Year : 2021 | Volume
: 12 | Issue : 1 | Page : 11--14
Hematological profile in COVID-19, whether it matters in children
Purnima Margekar1, Ashok Kumar2, Venu Gopal Margekar3, Shubha Laxmi Margekar4,
1 Department of Pediatrics, AIIMS, Raipur, Chhattisgarh, India
2 Department of Medicine, Santosh Medical College and Hospital, Ghaziabad, Uttar Pradesh, India
3 Department of Medicine, Yashoda Superspeciality Hospital, Ghaziabad, Uttar Pradesh, India
4 Department of Medicine, Lady Hardinge Medical College and SSK Hospital, New Delhi, India
Dr. Shubha Laxmi Margekar
Department of Medicine, Lady Hardinge Medical College, Room No. 1014, Old Building, 1st Floor, New Delhi - 110 001
Coronavirus disease 2019 (COVID-19) is an acute respiratory and systemic illness, and is a public health emergency which has involved all the continents. Though limited data is available for infection in pediatric population, infection seen in children is of milder form. During this pandemic, documentation of laboratory predictors to discriminate between mild and severe forms of this infection would be helpful. Various hematological parameter alterations in the pediatric COVID-19 cases show anemia, thrombocytopenia, eosinopenia, and inconsistent leukocyte indices. It may be too early to say right now as to what extent will these alterations help us in outlining the severity of disease or transmission of disease. However, it will be pertinent to understand these abnormalities, and keep track of them, so as to understand the disease, as the pandemic unfolds.
|How to cite this article:|
Margekar P, Kumar A, Margekar VG, Margekar SL. Hematological profile in COVID-19, whether it matters in children.Indian J Med Spec 2021;12:11-14
|How to cite this URL:|
Margekar P, Kumar A, Margekar VG, Margekar SL. Hematological profile in COVID-19, whether it matters in children. Indian J Med Spec [serial online] 2021 [cited 2023 Jan 29 ];12:11-14
Available from: http://www.ijms.in/text.asp?2021/12/1/11/306251
Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus, is a rapidly spreading and devastating infection which has become a global pandemic. The first case of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) disease (COVID-19) emerged in Wuhan City of Hubei Province China, in December 2019. There was a continuous growth in the cases and the virus was spreading globally which forced the World Health Organization to declare a global pandemic on March 11, 2020. It has affected more than 200 countries worldwide. As the pandemic is progressing over time, as of late October 2020, more than 300 million cases are diagnosed across the world, with more than 1 million reported deaths attributed to this disease.
Coronaviruses are RNA viruses with glycoprotein spikes that give them a crown-like appearance. Four species have been in circulation for a long time and cause mild respiratory disease. They have a huge genetic diversity and have jumped the species barrier, leading to severe respiratory disease (SARS virus in 2002–2003 and the MERS virus in 2012–2013). In December 2019, this novel coronavirus emerged in China that was later termed SARS-CoV-2 which causes the disease COVID-19.
Spread of Infection
It is mostly by droplets from infected people during sneezing and coughing. Large droplets that travel for 1–2 m, settle on surfaces on which they remain alive for hours or days. Infected person can also spread the infection even before the onset of symptoms. Infection is acquired by either inhalation of the infected droplets or touching surfaces/fomites contaminated with the infected droplets and then touching the eyes, nose, and mouth, but latter is not thought to be the main way the virus spreads.
The viral load in the nasopharynx of children is likely the same or higher as compared with that of adults. However, it is not very well clear whether children and adults both can equally transmit the virus effectively and whether children are as susceptible to infection by SARS-CoV-2 as compared to adults. Recent studies have suggested that children can spread the virus effectively in households and camp settings.,
The number of reported COVID-19 cases in pediatric population is low as compared to that of adults. The school closures and taking proper measures to reduce community transmission may explain the low incidence in children compared to adults. Comparing the period before and after the opening of school and other activities may be helpful in providing information regarding the trends in pediatric infections.
