Abstract

Heretofore, the COVID-19 pandemic continues to expand costing not just lives but also significant impact on the global economy. More than 212 countries and territories across the globe have been affected till now, causing approximately 4,043,068 confirmed cases and 277,016 deaths, and the numbers are rising expeditiously. The common symptoms are fever, dry cough, fatigue, sputum production, shortness of breath, sore throat, and headache, but atypical symptoms affecting cardiovascular system, gastrointestinal system, and neurological manifestations are not so uncommon and have been reported. Various governing bodies such as the World Health Organization, the National Institute for Health and Care Excellence, and the Centers for Disease Control and Prevention have laid down guidelines and recommendations for the same. In this review article, we have propounded the established knowledge about the causative agent in terms of epidemiological features, the etiopathogenesis, signs and symptoms, methods used for diagnosis, and the latest insight into the treatment and prevention according to the recent published recommendations. The current guidelines and the state-of-the-art updates for various active health-care personnel; allied departments such as radiology and microbiology, and those for the community have also been discussed.

| Figure 1: (a and b) COVID-19 cases and deaths worldwide by the World Health Organization – available at https://who.sprinklr.com/accessed April 22, 2020

Epidemiology

CoVs belong to the family of Coronaviridae and fall under the Coronaviridae subfamily which is a single-stranded (positive sense) RNA associated with a nucleoprotein within a capsid composed of matrix protein.[2] The envelope bears club or crown-shaped glycoprotein projections. According to Lauer SA et al. the median incubation period was estimated to be in the range of 5.1-15.6 days with an assumption that the 99th percentile of the cases will develop symptoms within 14 days of acquiring the infection.[3] There is an association of age and immunity status of the patient as evident by shorter incubation period seen in patients < 70 years of age than in those >70 years.[4] The positive cases (55.1%) in the age range of 15–49 years clearly outnumbered the other groups, which were seen as 28.9% in 50–64 years while 15.1% in age 65 years and above.[5] The World Health Organization (WHO) declared COVID-19 as a public health emergency of international concern.[6]

Mode of Spread

The predominant mode of spread is via airborne route with human-to-human infection between close contacts (< 6 feet) and as a droplet infection when an infected person coughs or sneezes; the infected droplets are either inhaled by the healthy individuals in the vicinity and or land up in the mouth or nose [Figure 2]. The other mode of spread to a healthy individual is via fomites which are infected or contaminated objects having viable virus on their surface.[7] The intermediate source of origin and transfer to humans is unknown; however, the possibility of it being a zoonotic disease (via infected bats) is likely.[8]

| Figure 2: Depiction of how droplets can travel in air and spread infection

Etiopathogenesis

The primary target of the virion is the epithelial cells of the lung with affinity of the receptor-binding domain spike on the envelope of the virus particle to the angiotensin-converting enzyme 2 receptor in the host.[9],[10] After its entry into the host cell, the genome is uncoated and is followed by transcription and translation; the virus replicates in the cells of ciliated epithelium, causing damage to the host cell, and incites inflammation.[11]

High-Risk Population

This includes the elderly typically 65 years and older; those living in long-term facility and nursing home; people with underlying medical conditions, for example, chronic lung disease, cardiac disease, liver disease, chronic kidney disease, diabetes, and immunosuppression secondary to HIV/AIDS, long-term steroid use, bone marrow and organ transplantation, and cancer patients.[12] Cancer patients undergoing treatment with chemotherapy and radiotherapy, those suffering from hematological neoplasm, or those who have received bone marrow transplant or stem cell transplant as a part of the treatment < 6 months' duration or are put on drugs altering the immune systems such as PARP inhibitors or protein kinase inhibitors are the most susceptible among the lot.[13]

Signs and Symptoms

The signs and symptoms of COVID-19 infection are highly variable and are nonspecific ranging from asymptomatic carrier to typical respiratory symptoms and/or rarely systemic manifestations pertaining to gastrointestinal and cardiovascular systems.[5],[14],[15],[16],[17] In the given current scenario, the symptoms in the pediatric population are milder as compared to the adults.[18],[19] The most common symptoms are fever (87.9%), followed by dry cough (67.7%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), headache (13.6%), myalgia/arthralgia (14.8%), chills (11.4%), nausea and vomiting (5.0%), nasal congestion (4.8%), diarrhea (3.7%), hemoptysis (0.9%), conjunctival congestion (0.8%), and acute respiratory distress syndrome (ARDS) (3%).[5] Various societies across the globe are coming up with guidelines and recommendations in various subspecialties; one such example is British Thoracic Society which has published the guidelines for the respiratory community – https://www.brit-thoracic.org.uk/quality-improvement/guidelines/. The clinical classification of cases given by the Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th ed.ition) is summarized in [Table 1].

