Comparison of Clinical Characteristics and Outcome of COVID-19 Patients Between the 4^th and 5^th Wave in a Tertiary Care Hospital in Karachi, Pakistan

By Jamal Azfar Khan¹, Muhammad Irfan Khattak¹, Muhammad Luqman Satti², Mahwash Bazanjo¹, Nadia Aziz Ather¹, Rabia Abbas³

Affiliations

1. Department of Medicine, Pakistan Naval Ship Shifa Hospital, Karachi, Pakistan
2. Department of Pathology, Pakistan Naval Ship Shifa Hospital, Karachi, Pakistan
3. Department of Neonatology, Pak Emirates Military Hospital, Rawalpindi, Pakistan

doi: 10.29271/jcpsp.2023.08.857

ABSTRACT      
Objective: To compare the clinical parameters of 4^th and 5^th COVID waves in Karachi, Pakistan.
Study Design: Descriptive study.
Place and Duration of the Study: PNS Shifa Hospital, Karachi, from July 2021 to February 2022.
Methodology: All patients with COVID-19 in PNS Shifa Hospital were included in the study. The patients were divided into two groups, those who had COVID-19 during the 4^th wave, and others who had it during the 5^th wave. The patients’ demographic details, comorbidities, vaccination status, initial presentation, the severity of disease, clinical progress, and final disposal from the hospital were noted. A comparison of severity, length of hospital stays, and mortality was made between the groups.
Results: There were 747 patients admitted during the Delta variant-dominated 4^th wave of COVID-19, and 490 patients during the 5th wave, dominated by the Omicron variant. A vast majority of fifth-wave patients had the mild disease (87.35% vs. 49.39%), with significantly lower critical patients (2.04% vs. 7.09%). Vaccination was effective against both the Delta and the Omicron variant of the SARS-CoV-2 virus. The mean length of stay in the hospital for patients was significantly lesser (p < 0.001) during the 5^th wave as compared to the 4^th wave (6.43 ± 3.37 vs. 9.56 ± 5.45 days). The mortality rate was 7.09% among patients admitted in the 4^th wave and 2.04% in the 5^th wave. This difference was statistically significant (p < 0.001).
Conclusion: The severity of disease, length of hospital stays, and mortality were higher in the Delta variant-dominated 4^th wave of COVID-19 as compared to the Omicron variant-dominated 5^th wave in Pakistan. The vaccination was effective against both the Delta and the Omicron variant of COVID 19, as the mortality rate among the vaccinated patients during the two waves was not significantly different.

Key Words: COVID 19, Vaccination, Disease outcome, Mortality.

INTRODUCTION

Numerous countries across the globe have encountered outbreaks of COVID-19 since 2020. The overall pattern of the coronavirus pandemic so far has been a series of COVID-19 waves, surges in new cases, with different characteristics, followed by declines. Several factors have had an impact on whether new COVID-19 cases are increasing or declining in different geographical locations.

These factors include the effectiveness of vaccines over time, human behaviour, infection prevention policies, changes to the coronavirus itself, and the number of people who are vulnerable because they have not developed some immunity, whether from natural infection or through vaccination.

The SARS-CoV-2 virus is prone to mutations.¹ As a result, numerous variants of the SARS-CoV-2 virus have emerged. In Pakistan the 4^th wave of COVID-19, dominated by its Delta variant, started in July 2021 and lasted till October 2021.² At the start of the fourth wave, only around 7% of the Pakistani population had received at least one dose of COVID-19 vaccine.³  

The fifth wave of COVID-19 in Pakistan was predominantly caused by the Omicron variant of the SARS-CoV-2 virus.⁴ The first case of Omicron was reported in Pakistan on 13^th December 2021.⁵ The fifth wave reached its peak on 27^th January 2022, in Pakistan with 8133 new cases reported by National Command and Operation Center (NCOC).⁶ At that time, almost 36% of the Pakistani population was fully vaccinated while a further 10% had received at least one dose of COVID-19 vaccine.³ Pakistan government had also started booster dose administration to all those who were fully vaccinated for over 6 months from December 2021.

