Accurate and prompt diagnosis of COVID–19 patients is of utmost importance in limiting spread of the disease as well as for identifying patients at risk for rapid deterioration. Epidemiological data from other countries, such as South Korea, China and Italy have shown that increased testing, identification of infected individuals, and prompt medical attention can result in markedly lower rates of R0, disease propagation and ultimately disease mortality. With several treatments currently under development and investigation, diagnosis will be of increasing importance.
Testing in the United State remains limited, with most centers only testing patients with lower respiratory symptoms and positive exposure history. The cohort presented herein, along with many other published studies, show that this testing strategy may be overly restrictive as there is a significant rate of communal and sub-clinical spread[4, 5, 12–15]. It is well documented that many patients who are RT-PCR-positive for COVID–19 may have an incubation period of five days and can transmit the virus without prolonged close contact with other individuals[5, 12]. Here, we show in seven patients without lower respiratory symptoms, documented fever or known exposure, that COVID–19 infection can not only be present, but subsequently result in high rates of intubation and mortality. Many centers do not incorporate imaging in their RT-PCR algorithms and there remains diagnostic uncertainty regarding patients with imaging consistent with COVID–19 but are otherwise of low clinical suspicion. We argue that patients with suspicious imaging findings, especially CT, even in the low-incidence and low clinical suspicion setting shown here, warrants prompt RT-PCR testing. Additionally, as detection of these patients is difficult, this data supports the institution of widespread quarantine protocols to contain disease propagation.
This patient cohort highlights an important potential blind spot in the use of PPE at the point-of-care and in the inpatient setting, potentially leading to increased nosocomial and healthcare worker transmission. The lab-confirmed disease incidence at the time of this report remained low, with only 30 lab-confirmed infections and nine in-hospital infections. Despite this, imaging was able to incidentally identify patients with suspected COVID–19 findings, ultimately resulting in seven additional diagnoses and prompt initiation of PPE and quarantine protocols. This suggests that even in the early stages of community spread, there may be a high rate of undetected disease and a much higher than suspected population incidence than established by RT-PCR, which has been suggested by other studies[13–15]. This is in part due to restrictive testing criteria, which would have excluded these patients without pulmonary symptoms. These patients present a unique risk to those at the point-of-care, as there is low-suspicion for COVID–19 at presentation and therefore the appropriate PPE precautions are not taken. Had these incidental imaging findings not been identified and correctly reported, or if these patients were not subsequently tested despite the reporting of suspicious imaging findings, these individuals may have continued to spread the infection to healthcare workers and within the community. This is highlighted by the two patients in this cohort who never developed symptoms who would have been sent home with a presumed negative COVID–19 diagnosis.
The rate of escalation to critical care, intubation, and mortality in this cohort was alarmingly high, suggesting these patients may have rapidly decompensated if sent home without a known diagnosis and possible lost to follow-up. Two patients were discharged to home quarantine for “rule-out” with a pending RT-PCR after initial suspicious imaging, who subsequently required admission and intubation. More research regarding which patients are at risk for rapid deterioration will be important to identify these patients.
This cohort identifies clinical findings that may be considered to be suspicious for COVID–19 infection in the absence of pulmonary or exposure history. Six out of seven (86%) of patients presented with abdominal complaints, consistent with an in-press publication suggesting nearly half of the patients in Hubei province China endorsed gastrointestinal symptoms and that these patients had a more severe course of illness. Classic pulmonary imaging findings in the absence of respiratory flu-symptoms may increase the specificity for COVID–19 infection as the incidence of differential considerations (such as other respiratory viruses) is lower in this clinical context. COVID–19 in contrast is known to have an asymptomatic or sub-clinical period with positive chest CT findings. Together, this may explain the high reported specificity of 88% in this small cohort of patients. Elevated inflammatory markers may be an important clinical correlate suggestive of a brewing COVID–19 infection, especially in the setting of leukopenia or a normal white blood cell count. Previous studies have shown that D-Dimer at the time of presentation may predict disease severity, which is concordant in this small cohort, with a markedly elevated D-Dimer range of 1396–3140 ng/mL among four patients, all of whom required eventual intubation and one of which expired during the admission. These findings suggest that expansion of clinical suspicion beyond lower respiratory symptoms and exposure may be important to identify a larger proportion of infected patients and for appropriate triage and PPE at the point-of-care.
Of note, five of the seven patients were seen in a health care setting within seven days of infection for an unrelated complaint, suggesting a possibility of nosocomial spread. Studies from China have suggested rates of in-hospital transmission to be as high as 41%.
The classic CT findings of COVID–19 include bilateral, round, ground glass opacities in a peripheral distribution, “crazy paving”, and vascular engorgement[7, 19, 20]. Unlike other viral pneumonias which primarily affect the airway resulting in tree-in-bud nonduality in a bronchial distribution, COVID–19 affects the Type II pneumocyte and results in a unique CT appearance that lends increased specificity. Emerging literature has shown that the initially reported rates of sensitivity may have been underestimated, with experienced radiologists and artificial intelligence successfully distinguishing COVID–19 from other pneumonias in upwards of 80% of cases[9, 10]. In a recent study of over 1000 patients, CT resulted in higher sensitivity in detection of SARS-COV2 as compared with initial RT-PCR from pharyngeal swab samples. Reported positive predictive values were upwards of 60%. Additional studies are emerging that further solidify this positive predictive value, with reports now uncovering a cohort of patients with high suspicion CT and false negative initial PCRs later discovered to have positive, concordant COVID–19 positive PCR . It remains to be seen how patients with positive cross-sectional imaging in the setting of high clinical suspicion, especially in the absence of other etiologies (for example, negative respiratory viral panel), should be managed, until higher rates of RT-PCR sensitivity and specificity are confirmed.
Chest radiography is not sensitive for the detection of ground-glass opacity and may demonstrate normal findings, especially in the early stages of infection. Bilateral peripheral, multifocal consolidations may be seen. Those in the late stage may present with findings of “white lung” and acute respiratory distress syndrome. In this study, suggestion of COVID–19 on chest radiograph resulted in subsequent positive testing in two patients, which raises the question of whether there may be a role for radiography as a supplement to RT-PCR, or in areas where laboratory testing may be especially scarce.
This study has limitations. This is a retrospective study of a small cohort size at a single center. In order to fully understand the value of imaging in low clinical suspicion patients, an analysis of all patients with imaging consistent with COVID–19 in this cohort, including negative RT-PCRs should be analyzed to assess for specificity; data which is currently being collected and analysis ongoing.