RT-PCR negative COVID-19

Abstract

Background COVID-19 is a multi-system infection with emerging evidence-based antiviral and anti-inflammatory therapies to improve disease prognosis. However, a subset of patients with COVID-19 signs and symptoms have repeatedly negative RT-PCR tests, leading to treatment hesitancy. We used comparative serology early in the COVID-19 pandemic when background seroprevalence was low to estimate the likelihood of COVID-19 infection among RT-PCR negative patients with clinical signs and/or symptoms compatible with COVID-19. Methods Between April and October 2020, we conducted serologic testing of patients with (i) signs and symptoms of COVID-19 who were repeatedly negative by RT-PCR (‘Probables’; N = 20), (ii) signs and symptoms of COVID-19 but with a potential alternative diagnosis (‘Suspects’; N = 15), (iii) no signs and symptoms of COVID-19 (‘Non-suspects’; N = 43), (iv) RT-PCR confirmed COVID-19 patients (N = 40), and (v) pre-pandemic samples (N = 55). Results Probables had similar seropositivity and levels of IgG and IgM antibodies as propensity-score matched RT-PCR confirmed COVID-19 patients (60.0% vs 80.0% for IgG, p-value = 0.13; 50.0% vs 72.5% for IgM, p-value = 0.10), but multi-fold higher seropositivity rates than Suspects and matched Non-suspects (60.0% vs 13.3% and 11.6% for IgG; 50.0% vs 0% and 4.7% for IgM respectively; p-values < 0.01). However, Probables were half as likely to receive COVID-19 treatment than the RT-PCR confirmed COVID-19 patients with similar disease severity. Conclusions Findings from this study indicate a high likelihood of acute COVID-19 among RT-PCR negative with typical signs/symptoms, but a common omission of COVID-19 therapies among these patients. Clinically diagnosed COVID-19, independent of RT-PCR positivity, thus has a potential vital role in guiding treatment decisions.

Factors associated with mortality, length of hospital stay and diagnosis of COVID-19: Data from a field hospital

“…Before the seventh day of symptom onset, the number of antibodies may be insufficient for the detection and diagnosis of COVID-19 [20] . Therefore, patients presenting with clinical criteria for COVID-19, even those with negative RT–qPCR results, should also receive treatment for acute disease [11] .…”

“…Despite limitations such as the long time it takes to release the results, and the possibility of false-negative results due to several factors, the gold standard is the quantitative real-time polymerase chain reaction molecular technique (RT–qPCR) using the reverse transcriptase assay [9] . In addition to the origin of the material collected, the result depends on the time elapsed between sample collection and the onset of symptoms, the fluctuation of viral load, and correct sample collection [9] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . In addition to RT–qPCR, serology, based on the detection of immunoglobulin antibodies in blood, serum, or plasma samples, is also used because it provides rapid results; however, has low sensitivity (15–76 %) and must be performed 7 days after the onset of symptoms [9] , [11] , [17] , [18] , [19] , [20] .…”

“…In addition to the origin of the material collected, the result depends on the time elapsed between sample collection and the onset of symptoms, the fluctuation of viral load, and correct sample collection [9] , [11] , [12] , [13] , [14] , [15] , [16] , [17] . In addition to RT–qPCR, serology, based on the detection of immunoglobulin antibodies in blood, serum, or plasma samples, is also used because it provides rapid results; however, has low sensitivity (15–76 %) and must be performed 7 days after the onset of symptoms [9] , [11] , [17] , [18] , [19] , [20] .…”

Sniffer dogs performance is stable over time in detecting COVID-19 positive samples and agrees with the rapid antigen test in the field

“…This indicates that the dogs’ response would increase the chances for a sample from the Control group being indicated by the dogs as negative to 100%. Assuming that highly sensitive tests are best used for screening, while highly specific tests are best for confirming diagnostics 22 , the high PPV and NPV achieved in the two estimated prevalence scenarios support the potential use of dogs both in sites of high SARS-CoV-2 prevalence to exclude individuals not needing RT-PCR, and in low prevalence sites to complement the standard quick diagnostic test in confirming that the virus is present 42 . Clearly, if a COVID-19 diagnosis is missed, this can lead to delayed, missed, or unneeded treatment for an inaccurate alternative diagnosis.…”

The Role of Computed Tomography in the Management of Hospitalized Patients With COVID-19

“…However, these tests have been noted to have variable sensitivity. One study found that during the first week after symptom onset, false negative rates ranged from 2% to 29% [12].…”