RT-PCR negative COVID-19

• Published in: BMC infectious diseases Vol. 22; no. 1; p. 149
• Main Authors: Parmar, Heta, Montovano, Margaret, Banada, Padmapriya, Pentakota, Sri Ram, Shiau, Stephanie, Ma, Zhongjie, Saibire, Kaheerman, Chopoorian, Abby, O'Shaughnessy, Michael, Hirsch, Mitchell, Jain, Priyanshi, Demirdjian, Gaiane, Karagueuzian, Magali, Robin, Thomas, Salvati, Michael, Patel, Bhavana, Alland, David, Xie, Yingda L
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13-02-2022; BioMed Central; BMC
• Subjects: Antibodies; Antibodies, Viral; Asymptomatic; Coronaviruses; COVID-19; COVID-19 - drug therapy; Diagnosis; Emergency medical care; Health aspects; Health services; Hematology; Humans; Hypoxia; Immunoglobulin G; Immunoglobulin M; Infections; Infectious diseases; Medical tests; Pandemics; Patients; Plasma; Pneumonia; Polymerase chain reaction; Reverse transcriptase; Reverse Transcriptase Polymerase Chain Reaction; RT-PCR; Sample size; SARS-CoV-2; Seroepidemiologic Studies; Serology; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; Suspects; Viral diseases; United States; COVID-19; SARS-CoV-2; Diagnosis; Suspects; RT-PCR
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-022-07095-x

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.
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).
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.
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.