Clinico-epidemiological profile of non-survivors of COVID-19 during the last two waves in a tertiary care hospital of North India: A retrospective descriptive study

Abstract

Background:

SARS-CoV-causing COVID-19 resulted in mortality, and the clinic-epidemiological profile at the time of admission of patients who died later could provide an insight into pathophysiological consequences due to infection.

Method:

Retrospective observational study of 64 RTPCR-confirmed COVID-19 non-survivors was conducted from April - June 2021 and January February 2022. Data were analyzed, and a P value<0.05 was taken as significant.

Results:

60.94% and 39.06 % were males and females, and 26.57% & 73.43 % of patients had moderate and severe disease, respectively. Fever, cough, and dyspnea were the most common presenting symptoms. 78.12% and 21.88% had pre-existing (diabetes and hypertension were most common) and no co-morbidities, respectively. 65.62 & 17.19 % of patients had bilateral and unilateral ground glass opacities, respectively. Thrombocytopenia, lymphopenia, neutrophilia, elevated monocytes, and neutrophil-lymphocyte ratio (NLR) of 7.52 were hematological findings. D dimer was elevated. ABG showed low PaO2 and SPO2 %. ALT and AST were elevated. Tachycardia was also present. Compared to the first wave, no significant association of gender with severity was found. However, the percentage of male patients was higher. The association of the duration of stay and co-morbidity with disease severity was significant in both the first and subsequent waves of COVID-19.

Conclusion:

Co-morbidity, disease severity, and radiological lung opacities play a role in the outcome of COVID-19. The associated findings are hematological, renal, liver, cardiovascular, and arterial blood gas derangements.

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took the world by storm after appearing for the first time in Wuhan, Hubei Province, China, in December 2019.[1] In India, from January 2020 to January 14, 2023, there have been 4,49,92,960 confirmed cases of coronavirus disease 2019 (COVID-19), with 5,31,892 deaths reported to the World Health Organization (WHO). Till May 2023, a total of 2,20,67,10,296 vaccine doses have been administered.[2] Strains of COVID-19 were found to be more contagious (B.1.617) but less fatal than those causing COVID-19 during the first wave; however, with a sharp increase in the daily caseload, the mortality was predicted to be high because of the increased burden on healthcare facilities and other contributory factors.[3] Similarly, studies have reported that seroconversion was less during the second wave, resulting in less severity of the infections; other factors for the observed trends were greater public awareness and use of COVID-appropriate behavior and, importantly, vaccination drive.[4] Reportedly, compared to the first wave, there was higher dyspnea, GIT symptoms, and infectivity in the young population. However, in contradiction to trends elsewhere, it was found that N95 masks were less prevalent in India owing to their higher costs.[5] The caseload of the second wave showed a steep increase in mid-April 2021, with a daily caseload of 0.2 million.[6] During the second wave, India was behind only USA and Brazil regarding cases reported daily.[7] However, studies have reported lower mortality in the second wave than in the first wave. Moreover, the mean age of patients in the second wave was reportedly lower than the first. Reportedly, females were affected more, and GIT symptoms predominated in the second wave.[3,8-10] The daily caseload was higher than the first. A few studies from North India have retrospectively analyzed the data of deceased patients admitted to the designated COVID-19 hospital. The records of the reverse-transcriptase polymerase chain reaction (RTPCR)-confirmed non-survivor patients in a tertiary care COVID-designated hospital in northern India were analyzed retrospectively to elucidate demographic, clinical, and laboratory findings. During this period, the hospitals were better prepared to tackle the pandemic, and the vaccination drive had started. The study findings are expected to enhance the available literature on non-survivors and provide insight to physicians regarding the biochemical and physiological derangements associated with mortality in COVID-19. Analysis of the demographic and clinical characteristics of deceased patients helps improve hospital care and services in the future. Also, it helps the physician to plan interventions, investigations, and treatment modalities in the future for similar situations and needs.

Study area: A designated COVID-19 hospital in North India by the Uttar Pradesh Government.

Study Population and sample size: Data from 64 non-survivor COVID-19 patients were analyzed. Consent of the guardians/relatives was taken.

Study Duration: Non-survivor COVID-19 patients admitted during April - June 2021 and January February 2022.

Study design: Retrospective observational study.

Ethical Consideration: The study was approved by the Institutional Ethical Committee of the Hospital (ECR/1418/Inst/UP).

