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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 7  |  Page : 10-15

Clinical manifestations, laboratory findings, and imaging in COVID-19


1 Department of Pediatric Critical Care and Pulmonology, Sri Balaji Action Medical Institute, New Delhi, India
2 Senior PICU Fellow, PICU, St George's Hospital, London, United Kingdom

Date of Submission15-Apr-2020
Date of Decision25-Apr-2020
Date of Acceptance30-Apr-2020
Date of Web Publication29-May-2020

Correspondence Address:
Dr. Pradeep Kumar Sharma
Flat No 48, Pocket-7, Sector-21, Rohini, New Delhi - 110 086
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPCC.JPCC_56_20

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  Abstract 


Coronavirus disease 2019 (COVID 19) caused by severe acute corona virus 2 (SARS-CoV2) strain is an ongoing pandemic affecting more than 200 countries worldwide. On April 15, 2020 total 2,000,995 persons are affected with 126,783 deaths worldwide. It is mainly an adult disease, but it can affect any age group. Children are less likely to be affected and severity and mortality is less compared to adults. Infants however are more prone to develop severe disease. The disease has human to human transmission with an incubation period of 2–14 days. It spread through respiratory droplets which enter the body through respiratory tract or conjunctiva. Children usually present with fever, cough, and breathing difficulty. Diarrhea and abdominal pain can also be seen. Pulmonary and extrapulmonary complications can occur, but these are less frequent in children except infants. Critical illness and mortality increase significantly with age and associated comorbidities. In children, no typical laboratory findings are seen. Radiological investigations are not specific and hence their routine use is not recommended especially in milder cases. Subpleural lesion with ground glass opacification is the most common radiological finding. Confirmation is done by real-time reverse transcriptase polymerase chain reaction. The management is mainly supportive. Drugs and vaccines are under trial. Prevention is done by breaking the chain of transmission.

Keywords: Clinical manifestations, corona virus, COVID 19, pediatric


How to cite this article:
Goswami G, Vinayak N, Kumar M, Sharma PK. Clinical manifestations, laboratory findings, and imaging in COVID-19. J Pediatr Crit Care 2020;7, Suppl S1:10-5

How to cite this URL:
Goswami G, Vinayak N, Kumar M, Sharma PK. Clinical manifestations, laboratory findings, and imaging in COVID-19. J Pediatr Crit Care [serial online] 2020 [cited 2020 Jul 14];7, Suppl S1:10-5. Available from: http://www.jpcc.org.in/text.asp?2020/7/7/10/285372




  Introduction Top


Corona viruses (CoV) belongs to the family Coronaviridae and it is a ribonucleic acid (RNA) virus containing glycoprotein spike on envelop hence the name (corona means crown in Latin). Its genome is approximately 27–34 kilobase, which is largest among all RNA viruses. Genetic recombination rate in CoV is very high due to transcription errors and RNA dependent RNA Polymerase jumps. It is a zoonotic pathogen causing infection in mammals and birds. The virus causes respiratory, gastrointestinal, hepatic, and neurological symptoms. Clinical features are varied ranging from mild respiratory infection to severe illness requiring intensive care unit admission.[1] Previously, it has caused severe acute respiratory infection (SARS) and Middle East respiratory syndrome. At present, a new strain of CoV known as novel coronavirus, (nCoV) or severe acute corona virus 2 (SARS CoV 2) has emerged and is responsible for coronavirus disease 2019 (COVID 19). On December 12, 2019, an unknown pneumonia emerged in Wuhan State of Hubei Province in China and on January 7, 2020 a new type of Coronavirus (nCoV) was isolated.[2] The World Health Organization (WHO) named this disease as COVID 19.[3] The virus has human to human transmission and is responsible for the current pandemic, involving 204 countries with a total of 2,000,995 confirmed cases among which 126,783 died.[3],[4] COVID 19 is mainly an adult disease however every age group is susceptible including newborn. The disease is less severe in children however, they may be very good source for transmission of disease. Children accounted for 1%–5% of confirmed COVID-19 cases and death is extremely rare.[5],[6],[7],[8],[9] According to Centre for Disease Control (CDC) China, children (0–19 years) constitute only 2% of all confirmed COVID-19 cases (72314 cases) among which only 0.9% were <10 years old.[8] As per CDC United States of America (USA) children less than 18 years accounted for 1.7% (2572/149082) of cases only.[9] In India, total of 11439 cases reported till April 15, 2020, and death toll has reached to 337.[10] Age-wise distribution showed that 8.6% of all confirmed cases were under 20 years, 41.9% were in 21–40 years age group, 32.8% in 41–60 years of age group and 16.7% cases were more than 60 years. Infection in males was 3 times more common than females. The aim of this review article is to characterize the clinical manifestations, laboratory, and imaging findings in COVID 19 particularly focusing on the pediatric age group.


