Prediction of COVID-19 severity associated with Pneumonia by chest CT scan and Serological results

 

Naveen Yadam1, Ganta Suhasin2

1M. Phamacy, GITAM Institute of Pharmacy, GITAM (Deemed to be University),

Visakhapatnam, Andhra Pradesh, India.

2Assistant Professor, GITAM Institute of Pharmacy, GITAM (Deemed to be University),

Visakhapatnam, Andhra Pradesh, India.

*Corresponding Author E-mail: yadamnaveen2@gmail.com, sganta@gitam.edu

 

ABSTRACT:

Since 2019 December, a rapid increase in a cluster of Pneumonia cases has been identified in Wuhan, China. The novel Coronavirus infection has similar symptoms related to pneumonia. Initially, the virus replicates in the upper respiratory tract (cough and fever), and in most cases, the human immune system can fight it and defeat it. In moderate to severe cases, it infects the alveoli in the lungs (SOB) and causes a robust immune response (release of several cytokines, such as IL-6, IL-7, TNF-α that damage the tissue), that further worsens the disease condition to acute respiratory distress syndrome (ARDS), Pneumonia, and lung injury. In most cases, this requires ICU transfer and artificial ventilation.  We studied the severity of the cases of COVID-19 associated with pneumonia. The serological tests, differential counts, and CT scans of 51 patients have been thoroughly observed and analyzed to determine these patients' mortality rates concerning their age. COVID-19 associated with pneumonia in older adults is fatal, associated with increased CRP (C reactive protein) levels, decreased lymphocytes, PCV/HCT, MCV. Our results suggest that the CT scans and serological parameters were found to be useful for clinicians in finding the severity of the COVID-19 associated with pneumonia in chronic phases, therapeutic decisions, and the disease prognosis

 

KEYWORDS: COVID-19, Pneumonia, CT scan, CRP, TMPRSS2.

 

 


INTRODUCTION:

Since 2019 December, a rapid increase in a cluster of Pneumonia cases has been identified in Wuhan, China.1 Which was then determined by the International Committee on the taxonomy of viruses as Severe Acute Respiratory Syndrome-Related Corona Virus-2 (SARS-CoV-2), which causes the disease named Coronavirus (COVID-19) with an unknown etiology.2 The novel coronavirus (2019 n-CoV) outbreak has been informed to the World Health Organization (WHO), which further added as it was caused by the novel beta coronavirus that belongs to the family Coronaviridae.3

 

Which is genetically similar to SARS-CoV, which is responsible for the SAR outbreak in 2002.4 The 2019 coronavirus is a global emergency, the WHO declared global emergencies only five times that is for Swine flu (2009), Ebola, Polio (2014), Zika virus (2016), Kivu Ebola (2018-2020), Coronavirus (2019-2020).5 This family of viruses causes the common cold and named for the spike proteins on its surface that make it look like a crown or a star.6 The first few cases were associated with a wholesale seafood market, which made us understand that Zoonotic (meaning transmitted from animal to human). Later on, it confirmed that the transmissions also occur from human to human. Most of them originated from bats (Virus reservoirs) and transmitted to humans through some intermediary host. In the following months, the cases have been rapidly increased and widely spread all over the world.7,8 Since pneumonia is also having almost the same symptoms as COVID-19, initially, it was thought to be related to pneumonia. Later, the pathogen's precise details have been noticed that the COVID-19 is as much like the SARS and MERS.9 The initial treatment is given to COVID-19 was similar to the SARS and MERS, but the results are not much as expected, so the treatment is still symptomatic.10

 

Pneumonia, particularly the inflammation in the alveoli or the bronchi, can be caused by both the microbes and the virus that invade the lung tissue and make breathing difficult by filling the alveoli with fluid and pus.11 The alveoli are the major site for transferring the O2 into the bloodstream and CO2 out from the body.12 So it makes breathing difficult at times, and it may be either single or double pneumonia meaning it may affect a single lung or both.13 The pneumonia symptoms may include coughing, shortness of breath, fastening of heart rate, sweating, fever, dehydration, and appetite loss. Usually, the body filters the organisms which enter into the lungs. Still, due to some issues like a weak immune system, the organisms would enter into the lung, which leads to congestion, red or gray hepatization.14,15 And further, clinically, pneumonia is classified into four types like Community-Acquired Pneumonia (typical/atypical/ aspiration pneumonia), Nosocomial Pneumonia (HAP, VAP, HCAP), Immunocompromised Pneumonia, Elderly Pneumonia. With the use of certain antibiotics like penicillins, we can treat pneumonia, and in certain cases, pneumonia can also be prevented by vaccination.16,17,18