Many infected individuals' symptoms range from mild, moderate, to severe and profound inflammatory response that leads to acute lung injury and hypoxemic respiratory failure. The most common cause of death in individuals (adults) with COVID-19 is acute respiratory distress syndrome. In pediatric population, symptoms are mostly mild and the number of severe and critical cases is less as compared to that of adult patients, which suggests that the clinical manifestations of COVID-19 in children may be less severe as compared to that in adult patients. Similar to adults, risk factors for severe illness for COVID-19 in children might be asthma, chronic lung disease, diabetes, obesity, sickle cell disease, or immunosuppression.
In the ongoing pandemic, optimization of the limited human and technical resources is of crucial importance. Early identification and use of routine laboratory parameters will help to identify the severity of disease and to improve the clinical situational awareness, to target patients at increased risk. Availability of testing (laboratory investigation) allows us to describe the disease more accurately.
The hematological alteration potentiality serves as an indicator to provide guidance for the assessment of severity, treatment, and prognosis for COVID-19 patients. A clear pattern of difference in inflammatory, hematologic, and immune parameter abnormalities could be found between patients with or without severe or critical disease. Very limited studies are available on hematological parameter alteration in pediatric COVID-19 cases worldwide and in India as a whole owing to the relatively lower incidence of the disease in the pediatric population. Moreover, laboratory data may provide hints to the underlying pathophysiology and the body's immunological response.
Hematological parameters in COVID-19
The common haematological parameters that are ascertained in the pediatric age group patients and reported by various studies are being discussed one by one, with whatever literature could be available.
In the cases of COVID-19 infection, lower level of hemoglobin is observed. In a study by Tiwari et al. (from North India) of 11 patients, 54.5% (6/11) of the children had anemia, with 45.5% (5/11) cases having hemoglobin level <10 mg/dL. In another study from China (Wuhan) of 244 confirmed cases, 193 children with symptomatic COVID-19 infection had significantly lower hemoglobin levels. Lower level of hemoglobin indicates the severity of infection. In a meta-analysis, hemoglobin value was significantly lower in COVID-19 adult patients with severe disease, compared to those with milder form.
Neutrophilia in COVID-19 patient indicates cytokine storm and hyperinflammatory state. As minimal data on severe cases of children are available, in a case series by Jiehao et al., which provided data of ten symptomatic children, only one of the three cases that had alternations in leukocyte or neutrophil counts also had radiologic changes suggestive of pneumonia. A study by Liu et al. in January 2020 showed three out of six cases with decreased neutrophil count. In a study conducted in North India by Tiwari et al., neutrophilia was observed in 36.3% of cases and children younger than 10 years, showed more predominant neutrophilia as compared to children above 10 years; normal total leukocyte count was found in 36.3% (4/11); leukopenia in 9.1% (1/11), and leukocytosis in another 54.5% (6/11) of cases.
Neutrophil-to-lymphocyte ratio (NLR) is a biomarker for the assessment of the severity of bacterial infections and the prognosis of patients with pneumonia and tumor. NLR may serve as a marker of early risk identification in COVID-19 infection. Among pediatric cases, 27.3% had raised NLR above the cutoff value of 3.13. In a study by Tiwari et al., the mean NLR of the adult cases was 2.7, which was below the cutoff value of 3.13
Lymphocytes are components of the cellular immune system and include B cells and T cells which are present in the peripheral blood; about 75% of the lymphocytes are T cells and 25% are B cells. Lymphocytopenia may go unnoticed if white blood cell (WBC) count is checked without differential as lymphocytes account for a small percentage (20%–40%) of the total WBC count.
Lymphopenia is a common finding in patients with COVID-19 infection. In adults, studies have reported very high rates of lymphocytopenia. Guan et al. studied 1099 patients and found that the rate was 83.2% in adults. However, in a study by Lu et al., among a total of 171 children, there were only 6 children (3.5%) with lymphocytopenia. Henry et al. in a meta-analysis on infants and children have shown that lymphocytopenia is much less common. The pattern of laboratory abnormalities was not consistent, as in a study by Ya-Nan et al. including seven children, none showed thrombocytopenia, whereas increased lymphocyte count was seen in a study by Du et al.
