A Case of Coronavirus Disease 2019 with Twice Negative Nucleic Acid Testing within 8 Days
Coronavirus disease 2019 (COVID-19) has rapidly spread across the globe, posing significant challenges to public health systems worldwide. Despite ongoing research, the exact sources of the virus, the duration of viral shedding after infection, and the mechanisms of viral propagation remain unclear. These uncertainties complicate efforts to control the spread of the virus and to treat infected individuals effectively. Rapid diagnosis and early isolation of infected cases are critical components of the overall strategy to prevent and control the disease. However, the diagnostic process is not without its challenges, as evidenced by cases where initial nucleic acid testing yields negative results despite the presence of clinical symptoms.
This report details the case of a 47-year-old woman who tested negative for the 2019 novel coronavirus (2019-nCoV) in two consecutive nucleic acid tests within 8 days of symptom onset, only to test positive on the 11th day. The patient had traveled to Wuhan, China, on January 13, 2020, with her mother, who was later confirmed to be infected with COVID-19. The patient developed an intermittent fever, with a highest recorded body temperature of 37.9°C, accompanied by coughing, on January 20, 2020. She was admitted to the Third People’s Hospital of Shenzhen two days later.
Upon admission, the patient’s blood test revealed a normal white blood cell count of 4.94 x 10^9/L and a decreased lymphocyte count of 1.06 x 10^9/L. Her oxygen saturation level was 99%. She was treated with atomized inhalation of interferon twice daily. Despite her symptoms, nucleic acid testing conducted on January 22 and 28 using throat swabs returned negative results for 2019-nCoV.
On June 29, 2020, the patient was transferred to the Shenzhen University General Hospital for further isolation and clinical observation. By this time, she had been experiencing symptoms for nine days. Her headache and cough had worsened, although her body temperature remained within the range of 36.0–37.2°C, and her oxygen saturation level was stable at 99%. A repeat blood test showed a normal white blood cell count of 5.81 x 10^9/L and a further decreased lymphocyte count of 0.91 x 10^9/L. Chest computed tomography (CT) scans revealed bilateral ground-glass opacity, a characteristic finding in COVID-19 patients. In addition to continuing the atomized inhalation of interferon, the patient was started on oseltamivir (75 mg) orally twice daily.
On January 31, 2020, the 11th day of symptom onset, the patient’s condition deteriorated significantly. Blood gas analysis revealed a partial pressure of oxygen of 65.5 mmHg, a partial pressure of carbon dioxide of 39.2 mmHg, and a sulfur dioxide level of 93.6%. A repeat 2019-nCoV nucleic acid test was performed using nasal swabs, which returned a positive result. This finding was subsequently confirmed by the Centers for Disease Control.
According to the New Coronavirus Infection Pneumonia Protocol (version 6) published by the National Health Commission of the People’s Republic of China, two consecutive negative respiratory 2019-nCoV nucleic acid test results, at least one day apart, are required to exclude a diagnosis of COVID-19. However, cases with a highly suspicious epidemiological history, typical clinical symptoms, and characteristic radiological findings cannot be excluded based solely on negative nucleic acid tests. In this case, the patient had a clear epidemiological history, characteristic pulmonary imaging findings, and typical clinical symptoms. Despite this, her nucleic acid tests remained negative for the first 8 days of her illness, only turning positive on the 11th day. This discrepancy highlights the non-parallel relationship between 2019-nCoV nucleic acid testing and clinical symptoms.
Nasal and throat swabs are commonly used for sampling in 2019-nCoV nucleic acid testing. Previous research on influenza virus diagnostic tests has shown that different subtypes of influenza viruses preferentially localize at different sites, leading to variations in positive detection rates depending on the sampling site. The biological characteristics of COVID-19, including its variant subtypes and preferred localizing sites, remain undefined. In this case, the change in sampling site from the throat to the nasal region may have contributed to the positive result. At the time of writing this report, the authors had observed four other patients with negative throat swabs who later tested positive using nasal swabs.
The digestive system is another potential route for 2019-nCoV infection, suggesting that the virus may localize differently depending on the route of infection. For patients suspected of having COVID-19, sampling from multiple sites may improve the chances of early detection. Additionally, the patient’s condition shortly before sampling should be considered, as anti-viral nebulization treatment may influence the positive detection rate.
Efforts to improve the efficiency of virus detection at an early stage are crucial for better prevention and control of COVID-19. This case underscores the importance of considering clinical symptoms, epidemiological history, and radiological findings in the diagnosis of COVID-19, even when initial nucleic acid tests are negative. It also highlights the need for further research into the biological characteristics of the virus and the optimization of diagnostic techniques.
In conclusion, this case report illustrates the challenges in diagnosing COVID-19, particularly in cases where initial nucleic acid tests are negative despite the presence of clinical symptoms. It emphasizes the importance of a comprehensive approach to diagnosis, taking into account multiple factors, and the potential benefits of sampling from different sites. Continued research and improvements in diagnostic methods are essential to enhance the early detection and management of COVID-19, ultimately contributing to better control of the pandemic.
doi.org/10.1097/CM9.0000000000000788
Was this helpful?
0 / 0