key: cord-0833921-cjax868m
authors: Smereka, Paul; Anthopolos, Rebecca; Latson, Larry A; Kirsch, Polly; Dane, Bari
title: Using Lung Base Covid-19 Findings To Predict Future Disease Trends and New Variant Outbreaks: Study Of First New York City (NYC) Outbreak.()
date: 2021-10-01
journal: Acad Radiol
DOI: 10.1016/j.acra.2021.09.023
sha: 4f934e2e4f15c69977f818648fcf1aab5f832ad4
doc_id: 833921
cord_uid: cjax868m

RATIONALE AND OBJECTIVES: Asymptomatic COVID-19 carriers and insufficient testing make containment of the virus difficult. The purpose of this study was to determine if unexpected lung base findings on abdominopelvic CTs concerning for COVID-19 infection could serve as a surrogate for the diagnosis of COVID-19 in the community. MATERIALS AND METHODS: A database search of abdominopelvic CT reports from 3/1/2020-5/2/2020 was performed for keywords suggesting COVID-19 infection by lung base findings. COVID-19 status, respiratory symptoms, laboratory parameters and patient outcomes (hospitalization, ICU admission/intubation, and death) were recorded. The trend in cases of unexpected concerning lung base findings on abdominopelvic CT at our institution was compared to the total number of confirmed new cases in NYC over the same time period. RESULTS: The trend in abnormal lung base findings on abdominopelvic CT at our institution correlated with the citywide number of confirmed new cases, including rise and subsequent fall in total cases. The trend was not mediated by COVID-19 testing status or number of tests performed. Patients with respiratory symptoms had significantly higher ferritin (median=995ng/ml vs 500ng/ml, p=0.027) and death rate (8/24, 33% vs 4/54, 9%, p=0.018) compared to those without. CONCLUSION: The rise and fall of unexpected lung base findings suggestive of COVID-19 infection on abdominopelvic CT in patients without COVID-19 symptoms correlated with the number of confirmed new cases throughout NYC from the same time period. A model using abdominopelvic CT lung base findings can serve as a surrogate for future COVID-19 outbreaks.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a strain of coronavirus causing the severe acute respiratory distress syndrome known as COVID-19 [1] . As of August 2021, more than 36 million cases have been reported in the United States, and over 200 million cases worldwide [2, 3] .

Though for a time the infection was thought to be under control due to use of multiple vaccines and preventive measures, the Delta Variant has raised concern for new outbreaks at a time when social restrictions have eased and less people are undergoing routine testing [4] [5] [6] [7] [8] . Typical COVID-19 symptoms include fever, cough, and shortness of breath, but numerous other symptoms and medical events have been attributed to the infection, including stroke, cardiac events, pulmonary embolism, bowel inflammation and digestive symptoms [1, [9] [10] [11] [12] [13] . Many infected people are asymptomatic or show atypical symptoms without respiratory manifestations, especially those having previously received the vaccine, which further complicates reliable diagnosis and disease containment [10, [14] [15] [16] [17] . Given the myriad of symptoms associated with the viral infection, infections from new variants, delays in presentation, lower than desired vaccine administration and testing rates, and the number of asymptomatic carriers, the diagnosis, treatment, and prevention of disease remains a challenge [1, 4, [18] [19] [20] .

The outbreak of COVID-19 in New York City (NYC) in March and April of 2020 was one of the first in the United States [3, 21] . The city experienced a rise and fall of cases much earlier than other major United States cities. As such, NYC offered a unique population for the study of disease spread and subsequent abatement. March 1st marked the first case of COVID-19 in New York State [22] . On March 20 th , there were 7,102 total confirmed cases and 46 total deaths in New York, with the majority found in NYC [3, 21] . The rate of infection continued to rise, reaching a peak during the week 3/29/20-4/4/20 (35,944 confirmed cases), after which the number of cases began to decline, displaying the effectiveness of safety measures and the willingness of New York residents to adhere to them [3] .

As the virus spread and then dissipated, we learned the challenges of diagnosis, containment, and treatment. Evidence arose that COVID-19 asymptomatic carriers can transmit SARS-CoV-2, and its infectivity was shown to be similar to that of symptomatic patients [23, 24] . Given the relatively high proportion of asymptomatic cases, it became clear that asymptomatic patients could be playing a large role in the transmission of the virus, and thus posed a significant infection control challenge [25, 26] .