Tools and Techniques: Data were described for the following:

1. Sex (male and female)

2. Symptoms at the presentation and the presence of co-morbidities like diabetes, systemic hypertension, chronic kidney/liver disease, and so on at presentation. Severity at the time of admission.

3. Biochemical tests, arterial blood gas, X-ray findings, and oxygen saturation at the time of presentation.

Data Analysis

The data (qualitative and quantitative) of patients admitted to the hospital during the second wave were described using descriptive statistics. Data regarding number (n), percentage (%), and mean ± standard deviation were presented. The number and percentage of mortality from COVID-19 were also represented. P value < 0.05 was taken as significant.

Results

In the present study, data from 64 COVID-19 patients with fatal outcomes admitted during the second and subsequent waves of the pandemic in the L3 designated tertiary care hospital of North India were analyzed. 60.94% were males, and 39.06% were females. 78.12% had pre-existing co-morbidities, and 21.88% had no co-morbidities at admission. 62.50% stayed in the hospital for more than 72 hours, and 37.50% stayed for less than 72 hours. Moderate and severe diseases were present in 26.57% and 73.43% of patients. 65.62% had bilateral ground glass opacities as the dominant radiological feature. Fever, cough, and dyspnea were the main symptoms at admission, whereas systemic hypertension and diabetes were the most commonly associated co-morbidities. Overall, 31.25% and 21.87% of patients had pre-existing hypertension and diabetes at admission, respectively [Tables 1-3]. Investigations showed thrombocytopenia, neutrophilia, lymphopenia, raised creatinine, elevated ALT, AST, low SPO2%, tachycardia, and elevated d dimer in non-survivors at admission [Table 4]. Lymphocyte (P = 0.007) and monocyte (<0.001) counts were significantly lower and higher, respectively, in non-survivors admitted with severe disease as compared to those admitted with moderate disease. RFT derangements were significant in the severely ill [blood urea nitrogen (BUN) and creatinine levels were significantly higher] compared to the moderately ill deceased. SPO2% was significantly reduced in the severely ill deceased at the time of admission (P < 0.001), and they also had significant tachycardia (P < 0.001). d-dimer levels were non-significantly higher in severely ill patients at admission (P = 0.148) [Table 5]. Compared with the first wave, the severity of infection and mortality was higher in later waves. There was no significant association of gender with severity; however, the percentage of male patients was higher. The association of duration of stay and co-morbidity with disease severity was found to be significant in both the first (P = 0.009 and 0.001, respectively) and later waves (P < 0.001 and 0.01, respectively) of COVID-19 [Table 6].

Table 1.

Demographic data, co-morbidities, severity, duration of stay and pulmonary manifestations

Variable	n (%)
Sex
Male	39 (60.94)
Female	25 (39.06)
Co-morbidity
Yes	50 (78.12)
No	14 (21.88)
Severity
Moderate	17 (26.57)
Severe	47 (73.43)
Duration of stay (hours)
<72	24 (37.50)
>72	40 (62.50)
X-ray findings
Normal	11 (17.19)
Bilateral ground glass opacities	42 (65.62)
Unilateral ground glass opacities	11 (17.19)

Table 3.

Associated co-morbidities

Co-morbidities	Non-survivors (n=64) n (%)
Systemic HTN	20 (31.25)
Type 2 Diabetes Mellitus	14 (21.87)
Type I Renal failure	13 (20.31)
Renal Diseases	05 (7.81)
Coronary Artery Disease	06 (9.37)
Hypothyroidism	03 (4.68)
Hepatitis	02 (3.12)
Chronic Kidney Disease	02 (3.12)
Cerebro-vascular Accident	01 (1.56)
Rheumatic Heart Disease	02 (3.12)
Tubercular Meningitis	02 (3.12)
Inflammatory Bowel Disease	01 (1.56)
Congestive Heart Failure	01 (1.56)
Myocardial Infraction	01 (1.56)
Tuberculosis (Pulmonary Koch)	01 (1.56)

Table 4.

