Pictorial guide for variants of Covid-19: CT imaging and interpretation

Typical radiologic images of Covid-19 pneumonia consists in a wide spectrum of chest manifestations, which range from peripheral predominant ground-glass opacities to an organizing pneumonia pattern, with additional features including crazy-paving, consolidations, fibrotic streaks and linear opacities. With variants imaging profile of Covid-19 evolves, producing relatively atypical/indeterminate CT pattern of pulmonary involvement, which overlap with imaging features of a variety of other respiratory diseases, including infections, drug reaction and hypersensitivity pneumonia. Our knowledge of these radiological findings is incomplete and there is a need to strengthen the recognition of the many faces of Covid-19 pneumonia.


INTRODUCTION
In March 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 caused by Sars-CoV2 virus (COVID-19) as a pandemic and global public health emergency. This is the first pandemic in modern era presenting with unknown clinical syndrome and therapy: both of them were defined progressively, after the spread of the disease.
At first COVID-19 was interpreted as an infectious disease limited to the lungs, whereas only afterwards the vasculitic pathogenesis was described as affecting other organs. COVID-19 outcome and long-COVID syndrome have been described only recently.
Imaging features of COVID-19 were likewise progressively portrayed, after the widespread of the disease, leading to a new nosographic radiological entity. 1 Additional aspects of this infectious disease are represented by the wave-shaped trend of the pandemic ("waves", variably named, depending on the countries), and by the outbreak of new variants of the virus. Few of them were declared by the WHO "Variant of Concern", given their enhanced transmissibility or virulence, and their potential to weaken the effectiveness of therapy and vaccination strategies. Five variants have been designated by the WHO: Although reference standard for diagnosis is RT-PCR, chest CT remains a complementary diagnostic tool limited to specific indications, playing a role in clinical assessment of patients with moderate to severe illness. 1 This is a short pictorial guide showing the key imaging features of variants of COVID-19, which could be useful in daily radiological practice.

CT PROTOCOL
CT is the gold-standard in diagnostic imaging of COVID-19 pneumonia.
Chest CT examination should be performed with high-resolution non-contrast technique with a reconstructed slice thickness of 1.0-1.5 mm. 1

IMAGING FINDINGS
The subsequent waves of pandemic showed different and atypical chest CT features, that are less specific or relatively uncommon, and can occur in association with or even mimic a variety of infectious and non-infectious processes. 4

GGO with predominant upper lobes involvement and random distribution
The typical Covid-19 started as bilateral ground-glass opacities (GGOs) in posterior segments of lower lobes with peripheral distribution, which then developed into the crazy paving appearance and subsequent consolidation. 5 With variants, GGO may present random distribution (no predilection for subpleural or central regions), with prevalent/exclusive involvement of upper lobes ( Figure 1).

Single isolated involvement
During third and fourth wave, we observed solitary involvement in any lobe, in the form of GGO or denser (Figures 2 and 3): in early stage of disease, if this sign is not accompanied by other features or patterns, like small areas of consolidation or interlobular septal thickening, alternative diagnoses should be considered. Crucial is the correlation with clinic and laboratory.

Isolated lobar consolidation
Consolidations were described as patchy, multifocal or segmental in the late phase of the disease, during first wave of pandemic; they also represented a possible indicator of disease progression. 6     With variants, we observed homogenous consolidations involving exclusively one lobe, with visible air-bronchogram sign.
This feature is not specific, since it could be caused by different infectious agents, like Pneumococcus or Legionella species (Figure 4). 7 Pulmonary target sign (bullseye sign) Considered as a variant of reverse halo sign, this pulmonary feature consists of central high attenuation focus surrounded by an inner ring of air and an outer complete or incomplete ringlike consolidation. 8 The central nodule is centrilobular, the outer ring of ground glass perilobular, while the inner ring of air corresponds to sparing of the remainder lobule ( Figures 5 and 6).

Tree-in-bud appearance
Tree-in-bud appearance consists of centrilobular nodules connected to multiple branching linear structures, most observed in lung's periphery (Figures 7 and 8). Originally described in cases of endobronchial Tubercolosis, this pattern is now considered as a CT feature of many differents infectious agents. 9 Diffuse GGO with centrilobular distribution Variants show also diffuse symmetric, ill-defined GGO in both lung with centrilobular predominant distribution (Figures 9 and  10); this imaging pattern overlaps with other viral infections, such as CMV pneumonia. 10

White lung
As pulmonary impairment gets worse, GGOs increase, spreading to more lobes and merging each other, with inter-and     intralobular septal reticular thickening and partial consolidation. In patients with complicated pneumonia, dense consolidation involving all lobes become prevalent. This pattern, called "white lung", can also be observed in other lung diseases (viral infection, drug toxicity). It represents the CT correlate of the underlying pathophysiology of pneumonia as it progresses to acute respiratory distress syndrome (ARDS), predicting a worse outcome. 10 (Figures 11 and 12)

Cavitation
Cavitation is a circumscribed abnormal gas-filled space of the lung, seen as a low-density area within a pulmonary consolidation, a mass, a nodule. Salehi et al showed that cavitation represents the evolution of lung consolidation, visible on CT in later stage of Covid-19 pneumonia 11 (Figure 13).

Pericardial effusion
Several studies stated that pericardial effusion is a rare finding in Covid-19 patients (5% of total population infected with wild type), especially in the later stage of pneumonia, representing a sign of disease progression. 11,12 Patients infected with variants frequently showed this feature from the earliest stage of disease ( Figure 14).

CONCLUSIONS
This pictorial assay summarizes main chest radiological features identified in a wide range of spectrum of manifestation, in patients infected with Covid-19 variants, highlighting differences compared to wild type virus. In our routine screening CT for diagnosis in emergency department of Policlinico Umberto I, we reported atypical chest findings, non-specific or uncommon for Covid-19 pneumonia, potentially attributable to variants, that could be observed in a large number of conditions, leading to diagnostic difficulty.
The imaging hallmark of Covid-19 pneumonia, described in many publications, is a bilateral confluent and extensive GGO and patchy consolidation with prevalent subpleural distribution and lower lobes predominance, mostly posterior basal segments. Inter-and intralobular septal thickening may be present in more advanced cases (crazy paving).
Covid-19 variants produce different chest CT pattern, characterized by GGO with random distribution (both peripheral and central interest) and mainly upper lobe involvement; we reported single isolated GGO or lobar consolidation, thee-in-bud pattern, targeted pulmonary sign.    In the most critical cases, CT scan showed widespread consolidation involving all lobes (white lung).
Furthermore cavitation and pericardial effusion, quite rare findings during first wave of pandemic, were frequently observed with variants.
Diagnostic imaging of COVID has its own limitations. Imaging profile of Covid-19 infection is composite and constantly evolving, with a wide range of CT features, as well as clinical manifestations.
Our pictorial essay displays imaging findings of variants, to help radiologists in their detection to speed-up diagnostic workflow in symptomatic patients; these CT manifestations are not pathognomonic and are observed in other lung infectious and non-infectious processes; a lack of their detection may lead to misdiagnosis and delay in the isolation of Sars-CoV-2 patients.
Those limitations due to aspecific and variable CT features could be partially overcome by correlating them with clinical history.
The findings described and main differential diagnoses are summarized in Table 1.