 

Pneumonia related to COVID-19

Pneumonia is an inflammation in the alveoli by infection causing fever, cough, chest pain, sputum formation, and an increase in the heart rate.19 The COVID-19 Pneumonia is also similar but not often associated with chest pain and sputum in the patient. The major symptoms of COVID-19 are breathlessness, dry cough, and fever with body weakness, but 50% of patients might be asymptomatic or present mild symptoms, although they would still be highly infectious.20,21 In some cases, loss of smell and other severe effects such as blood clot formation have been reported. The major problem is the patient's oxygen saturation levels, which gradually decreased (below 95%).22 it is an early predictor of the severity of COVID-19 infection.23,24. The spike protein on the Coronavirus surface binds to the angiotensin-converting enzyme 2 (ACE-2) receptors on the target cell's surface.25 The type 2 transmembrane serine protease (TMPRSS2) or the other cellular proteases cleaves the ACE-2 receptors and activates the spike protein. Viral entry is facilitated by the cleaved ACE-2 and activated spike proteins. Once the virus is inside the cell, it starts to replicate.26,27 The information in the viral RNA is used to produce all the viral proteins (polyproteins), including RNA-dependent RNA polymerase, the S-protein, 3-chymotrypsin-like protease, papain-like protease, helicase, glycoprotein, and accessory proteins.28 The genetic RNA is also replicated, and all the viral components are assembled, and finally virus buds out from the host cell.29 Initially, the virus replicates in the upper respiratory tract (cough and fever), and in most cases, the human immune system can fight it and defeat it. In moderate to severe cases, it infects the alveoli in the lungs (SOB) and causes a robust immune response (release of several cytokines, such as IL-6, IL-7, TNF-α that damage the tissue). Worsens the disease condition to acute respiratory distress syndrome (ARDS), Pneumonia, and lung injury. In most cases, this requires ICU transfer and artificial ventilation. ARDS may lead to multi-organ failures and death.30-33

 

Risks related to COVID-19 pneumonia:

The risks of COVID-19 are quite severe, and these could worsen day by day, so the patient should move to intensive care.

 

METHODS:

An observational study was done on 51 COVID-19 patients associated with pneumonia who were admitted to the designated hospitals in Visakhapatnam. Based on their serological, hematological, and CT scan reports, along with the Widal and QBC test using slide agglutination method, Immunochromotography, the results were analyzed for the effect of age on the mortality rate and calculated.

 

FINDINGS:

Case Study-1, A 46-year-old man was diagnosed with severe chest pain, shortness of breath, body weakness, and weight loss. Previously two years back, the patient was treated for elderly pneumonia by antibacterial treatment. The serology check has been performed with the aid of Immunochromotography for dengue, and the affected person was examined badly for Dengue NS 1Antigen, Dengue IgG Antibody, Dengue IgM Antibody. And next Widal Test has been performed by Slide Agglutination Method and the results were as follows: Salmonella Typhi – O – 1:80 (Dilutions < 1:20), Salmonella Typhi – H – 1:80 (Dilutions < 1:20), Salmonella Para Typhi – AH – 1:20 (Dilutions < 1:20), Salmonella Para Typhi – BH – 1:20 (Dilutions < 1:20). The patient was taken for the CRP (C-Reactive Proteins) test, which was done by Turbidic Metric Immunoassay, which showed positive 200.41mg/L (normal range: 0-6.0 mg/dl). The ASO (Antistreptolysin O) test was also done using the same method, and the results were negative. The hemoglobin levels of the patients were checked, and the levels were slightly decreased which indicates less O2 supply from lungs to the rest of the body 11.9gm% (normal range 13.0-17.0gm%) and the WBC count was found to be normal 10,400 cells/cumm (4000-11000 cells/cumm) and the differentials counts was Neutrophils 80% (normal range 40-75%), Lymphocytes 17% (normal range 20-40%), Eosinophils 2% (normal range 01-04%), Monocytes 1% (normal range 0-2%), Basophils 0% (normal range 00-01), Total RBC Count4.21 million/cumm (normal range 4.5-5.5millions/cumm), PCV/HCT34.0 Vol% (normal range 40-50Vol%), MCV80.8fl (normal range 83.0-101.0fl), MCH 28.3pg (normal range 24.0-30.0pg), MCHC35gm/dl(normal range 31.50-34.50gm/dl), Platelet count 2.71 lakhs/cumm (normal range 1.50-4.5lakhs/cumm), AEC (Absolute eosinophil count) 200cells/cumm (normal range 40-440). Then we performed QBC, a Test for Malaria parasites for which the patient tested negative for both Plasmodium Vivax and Plasmodium Falciparum.