Results of investigations in patients

Variables	Mean±SD (NLR average)*
Hematological profile
Hb (gm/dl)	12.94±0.70
Platelet (103/mm3)	129.99±29.18
TLC (103/mm3)	10.06±3.88
Neutrophil %	72.92±9.08
Lymphocyte %	12.00±4.46
Monocyte %	4.91±1.77
eosinophil %	0.80±0.08
basophil %	0.59±0.09
NLR*	7.52
RFT
BUN (mgm/dl)	21.15±10.12
Serum Creatinine (mgm/dl)	1.47±0.59
LFT
Serum bilirubin (mgm/dl)	0.62±0.26
ALT (U/L)	65.48±16.68
AST (U/L)	76.45±25.83
ABG
pH	6.89±1.10
PCO2 (mm Hg)	36.30±8.82
PO2 (mm Hg)	56.90±16.27
HCO3 (mmol/L)	22.14±4.93
Lactate (mmol/L)	2.56±1.12
SPO2%	75.31±11.01
CVS parameters
PR per minute	101.25±11.05
SBP (mm Hg)	113.24±12.97
DBP (mm Hg)	68.82±8.59
D-dimer	1049.39±530.92

Table 5.

Comparison of investigations on the basis of severity of disease at the time of admission

Variable	Severity		P
	Moderate (n=17)	Severe (n=47)
Age (years)	55.06±2.40	58.24±12.58	<0.001*
Hematological
Hb	12.79±0.57	13.00±0.75	0.300
Platelet	134.91±10.19	128.20±33.44	0.421
TLC	9.22±2.97	10.36±4.14	0.301
Neutrophil	69.73±8.41	74.07±9.13	0.091
lymphocyte	14.44±4.57	11.12±4.11	0.007*
monocyte	4.21±1.37	6.89±1.18	<0.001*
Eosinophil	0.83±0.06	0.79±0.09	0.223
Basophil	0.63±0.10	0.59±0.08	0.084
RFT
BUN	16.78±9.33	22.73±10.01	0.036*
Serum Creatinine	1.04±0.14	1.61±0.62	<0.001*
LFT
Serum bilirubin	0.56±0.18	0.63±0.29	0.319
ALT	64.39±6.81	68.64±30.77	0.365
AST	68.05±22.60	79.49±26.47	0.119
ABG
pH	6.91±1.02	6.84±1.02	0.851
PCO2	34.85±8.00	36.82±9.13	0.435
PO2	57.49±16.02	55.30±17.33	0.637
HCO3	24.06±3.97	21.45±5.09	0.061
SPO2%	87.70±3.51	70.83±9.20	<0.001*
Lactate	2.46±1.20	2.60±1.10	0.677
CVS parameters
PR	93.23±11.63	104.00±9.75	<0.001*
SBP	109.76±11.80	114.83±13.51	0.177
DBP	69.89±7.63	67.64±10.60	0.354
D-dimer	1006.02±510.96	1226.76±588.17	0.148

Table 6.

Association of severity with gender, duration of stay and co-morbidity among non-survivors during the first and last two waves

Variables	Severity in waves				Chi square, P (first* and subsequent waves#, ** significant difference)
	First wave (n=47)		Subsequent waves (n=64)
	Moderate n (%)	Severe n (%)	Moderate n (%)	Severe n (%)
Gender
Male	08 (17.02)	15 (31.92)	10 (15.62)	29 (45.32)	0.464*
Female	06 (12.76)	18 (38.30)	07 (10.94)	18 (28.12)	0.835#
Duration of Stay in the hospital (hours)**
<72	14 (29.79)	21 (44.68)	17 (26.56)	07 (10.94)	0.009*
>72	00 (00)	12 (25.53)	00 (00)	40 (62.50)	<0.001#
Co-Morbidities**
Yes	14 (29.79)	16 (34.04)	17 (26.57)	33 (51.56)	0.001*
No	00 (00)	17 (36.17)	00 (00)	14 (21.87)	0.01#

Table 2.

Symptoms at the time of admission

Symptoms	Non-survivors (n=64) n (%)
Fever	34 (53.12)
Cough	27 (42.18)
Dyspnea	37 (57.81)
Fatigue	07 (10.93)
Headache	02 (3.12)
Bodyache	02 (3.12)
Sore throat	02 (3.12)
Chest pain	02 (3.12)
Altered sensorium	01 (1.56)

