Original Research
DOI: 10.31557/apjcc.2022.7.4.637-642
Submitted: 2022-07-28
Published: 2022-11-10

Analysis of Biochemical and Hematological Parameters During the First and Second Wave of SARS-CoV-2 Infection among North-East Indian Cancer Patients

Department of Biochemistry, Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati 781016, Assam, India.
Department of Oncopathology, Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati 781016, Assam, India.
DBT Centre for Molecular Biology and Cancer Research, Dr B Barooah Cancer Institute, Gopinath Nagar, Guwahati 781016, India.
DBT Centre for Molecular Biology and Cancer Research, Dr B Barooah Cancer Institute, Gopinath Nagar, Guwahati 781016
Department of Microbiology, Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati 781016, Assam, India.
Department of Radiation Oncology, Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati 781016, Assam, India.
Department of Gynaecologic Oncology, Dr B Borooah Cancer Institute, Gopinath Nagar, Guwahati 781016, Assam, India.
DBT Centre for Molecular Biology and Cancer Research, Dr B Barooah Cancer Institute, Gopinath Nagar, Guwahati 781016, India.
SARS-CoV-2 Cancer Biochemical parameters hematological parameters

Abstract

Introduction: SARS-CoV-2 (COVID-19) affects respiratory airways as well as the kidneys, hearts etc. This study aims to demonstrate the impact of COVID-19 infection on biochemical and hematological parameters in cancer patients of North-East India.
Methods: The study includes biochemical parameters for 907 and hematological parameters for 1103 cancer patients who were tested for COVID-19 between 1st June 2020 and 1st June 2021. All the data were analyzed by the statistical software SPSS (ver20).
Results: AST (p = 0.023), GGT (p = 0.026) and Urea (p = 0.004) significantly increased in COVID-19 positive cancer patients compared to negative cancer patients. Eosinophils (p=0.01), eosinophils absolute (p=0.01), monocyte (p=0.04) and MCHC (p=0.01) were significantly decreased in COVID-19 positive cancer patients compared to negative. Various biochemical and haematological parameters analysed in our study were found to be altered between the COVID-19 positive and negative group but their association was not found to be statistically significant.
Conclusion: We conclude that in cancer patients of North-East India, significant alterations of biochemical and hematological parameters AST, GGT, Urea, Eosinophils, eosinophils absolute, monocyte and MCHC were found in COVID-19 positive cancer patients compared to negative cancer patients.

Introduction

The SARS-CoV-2 (COVID-19) pandemic has been spreading around the world from 2019. More than 380 lakh people have been infected by this virus in India and almost 4.88 lakh people have lost their lives [1,2]. There is an increased risk of hospitalization and mortality for individuals with co-morbidities such as kidney disease, cardiac disease, heart disease and cancer [3]. The World Health Organization (WHO) has identified and reported multiple variants of SARS-CoV-2 including alpha, beta, gamma, delta and omicron. The effects of different variants of COVID-19 vary from individual to individual and organ to organ [4].

Patients diagnosed with COVID-19 showed changes in haematological and biochemical parameters which may lead to other complications [5]. SARS-CoV-2 due to damage to endothelial cells in various organs resulting in lymphocytic endotheliitis and vasoconstriction [6]. Due to SARS-CoV-2 infection, some other complications like pulmonary embolism (PE), deep vein thrombosis (DVT), venous thrombo-embolism, corpulmonale, systemic, pulmonary arterial thrombosis, embolism and myocardial infarction (MI) were also reported [7-9]. Mortality of COVID-19 patients was found to be most commonly associated with pulmonary embolism and deep vein thrombosis is common among the dead [10]. Various cardiac complications as ischemic cardiac injury can occur in patients [11, 12]. COVID-19 also affects the brain as ACE2 receptors are present in the cerebral cortex and brain stem. Neurological manifestations may be the only ones which can be observed or may occur in combination with respiratory or other symptoms [8,13]. It was also reported that skin, gastrointestinal tract, eyes along with mental complications were also adversely affected due to SARS-CoV-2.