In another study by Wu et al. abnormal lymphocyte count was found in ten cases (13.5%), among whom six (8.1%) had an increased number of lymphocytes (highest value 9.03 × 109/L) and four (5.4%) had a reduced number of lymphocytes (lowest value 0.80 × 109/L). Despite the normal leukocyte count, lymphocytopenia, neutropenia, and neutrophilia were seen in 30.0%, 23.3%, and 13.3% of children, respectively, according to Yarali et al.
Four mechanisms are responsible for lymphopenia in COVID-19. First, this virus may directly invade lymphocytes that leads to lymphocyte death. Lymphocytes express angiotensin-converting enzyme-2 receptor, which is specific for coronavirus and is a direct target for this agent. Second, SARS-CoV-2 infection could directly destroy lymphatic organs, such as thymus and spleen. Third, the various inflammatory cytokines that are released during the course of COVID-19 infection may result in lymphocyte apoptosis. These cytokines including tumor necrosis factor-α and interleukin-6 may lead to lymphocyte deficiency. Fourth, coexisting lactic acidosis could inhibit lymphocytes. Hyperlactic acidemia, which is a complication of severe type of COVID-19, might suppress lymphocyte proliferation.
Du et al. reported that WBC and lymphocyte counts were found to be highly decreased in symptomatic cases than that in asymptomatic cases, which can be explained by a lower inflammatory response in asymptomatic children. Interestingly, higher value of lymphocyte was reported in symptomatic cases. Due to the relative immaturity of immune system of children and differences in the immune response as compared to that of adults, lymphocytopenia may not be seen., Moreover, there may be limited number of severe cases of COVID-19 in children.
A pattern of neutropenia and lymphocytopenia was observed in SARS (emerged in 2002), showing that the WBC count is typically normal or reduced with decreased neutrophil and/or lymphocyte count.,,, Henry et al. reported similar finding in their study of SARS epidemic 2002 with lymphocytopenia in 46% and neutropenia in 52% of children. Furthermore, abnormal lymphocyte count was found in the studies by Wu et al. and Tiwari et al., with the presence of lymphocytosis in 8.1% and 27.3% as well as lymphocytopenia in 5.4% and 27.3% of cases, respectively.,
In two studies by Chen et al. and Sun et al., a total of 9 cases, reported lymphocyte subsets, of which 44.4% had an increase in CD4+ cell counts, with only 1 patient (11.1%) having increased CD8+ cell count. However, 66.6% (6/9) of patients had decreased counts of natural killer cells.
Monocyte count was normal in 81.8% of the pediatric cases, while only 18.2% of the cases showed mild monocytosis in an observation made by Tiwari et al. Minimal data is available regarding the documentation of monocytosis in pediatric cases. However, for adults, Henry et al. in a meta-analysis on 3377 patients demonstrated reduction of monocytes in COVID-19. Moreover, Xiong et al. report higher monocyte counts in symptomatic as compared to asymptomatic COVID-19 children.
One cohort study reported vacuolated monocyte (13.3%) and hypergranulation/lobulation abnormalities in neutrophils (36.7%) in peripheral smears of children with COVID-19 which was high compared to that of COVID-19-negative cases.
In the early stages of COVID-19 infection, eosinophil count decreases. The mechanism may be related to glucocorticoid exposure. Due to stress response in these patients, glucocorticoid secretion could result in inhibition of eosinophil release in the bone marrow. Eosinopenia was seen in 36.3% (4/11) of pediatric cases. Most studies have reported eosinopenia in their adult patients. Zhang et al. reported that more than half of the patients admitted with COVID-19 (53%) had eosinopenia. Similarly, Du et al. reviewed 85 fatal cases of COVID-19 and noticed 81% of the patients with absolute eosinophil counts below the normal range. Furthermore, eosinophil levels improved in all patients before discharge, which suggests that resolution of eosinopenia may be an indicator of improving clinical status in case of adult patients.