Table 1 Clinical classification of cases given by Chinese clinical guidance for COVID-19 pneumonia diagnosis and treatment (7th edition)

Diagnosis

The state-of-the-art test for COVID-19 is real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The specimen for endemic forms of human CoV infections has been isolated from various areas, namely, nasal swab or nasopharyngeal (NP), throat, sputum, and bronchoalveolar lavage (BAL). The current Centers for Disease Control and Prevention (CDC) recommend collection of specimens from upper respiratory tract, preferably NP swab.[20] Laboratories are required to maintain the adequate temperature chain to store the specimen, i.e., maintaining refrigerated temperature for up to 72 h or frozen at −70° or even below it.[18] Regarding the biosafety guidelines, the CDC has recommended the BSL 2 laboratories to deal with regulation of the specimen.[21] Early infections may be missed and repeat swabs may be taken for highly suspicious cases later in the course of illness. Serum and rectal specimens alternatively can be used.[22]

Laboratory diagnosis

It mainly consists of a battery of routine blood investigations with few generalized observations such as lymphopenia, which tends to be a poor prognostic indicator.[23] There is a rise in the acute-phase reactants such as C-reactive protein (CRP), lactate dehydrogenase (LDH), prothrombin time (PT), D-Dimer, and liver enzymes. Later, in the disease, there may be rise in the organ-specific proteins and markers, which heralds the poor prognosis of the individual.[23]

Role of Radiology and Imaging

The role of diagnostic radiology as a tool in the current scenario is being constantly updated with various publications, review articles, and their immediate incorporation into various guidelines given by international and national health governing bodies. The role of screening computed tomography (CT) for COVID-19 has been called off by many radiological societies.[24] Lately, plain radiography and CTs are used as a part of diagnostic armamentarium with acceptable levels of detection and follow-up of cases under specific regulations and indications. Chest radiography despite being less sensitive than CT continues to be used the first radiological investigation across the globe.[25] In conjunction to it, the Indian chest societies such as IRIA ICRI chest subspecialty group have also come up with the same. To minimize the risk of contamination of the radiology department and the radiology personnel, special emphasis is laid on the use of portable radiography using dedicated machinery with defined protocols as directed by various health-care providers across nations and the world.[26]

The radiographic evidence of abnormality is most obvious at 10–12 days after development of symptoms, whereas in the early or mild course of the disease, no abnormality is detected.[25] The sensitivity and specificity of chest radiography is low as compared to that of the CT. The predominant abnormality on radiographs is patchy areas of consolidation (28.1%) followed by ground-glass opacities (GGOs) (20.1%) and rarely interstitial abnormalities (4.4%). These changes were more frequently present in bilateral distribution as seen in a study conducted by Guan et al.[5] Lately, many publications have come up describing the imaging in COVID-19, emphasizing on CT features.[27],[28],[29],[30],[31] These studies were able to decipher the common patterns of lung affection on CT such as GGOs, frequently bilateral and multilobar and infrequently as mass like or nodular pattern of opacities.[31] The classic CT depicter for COVID-19 is diffuse involvement of lungs bilaterally with GGOs rendering crazy paving appearance with or without consolidation predominantly in peripheral and posterior aspect.[27],[28],[29],[30],[31],[32] Lymphadenopathy, pleural effusions, multiple tiny pulmonary nodules, tree in bud pattern, and cavitation have been rarely described in the spectrum as atypical findings and may represent superadded infections.[33] A normal CT chest may be expected early in the course of disease.[34],[35],[36] The sensitivity and specificity of CT varies in the range of 60%–98% and 25%–53%, respectively.[37],[38],[39],[40] [Table 2] - summarises the COVID-19 pneumonia imaging classification.

Table 2 COVID-19 pneumonia imaging classification

Recently, there have been recommendations regarding the reporting language for COVID-19 to even out the discrepancy of findings on imaging and maintain homogeneity among the fraternity. The proposed reporting language with the CT findings are adapted from the Society of Thoracic Radiology, the American College of Radiology, and RSNA.[24] [Figure 3]a] and [Figure 3]b] shows the CT image of a confirmed case of COVID-19. COVID mimics – few examples of mimics of the disease owing to the varied patterns on CT imaging are shown in [Figure 4] and [Figure 5]a],[Figure 5]b],[Figure 5]c],[Figure 5]d].