  Clinical Manifestations Top


The median incubation period is estimated to be 5.1 days (2–14 days) and 97.5% of those who develop symptoms will do so within 12 days of infection.[11] Children with COVID-19 infection usually have milder symptoms than adults. No specific clinical feature can reliably distinguish COVID-19 from other viral respiratory infections. Common presenting symptoms are fever, cough, sore throat, and shortness of breath. Rhinorrhea/nasal congestion, conjunctivitis, nausea, vomiting, abdominal pain, and diarrhea are less commonly seen.[9],[12],[13],[14] Fever in children with COVID-19 tends to subside within 3 days and cough is usually dry and nonproductive.[13]

Dong et al., in his study of 2143 suspected children observed that 34.1% had laboratory confirmed disease. The median age was 7 years (interquartile range 2–13 years) and 56.6% were boys. They observed that 94 (4.4%), 1091 (50.9%), and 831 (38.8%) patients were diagnosed as asymptomatic, mild, or moderate cases, respectively. Severe disease and critical illness were seen in 5.2% and 0.6%, respectively. The proportion of severe and critical cases by age was 10.6% (<1 year), 7.3% (1–5 years), 4.2% (6–10 years), 4.1% (11–15 years), and 3% (>16 years).[12]

Lu et al., in his series of 171 confirmed positive children observed that the most common symptoms were cough (48.5%), pharyngeal erythema (46.2%), and fever of at least 37.5°C (41.5%). Fever >38°C was observed in 32.1% children. Diarrhea, fatigue, rhinorrhea, and vomiting were observed in 8.8%, 7.6%, 7.6%, and 6.4% children, respectively. Low oxygen saturation (<92%) were observed only in 2.3% and tachypnea in 28.7% cases.[13]

According to a recent USA CDC report, 73% of 291 children were symptomatic, with fever (56%) and cough (54%) being the most common symptoms. Shortness of breath was seen in 13% cases and intensive care admissions were reported in 0.6%–2% of cases.[9] Wang et al. in his series of 34 children observed that 50% had fever, 38% had respiratory symptoms such as cough, 26% had mild disease, and 9% were asymptomatic.[14] All these pediatric series observed a positive COVID-19 family contact in 80%–90% cases.[9],[12],[13],[14]

High grade fever at the time of admission in adults predicts poor outcome but in children no such correlation is observed.[15] At the end of 1st week of infection, a subset of patients develops severe pneumonia and acute respiratory distress syndrome (ARDS), which is due to cytokine storm.[16] The median duration between appearance of symptoms and dyspnea is 5 days and ARDS is 8 days. From published data, it is observed that 5%–30% adults and 1%–2% of children require intensive care admission.[9],[17] Complications and severe disease are more common in elderly population and patients with comorbidities such as diabetes, chronic respiratory diseases, cardiovascular diseases, hypertension, malignancy, and patients on immunosuppressant. Case fatality rate among these patients varies between 5% and 10% as compared to 0.9% in patients without any comorbidity.[17] Pulmonary complications are acute lung injury, ARDS, and respiratory failure. Extrapulmonary complications include acute kidney injury, viral hepatitis, cardiac injury, encephalopathy, shock, coagulopathy, and multiorgan dysfunction.[12],[18] However, these were rarely observed in children except infants.[9],[12] Median duration of hospital stay in those who recovered was 10 days, however pediatric-specific data are lacking.