Discussion

60.94% of admitted patients were males, and 39.06% had co-morbidities. Diabetes and hypertension were the most common co-morbidities. Diabetes, hypertension, and cardiovascular diseases have been reported to be the most common co-morbidities in COVID-19 patients.[10,11] In our study, most patients were males, consistent with earlier reports. The weakening of T-cell responses in older males increases the susceptibility to infections. Associated co-morbidity increased mortality in the elderly age group, as reported in India.[12] The risk of infection with variants of coronavirus and mortality increases with advancing age because of associated co-morbidities, declining immunity, deterioration of organ functions, and higher expression of ACE-2.[13-15] Advancing age, presence of co-morbidities, and male gender are risk factors for severe COVID infection.[16,17] In our study, the mean age of the patients admitted with severe disease was 58.24 ± 12.58 years, and 73.43% and 78.12% of non-survivors had severe disease and co-morbid conditions, respectively. 11–27% (moderate and severe, respectively) of deaths occurred within 72 hours of admission. An earlier study has reported the majority of deaths in the age group of 41–60 years with male preponderance and 28% of deaths within days 1–3 and hypertension, followed by diabetes as the commonly associated co-morbidity.[18] Similar trends were found in our study also. In our study, most admitted patients had fever, cough, dyspnea, and fatigue as the main symptoms, consistent with the reported symptoms.[19,20] In our study, 57.81% of non-survivors presented with dyspnea, and 3.12% had chest pain. An earlier study reported that dyspnea and chest pain were more in the deceased than in recovered patients of COVID-19.[21] In our study, 26.57% and 73.43% of non-survivors had a moderate and severe presentation at admission, and 65.62% had bilateral ground glass opacities as radiological findings. The results are consistent with earlier studies. Ground glass opacities involving both lungs were reported to be the most common radiological finding in COVID-19 patients. The results are consistent with earlier studies.[22-25]

In our study, deceased patients had thrombocytopenia, neutrophilia, and lymphopenia at admission. An increase in neutrophils and decreased levels of lymphocytes and platelets have been reported in a study conducted in non-surviving COVID-19 patients. The mechanisms for hematological changes observed could probably be attributed to virus binding to ACE-2 receptors expressed in various organs like the lung, heart, and liver, and the resultant cytokine release, virus entry into the lymphocytic organs, ACE2-mediated destruction of the lymphocytes, and inflammatory cytokine-mediated lymphocyte damage also led to observed changes.[26-30] Lymphopenia at the time of presentation correlates with poor prognosis.[31]

In our study, severely ill patients had significantly reduced lymphocytes (P = 0.007) and elevated (P < 0.001) monocyte counts as compared to those with moderate presentation. The NLR was found to be 7.52 in deceased patients. An earlier study has reported that lymphopenia and high NLR are independent risks for mortality in COVID-19 severely ill patients.[32] Research is suggestive that COVID-19 severity and mortality are associated with neutrophilia, lymphopenia, thrombocytopenia and low basophil and eosinophil counts. Inflammatory cytokines like IL-4 and IL-10 affect erythropoiesis and leucopoiesis. Low and no changes in Hb counts have been reported in COVID-19 patients. In our study, the platelet count of patients at the time of admission was lower. Thrombocytopenia is considered to be a risk for mortality, and platelet counts may act as a predictor of mortality in COVID-19 patients.[33]

Renal function abnormalities in severe non-surviving COVID-19 patients at the time of admission in our study showed significantly higher values of urea nitrogen (P = 0.036) and serum creatinine (P < 0.001) as compared to moderately ill deceased. Deterioration of renal functions is associated with poor progression and mortality and has been reported in earlier studies. The binding of the virus to the renal tubular epithelial cells’ ACE-2 receptors and subsequent inflammation are possible mechanisms of renal dysfunction in COVID-19. Elevated BUN in COVID-19 patients could be attributed to increased reabsorption of water and urea due to virus-induced enhanced RAAS activity. Other probable reasons are inflammation, organ hypoperfusion, excess steroid use, and a catabolic state.[26,34,35]

ALT and AST were non-significantly elevated at admission in moderate and severely ill deceased patients. Hypoxia, infection, and inflammation have been postulated to be the mechanisms responsible for liver function derangement in COVID-19. AST and ALT elevation are reported in COVID-19.[36] Hepatic injury due to drugs, liver congestion, oxidant–anti-oxidant imbalance, immune-mediated inflammation and elevated inflammatory cytokines, transaminase release, and liver infection are possible explanations. Also, the virus binds to the ACE-2 receptors expressed abundantly in liver cholangiocytes, resulting in liver function abnormalities. Elevations in liver enzymes are reportedly associated with a higher risk of mortality. The results of our study are consistent with earlier studies which reported that serum bilirubin is not elevated during COVID-19 and AST rise is slightly more than that of ALT owing to micro thrombosis, resulting in perfusion abnormalities in liver and COVID-19-induced steatosis and mitochondrial dysfunction.[17,37-39]