Globally, cancer ranks among the top 10 causes of death. As per the National Cancer Registry Program,

13.9 lakh cancer cases were reported in 2020. Further, in North-East India, the number of cancer patients is increasing throughout the year. The National Centre for Disease Informatics and Research (NCDIR) and the Indian Council of Medical Research suggested in their report that the number of new cancer cases in North East India will rise to 57131 by 2025. Due to the alterations in biochemical and hematological parameters that SARS- CoV-2 causes, a cancer patient’s ability to combat the virus is greatly compromised, which increases mortality. In India, the mortality rate of COVID-19 patients is higher in 2021 than in 2020 because of the emergence of various COVID-19 variants. With this study, we intend to compare the biochemical and hematological parameters of various cancer patients infected with COVID-19 in 2020 and 2021. The study was conducted at a comprehensive tertiary cancer treatment centre, Dr B Borooah Cancer Institute (Dr BBCI) Guwahati. Due to the ongoing COVID-19 pandemic, the COVID-19 testing centre and COVID ward facility are available at the Institute. All the prescribed rules and regulations by State and Central governments regarding COVID-19 were followed. Before admission to the Institute, all new patients must undergo RT-PCR tests for SARS-CoV-2. The objective of the study is to determine the effect of SARS-CoV-2 on the haematological and biochemical parameters of cancer

patients by using their mean values.

Materials and Methods

It was a retrospective and cross-sectional analytic study of biochemical parameters of 907 cancer patients and haematological parameters of 1103 cancer patients tested for COVID-19 by using Real-Time Polymerase Chain Reaction (RT-PCR). Biochemistry and haematological parameters for the blood samples of cancer patients were determined by using the fully automated biochemistry analyzer OCD 6500 (Orthoclinical Diagnostics Vitros 6500) and fully automated haematology analyzer (Sysmex XN-1000) respectively at the Biochemistry Laboratory of our Institute. The RT-PCR test for SARS-CoV-2 virus detection; the nasopharyngeal and oropharyngeal swab samples of cancer patients were collected and the samples were processed for the RT-PCR test within 6 hours from the collection of samples. All the biochemical and haematological parameters were collected for those cancer patients tested for COVID-19 by RT-PCR test from 1st June 2020 to 1st June 2021. Biochemical and haematological parameters of COVID-19 positive and COVID-19 negative cancer patients were statistically analyzed by calculating the mean, standard deviation and P-value for all the parameters. We prepared the comparative statistical analysis of COVID-19 impacts on biochemical and haematological parameters separately by comparing the data with the normal value as standardized by our Institute.

Results

Association of biochemical parameters with COVID-19 infection: A total of 907 SARS-CoV-2 tested cancer patients were enrolled for the study of COVID-19 effects on biochemical parameters of cancer patients. Out of 907 (male (n=530) female (n=377)) cancer patients, 26.75% (n=241) patients were tested COVID-19 positive and the remaining 73.42% (n=666 patients) were COVID-19 negative. The mean age for the negative group was 48.15 and for the positive group was 47.79. The age range for the positive group was 1-85 years and for the negative group was 2-88 years.

In Table1, the mean value of the biochemical parameters are being compared with the normal range.

Biochemistry Parameters Normal Range Negative (n=666) Positive (n=241) p-value
Mean Mean
Age (Years) 48.15 46.79 0.596
RBG (mg/dL) 80.0-130.0 118.83 116.06 0.93
Sodium (meq/l) 130.0-140.0 136.17 135.68 0.232
Potassium (meq/l) 3.5-5.0 4.12 4.12 0.832
Chlorides (mmol/i) 95.0-106.0 100.23 99.49 0.366
Protein (g/dl) 5.7-8.0 7.33 7.15 0.008
Albumin (g/dl) 3.5-5.0 3.84 3.74 0.106
Globulin (g/dl) 2.6-3.5 3.49 3.4 0.03
Alkaline Phosphatase (IU/l) 96.0-297.0 155.63 158.31 0.271
Total Bilirubin (mg/dl) 0.3-1.2 1.14 0.96 0.495
Direct Bilirubin (mg/dl) 0.1-0.4 0.65 0.48 0.664
Indirect Bilirubin (mg/dl) 0.2-0.6 0.5 0.48 0.763
AST (IU/l) 5.0-35.0 46.46 49.27 0.023
ALT (IU/l) 4.0-35.0 40.61 37.29 0.26
Calcium (meq/l) 8.8-10.8 9.25 9 0.098
GGT (IU/l) 0.0-30.0 69.59 77.55 0.026
Urea (mg/dl) 10.0-50.0 27.7 32.63 0.004
Uric Acid (mg/dl) 2.6-6.0 4.38 4.44 0.942
Creatinine (mg/dl) 0.5-1.0 0.72 0.73 0.217
Table 1. Association of Biochemical Parameters between COVID-19 Positive and Negative Cancer Patients.

