We conducted a multicentre cross sectional observational study of laboratory, public health and hospitalisation data for PCR-confirmed COVID-19 cases within the New Zealand Northern Region, between 12 February and 8 June 2020. The aim of this study was to describe population level SARS-CoV-2 upper respiratory tract (URT) viral load dynamics by stratifying positivity rates and polymerase chain reaction (PCR) cycle threshold (Ct) values of URT samples from COVID-19 cases by days since symptom onset, and to explore utility of Ct values in determining length of time post-infection and thus potential infectivity. Of 123,124 samples tested for SARS-CoV-2 by PCR, 579 samples (407 positive and 172 negative) from 368 symptomatic non-hospitalised individuals with PCR-confirmed infection were included. Sample positivity rate was 61.5% (8/13) for pre-symptomatic samples, rising to 93.2% (317/340) for samples collected during the purported symptomatic infectious period (days 0-10 post-symptom onset), and dropping to 36.3% (82/226) for postinfectious period samples (day 11 onwards). URT viral load peaked shortly after symptom onset, with median Ct values ranging 20.00-29.99 until 15 days post-symptom onset, and >30.00 after this time. Of samples with a Ct value of <20.00, 96.1% were collected during the symptomatic infectious period. However, of samples with a Ct value 30.00 and 35.00, 46.9% and 18.5%, respectively, were also collected during the symptomatic infectious period. The findings of this study indicate that at or soon after symptom onset represents the optimum time to test for SARS-CoV-2 in the URT, with median Ct values suggesting the useful testing window extends until around 15 days post-symptom onset. In asymptomatic individuals or those with unknown dates of symptom onset, Ct values <20.00 imply recent onset/potential infectivity, but Ct values 30.00 or 35.00 do not exclude recent onset/potential infectivity. Individual sample Ct values should not be used as an absolute marker of length of time post-infection or to exclude infectivity where date of symptom onset is unavailable.
Case report: A previously well 34-year-old man with mild COVID-19 symptoms tested positive by SARS-CoV-2 RT-PCR on 14/08/2020 (Ct 17.6). He was epidemiologically and genomically linked to the Auckland August 2020 cluster. He represented with acute breathlessness 150 days later on 11/01/ 2021, and tested positive on two different SARS-CoV-2 RT-PCR assays (Ct 36.9/38.4). At this time, excluding two discrete community clusters, COVID-19 transmission had been eliminated in New Zealand since May 2020. The patient denied infective symptoms and could not be linked to any imported COVID-19 cases or high risk exposures. His breathlessness was due to bronchial obstruction from sarcoidosis mediastinal lymphadenopathy. Genome sequencing of the 11/01/ 2021 result failed to yield analysable sequence, but re-infection was unlikely, and with an alternative diagnosis for his breathlessness the result was attributed to prolonged upper respiratory tract viral shedding. He was discharged without further isolation. He had tested negative twice in the interim since his initial positive result. In individuals with previous COVID-19, sporadic positive RT-PCR results may be obtained many months after initial infection, even with multiple negative results in the interim. This represents one of the longest shedding durations reported, and has important implications for interpretation of RT-PCR results in previously infected individuals.
Background Urinalysis (UA) and urine culture (UC) are commonly used in patients with bacteraemia to diagnose a urinary focus of infection. The predictive value of these investigations in patients without localizing urinary features is uncertain. We hypothesized that UA/UC would have extremely low predictive value in patients with bacteraemia and neither localizing urinary features nor risk factors for bacteraemic UTI (bUTI). Methods This was a retrospective cohort study of hospitalized adults with community-onset bacteraemia in 2019 at Middlemore Hospital (Auckland, New Zealand). The suspected focus of infection at first assessment was determined by reviewing clinical notes from the initial presentation using the admitting clinician’s preferred diagnosis plus at least one supportive clinical feature. The final diagnosis of focus of bacteraemia (bUTI versus non-urinary) was determined by investigators based on blood and urine culture concordance, with supportive clinical, laboratory or imaging features. Defined localizing urinary features were determined by investigators from notes. Positive and negative predictive value of UA/UC for diagnosing bUTI was calculated among those with initially unclear or non-urinary focus of infection. Univariate analysis was performed for patients with initially unclear focus of infection, for risk factors associated with final diagnosis of bUTI. Results In total, 871 patients were included. The admitting clinician’s suspected focus was urinary in 219, unclear in 304 and non-urinary in 348. A final diagnosis of bUTI was found in 342 (39.3%), of whom 110 (32.2%) lacked any localizing urinary features. After excluding localizing urinary features, bUTI was diagnosed in 98/243 (40.3%) with initially unclear focus and 12/326 (3.7%) with suspected non-urinary focus. UA/UC PPV was 5.2%/25%, respectively, when initial focus was non-urinary, but 51.5%/75% when initial focus was unclear. Amongst patients with initially unclear focus, risk factors for bUTI included age >75, urinary catheter/nephrostomy, invasive urologic procedure within 3 months and cognitive impairment. However, of those with bUTI, 22/98 (22.4%) had none of these risk factors. Conclusions bUTI occurs in a significant minority of bacteraemic patients where initial focus is unclear and where localizing urinary features are absent, including in patients without associated risk factors. UA/UC is a reasonable investigation in bacteraemia of uncertain focus, but results should be interpreted cautiously. UA has excellent NPV but very poor PPV. Among patients with bacteraemia, initially suspected non-urinary focus of infection, and without localizing urinary features, UA/UC can be safely withheld and bUTI is very uncommon. A prospective study using initial clinical criteria would provide more relevant predictive values for clinicians.
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