1. Title of the project:  Laboratory variables and outcome measures of Covid 19 in patients: A data based retrospective study from Udupi district

2. Type of Study:   Retrospective

3. Aims & objectives (hypotheses if applicable) :

1) To assess the biochemical and hematological perturbations in confirmed Covid 19 patient

Haematological parameters recorded: CBC, ESR, APTT, Peripheral smear.

Biochemical parameters: FBS, HbA1c, RFT, Total & direct bilirubin, total protein, liver enzymes, electrolytes (Na, K, Ca, P, Mg), CRP, LDH, ferritin, D Dimer, CPK, Trop T, pro BNP, ABG at admission)

2) To correlate the laboratory findings with the clinical severity of the disease

3) To investigate the influence of comorbid conditions on the laboratory based and clinical progression of the disease

4) To compare the laboratory findings with the patient outcomes (time to discharge/ recovery and mortality)

4. Justification for study (whether of national significance with rationale) :

As a lot of evidences continue to be added and guidelines continue to be modified, there is a relative scarcity of Indian literature on the hematological, biochemical and inflammatory perturbations in Covid 19 patients, and also the influence of comorbidities on these perturbations and prognostic value to these disturbances in patient outcomes which has to be emphasized.

5. Departments involved:

Department of Biochemistry, KMC, Manipal

Division of Ayurveda, CIMR, Manipal

Department of Critical Care, KMC, Manipal

6. Study period: 6 months

7. Sample size:

500 patients (Convenience sampling will be used and the sample size is kept towards a lower minimum for the ease of accessibility and the absence of prevalence data in the face of the sudden pandemic).

8. Materials and methods:   

a) Inclusion and exclusion criteria:

i. Inclusion criteria:

All patients with confirmed Covid 19 infection admitted (30/05/2020 to 30/08/2020) to Kasturba Hospital, Manipal, Manipal Academy of Higher Education, Manipal can be enrolled in the study

ii. Exclusion criteria:

Any patient without confirmed Covid 19 or any patient with non Covid SARI will be excluded from the study.

b) Biological materials required (type - blood, tissue etc and quantity) : NIL

c) Statistical methods:

i. Quantitative characteristics will be tabulated and presented using descriptive statistics.

ii. Group differences will be evaluated using ANOVA for quantitative characteristics. P value less than 0.05 will be considered statistically significant.

iii. The relationship between the various parameters will be quantified by Spearman’s Rank correlation coefficient test.

iv. ROC curves of various parameters and a combination of different parameters and scores will be calculated. Sensitivity, specificity, AUC, NPV & PPV will be determined for the same.

d) Tools used:

A high risk progression RISK CALCULATOR generated inhouse by a team (Covid Hackathon) will be used to obtain risk scores from the laboratory reports, and the generated risk scores will be correlated with the outcome measures.

9. Detailed description of procedure / processes:  

Patients with confirmed Covid 19 admitted to Kasturba Hospital, Manipal will be enrolled in the study (male/female)

 The participants will be divided into mild, moderate and severe cases of Covid 19 based on standard guidelines

 Laboratory test reports (Hematology, Biochemistry and microbiology) will be extracted from the Laboratory Information System

 A detailed information about the past history of the patients will be obtained from the patient records archived in the Medical Records Department of the Hospital. The data would be entered in the risk calculator to generate risk scores.

Further, combinations of laboratory and clinical variables would be assessed for their prognostic and risk stratification potential with respect to each of the outcome variables

 Participants will be followed for prognostic outcomes (time to recovery/ discharge, duration of admission at ICU/ CCU, duration of oxygenation support required/ mortality

(Note: Haematological parameters recorded: CBC, ESR, APTT, Peripheral smear.

Biochemical parameters: FBS, HbA1c, RFT, Total & direct bilirubin, total protein, liver enzymes, electrolytes (Na, K, Ca, P, Mg), CRP, LDH, ferritin, D Dimer, CPK, Trop T, pro BNP, ABG at admission)

10. Outcome measures:

1) Duration of hospital stay/ time to discharge

2) Mortality

3) Development of secondary severe complications like pulmonary embolism, MI, cardiac arrest etc

4) Need for ICU admission

5) Need & duration of HFNC/ NIV/ Mechanical ventilation support

6) Development of Multisystem inflammatory syndrome

7) Severity of perturbations of laboratory analytes

11. Potential risks and benefits:

Since it’s a retrospective study, only a minimal risk is involved in the conduct of the study. However, the benefit of this study is immense because it could help us arrive at an algorithm to assess risk/ patient outcome and hence institute rigorous therapy and strict monitoring of patients at a risk of deterioration/ adverse outcome. Also, the study would help in in-depth validation of a high risk progression RISK CALCULATOR, developed by MAHE and freely available online to the health care workers for the greater benefit of the medical fraternity.

12. Ethical considerations and methods to address issues:

Ethical clearance will be obtained from the Institutional Ethical Committee. The data will be handled with utmost confidentiality and will remain accessible only to the key research members, who would strictly agree upon and adhere to the ethical code of conduct and patient confidentiality, data would be anonymized while result entry and reporting.