 

Case study -2 A 54year older adult diagnosed with mild dyspnea with no previous history of lung pneumonia. Before 30 days, the patient had contact with a covid patient. After seven days, he had a fever and shortness of breath, and the patient went for the swab test. The report was negative, and after ten days again, the patient's condition was still ill, so he went for the second swab test, and the report was positive. Hence, he went for the CT scan to confirm, and the results also showed positive for the CRP test with a mild increase in CRP value 98.01 mg/L (normal range: 0-6.0mg/dl). And the lymphocyte count is decreased to 18% (normal range 20-40%), Neutrophils 79% (normal range 40-75%), and the RDT was finally performed to check for the SARS-CoV-2, and the reports showed positive for the SARS-CoV-2 antibodies.

 

Case study- 3 A 29years adult man was diagnosed with fever and illness, and body pains. The patient has a previous history of close contact with a covid patient and has been traveling with him for five days. So he was sent for the swab test. The patient has tested negative, and further, the patient has experienced shortness of breath. Therefore, he went for the HRCT scan, where the patient was checked for the serological test. The patient tested negative for Dengue NS 1Antigen, Dengue IgG Antibody, Dengue IgM Antibody. In the CRP test, the patient showed increased CRP value levels90.35 mg/L (normal range: 0-6.0mg/dl). ASO test was also done, and the results were negative. The patients' hemoglobin levels were checked, and these showed decreased hemoglobin levels 12.2gm% (normal range 13.0-17.0gm%). The WBC count was found to be normal 10,700 cells/cumm (4000-11000 cells/cumm), and the differentials count was found to be Neutrophils 78% (normal range 40-75%), Lymphocytes 19% (normal range 20-40%), Eosinophils 2% (normal range 01-04%), Monocytes 1% (normal range 0-2%), Basophils 0% (normal range 00-01), Total RBC Count4.12 mill/cumm (normal range 4.5-5.5mill/cumm), and the Platelet count was 3.46 lakhs/cumm (normal range 1.50-4.5 lakhs/cumm).


 

 

Fig. 1CT Scan findings of COVID-19 associated with and without pneumonia: 1 and 2. COVID-19 without pneumonia in the old patient: 3. COVID-19 with pneumonia in old patient 4,5. COVID-19 with pneumonia in the adult patient. Orange arrow indicating Corona virus pathogen, yellow arrow indicating pneumonia infection/ground glass opacity (GGO)


 

Fig 2: Serological parameters

 

Fig 3: Hematological parameters

 

Table 1: Serological and hematological parameters

Feature

Mean

STD

Median

C-REACTIVE Protein CRP (mg/L)

136.23

40.83

147.72

HEAMOGLOBIN Hb (gm%)

11.31

0.62

11.4

NEUTROPHILS (%)

78.25

2.73

78

LYMPHOCYTES (%)

17.88

0.83

18

RBC (millions/cumm)

4.13

0.17

4.18

PCV (Vol%)

37.58

3.37

38

MCV (fl)

80.05

1.52

80.2

MCHC (gm/dl)

35.75

0.87

35.8

 

Fig 4: The mortality rate related to age

 

DISCUSSION:

In this study, we collected the data of 51 novel coronavirus patients associated with pneumonia from a designated hospital in Visakhapatnam. We compared the serological, hematological, and CT scans of all 51 cases. Coronavirus pathogen was determined first and then checked for the alternative comorbidities. Patients associated with pneumonia were selected and found that the Coronavirus associated with pneumonia is causing more mortality rate in old age. In the first case, the patient has been associated with pneumonia previously, the CRP levels, which is an inflammatory marker, has been increased up to 200mg/L, indicating there is an infection or inflammation in the body and the patient has variations in the differential counts like the Neutrophils 80% Lymphocytes 17%. Decreased RBC count (4.21 million/cumm) indicate folate deficiency. The neutrophil count also increased, so there is a high chance of severe infection and inflammation. The decreased levels of the lymphocytes here indicate a weak immune system. The low level of the PCV (PCV/HCT 34.0 Vol%) showed the cell destruction. The lowered levels of MCV (80.8 fl) indicated the microcytic anemia and MCHC (35gm/dl). The variations in the above parameters might be due to the weak immune responses against the pathogen. In the second stated case, the person is not affected with pneumonia but has almost the same serological and differential counts similar to the first case. They were indicating that he is also weak in immunity, which might be related to his age.