| Figure 3: (a and b) A 45-year-old male patient had a history of contact with a COVID-19-positive family member who presented to the COVID clinic with a history of cough and fever of 3 days’ duration. The patient had sudden clinical deterioration and breathlessness; a computed tomography thorax was advised. The findings on computed tomography thorax axial and coronal images (a and b) revealed multifocal patchy areas of round to ill-defined consolidation predominantly in the posterior and basal segments of the lung with surrounding ground-glass opacities. Reverse transcriptase-polymerase chain reaction tested positive for COVID-19

| Figure 4: A 45-year-old female patient with carcinoma breast developed fever and breathlessness after infusion of paclitaxel therapy. Computed tomography axial image was suggestive of faint bilateral ground-glass opacities predominantly in the bilateral lung bases. On cessation of therapy, there was significant improvement in the ground-glass opacities

| Figure 5: (a) An elderly patient presented with haemoptysis and breathlessness. Axial computed tomography lung window demonstrates patchy areas of ground-glass opacities with interlobular and intralobular septal thickening – giving “crazy paving pattern” in the right upper lobe and also in the bilateral lower lobes. Imaging findings were consistent with diffuse pulmonary haemorrhage. (b) Patient presented to the casualty with acute-onset of chest pain and cough. Axial computed tomography image lung window demonstrates a patch of consolidation in the subpleural location with central ground-glass opacities – “atoll sign” (reverse halo sign) in the right upper lobe was consistent with cryptogenic organizing pneumonia. Significant resolution was seen with corticosteroid treatment. (c) Selected axial computed tomography image lung window shows diffuse randomly distributed tiny parenchymal nodules “miliary pattern” in this elderly female patient on chemotherapy presenting with a new onset of cough, breathlessness, and fever since a month. Overall findings are in favour of infective etiology – miliary tuberculosis. Sputum was positive for acid-fast bacilli. The patient is on ATT and follow- up (d) Selected axial sections of CT chest lung window with bilateral perihilar ground glass opacities multiple pulmonary cysts with relative peripheral and subpleural sparing. No evidence of pleural effusion or mediastinal lymphadenopathy. Overall findings were in favour of pneumocystis jiroveci pneumonia which is a common opportunistic pathogen in immunocompromised individuals. The patient presented with sudden loss of consciousness and breathlessness and workup revealed HIV positive status with low CD4 counts 28 cells/mm³

Indications of Imaging

The Fleischner society has described the role of imaging and its use in the given setting of the pandemic on the basis of various clinical criteria and their features, as given in [Table 3].[41]

Table 3 Clinical criteria and features to categorize and segregate patients for imaging according to Fleischner society

Recommendation

1. Mild disease: No role of chest imaging in mild disease regardless of risk factors and positive test result for COVID-19 but indicated in those showing worsening of dyspnea or hypoxemia

2. Moderate-to-severe disease: Imaging in patients with positive COVID-19 status is recommended serving as a baseline study, to identify those with underlying cardiovascular disease for risk assessment and assess disease progression and superadded abnormalities and infections.

Other subsets of patients who are either not tested or have a negative test should undergo imaging as a part of routine care and for evaluation of the underlying pathology. If imaging features are suspicious of COVID-19 infection, these cases should be dealt further according to risk factors and lab test availability including repeat tests for COVID-19.

COVID-RADS is another such example and can be used for the structured reporting of the cases in clinical trials and can be accessed at covid19action-radiology.github.io.

The lack of dedicated CT units for the suspected patients or cases in a hospital setting and effortful sterilization and low specificity has led to the lack of endorsement in developing countries such as India.[42] The role of ultrasonography (USG) as point of care ultrasound (POCUS) is surging as a tool because of ease of portability and sterilisation techniques, and also, it can be used as dedicated unit in isolation and critical care wards.[43],[44],[45] It has been reinforced by recent studies in China in critical care settings.[46] Its role is being assessed in triage and risk stratification and detection of complications such as pleural effusions. The imaging findings comprise multiple B lines and waterfall sign secondary to thickening of the interlobular septa in subpleural location, areas of focal or diffuse consolidation with air sonograms, and irregular pleural thickening with or without pleural effusion with reduced blood supply on Doppler.[47] The preparation of ultrasound transducer consists of cleaning and disinfection as recommended by the International Society of Ultrasound in Obstetrics and Gynecology with the use of low- or high-level disinfectants compiled and available on https://obgyn.onlinelibrary.wiley.com/doi/epdf/10.1002/uog.22027, and also the methods and compatibility with the equipment have been already provided by various vendors. The technique of performing ultrasound of chest for the patients has been stipulated by Soldati, et al.,[48] which recommends the use of convex or linear transducers according to the individual patients with low mechanical index < 0.7 and suggests to avoid the usage of tissue harmonic imaging, Doppler imaging, compound, and contrast enhancing methods. For those who are not able to maintain a sitting position or are on invasive method of ventilation, the checklist consists of a minimum of eight areas which would amount to the total scan duration of approximately 2–3 min. The region of interest is anteriorly in the mid clavicular line above and below the internipple line, laterally midaxillary line both above and below the internipple line, and posteriorly the base of the lung on both sides.[49] Similarly, for stable patients, they have proposed 14 sites to be examined along the anterior, laterals and posterior aspects of the chest wall.[48]

