Purpose: Persistent negative results (at least 3 times) of reverse transcription–polymerase chain reaction (RT-PCR) from pharyngeal swabs are not rare in coronavirus disease 2019 (COVID-19) patients, but their characteristics have not yet been well studied. Methods: PCR confirmed, serum antibody confirmed with persistent negative PCR results, and clinically diagnosed patients hospitalized in two medical centers during February and March 2020 were included. Differences in clinical, imaging and laboratory characteristics as well as factors affecting their prognosis were analyzed. Results: There were 114 PCR confirmed, 17 serology confirmed and 21 clinically diagnosed patients included. Time from onset of disease to the first PCR and admission were similar among the groups. Compared with PCR-confirmed patients, serology-confirmed patients were older and likely to have hypertension, vomiting, or symptoms of chest pain and dyspnea. Regarding imaging manifestations, serology-confirmed patients were more prone to pleural effusion. In addition, higher levels of C-reactive protein, neutrophil-to-lymphocyte ratio, total bilirubin, D-dimer, fibrinogen, troponin, interleukin-6 and IL-8 were also found. Although with similar mortality, serology confirmed patients were more likely to have disease progression. High levels of D-dimer and IL-6 were possibly the underlying factors leading to their worse prognosis. On the other hand, clinically diagnosed patients were more similar to PCR-confirmed patients. Conclusion: Serology confirmed COVID-19 patients with at least three negative PCR results had different clinical characteristics and were likely to have disease progression, possibly due to more severe hypercoagulation status and cytokine storm.
More severe hypercoagulation status, cytokine storm, and disease progression in coronavirus disease 2019 with persistent RT-PCR negative results: a multicenter prospective study