key: cord-0684816-p3bflvms
authors: Murillo-Zamora, Efrén; Mendoza-Cano, Oliver; Cárdenas-Rojas, Martha I.; Hernandez-Suarez, Carlos M.; Guzmán-Esquivel, José
title: Survival in adult pneumonia inpatients fulfilling suspected CoViD-19 criteria and baseline negative RT-qPCR
date: 2021-05-05
journal: Public Health
DOI: 10.1016/j.puhe.2021.04.023
sha: 12689faf310f33ec0bd5a57ca2af7d6d59ed1b90
doc_id: 684816
cord_uid: p3bflvms

Objective To evaluate the survival experience of suspicion COVID-19 hospitalized patients with pneumonia and negative baseline RT-qPCR test results. Study design We conducted a nationwide retrospective cohort study in Mexico. Method Adult pneumonia inpatients fulfilling suspected COVID-19 criteria, and hospital entry from March to August 2020, were enrolled. The Kaplan-Meier method was to use to compare survival estimates among patients with negative RT-qPCR nasopharyngeal or oropharyngeal swabs and those with a baseline positive test. Results Data from 64,624 individuals fulfilling suspected CoViD-19 criteria were analyzed and 1.6% of them had negative RT-qPCR tests. The overall mortality rate was higher among laboratory-positive patients (48.5% vs. 34.2%, p < 0.001) and, at any given threshold, the survival estimates were higher among RT-qPCR negative pneumonia inpatients. Conclusions The pathogenic mechanism of COVID-19 remains poorly understood and suspected cases with pneumonia and negative laboratory results represent a major challenge for healthcare systems. Our findings suggest that RT-qPCR negative inpatients may have an improved disease prognosis but the in-hospital mortality was still high among them. However, further research is needed to clarify the clinical and epidemiological implications of our results.

Efrén Murillo-Zamora a,b , Oliver Mendoza-Cano c , Martha I. Cárdenas-Rojas d , Carlos M.

Hernandez-Suarez e ,and José Guzmán-Esquivel b,f * a. Departamento The coronavirus disease 2019 (CoViD-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic needs an opportune and accurate medical diagnosis to provide early management, patient allocation into healthcare settings, and to reduce the community viral spread [1] . Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) is the gold standard for SARS-CoV-2 infection diagnosis, however its sensitivity may be as low as 38% [2] .

The clinical management of suspicion CoViD-19 cases with pneumonia and negative RT-qPCR may be challenging, particularly in settings with high viral transmission like Mexico where, by the start of November, more than 933 thousand laboratory-confirmed cases and 92 thousand deaths had been registered [3] .

To the best of our knowledge, there are not published studies evaluating the survival of pneumonia inpatients with clinical characteristics of CoViD-19 but with negative analytical evidence. This study aimed to evaluate the survival experience of pneumonia inpatients with suspicion COVID-19 and negative baseline RT-qPCR test results.

We performed a retrospective and nationwide cohort study during October 2020 in Mexico. A broader description of the study methods was previously published [4] .

Suspicions CoViD-19 adult (aged 20 years or older) inpatients with clinical (SpO2 <94% on room air at sea level, a ratio of the arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mmHg, respiratory frequency >30 breaths per minute, or lung infiltrates >50%) [5] and radiographical (polished glass, bilateral opacities or consolidation areas in computed tomography scan) [6] findings of pneumonia, with illness onset from February to August 2020, were potentially eligible.

A total of 1,066 adults with baseline negative upper respiratory (nasopharyngeal or oropharyngeal) swabs were identified and 53 of them were excluded due to missing data about the disease outcome; 3,045 pneumonia patients by laboratory-positive SARS-CoV-2 (from 66,656 eligible subjects) were excluded for the same reason.

The SARS-CoV-2 detection analytical procedure was also described previously [4] . We analyzed the survival time of hospitalized pneumonia patients measured as the time elapsed from the date of hospital entry (starting event) to the date of in-hospital death (final event).

The censored variable was defined as the patients who did not present the event (did not die) during the follow-up period and the date of hospital discharge was used to compute the time-at risk. The 95% confidence interval (CI) were also computed. The log-rank test was used to compare the survival experience of RT-qPCR negative and positive subjects. The median (interquartile range, IQR) elapsed days from illness onset to specimen collection was shorter in cases reported as negative to SARS-COV-2 (4 [2] [3] [4] [5] [6] Factors affecting the RT-qPCR sensitivity are numerous and include mutations in the primer and probe-target regions in the SARS-CoV-2 genome and viral load kinetics [7] .

Published data suggest that increasing viral load is associated with the risk of CoViD-19 mortality and may be determining, at least partially and given the high SARS-CoV-2 transmission rates documented in Mexico [8] , our findings [9] .

There are several potential limitations of our analysis. First, data regarding other respiratory viral pathogens were not available. This may be particularly relevant for the influenza virus; however, its transmission during the analyzed period (February to August 2020) is low. Second, the observed mortality in real-negative RT-qPCR pneumonia patients may be increased since pneumonic subjects are commonly allocated with other similar patients (despite the RT-qPCR result) and the nosocomial transmission of SARS-CoV-2 has been documented [10] .

The CoViD-19 by SARS-CoV-2 remains poorly understood and, given the current analytical limitations in its diagnosis, the medical management of suspected cases with pneumonia and negative laboratory results represent a major challenge. Our findings suggest that baseline RT-qPCR negative inpatients may have an improved disease prognosis but the in-hospital mortality was still high. However, further research is needed to clarify the clinical and epidemiological implications of our results.

This study was self-funded by the researchers.

None to declare. 

Should RT-PCR be considered a gold standard in the diagnosis of COVID-19

Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients

Male gender and kidney illness are associated with an increased risk of severe laboratoryconfirmed coronavirus disease

Clinical Presentation of People with SARS-CoV-2 Infection

Mexican Institute of Social Security. Interim Guidelines for Medical Care of CoViD-19

Real-time RT-PCR in COVID-19 detection: issues affecting the results

Using COVID-19 deaths as a surrogate to measure the progression of the pandemics

SARS-CoV-2 viral load predicts COVID-19 mortality

Nosocomial transmission of COVID-19: a retrospective study of 66 hospital-acquired cases in a London teaching hospital

The research group would like to thank Sandra Vallejo Toscano for the valuable support provided during data collection.J o u r n a l P r e -p r o o f