  Diagnosis Top


A COVID-19 case is suspected when a patient with acute onset fever and respiratory illness has history of travel to a country or an area reporting local transmission or has contact with a confirmed COVID-19 case within 14 days prior to onset of symptoms. Case definitions for suspected, probable and confirmed COVID-19 cases as given by the WHO.[19]

Suspect case

  1. A patient with acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset


  2. OR

  3. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case (see definition of contact) in the past 14 days prior to symptom onset


  4. OR

  5. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation.


Probable case

  1. A suspect case for whom testing for the COVID-19 virus is inconclusive


  2. OR

  3. A suspect case for whom testing could not be performed for any reason.


Confirmed case

A person with laboratory confirmation of COVID-19 infection, irrespective of clinical signs and symptoms.


  Investigations Top


Confirmatory tests

Molecular diagnostics

Laboratory testing of a suspected case is confirmed by the detection of nCoV-2019 RNA by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Upper respiratory samples (nasopharyngeal swab or throat swab) and lower respiratory samples (expectorated sputum, endotracheal aspirate, and bronchoalveolar lavage) are used for testing.[20] Induction of sputum is however not recommended. Negative results do not rule out the possibility of COVID-19 virus infection. This may be due to (i) poor quality of the specimen, (ii) the specimen is collected very early or late in the infection, (iii) the specimen is not handled and shipped appropriately, or (iv) technical reasons inherent in the test, for example, virus mutation or PCR inhibition. Repeat or additional testing is advised in case of high suspicion if first test is negative.

Serological test

These are rapid diagnostic tests and are typically a qualitative lateral flow assay that is small, portable, and can be used at point of care. These tests may use blood samples from a finger prick, saliva samples, or nasal swab fluids. These tests most frequently test for patient immunoglobulin G (IgG) and IgM antibodies against nCoV-2019. Results of these tests are available within hours and these are more cost effective than molecular tests. However, these tests lack sensitivity (34% to 80%) and negative report needs to be confirmed either with rRT-PCR or repeating antibody testing after 10 days. Recently, the Indian Council of Medical Research (ICMR) has approved its use for screening of areas reporting clusters (containment zone) and in large migration gatherings/evacuees centers.[21]

ICMR has recommended a revised strategy of COVID-19 testing in India according to which all individuals meeting the following criteria should be tested for COVID-19.[22]

  1. All symptomatic individuals who have undertaken international travel in the last 14 days
  2. All symptomatic contacts of laboratory confirmed cases
  3. All symptomatic health-care workers
  4. All patients with severe acute respiratory illness (fever AND cough and/or shortness of breath)
  5. Asymptomatic direct and high-risk contacts of a confirmed case should be tested once between day 5 and day 14 of coming in his/her contact
  6. In hotspots/cluster and in large migration gatherings/evacuees centers: All symptomatic individuals having influenza such as illnesses (fever, cough, sore throat, runny nose) should be tested by rRT-PCR (within 7 days of illness) OR by antibody test (after 7 days of illness). A negative antibody test should be confirmed by rRT-PCR.


Laboratory test

Children having COVID-19 do not show consistent derangements in white blood cell count. Normal leukocyte count was found in 69.6%, with 15.2% having an increased count and 15.2% having a decreased count.[23] In adults, lymphocytopenia was reported in up to 70% cases whereas in children it was seen in 3.5% cases only.[13],[23],[24]

Inflammatory markers such as C-reactive protein and procalcitonin were elevated in 13.6% and 10.6% cases, respectively. Procalcitonin levels usually do not elevate in COVID-19, therefore bacterial pneumonia or COVID-19 with superimposed bacterial infection should be suspected if procalcitonin levels are elevated.[13],[25]