We observed that protein (p = 0.008) and globulin (p = 0.030) were significantly decreased in COVID-19 positive cancer patients compared to negative patients. AST (p = 0.023) and GGT (p = 0.026) were also significantly increased in COVID-19 positive cancer patients. There was also a further increase from the normal range post-infection. Urea was also (p = 0.004) significantly increased in COVID-19-positive cancer patients but remain within the normal range. Direct bilirubin and ALT were also decreased after COVID-19 infection. Alkaline phosphatase, uric acid and creatinine were in the normal range for both positive and negative cancer patients. RBG, sodium, chlorides, albumin, total bilirubin, indirect bilirubin, potassium, and calcium had not shown any significant difference between COVID-19 positive and negative cancer patients (Table 1). Association of haematological parameters with COVID-19 infection: Analysis of haematological parameters of COVID-19 tested cancer patients (n=1101) was done. COVID-19 positive cancer patients constitute 26.16 % (n=288) and 73.84% (n=813) were COVID-19 negative. Male cancer patients were higher in number (n=644) as compared to female patients (n=457).

We found that eosinophils (p=0.01), eosinophils absolute (p=0.01), monocyte (p=0.04) and MCHC (p=0.01) were significantly decreased in COVID-19 positive cancer patients. The mean age for COVID-19 positive cancer patients was 45.67 years and 47.08 years for COVID-19 negative cancer patients. Basophil, HCT and lymphocytes were lower than the normal range in the COVID-19 positive and negative group of cancer patients.

TLC and neutrophils absolute were in the normal range in cancer patients before COVID-19 infection but they exceeded the normal range post-COVID-19 infection. Neutrophil, basophil absolute, Hb, lymphocyte absolute, MCH, MCV, PCT, PDW and RBC were in the normal range and they have not shown any statistically significant difference between COVID-19 positive and negative groups (Table 2).

Hematological Parameters Normal range Negative (n=813) Positive (n=288) p value
Mean Mean
Eosinophils (%) 1.0-6.0 3.21 2.5 0.01
Neutrophil (%) 40.0-80.0 73.81 74.99 0.105
Basophils (%) 1.0-2.0 0.21 0.19 0.107
Basophils abs (10e9/L) 0.02-0.1 0.02 0.02 0.947
Eosinophils abs (10e9/L) 0.02-0.1 0.23 0.17 0.019
HB (g/dl) 12.0-15.0 10.55 10.66 0.734
HCT (%) 36.0-46.0 32.45 33.03 0.214
Lymphocyte (%) 20.0-40.0 18.85 18.62 0.235
Lymphocyte abs (10e9/L) 1.0-3.0 1.24 1.31 0.968
Monocyte (%) 2.0-10.0 3.86 3.6 0.042
Monocyte abs (10e9/L) 0.2-1.0 0.32 0.41 0.356
MCH (pg) 27.0-32.0 27.46 27.49 0.666
MCHC(g/Dl) 31.5-34.5 32.35 32.18 0.013
MCV (fL) 83.0-101.0 85.04 85.46 0.809
MPV (fL) 7.5-10.5 11.74 11.93 0.051
Neutrophils abs (10e9/L) 2.0-7.0 6.41 7.33 0.164
PCT(%) 0.12-0.36 0.33 0.32 0.899
PDW(%) 25.0-65.0 15.18 15.25 0.949
PLATELETS (10e9/L) 150-400 249.15 235.86 0.09
RBC (10e9/L) 3.8-4.8 3.86 3.89 0.65
RDW(% CV) 11.6-14.0 17.02 17.24 0.069
TLC (10e9/L) 4.0-10.0 8.93 10.12 0.137
Table 2. Association of Haematological Parameters between COVID-19 Positive and Negative Cancer Patients.

We observed that in COVID-19-positive cancer patients mean value for all biochemical parameters except urea has decreased in the second wave compared to the first wave of COVID-19 positive cancer patients. Urea level was significantly increased in COVID-19 positive cancer patients of first wave only. Though biochemical parameters have shown alterations in first and second wave COVID-19-positive cancer patients but these differences failed to achieve the statistical significance. (Table 3).