Both the Delta and the Omicron variants of SARS-CoV-2 virus were infectious. However, the Omicron variant was considered to spread even more rapidly than the Delta variant.⁷ In addition, there were concerns about the efficacy of vaccination against the Omicron variant of the virus.⁸

This study aimed to analyse and compare the 4^th and the 5^th wave of SARS-CoV-2 in terms of the severity of the disease, hospitalisations, and mortality.

METHODOLOGY

The study was a descriptive study conducted in Pakistan Naval Ship (PNS) Shifa Hospital, Karachi, from July 2021 to February 2022. All patients who were diagnosed with COVID-19 (COVID-19 Polymerase Chain Reaction test positive) in PNS Shifa Hospital were included in the study. These patients comprised of those who were admitted through the COVID-19 Clinic, emergency room, or in the wards.

The patients who had COVID-19 clinically but the diagnosis could not be confirmed by PCR test for COVID-19 were excluded. The Ethical Review Committee approved the study vide letter number ERC/2022/MEDICINE/04. The patients were divided into two groups, those who had COVID-19 during the 4^th wave, and others who had it during the 5^th wave. The 4^th wave of COVID-19 was considered to have lasted from 1^st July 2021 to 30^th September 2021, as that was the time when a surge of the Delta variant-infected COVID-19 patients was seen. The 5^th wave of COVID-19 was considered to have started from 1^st January 2022 up till 15 February 2022, as the number of Omicron variant-infected COVID-19 patients had dominated during that period. The hospital record of COVID-19 patients was accessed. The patients’ demographic details, comorbidities, vaccination status, initial presentation, the severity of disease, clinical progress, and final disposal from the hospital were noted.

Data were analysed using IBM SPSS v 25. Numerical variables were expressed as mean and SD values after applying descriptive statistics. Categorical variables were expressed as percentages and frequencies. The two groups (the patients treated during the 4^th and 5^th wave of COVID-19) were compared for their age, gender distribution, and comorbidities. A comparison of severity, length of hospital stays, and mortality was made between the patients admitted during the 4^th and the 5^th COVID-19 waves. Chi-square test was used to find out if there was a significant difference in the severity of the disease between the 4^th and the 5^th wave. The t-test was done to find out any significant difference in the duration of hospital stays during the 4^th and the 5^th wave. The same analyses were done to compare the vaccinated and the non-vaccinated patients. The  p-value  of  less  than  0.05  was  considered  significant.  

RESULTS

There were 747 patients admitted during the Delta variant dominated 4^th wave of COVID-19, 370 of them having been vaccinated against COVID-19 while 377 were non-vaccinated.

During the 5^th wave, dominated by the Omicron variant, 490 patients were admitted, 486 of whom had been vaccinated against COVID-19.

The comparison of demographic distribution and comorbidities between the Delta variant-dominated fourth wave and Omicron variant-dominated fifth wave is given in Table I.

The  severity  of  the  disease  also  varied  between the fourth and the fifth wave. A vast majority of the fifth-wave patients had mild disease. The number of critical patients was also significantly lower in the fifth wave. The comparison of disease severity between the fourth and the fifth wave is given in Figure 1.

Table I: Comparison of demographic distribution and comorbidities between patients of the fourth and fifth wave of COVID-19.

Characteristics	Fourth Wave n (%)	Fifth Wave n (%)
Gender
Male	521 (69.75)	425 (86.73)
Female	208 (27.85)	65 (13.27)
Age (years)
1-20	54 (7.23)	46 (9.39)
21-40	362 (48.46)	312 (63.67)
41-60	210 (28.11)	90 (18.37)
61-80	101 (13.52)	35 (7.14)
81-100	20 (2.68)	7 (1.43)
Comorbidities
Hypertension	24 (3.21)	53 (10.82)
Diabetes	20 (2.68)	30 (6.12)
Ischemic heart disease	5 (0.67)	15 (3.06)
Bronchial asthma	3 (0.4)	9 (1.84)
Cerebrovascular accident	3 (0.4)	2 (0.41)
Malignancy	2 (0.27)	2 (0.41)
Chronic kidney disease	2 (0.27)	1 (0.20)
Hyperthyroidism	1 (0.13)	2 (0.41)
Hepatitis C	1 (0.13)	0 (0)
Acute demyelinating polyneuropathy	0 (0)	1 (0.20)

Figure 1: Comparison of disease severity between the 4^th and the 5^th wave of  COVID-19.

