaning of this pattern. One possible approach was to look for systemic signs of humoral and cellular immune responses to the virus. In order to detect this, the scientists assessed both specific antibodies and T cells (CD4+ and CD8+) elicited against SARS-CoV-2 at a median of 1.5 months (42 days) after the positive PCR test.
Interestingly, only one individual had signs of systemic immune response, out of 11.
In view of this finding, the researchers comment:
A single positive PCR-test in asymptomatic individuals might be a result of a transient colonization confined to the upper respiratory tract.”
They postulate that a strong local immune response may have led to viral neutralization at the mucosal surface itself, preventing its entry beyond the local level and precluding a systemic immune response.
Another possibility is that contamination occurred during testing, since these patients were mostly asymptomatic, nor did they develop systemic immunity. But the quality of the testing system seems to rule out contamination on such a large scale.
False-negative PCR results were also considered as a potential source of error, but the repeated negatives seem to militate against this possibility.
What are the implications?
In the current state of knowledge, it would seem that SARS-CoV-2 can establish its presence for a short period on some individuals, while not being able to infect the tissues or cause-specific adaptive immunity. Strangely, scientists seem to have missed this obvious pattern so far, despite its being present in over a tenth of positive cases. This is inferred from the point that retests are rarely ordered after a PCR test comes back positive.
The scientists conclude:
Further characterization of transient colonization regarding contagiousness is warranted, as preventive measures such as isolation and contact tracing may not be justified in these cases.”
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.