 

Whereas in the adult age (case 3), the serological and the differentials counts and the CT scans were similar, but the only difference is the lymphocyte count, which is slightly high., which indicated the normal or equal to the regular immune activity. These showed a better response against the pathogen and made the patient survival rate better than that of the old aged.

 

CONCLUSION:

This study analyzed the patients' CT scans and serological parameters affected by COVID-19 associated with Pneumonia and checked for the patients' mortality rate based upon different age groups. We found that the patients from age groups 60 to >80 (old age) have more mortality rates than adults. COVID-19 associated with pneumonia in older adults is fatal, associated with increased CRP levels, decreased lymphocytes, PCV/HCT, MCV. The CT scans and serological parameters were found to be useful in finding the severity of the COVID-19 associated with pneumonia in chronic phases and can give early alertness for evidence-based treatment, reducing the mortality rate in the elderly.

 

CONFLICT OF INTEREST:

The authors have declared no conflict of interest.

 

ABBREVIATIONS:

CT – Computed tomography; SARS-CoV – Severe Acute Respiratory Syndrome Coronavirus; MERS- Middle East Respiratory Syndrome; HAP- Hospital-acquired Pneumonia; CAP- Community-acquired Pneumonia; VAP- Ventilator-associated Pneumonia; HCAP- Healthcare-associated Pneumonia; ACE-2- Angiotensin-Converting Enzyme 2; TMPRSS- Transmembrane Serine Protease; IL– Interleukins; QBC - Quantitative buffy coat; ASO- Antistreptolysin O; CRP - C-Reactive Proteins; Hb – Hemoglobin; WBC – White blood Cells; RBC – Red blood Cells; PCV - packed cell volume; MCV- Mean corpuscular volume; MCHC- mean corpuscular hemoglobin concentration; AEC- Absolute Eosinophil Count; RDT- Rapid Diagnostic Test.

 

REFERENCES:

1.      Sindhu. T. J, Arathi. K. N, Akhilesh K. J, Anju. Jose, Binsiya K. P, Blessy Thomas, Elizabeth Wilson. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J. Pharm. Tech. 2020; 10(2): 60-64.

2.      Mayur S. Jain, Shashikant D. Barhate. Corona viruses are a family of viruses that range from the common cold to MERS corona virus: A Review. Asian J. Res. Pharm. Sci. 2020; 10(3): 204-210.

3.      J. Lei, J. Li, X. Li, X. Qi. CT imaging of the 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology 2020; 295(1): 17-18

4.      Abbas KinbarKuser, SagbanMarjaTarar, Omar MansibKassid, Nael Hussein Zayer. CNS and COVID-19: Neurological symptoms of Hospitalized Patients with Coronavirus in Iraq: a surveying case sequences study. Research J. Pharm. and Tech. 2020; 13(12): 6291-6294.

5.      Smith AC, Thomas E, Snoswell CL, et al. Telehealth for global emergencies: Implications for coronavirus disease 2019 (COVID-19). Journal of Telemedicine and Telecare. 2020; 26(5): 309-313.

6.      Peiris JS, Lai ST, Poon LL, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003; 361(9366): 1319‐1325. 

7.      Ali Adel Dawood. SARS-CoV-2 is Originated from Bat Corona Virus. Research J. Science and Tech. 2021; 13(1): 31-32.

8.      Drosten C, Günther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. New England Journal of Medicine 2003; 348: 67-76.

9.      Sarfaraz Ahmad, AmbreenShoaib, Sajid Ali, et al. Epidemiology, risk, myths, pharmacotherapeutic management and socioeconomic burden due to novel COVID-19: A recent update. Research J. Pharm. and Tech 2020; 13(9): 4435-4442.

10.   Navas-Martin, S. R., and S. Weiss. 2004. Coronavirus replication and pathogenesis: implications for the recent outbreak of severe acute respiratory syndrome (SARS), and the challenge for vaccine development. Journal of Neurovirology. 2004; 10(2): 75-85. 

11.   Grant Mackenzie, The definition and classification of pneumonia. Pneumonia (Nathan). Biomedical center, 2016; 22(8): 14.