      1stwave of COVID     2nd wave of COVID  
Biochemistry Parameters Normal Range Positive Negative P value Positive Negative P value
    Mean Mean   Mean Mean  
Alkaline Phosphatase (IU/l) 96.0-297.0 159.24 137.87 0.112 158.31 182.53 0.126
Total Bilirubin (mg/dl) 0.3-1.2 1.16 1.27 0.18 0.96 1.12 0.085
Direct Bilirubin (mg/dl) 0.1-0.4 0.69 0.77 0.16 0.48 0.59 0.096
AST (IU/l) 5.0-35.0 51.42 47.1 0.06 49.27 44.81 0.258
ALT (IU/l) 4.0-35.0 40.2 42.5 0.361 37.29 38.55 0.24
GGT (IU/l) 0.0-30.0 106 72.42 0.062 77.55 48.15 0.19
Urea (mg/dl) 10.0-50.0 30.2 23.83 0.002 32.63 27.43 0.074
Table 3. Association of Biochemical Parameters in Cancer Patients During 1st and 2nd wave of COVID-19 Infection.

Eosinophils (p 1st wave -0.023, p 2nd wave -0.041) and eosinophils absolute (p 1st wave -0.039, p 2nd wave-0.044) had shown significant differences between COVID-19 positive and negative cancer patients in first and second wave of COVID-19 infection. Whereas, MPV (p 1st wave - 0.001) and neutrophils absolute (p 1st wave - 0.014) has shown significant difference between positive and negative cancer patients in the first wave but not in the second wave. Even though there were alterations in the other hematological parameters but they were not statically significant. (Table 4).

Biochemistry Parameters     1st wave of COVID     2nd wave of COVID  
  Normal Range Positive Negative P value Positive Negative P value
    Mean Mean   Mean Mean  
Eosinophils (%) 1.0-6.0 3.2 2.51 0.023 3.27 2.46 0.041
Basophils (%) 1.0-2.0 0.21 0.18 0.076 0.2 0.21 0.37
Eosinophils abs (10e9/L) 0.02-0.1 0.22 0.17 0.039 0.3 0.18 0.044
Lymphocyte (%) 20.0-40.0 18.85 18.35 0.332 18.88 19.2 0.432
Monocyte abs (10e9/L) 0.2-1.0 0.33 0.47 0.189 0.25 0.27 0.224
MPV (fL) 7.5-10.5 11.68 12 0.001 12.11 11.79 0.065
Neutrophils abs (10e9/L) 2.0-7.0 6.34 7.52 0.014 6.84 6.95 0.434
PLATELETS (10e9/L) 150-400 251.06 235.83 0.089 236.94 234.28 0.439
RDW (% CV) 11.6-14.0 16.93 17.05 0.313 17.6 17.67 0.445
TLC (10e9/L) 4.0-10.0 8.72 9.67 0.179 10.25 11.13 0.294
Table 4. Association of Haematological Parameters in Cancer Patients During 1st and 2nd Wave of COVID-19 Infection.

Discussion

It has been demonstrated in various studies that several biochemical and haematological factors can predict COVID-19 related severity of symptoms and associated mortality. In our study we found that AST, GGT, Urea were significantly higher whereas protein, globulin, direct bilirubin, ALT were decreased in COVID-19 positive cancer patients.

The results of the previous meta-analysis revealed that severe COVID-19 cases displayed higher ALT, AST and total bilirubin levels as compared to non-severe patients. Whereas the value of albumin was significantly lower in severe cases. It was also reported that albumin was significantly lower in a progression group than in the improvement or stabilization group of COVID-19 patients [14]. Huang et al. introduced decreased albumin along with increased LDH, ALT and total bilirubin levels as appropriate biomarkers with the ability to discriminate between severe and non-severe groups of COVID-19 patients [15].

COVID-19-related liver damage could be traced back to the early report in Wuhan, China. It was reported that 28% of patients had abnormally elevated ALT and 35% of COVID-19 patients had abnormally elevated AST in which patients had severe liver damage [16]. Another Chinese study reported 22.2% and 21.3% of patients had abnormally elevated AST, and ALT [17]. It was also reported that overall survival among the severe COVID-19 patients may be predicted by very high level of AST [16]. Higher levels of bilirubin, AST and GGT were predominantly observed in COVID-19 related mortality [16]. It was reported that related bio-markers such as LDH [18, 19], AST and ALT [18, 19] bilirubin [19] and creatinine [20] were also found to be COVID-19 severity

predictors.

