Since the start of the coronavirus 2019 (COVID-19) pandemic, arising from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) viral infection, approximately 13,000 patients have been admitted to critical care in the United Kingdom; most have required advanced respiratory support. 1 Samples for SARS-CoV-2 detection can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum/endotracheal aspirate/BAL). 2 Viral RNA is detected using reverse transcriptase polymerase chain reaction (RT-PCR). The Cycle threshold (Ct) has a simple negative linear correlation with the logarithm of the number of gene copies in the original sample and thus can be used to provide a semiquantitative estimate of the viral RNA in a specimen. 3 SARS-CoV-2 has been suggested to be shed predominantly from the upper respiratory tract, distinguishing it from SARS-CoV-1, in which replication occurs mainly in the lower respiratory tract. 4-6 A recent multi-site viral detection study 5 indicated higher nasopharyngeal (NP) viral loads in some patients early in the course of disease, although they generally detected viral RNA in sputum for longer. However, this study 5 was conducted on patients with mild disease, and whether the results pertain to critically ill patients is unclear.
Introduction Samples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load. Objectives The objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients. Methods SARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated. Results Results collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO). Conclusions It has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.
In conclusion, the two aforementioned studies underline the critical importance of the population being examined. It is key that BAL and less invasive methods be compared prospectively in a cohort of consecutive patients with suspected SARS-Cov-2 infection who have been enrolled based on criteria decided beforehand, preferably across a wide spectrum of disease severity. This would allow us to decide reliably when it is clinically useful to perform an invasive procedure that, in this specific setting, implies organizational complexity and risks to the health-care staff.
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