| Figure 6: Tips for preventing the spread of germs, according to the Centers for Disease Control and Prevention – source: https://www.cdc.gov/coronavirus/2019-ncov/downloads/stop-the-spread-of-germs.pdf

Conclusion

The rapidly spreading COVID-19 pandemic has emerged as a critical challenge to the community and the health-care individuals, placing their lives in jeopardy. The infection continues to spread and various measures are being taken for its containment including rigorous government decisions and emphasis of social distancing, hand sanitization, cough etiquettes, and use of masks to bring down its impact in terms of lives lost and rate of spread of infection. The only available laboratory test is RT-PCR which is variable through the course of illness; other supportive laboratory parameters are lymphopenia, raised erythrocyte sedimentation rate, CRP, LDH, etc., The crucial yet elusive role of imaging has been evolving in parallel with the knowledge of the disease. A summary of the review of the pandemic is given in [Table 5].

Table 5 Summary of the review of pandemic

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflict of Interest

There are no conflicts of interest.

Acknowledgment

The authors would like to thank Dr. Rajat Agrawal, Junior Resident, Department of Radiodiagnosis, Tata Memorial Hospital, Mumbai, Maharashtra, India.

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Address for correspondence

Publication History

Received: 10 May 2020
Accepted: 25 June 2020
Article published online:
17 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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| Figure 1: (a and b) COVID-19 cases and deaths worldwide by the World Health Organization – available at https://who.sprinklr.com/accessed April 22, 2020

| Figure 2: Depiction of how droplets can travel in air and spread infection

| Figure 3: (a and b) A 45-year-old male patient had a history of contact with a COVID-19-positive family member who presented to the COVID clinic with a history of cough and fever of 3 days’ duration. The patient had sudden clinical deterioration and breathlessness; a computed tomography thorax was advised. The findings on computed tomography thorax axial and coronal images (a and b) revealed multifocal patchy areas of round to ill-defined consolidation predominantly in the posterior and basal segments of the lung with surrounding ground-glass opacities. Reverse transcriptase-polymerase chain reaction tested positive for COVID-19

| Figure 4: A 45-year-old female patient with carcinoma breast developed fever and breathlessness after infusion of paclitaxel therapy. Computed tomography axial image was suggestive of faint bilateral ground-glass opacities predominantly in the bilateral lung bases. On cessation of therapy, there was significant improvement in the ground-glass opacities

| Figure 5: (a) An elderly patient presented with haemoptysis and breathlessness. Axial computed tomography lung window demonstrates patchy areas of ground-glass opacities with interlobular and intralobular septal thickening – giving “crazy paving pattern” in the right upper lobe and also in the bilateral lower lobes. Imaging findings were consistent with diffuse pulmonary haemorrhage. (b) Patient presented to the casualty with acute-onset of chest pain and cough. Axial computed tomography image lung window demonstrates a patch of consolidation in the subpleural location with central ground-glass opacities – “atoll sign” (reverse halo sign) in the right upper lobe was consistent with cryptogenic organizing pneumonia. Significant resolution was seen with corticosteroid treatment. (c) Selected axial computed tomography image lung window shows diffuse randomly distributed tiny parenchymal nodules “miliary pattern” in this elderly female patient on chemotherapy presenting with a new onset of cough, breathlessness, and fever since a month. Overall findings are in favour of infective etiology – miliary tuberculosis. Sputum was positive for acid-fast bacilli. The patient is on ATT and follow- up (d) Selected axial sections of CT chest lung window with bilateral perihilar ground glass opacities multiple pulmonary cysts with relative peripheral and subpleural sparing. No evidence of pleural effusion or mediastinal lymphadenopathy. Overall findings were in favour of pneumocystis jiroveci pneumonia which is a common opportunistic pathogen in immunocompromised individuals. The patient presented with sudden loss of consciousness and breathlessness and workup revealed HIV positive status with low CD4 counts 28 cells/mm³

| Figure 6: Tips for preventing the spread of germs, according to the Centers for Disease Control and Prevention – source: https://www.cdc.gov/coronavirus/2019-ncov/downloads/stop-the-spread-of-germs.pdf

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