We found that eosinophils, eosinophils absolute, monocyte and MCHC were significantly decreased in COVID-19 positive cancer patients. Neutrophil, basophil absolute, Hb, lymphocyte absolute, MCH, MCV, PCT, PDW and RBC were in the normal range and they have not shown any statistically significant difference between COVID-19 positive and negative groups. Previous studies reported that eosinophils, basophils and platelets were decreased whereas lymphocytes counts, neutrophils, monocytes were variable or remain unchanged after COVID-19 infection [21-29].

We had also compared the biochemical and hematological parameter differences between the COVID-19 positive and negative cancer patients during the first and second wave of COVID-19 infection. Only Eosinophils and eosinophils absolute had shown significant differences between COVID-19 positive and negative cancer patients in both first and second wave of COVID-19 infection.

Cancer patients are more prone to infect with COVID-19. After the COVID-19 infection, changes in the parameters adversely affect normal body function and changes may lead to the mortality rate among various cancer patients.

In conclusion, in cancer patients of North-East India, we found significant alteration of AST, GGT, Urea, Eosinophils, eosinophils absolute, monocyte and MCHC in COVID-19 positive cancer patients as compared to negative cancer patients. Comparing the first and second wave of COVID-19 infections (driven by different variants of SARS-CoV-2) impact in cancer patients of North-East India we observed that patterns of alterations in haematological and biochemical parameters were more or less similar. Future studies with a larger cohort of cancer patients will be required to validate our current observations.

Acknowledgements

The authors acknowledge the Director Dr B Borooah Cancer Institute for providing the laboratory support for SARS-CoV-2 testing.

Conflicts of interest

There are no conflicts of interest. This study has not received any financial support.

