Introduction:
At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. It rapidly spread, resulting in an epidemic throughout China, followed by an increasing number of cases in other countries throughout the world. (1). Following the detection and announcement of the first cases of COVID-19 on February 20, the infection rate and death toll from the disease has been on the rise (2). The responsible causative agent, namely SARS-CoV-2, is an enveloped RNA virus of Coronaviridae family. The transmission of COVID19 occurs via respiratory droplets or contaminated surfaces (3). The symptoms of COVID-19 are non-specific, which range from asymptomatic to severe pneumonia and can lead to death (4). The majority of patients present with mild respiratory tract infection, mostly commonly fever (82%) and cough (81%). Severe pneumonia and acute respiratory distress syndrome (ARDS) have been reported in 14% of cases with overall mortality rate of 2% (5). Nevertheless, these figures are rising concomitant with the expansion of pandemic depending on the country involved (6). SARS-CoV infection in humans leads to an acute respiratory illness varying from mild febrile disease to ALI and in some cases ARDS and death (7, 8). Considering the high infectivity of COVID-19, rapid and precise diagnostic methods are urgently required to detect, isolate and treat the patients as soon as possible, which might decrease mortality rates and the risk of community contamination (9). Computed tomographic (CT) imaging is extensively applied for the early diagnosis of COVID-19, but chest CT may not distinguish this disease from other viral pneumonias (10, 11). Nucleic acid assay, gene sequencing, and serology tests (IgM and IgG) from throat swabs or blood samples have been developed to confirm the diagnosis of COVID-19 (12). However, clinicians from Wuhan have addressed the issue of high false negative rates of PCR or antibody detection (13). However, rRT-PCR results often require 5 to 6 hours to be prepared, while CT results can be obtained much faster (9). Chunqin Long et al. revealed that the sensitivity of CT examination was 97.2% at presentation, whereas the sensitivity of first round rRT-PCR was 84.6% (9). This difference may be a function of sample collection because pharyngeal and nasal sampling are more straightforward collection methods, while lower respiratory tract sampling is relatively difficult to perform and bears the risk of infection for susceptible medical staff (14). The sensitivity of rRT-PCR kit can also give rise to false negative results (9).
Simultaneous use of medical history, clinical manifestations, chest CT, and viral test has been found to present high sensitivity (92–97%) (15, 16).
A major challenge for the restriction of SARS-CoV-2 spread is that pre-symptomatic people are infectious for others (17). Recent reports indicated that patients can be infectious 1-3 days before the onset of symptoms and that up to 40-50% of cases may be attributable to transmission from asymptomatic or presymptomatic individuals (18, 19). Patients have high nasopharyngeal loads of virus just before or soon after the onset of symptoms , which subsequently fall over the course of approximately one week (20). Patients with severe disease can release the virus for longer periods, although the shedding duration of infectious virus is not precisely known (21). Evaluation and management of COVID-19 is determined by the severity of the illness. According to initial data taken from China, 81% of people with COVID-19 had mild or moderate disease (including people without pneumonia and those with mild pneumonia), 14% had severe disease, and 5% showed critical illness (22).
According to the guidelines of World Health Organization (WHO), the risk of COVID-19 virus infection is not ruled out if one or more negative PCR tests are observed. Factors such as low sample quality (lack of sufficient DNA in the sample), inappropriate time of sampling (delayed or early sampling), improper storage and transportation of the sample, and inherent technical reasons for testing including virus mutations or PCR inhibitions (such as improper swap use, etc.,) can affect PCR testing and lead to false negative responses (23).
Due to the rapid spread of COVID19 disease in Iran, increasing number of patients in a short period of time, lack of cooperation of some patients in the sampling process, limited access to RT-PCR testing, assuming PCR as a time consuming test and inability to repeat negative tests, many suspected patients with COVID19 were hospitalized in medical centers based on clinical symptoms, vital signs, laboratory data and CT-Scan findings.
Due to limitation of available hospital beds, some of the hospitalized patients showing minor clinical symptoms, mild CT-Scan changes and improved vital signs who had negative PCR results were discharged by physician’s clinical judgement within a few days of admission. There were several reports of exacerbated symptoms and re-hospitalization of patients in severe conditions .Meanwhile, the positive or negative PCR results have at times led the physicians into misinterpretation of patient’s clinical conditions. The decision to continue treatment or discharge the patient from the hospital in those with mild clinical symptoms, negative PCR test and positive CT is an important question for physicians.
Accordingly, the goal of this study is to investigate the importance of clinical symptoms, initial vital signs, laboratory findings and chest CT-Scan findings among patients with negative and positive PCR results.