Patients having severe COVID-19 infection may have multiorgan dysfunction with deranged coagulation profile, liver function test, and renal function test. D-dimer, lactate dehydrogenase, and creatine phosphokinase may also be elevated. Critically sick patients may have elevated interleukin (IL) 2, IL-6, IL-7, IL-10, granulocyte colony-stimulating factor, interferon gamma-induced protein 10, monocyte chemotactic protein 1, macrophage inflammatory protein alpha, and tumor necrosis factor-α.[24] Elevated ferritin, neutrophil count, D-dimer, blood urea, and creatinine levels are associated with poor prognosis.[26]

Radiology

Radiological abnormalities are common in COVID 19 patients. Even asymptomatic children may have radiological abnormalities. Chest X-ray shows bilateral infiltrates or ground glass opacities, but they may not be apparent in early disease [Figure 1]. Computed tomography (CT) scan is more sensitive in detecting lung abnormalities. Xia et al. found that 80% children had an abnormal CT scan. Ground glass opacities were observed in 60%, consolidation with surrounding halo sign in 50% and fine mesh shadows in 20% of CT scans. Most of the lesions were subpleural in distribution (100%) and bilateral disease distribution was seen in 50% cases.[25] Lu et al. described ground glass opacities in 32.7%, local patchy shadow in 18.7%, bilateral patchy shadows in 12.35%, and interstitial abnormalities in 1.2% of CT scans.[13] No studies have described lobar collapse, pneumothorax, or effusion in children with COVID 19. In view of disease being mostly nonsevere in children routine use of CT is not recommended.
Figure 1: Reference chest X-ray of a 13-year-old child on day 5 of illness showing bilateral consolidation and ground glass opacities in lower and middle zone and subpleural regions

Click here to view


Management

There is no specific treatment for COVID-19 till date. The management remains symptomatic and supportive.[27] The detailed management is available in subsequent articles in this issue.

Prevention

Prevention can be done by breaking the chain of transmission. Suspected or confirmed case should be isolated in a well-ventilated room with adequate sunlight. Patient and caregiver both should wear mask and practice hand hygiene. In hospital settings, patients should be isolated in a separate room. Negative pressure room is usually not required but air condition should turn off to prevent spreading of contaminated air outside the room. Health-care workers treating the COVID 19 patients should wear personal protective equipment's with proper donning and doffing technique. The room, surface, and equipment's should be decontaminated regularly. Patients can be discharged when they are afebrile for 3 days and 2 consecutive negative molecular tests at 24-h interval. At community level people should avoid gathering, practice hand hygiene and cough etiquette and avoid nonessential outing or travel, maintain social distance of 1 m and avoid touching mouth and nose.[28]


  Summary Top


COVID-19 caused by SARS-CoV 2 strain is an ongoing pandemic affecting more than 200 countries worldwide. It is mainly an adult disease but it can affect any age group. The silver lining for pediatric COVID-19 disease is that children are less likely to be affected and severity and mortality is less compared to adults. Infants however are more prone to develop severe disease. Critical illness and mortality increase significantly with age and associated co-morbidities. The disease has human to human transmission with an incubation period of 2–14 days. It spread via respiratory droplets which enter the body through respiratory tract or conjunctiva. Children usually present with fever, cough, and breathing difficulty. Diarrhea and abdominal pain can also be seen. A simple clinical classification of pediatric COVID-19 is shown in [Table 1]. Pulmonary and extrapulmonary complications can occur, but these are less frequent in children except infants. No typical laboratory findings are seen. During the 1st week of illness patients should be monitored for deterioration of respiratory symptoms and during the 2nd week for cytokine storm with rise in inflammatory markers such as ferritin, triglycerides, and IL 6. Radiological investigations are not specific and hence their routine use is not recommended especially in milder cases. Subpleural lesion with ground glass opacification is the most common radiological finding. Confirmation is done by rRT-PCR. Management is mainly supportive. Drugs and vaccines are under trial. Prevention is done by breaking the chain of transmission.
Table 1: Clinical classification of pediatric COVID 19

Click here to view


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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