ABG abnormalities in our study included higher values of PCO₂ and lactate and lower values of bicarbonate, PO₂, and oxygen saturation in non-survivors, and the derangements were more in those with a severe presentation at the time of admission. The results are consistent with the study conducted by Bezuidenhout MC et al.,[40] 2021, who found that lactate and PCO₂ were higher and oxygen saturation was lower in non-survivors. The results suggest that non-survivors suffer from respiratory acidosis, hypoxemia, respiratory failure, and subsequent multi-organ dysfunction in patients. Acidemia is reportedly a poor prognostic feature in patients with COVID-19. An increase in ventilation and dyspnea may result from PO₂ less than 60 mm Hg and PCO₂ greater than 39 mm Hg.[41] Higher lactate values with increased disease severity could be due to tissue hypoxia, microvascular thrombosis, and increased WBC counts.[42] Respiratory failure and hepatic and renal function impairments are higher in non-survivors, as reflected by lower PaO₂, elevated AST, and creatinine levels. Similar derangements were found in another study.[43] The severely ill patients had significant tachycardia and non-significantly more systolic and low diastolic blood pressure compared to moderately ill patients. Cardiovascular changes were consistent with earlier studies.[44]

D-dimer is a marker of intravascular clot and fibrin degradation and is a predictor of the severity of the disease and mortality. In our study, the d-dimers were higher in deceased patients, consistent with earlier reports.[45-47] Mortality in subsequent waves was higher than in the first wave.[45] There was no significant association of gender with severity; however, the percentage of male patients was higher. The results are in line with earlier reports.[12] The association of the duration of stay and co-morbidity with disease severity was significant in the first and last two waves of COVID-19. Similar trends were reported in earlier studies.[20]

Summary

Overall, the results are comparable to earlier studies. Chen T et al.[48] analyzed the data of 113 non-survivors. They found that male gender, hypertension, tachycardia, elevated systolic blood pressure, lymphopenia, elevated ALT, AST, d-dimer, creatinine, and bilateral ground glass opacities were pre-dominant characteristics at admission. Similarly, high NLR and D-Dimer at the time of admission are independent mortality risks, as reported by an earlier study.[49] In our study, a higher percentage of deceased patients stayed longer, which aligns with earlier reports. Admission WBCs more than 10X10⁹ cell/L, neutrophils >6.3 X 10⁹ cell/L, and PaO₂ <60 mm Hg were risks for mortality in COVID-19 patients, as shown by Du R-H et al.[43] Moreover, NLR >3-11, lymphopenia, and heart rate >100 beats per minute were found to be risks for mortality in COVID-19 patients.[50] Admission TLC is non-significantly higher in non-survivors with severe infection as compared to those with moderate severity. Lymphocytes were significantly lower in the former group at admission (P = 0.007). ALT and d-dimers were found to be higher at the time of admission in those presenting with severe infection. The results are in accordance with a study done by Chen G et al.[51]

Conclusions

The analysis of the data of deceased patients admitted during later waves indicates that non-survivors had co-morbidity, raised levels of urea nitrogen and serum creatinine, raised AST, high neutrophils, low platelets and low lymphocytes, and deranged ABG in terms of low oxygen saturation and bicarbonates and higher levels of lactate and PCO₂. The coagulation defects were manifested in the form of elevated d-dimers. Cardiovascular parameters showed relative systolic and diastolic blood pressure changes and higher pulse. Results indicate a significant association between severity, duration of stay, and co-morbidity in both the first and later waves.

Robust mechanisms to manage and treat the complications are required. Early identification of patients will help in early admissions, thereby preventing derangements, and will help reduce mortality. Analyzing the data of deceased patients also provides an opportunity to improve patient care and hospital services in the future.

Limitations

The sample size needs to be higher to prevent a paucity of data. Changes in the study parameters during the stay could yield better results. Certain parameters could not be analyzed due to missing data. The results are of a single center. Thus, a multi-centric study will generate better insights into the mortality data.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.