Tiwari et al. reported that 81.8% of cases had platelets within normal limit, while 18.2% of the cases had some degree of thrombocytopenia. On the other hand, Han et al. reported that 14.3% of children showed thrombocytosis. In a cohort study by Yarali et al., thrombocytopenia was detected in four patients, of which one patient had aplastic anemia and COVID-19 and the rest three had SARS-CoV-2 negativity. In a meta-analysis, low platelet count was associated with increased severity and increased mortality in adults with COVID-19. The minimal reporting of thrombocytopenia in children may be related to the better clinical prognosis of the disease.
Platelet–lymphocyte ratio (PLR) is a parameter for predicting the degree of cytokine storm, which might provide a new indicator in the monitoring of patients with COVID-19., Adult patients with higher PLR during treatment had longer average hospitalization days. In their study, Tiwari et al. reported that PLR was slightly higher in pediatric patients as compared to that of adult patients.
A consistent pattern of laboratory derangements is yet to be observed in children with confirmed COVID-19, unlike adults. Milder form is seen in SARS-CoV-2; the possible explanations include less frequent exposure to the main sources of transmission (closed schools); presence of asymptomatic or mildly symptomatic patients, therefore testing is less often, leading to an underestimate of the true numbers of infected individuals; the immature immune system; and the presence of unidentified factors.
PLR might act as a new indicator in monitoring patients with COVID-19. NLR is a biomarker for the assessment of the severity of infections and a marker for early risk identification in COVID-19.
Leukocyte indices do not appear to be a reliable marker for assessing the severity and diagnosis of disease as they appear to be inconsistent in children as compared to adults with SARS-CoV-2. Hence, further studies can be conducted on the role of lymphocyte and other hematologic markers and their interaction with SARS-CoV-2 for timely assessment of the severity of COVID-19.
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|1||Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020;26:450-2.|
|2||World Health Organization. WHO Timeline—COVID-19, 2020. Available from https://www.who.int/news-room/detail/27-04-2020-who -timeline—covid-19. [Last accessed on 2020 Nov 04].|
|3||World Health Organization. WHO Timeline—COVID-19, 2020. Available from https://www.who.int/data/detail/19-10-2020-who -timeline—covid-19. [Last accessed on 2020 Nov 04].|
|4||Joseph T, Ashkan M. International Pulmonologist's Consensus on Covid-19. Joseph T, India. 1st edn; 2020. p. 1-38.|
|5||Heald-Sargent T, Muller WJ, Zheng X, Rippe J, Patel AB, Kociolek LK. Age-related differences in nasopharyngeal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) levels in patients with mild to moderate coronavirus disease 2019 (COVID-19). JAMA Pediatr 2020;174:902-3.|
|6||Park Y, Choe Y, Park O, Park S, Kim Y, Kim J, et al. Contact tracing during coronavirus disease outbreak, South Korea, 2020. Emerg Infect Dis 2020;26:2465-8.|
|7||Szablewski CM, Chang KT, Brown MM, Chu VT, Yousaf AR, Anyalechi N, et al. SARS-CoV-2 transmission and infection among attendees of an overnight camp Georgia, June 2020. MMWR Morb Mortal Wkly Rep 2020;69:1023-5.|
|8||Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics 2020;doi: 10.1542/peds.2020-0702.|
|9||Henry BM, de Oliveira MH, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): A meta-analysis. Clin Chem Lab Med 2020;58:1021-8.|