References

References

  1. Andrews M. A., Areekal B, Rajesh K. R., Krishnan J, Suryakala R., Krishnan B, Muraly C. P., Santhosh P. V.. First confirmed case of COVID-19 infection in India: A case report. The Indian Journal of Medical Research. 2020; 151(5)DOI
  2. Datta S, Chakroborty NK, Sharda D, Attri K, Choudhury D. Covid-19 pandemic in India: Chronological comparison of the regional heterogeneity in the pandemic progression and gaps in mitigation strategies. 2021.
  3. Biswas M, Rahaman S, Biswas TK, Haque Z, Ibrahim B. Association of Sex, Age, and Comorbidities with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis. Intervirology. 2020. DOI
  4. McLean G, Kamil J, Lee B, Moore P, Schulz TF, Muik A, Sahin U, Türeci Ö, Pather S. The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines. mBio. 2022; 13(2)DOI
  5. Lee R. J., Wysocki O., Bhogal T., Shotton R., Tivey A., Angelakas A., Aung T., Banfill K., Baxter M., Boyce H., Brearton G., Copson E., Dickens E., Eastlake L., Gomes F., Hague C., Harrison M., Horsley L., Huddar P., Hudson Z., Khan S., Khan U. T., Maynard A., McKenzie H., Palmer D., Robinson T., Rowe M., Thomas A., Tweedy J., Sheehan R., Stockdale A., Weaver J., Williams S., Wilson C., Zhou C., Dive C., Cooksley T., Palmieri C., Freitas A., Armstrong A. C.. Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome. ESMO open. 2021; 6(1)DOI
  6. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet (London, England). 2020; 395(10234)DOI
  7. Zini G, Bellesi S, Ramundo F, Onofrio G. Morphological anomalies of circulating blood cells in COVID-19. American Journal of Hematology. 2020; 95(7)DOI
  8. Helms J, Kremer S, Merdji H, Clere-Jehl R, Schenck M, Kummerlen C, Collange O, Boulay C, Fafi-Kremer S, Ohana M, Anheim M, Meziani F. Neurologic Features in Severe SARS-CoV-2 Infection. The New England Journal of Medicine. 2020; 382(23)DOI
  9. Maccio U, Zinkernagel AS, Shambat SM, Zeng X, Cathomas G, Ruschitzka F, Schuepbach RA, Moch H, Varga Z. SARS-CoV-2 leads to a small vessel endotheliitis in the heart. EBioMedicine. 2021; 63DOI
  10. Wichmann D, Sperhake J, Lütgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schröder AS, Burdelski C, Heer G, Nierhaus A, Frings D, Pfefferle S, Becker H, Bredereke-Wiedling H, Weerth A, Paschen H, Sheikhzadeh-Eggers S, Stang A, Schmiedel S, Bokemeyer C, Addo MM, Aepfelbacher M, Püschel K, Kluge S. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Annals of Internal Medicine. 2020; 173(4)DOI
  11. Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA cardiology. 2020; 5(7)DOI
  12. Akhmerov A, Marbán E. COVID-19 and the Heart. Circulation Research. 2020; 126(10)DOI
  13. Lahiri D, Ardila A. COVID-19 Pandemic: A Neurological Perspective. Cureus. 12(4)DOI
  14. Liu W, Tao Z, Wang L, Yuan M, Liu K, Zhou L, Wei S, Deng Y, Liu J, Liu H, Yang M, Hu Y. Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese Medical Journal. 2020; 133(9)DOI
  15. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Qi, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England). 2020; 395(10223)DOI
  16. Chen C, Jiang J, Xu X, Hu Y, Hu Y, Zhao Y. Dynamic liver function indexes monitoring and clinical characteristics in three types of COVID-19 patients. medRxiv. 2020.
  17. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, Liu L, Shan H, Lei C, Hui DS, Du B, Li L, Zeng G, Yuen K, Chen R, Tang C, Wang T, Chen P, Xiang J, Li S, Wang J, Liang Z, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zhong N. Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal of Medicine. 2020; 382(18)DOI
  18. Xu L, Mao Y, Chen G. Risk factors for 2019 novel coronavirus disease (COVID-19) patients progressing to critical illness: a systematic review and meta-analysis. Aging. 2020; 12(12)DOI
  19. Borges do Nascimento IJ, Cacic N, Abdulazeem HM, Groote TC, Jayarajah U, Weerasekara I, Esfahani MA, Civile VT, Marusic A, Jeroncic A, Carvas Junior N, Pericic TP, Zakarija-Grkovic I, Meirelles Guimarães SM, Luigi Bragazzi N, Bjorklund M, Sofi-Mahmudi A, Altujjar M, Tian M, Arcani DMC, O'Mathúna DP, Marcolino MS. Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis. Journal of Clinical Medicine. 2020; 9(4)DOI
  20. Moutchia J, Pokharel P, Kerri A, McGaw K, Uchai S, Nji M, Goodman M. Clinical laboratory parameters associated with severe or critical novel coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. PloS One. 2020; 15(10)DOI
  21. Qian G.-Q., Yang N.-B., Ding F., Ma A. H. Y., Wang Z.-Y., Shen Y.-F., Shi C.-W., Lian X., Chu J.-G., Chen L., Wang Z.-Y., Ren D.-W., Li G.-X., Chen X.-Q., Shen H.-J., Chen X.-M.. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series. QJM: monthly journal of the Association of Physicians. 2020; 113(7)DOI
  22. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. The Journal of Clinical Investigation. 2020; 130(5)DOI
  23. Zhang B, Zhou X, Qiu Y, Song Y, Feng F, Feng J, Song Q, Jia Q, Wang J. Clinical characteristics of 82 cases of death from COVID-19. PloS One. 2020; 15(7)DOI
  24. Ferrari D, Motta A, Strollo M, Banfi G, Locatelli M. Routine blood tests as a potential diagnostic tool for COVID-19. Clinical Chemistry and Laboratory Medicine. 2020; 58(7)DOI
  25. Liao D, Zhou F, Luo L, Xu M, Wang H, Xia J, Gao Y, Cai L, Wang Z, Yin P, Wang Y, Tang L, Deng J, Mei H, Hu Y. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. The Lancet. Haematology. 2020; 7(9)DOI
  26. Thomas W., Varley J., Johnston A., Symington E., Robinson M., Sheares K., Lavinio A., Besser M.. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thrombosis Research. 2020; 191DOI
  27. Yang Y, Shen C, Li J, Yuan J, Yang M, Wang F, et al. Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome. MedRxiv. 2020.
  28. An X, Li X, Shang F, Yang S, Zhao J, Yang X, Wang H. Clinical Characteristics and Blood Test Results in COVID-19 Patients. Annals of Clinical and Laboratory Science. 2020; 50(3)
  29. Tan T, Khoo, Mills EG, Phylactou M, Patel B, Eng PC, Thurston L, et al. Association between high serum total cortisol concentrations and mortality from COVID-19. The Lancet. Diabetes & Endocrinology. 2020; 8(8)DOI