12.   Schleupner CJ1, Cobb DK, A study of the etiologies and treatment of nosocomial pneumonia in a community-based teaching hospital. Infection Control and Hospital Epidemiology, 1992, 13(9): 515-525.

13.   Muhe, l.; tilahun, etal. Etiology of Pneumonia, sepsis and meningitis in infants younger than three months of age in Ethiopia. The Pediatric Infectious Disease Journal.1999; 18(10): S56-S61.

14.   Chen, Chih-Jung MD, Ph D*† et al. Etiology of Community-acquired Pneumonia in Hospitalized Children in Northern Taiwan. The Pediatric Infectious Disease Journal.2012; 31(11): 196-201.

15.   Sopena N, et al. Prospective study of community-acquired pneumonia of bacterial etiology in adults. European Journal of Clinical Microbiology and Infectious Diseases.1999; 18(12): 852-858.

16.   R. Danasu, R. Sridevi, A. Santhanalakshmi. A Comparative Study to assess the efficacy of CPI Score Vs APACHE Score to predict ventilator associated pneumonia among patients admitted in ICU at SMVMCH, Puducherry. Int. J. Nur. Edu. and Research. 2019; 7(4): 584-589.

17.   Fang GD, et al. New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. Medicine.1990; 69(5): 307-316.

18.   Krushna K. Zambare, Avinash B. Thalkari. Overview on Pathophysiology of Pneumonia. Asian J. Pharm. Res. 2019; 9(3): 177-180.

19.   Akshay R. Yadav, Shrinivas K. Mohite. A Review on Severe Acute Respiratory Infection (SARI) and its Clinical Management in Suspect/ Confirmed Novel Coronavirus (nCoV) Cases. Res. J. Pharma. Dosage Forms and Tech.2020; 12(3): 178-180.

20.   RamyaChellammal M. Bacterial Pneumonia. Asian J. Nur. Edu. & Research. 2014; 4(3): 317-320.

21.   SherendraSahu, PriyawatiSahu, U.R. Singh, Neeta Singh. Comparative study of Clinical Parameters of Pneumocystis pneumonia with healthy controls in Vindhya Region. Res. J. Pharmacognosy and Phytochem. 2017; 9(2): 59-63.

22.   Ken B Waites. New concepts of Mycoplasma pneumonia infections in children Pediatric Pulmonology. 2003; 36(4): 267-78.

23.   Barker J, et al. pneumonia in children in the eastern highlands of Papua New Guinea: a bacteriological study of patients selected by standard criteria. Journal of Infectious Disease, 1989; 159: 348-52.

24.   Chambers ST, et al. Chlamydia pneumonia and Mycoplasma infection in patients admitted to Christchurch Hospital with Pneumonia. The New Zealand Medical Journal.1999; 112(1090): 222-224.

25.   Phillips, J. J., et al. Pathogenesis of chimeric MHV4/MHV-A59 recombinant viruses: the murine coronavirus spike protein is a major determinant of neurovirulence. Journal of Virology. 

26.   Lu R, Zhao X, Li J, et al. Genomic characterization and epidemiology of 2019 novel Coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224): 565‐574.

27.   Prof.NanshanChenMDa† et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, The Lancet. 2020; 395(10223): 507-513.

28.   Perlman, S. Pathogenesis of coronavirus-induced infections. Review of pathological and immunological aspects. Advances in Experimental Medicine and Biology. 1998; 440: 503-513.

29.   Yixuan Wang, et al. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID‐19) implicate special control measures. Journal of Medical Virology.2020; 92(6): 568-576

30.   Zhonghua, et al. Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID‐19) in China. Zhonghua Liu Xing Bing XueZaZhi. 2020; 41(2): 145‐151.

31.   RenLL, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chinese Medical Journal. 2020; 133(9): 1015-1024.

32.   Hui DSC, Zumla A. Severe acute respiratory syndrome: historical, epidemiologic, and clinical features. Infectious Disease Clinics of North America. 2019; 33(4): 869‐889.

33.   A. Assiri, et al. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study. The Lancet Infectious Disease. 2013; 13(9): 752-61.

 

 

 

Received on 24.02.2021            Modified on 02.05.2021           

Accepted on 09.06.2021      ©Asian Pharma Press All Right Reserved

Asian Journal of Pharmacy and Technology. 2021; 11(3):198-202.

DOI: 10.52711/2231-5713.2021.00032