|10||Tiwari N, Nath D, Madan J, Bajpai P, Madan U, Singh S, et al. Novel insights into the hematological parameter abnormalities in pediatric COVID-19 cases: Observation from a preliminary study of 11 pediatric COVID-19 cases in a tertiary care center of North India. Saudi J Pathol Microbiol 2020;5:276-84.|
|11||Xiong X, Chua GT, Chi S, Kwan MY, Wong WH, Zhou A, et al. Haematological and immunological data of Chinese children infected with coronavirus disease 2019. Data Brief 2020;31:105953.|
|12||Lippi G, Mattiuzzi C. Hemoglobin value may be decreased in patients with severe coronavirus disease 2019. Hematol Transfus Cell Ther 2020;42:116-7.|
|13||Jiehao C, Jin X, Daojiong L, Zhi Y, Lei X, Zhenghai Q, et al. A case series of children with 2019 novel coronavirus infection: Clinical and epidemiological features. Clin Infect Dis 2020;71:1547-51.|
|14||Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med 2020;382:1370-1.|
|15||Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage. medRxiv 2020;18:206.|
|16||Guan WJ, Ni ZY, Hu YU, Liang W-H, Ou C-Q, He J-X, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.|
|17||Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 infection in children. N Engl J Med 2020;382:1663-5.|
|18||Henry BM, Lippi G, Plebani M. Laboratory abnormalities in children with novel coronavirus disease 2019. Clin Chem Lab Med 2020;16:16.|
|19||Han Y-N, Feng Z-W, Sun L-N, Ren X-X, Wang H, Xue Y-M, et al. A comparative- descriptive analysis of clinical characteristics in 2019-coronavirus-infected children and adults. J Med Virol 2020;92:1596-602.|
|20||Du W, Yu J, Wang H, Zhang X, Zhang S, Li Q, et al. Clinical characteristics of COVID19 in children compared with adults in Shandong Province, China. Infection 2020;16:1-8.|
|21||Wu Q, Xing Y, Shi L, Li W, Gao Y, Pan S, et al. Coinfection and other clinical characteristics of COVID-19 in children. Pediatrics 2020;146:e20200961.|
|22||Yarali N, Akcabelen YM, Unal Y, Parlakay AN. Hematological parameters and peripheral blood morphologic abnormalities in children with COVID-19. Pediatr Blood Cancer 2020;e28596.|
|23||Hashemieh M. Hematologic parameters of COVID – 19: A review on alteration of hematologic laboratory findings. Int J Pediatr 2020;8:11321-929.|
|24||Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016;16:626-38.|
|25||Chen F, Liu ZS, Zhang FR, Xiong RH, Chen Y, Cheng XF, et al. First case of severe childhood novel coronavirus pneumonia in China. Chin J Pediatrics 2020;58:179-82.|
|26||Zimmermann P, Curtis N. COVID-19 in children, pregnancy and neonates: A review of epidemiologic and clinical features. Pediatr Infect Dis J 2020;39:469-77.|
|27||Hon KLE, Leung CW, Cheng WT, Chan PK, Chu WC, Kwan YW, et al. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet 2003;361:1701-3.|
|28||Chiu WK, Cheung PC, Ng KL, Ip PLS, Sugunan VK, Luk DCK, et al. Severe acute respiratory syndrome in children: Experience in a regional hospital in Hong Kong. Pediatr Crit Care Med 2003;4:279-83.|
|29||Bitnun A, Allen U, Heurter H, King SM, Opavsky MA, Ford-Jones EL, et al. Children hospitalized with severe acute respiratory syndrome-related illness in Toronto. Pediatrics 2003;112:e261.|
|30||Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatrics 2020;16:251-9.|
|31||Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy 2020;75:1730-41.|
|32||Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan: A retrospective observational study. Am J Respir Crit Care Med 2020;201:1372-9.|
|33||Li Q, Xiuli Ding M, Geqing Xia M, Zhi Geng M, Wang Z, Wang L. A simple laboratory parameter facilitates early identification of COVID-19 patients. medRxiv 2020 https://doi.org/10.1101/2020.02.13.20022830.|
|34||Qu R, Ling Y, Zhang YHZ, Wei LY, Chen X, Li X-M, et al. Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19. J Med Virol 2020;10.1002/jmv.25767.|