13. Budget (give details) and proposed funding source:

The present study does not require any funding support since it’s a retrospective study and uses laboratory and clinical records along with a freely available online calculator for the purpose of risk stratification and outcome assessment.

14. Review of literature (within 1000 words):  

Corona viruses belonging to the family of Coronaviridae, long considered inconsequential pathogens often causing mild cold to severe acute respiratory syndrome in an extreme few. This has challenged the world and humanity by emergence of a highly pathogenic 2019 novel coronavirus (2019-nCoV) causing SARS in millions across the world [1]. After its emergence, in Wuhan in November 2019, the World Health Organization declared Covid 19 a global pandemic on March 11, 2020 [2]. In March 2020 first case of Covid 19 was diagnosed in India [3] following which Ministry of Health, Government of India proposed standard precautions to prevent the spread of this virus by washing hand repeatedly with water, soap or alcohol based solution for 20 seconds [4]. Beside the people have been alerted to maintain social distancing, minimize the gathering, to wear mask and avoiding contacts with people with cold, cough and fever. As we witness the outbreak taking exponential trajectories, the ultimate scope of this global pandemic is impossible to predict. To date, our understanding of the disease pathophysiology, clinical manifestations, diagnostic and therapeutic regimens and prognostic indicators continue to rapidly evolve and researchers from the globe aid in rapid updation of healthcare guidelines.

While most patients infected with SARS-CoV-2 have mild symptoms, the viruses can cause severe lung pneumonia, acute respiratory distress syndrome, multiple organ failure, and finally death [5]. In severe cases with critical condition, a specialized management at intensive care units is needed [6]. To our knowledge, however, there is presently a restricted standardised method for predicting which infected patient may stay moderately symptomatic or progress towards more serious disease [7].  Extreme pulmonary disease with severe alveolar damage and progressive respiratory failure results in fatal consequences [8,9]. High mortality rates occur in the elderly, and people with diabetes, co-morbidities and immunosuppressant [10]. Although most published papers explored the clinical features and imaging findings of COVID-19, few studies examined the diagnostic and prognostic importance of abnormal laboratory findings [11]. The contribution of laboratories goes far beyond etiological detection and it is now almost undeniable that this branch of medical science is effectively involved in prognosis and diagnosis determination and patient monitoring [12].  Although in vitro diagnostics contribute effectively to early detection of SARS-CoV-2 infection, there is evidence that laboratory medicine can also provide critical assistance in distinguishing between extreme and non-serious COVID-19.

Although in vitro diagnostics efficiently contribute to the early identification of SARS-CoV-2 infection, there is evidence that laboratory medicine may also provide essential assistance to discriminate between severe and non-severe COVID-19. The broad variations in the clinical characteristics of the disease, ranging from asymptomatic to fatal, require the detection and application of new laboratory biomarkers to predict COVID-19 prognosis quickly and economically [13].

To gain a better understanding of the role of haematological and biochemical parameters in predicting COVID-19’s mild to severe progression, it is essential to investigate these results for further updating in order to study the virus effect in detail.          

15. References:

1. Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation and Treatment Coronavirus (COVID-19) [Updated 2020 Jul 4]. In: StatPearls [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/

Accessed on 12 August 2020.

2. World Health Organization. Coronavirus disease (COVID-19) pandemic. Copenhagen: WHO Regional Office for Europe. c2020 (Cited on 12 August 2020) Available from: https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19

3. Devesh Kumar. Half a million COVID-19 cases in India: How we got to where we are. India: The Wire, Covid 19 India timeline. c2020 (Cited on 12 August 2020). Available at: https://thewire.in/covid-19-india-timeline

4. https://www.mohfw.gov.in/pdf/PreventivemeasuresDOPT.pdf

5. N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395:507-513.

6. Z. Xu, L. Shi, Y. Wang, J. Zhang, L. Huang, C. Zhang, S. Liu, P. Zhao, H. Liu, L. Zhu. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respiratory Med. 2020; 8(4):420-422.

7. Liu, X., Zhou, H., Zhou, Y. et al. Temporal radiographic changes in COVID-19 patients: relationship to disease severity and viral clearance. Sci Rep. 2020; 10:10263. doi: https://doi.org/10.1038/s41598-020-66895-w

8. Chen, N. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395:507–513.

9. Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395:497–506.

10. Song, J., Zhang, C., Fan, X. et al. Immunological and inflammatory profiles in mild and severe cases of COVID-19. Nat Commun. 2020; 11:3410. doi: https://doi.org/10.1038/s41467-020-17240-2

11. G. Lippi, M. Plebani. Laboratory abnormalities in patients with COVID-2019 infection. Clin. Chem. Lab. Med. 2020; 58(7):1131-1134. doi: 10.1515/cclm-2020-0198.

12. G. Lippi, M. Plebani. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin. Chem. Lab. Med. 2020; 58(7):1063-1069. doi: 10.1515/cclm-2020-0240.

13. Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory Findings in COVID-19 Diagnosis and Prognosis. Clinica Chimica Acta. 2020; 510: 475-482.