With these factors in mind, our study set out to evaluate the patients who presented to our institution without respiratory symptoms, but were found to have abnormal findings in their lung bases on abdominopelvic CT, and to compare the rate of these findings with patient COVID-19 PCR testing status. Therefore, the overall purpose of this study was to compare the frequency of abnormal lung base findings on abdominopelvic CT at our institution to the total number of confirmed new cases in NYC during the same time period.

This retrospective, Health Insurance Portability and Accountability Act-compliant, Institutional Review Board-approved study used a departmental database to search for abdominopelvic CT reports which included the keywords "groundglass," "atypical agents," "pneumonia," and/or "pneumonitis," from the time period March 1, 2020 to May 2, 2020 (figure 1), at our academic medical institution in NYC. The inclusion criteria was all outpatient and emergency department patients older than 18 years of age undergoing abdominopelvic CT during the above dates. The initial database search identified 319 patients. Exclusion criteria included all inpatient CT scans (n=68), patients without lung findings (n=27, i.e, groundglass described in bone findings, or the phrase "no groundglass opacity" included in the report), reports describing a solitary groundglass opacity < 5mm and reports describing a groundglass or For comparison, the departmental database was searched for abdominopelvic CTs during the same time period from one year prior (3/1/2019-5/2/2019), and total abdominopelvic CT reports including "groundglass," "atypical agents," "pneumonia," and pneumonitis" were recorded. Patient age, sex, and respiratory symptoms were recorded, as were the same laboratory parameters and additional information as the patients from 2020. The search resulted in 61 cases; 4 with respiratory symptoms and 57 without.

A manual review of the EMR was performed for all included patients by an abdominal radiologist. Figure 1 ). For each of these groups, hospitalization, hospital stay length, intubation or admission to ICU, and death were recorded.

A cardiothoracic radiologist with seven years post-fellowship experience blinded to initial imaging interpretation recorded whether the findings in the lung bases on abdominopelvic CT were suspicious for COVID-19 infection or not, based on recent clinical experience with chest CT findings of the virus. The chest radiologist described ground-glass opacities (GGO), consolidation, atelectasis, interlobular septal thickening, pleural effusions, tree-in-bud nodularity, and the lobar distribution (one lobe vs. multilobar).

Our cardiothoracic radiologist provided an analysis of each case and rationale for characterization as "likely COVID-19 in the appropriate clinical setting", "possible COVID-19 versus other etiologies," or "not COVID-19" based on the constellation of imaging findings. The radiologist was blinded to COVID-19 laboratory results and patient respiratory symptoms for each study, as well as the date including year during which the study was performed.

Characteristics of patients with COVID-19 positive laboratory test results were described by respiratory symptom status. Categorical and continuous variables were summarized with frequencies and percentages, median and interquartile range. Association of patient characteristics with respiratory symptoms status was determined using Chi-square (categorical variables) and Kruskal-Wallis tests (continuous variables). For categorical variables, Pearson's chi-squared test was used. For two-by-two categorical comparisons involving expected cell counts less than five, Fisher's exact test was used. A pvalue less than 0.05 indicated statistical significance [27] . 

Order Correlation was used to measure the association between patients with abnormal lung base findings on abdominopelvic CT at our institution from 3/8/20-5/2/20 and the total number of documented cases in NYC during the same time period.

All analyses were performed in R Statistical Software [27] .

This study was approved by our Institutional Review Board. When comparing COVID-19 positive patients with and without respiratory symptoms, the respiratory symptom group showed a significantly higher ferritin level (995 vs 500ng/ml p=0.03) and death rate (8/24 vs 5/53, p=0.02). There was no significant difference between the groups for age, sex, hospitalizations, length of hospital stay, intubation/ICU stay, D-dimer, ESR, or CRP level (p=0.21-0.85).

Of the 189 included CTs from 3/1/20-5/2/2, 85 (45.0%) were interpreted as "multifocal GGO, COVID-19 likely in the appropriate setting" by expert chest radiologist review (Figure 2a) . 70 (37.0%) were interpreted as "possible COVID-19 infection versus other etiologies", which included descriptors "very mild GGOs," "minimal GGO," "moderate GGO," and "GGO confined to one lobe" (Figure 2c ). 34 (18.0%) cases with descriptors "atelectasis", "motion," "scarring," "aspiration," "tree-in-bud," "effusions," "edema," "lymphangitic," "bacterial pneumonia," or some combination thereof were interpreted as "not COVID-19 infection" by chest radiologist review (Figure 2d) .

