Clinical characteristics, inflammatory markers, and serological response in RT-PCR negative patients with high clinical and radiological suspicion of COVID-19

Background: Reverse transcription-polymerase chain reaction (RT-PCR) is the primary diagnostic tool for coronavirus disease 2019 (COVID-19), but false-negative results can delay treatment in patients with suggestive clinical and radiological findings. Aims and Objectives: The aim of the study was to characterize the clinical profile, inflammatory marker levels, and immunoglobulin G (IgG) antibody responses in RT-PCR negative patients with high suspicion of COVID-19 based on CO-RADS 5 high-resolution computed tomography (HRCT) chest findings. Materials and Methods: A prospective observational study was conducted at Sher-i-Kashmir Institute of Medical Sciences (SKIMS), Soura, India, from October 2020 to January 2022, enrolling 122 patients aged >18 years with acute pulmonary infiltrates, CO-RADS 5 HRCT findings, and negative RT-PCR results. We assessed demographics, symptoms, comorbidities, disease severity per Infectious Diseases Society of America guidelines, inflammatory markers (interleukin-6 [IL-6], D-dimer, ferritin, lactate dehydrogenase, creatine phosphokinase, C-reactive protein), and IgG antibodies. Data were analyzed using SPSS v20. Results: The cohort had a mean age of 57.5±16 years; 63 (51.6%) were male, and 66 (54.1%) were urban residents. Fever (98, 80.3%), cough (90, 73.8%), and dyspnea (80, 65.6%) were predominant symptoms. Hypertension (50, 41.0%) and diabetes (43, 35.2%) were common comorbidities. Disease severity was severe in 64 (52.5%), critical in 35 (28.7%), and moderate in 23 (18.9%); mortality was 13 (10.7%), mostly in patients >65 years (7, 53.8% of deaths). IgG antibodies were positive in 105 (86.1%) at 12±3 days post-symptom onset. Inflammatory markers were elevated in critical cases (e.g., IL-6: 145±20 pg/mL, F=12.34, P<0.001; D-dimer: 1715±300 ng/mL, F=15.67, P<0.001) and correlated with CT severity scores. Methylprednisolone (45, 36.9%) had higher mortality (6, 13.3%) than dexamethasone (80, 65.6%; 4, 5.0%) or no steroids (39, 32.0%; 3, 7.7%) (Chi-square=6.78, P=0.034). Conclusion: RT-PCR negative patients with CO-RADS 5 findings and elevated biomarkers require prompt COVID-19 management, high lighting the role of HRCT and inflammatory markers in diagnosis.