Of the 61 patients with abnormal lung base findings from the year prior (3/1/19-5/2/19), 11 (18%) had findings "COVID likely in appropriate setting," if the CT had been performed during the COVID-19 pandemic. 13 (21%) had "possible COVID versus other etiologies," and 37 (60.6%) were interpreted as "not consistent with COVID-19".

Using all patients with PCR COVID-19 tests (and including all 2019 patients as COVID-19 negative), and including interpretation of "Likely COVID" and "COVID possible" in the positive category, resultant sensitivity, specificity, and accuracy of abdominopelvic CT lung base findings was 92%, 59%, and 75%, respectively. 

An increased rate of abnormal lung findings was seen in both patients with COVID-19 positive results and patients with COVID-19 negative result or no COVID-19 test ( Figure 5 ). The rate of increase in abnormal findings was higher in COVID-19 positive patients. This trend was not mediated by COVID-19 positive laboratory test status. The trend was seen despite a sharp decrease in the number of total abdominopelvic CT scans performed at our institution. The trend in abnormal lung findings in 2020 during the COVID-19 outbreak was distinctive compared to a comparison of the same time period during 2019 ( figure 6 ).

Our results show that abnormal lung base findings on abdominopelvic CT during the COVID-19 outbreak in NYC (3/1/20-5/2/20) follow a similar trend to total confirmed new cases throughout NYC during the same time period. While these patients cannot be considered "asymptomatic" (as numerous abdominal findings have been attributed to the viral infection), they do represent a "respiratory asymptomatic" patient population [1, 28] . Consequently, the rise in suspicious lung base findings in "respiratory asymptomatic" patients could stand as a surrogate for COVID-19 community infection rates.

With the rise of new variants, breakthrough infection in vaccinated individuals, spread of COVID-19 infection among "asymptomatic" individuals, reduced COVID-19 testing and contact tracing [2, 3, 8, 29] , the ability to provide a surrogate marker of community viral load is essential. Therefore, the ability to model community infection load via unexpected imaging findings on abdominopelvic CT is useful.

The chest radiologist's assessment confirmed that the original non chest radiologist-trained radiologist's assessment of the lung bases was highly sensitive for COVID-19 or other atypical infection, and that this original assessment could be used to trend infection rates. High sensitivity is favorable in the evaluation for COVID-19. Our chest Radiologist's criteria for identifying COVID-19 infection versus other infectious lung diseases agrees with recently published data differentiating the two groups [30] . As specific criteria for COVID-19 lung findings become more established, machine-learning algorithms could potentially be used to monitor the rate of such findings in the population, as an early warning or surrogate measure of new or on-going outbreaks [31] .

In our study, among patients with positive COVID-19 PCR tests, patients with respiratory symptoms on presentation had significantly elevated ferritin level (995 vs 500ng/ml) and death rate (33% versus 9 %) compared to those without respiratory symptoms (Table 1 ). Ferritin has been associated with more severely ill patients in a number of diseases, including COVID-19, where it has been shown to be an independent risk factor for disease severity [32] [33] [34] [35] . While all inflammatory markers and a patient's clinical picture should be assessed when evaluating the severity of a patient's illness, our study suggests that ferritin may be a particularly important marker in predicting the development of respiratory symptoms and more severe cases.

This study had a number of limitations. First, a large number of the respiratory asymptomatic patients (79/151) were untested for COVID-19. Second, the COVID-19 PCR test, our reference standard, is not 100% accurate, with sensitivity ranging from 25 to 97% and specificity from 25 to 70%, based on meta-analysis of multi-test studies [36] [37] [38] [39] . Third, the NYC database for counting of confirmed COVID-19 cases does not include people with COVID-19 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative [36] . Finally, the increased rate of atypical lung base findings may also be spuriously elevated, as radiologists at the time were aware of the community COVID-19 infection rates.

In conclusion, the rate of abnormal lung base findings on abdominopelvic CT at our institution in NYC was highly correlated with the citywide COVID-19 positive testing rate during the same time period, regardless of patient COVID-19 PCR test result. This suggests that the increasing incidence of abnormal lung base findings on abdominopelvic CT could be used as a surrogate for community COVID-19 infection rates. Future research with larger sample sizes could potentially help to produce a model in which concerning lung base findings on abdominopelvic CT are used to predict future outbreaks of 

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