The mortality rate of patients admitted in the 4^th wave was 7.09% whereas it was 2.04% in the 5^th wave. This difference was statistically significant (p < 0.001).

There were 370 vaccinated patients treated during the 4^th wave, 15 (4.05%) of whom died. During the 5^th wave, 486 vaccinated patients were treated, 10 (2.06%) of whom died. The difference in mortality rate was not significant (p = 0.102).

Amongst the non-vaccinated patients, the mortality rate was higher during the 4^th wave, as 38 (10.08%) non-vaccinated patients died due to their illness. In the 5^th wave, only 4 non-vaccinated patients were admitted, all of whom survived.

The mean length of stay in the hospital for COVID-19 patients during the 4^th wave was 9.56 ±5.45 days. During the 5^th wave, the mean hospital stay was 6.43 ± 3.37 days. The difference between the two was significant (p < 0.001).

The vaccinated patients stayed in the hospital for an average 9.89 ± 4.79 days during the 4^th wave and 6.42 ± 3.37 days during the 5^th wave. The difference was statistically significant (p < 0.001). The non-vaccinated patients had mean hospital stay of 9.25 ± 6.02 days during the 4^th wave, and 8.75 ± 2.5 days during the 5^th wave. The difference was not significant (p = 0.723).

DISCUSSION

To the best of the authors’ knowledge, this is the first reported study in Pakistan on comparison of Delta and Omicron COVID-19 waves in terms of severity of disease, hospitalisation, and mortality. Early in July 2021, Pakistan witnessed the start of 4^th wave dominated by Delta variant.⁹ The wave lasted for about 4 months. The Omicron variant was first detected in South Africa and it was declared as “variant of concern” by WHO.¹⁰ The Omicron variant has demonstrated a higher transmissibility but lower severity.¹¹ In Pakistan, the surge of the 5^th wave dominated by Omicron variant,¹² started in mid-December 2021 and lasted for about two months.

In this study, majority of the patients (69% in 4^th wave and 86% in 5^th wave) were males. More male population was affected by 5^th wave as compared to 4^th wave. This was in contrast to a study done by Bouzid, et al. in which the Omicron wave was more common in females (53%).¹³ This could be due to the fact that the hospital predominantly receives the young male military population. Similarly, young population (21-40 years) was predominantly affected (48% in 4^th wave and 63% in 5^th wave).

This study demonstrated that hypertension (3% and 10%, respectively) was a predominant associated risk factor in both waves followed by diabetes (2% and 6%, respectively). The present findings were consistent with another study in which hypertension was the predominant associated comorbid condition followed by diabetes.¹³

Number of studies have demonstrated that infection caused by the Omicron variant is usually mild and has reduced severity as compared to the Delta variant.^14-17 In this study, 87.3% patients admitted during 5^th wave, and 49.3% admitted during 4^th wave, had mild disease. Similarly, there was a significant difference in mortality between Delta and Omicron variant, mortality was 7.09% in the 4^th wave and 2.04% in 5^th wave. These results are consistent with results of study by Bouzid, et al.¹³ In their study, the mortality rate was 9.5% in Delta variant and 4.0% in the Omicron wave.

In the present study, mortality among vaccinated persons was 4.05% during the 4^th wave while it was 2.06% in 5^th wave. These findings suggest that vaccination was equally effective against Delta and Omicron variants. However, mortality among non-vaccinated patient was significantly high (10.08%) in the Delta wave. All four non-vaccinated patients in Omicron wave survived. Another observation was that during the 4^th wave, almost half of the patients (50.4%) were not vaccinated; while in 5^th wave dominated by Omicron variant, almost all (99.1%) patients were fully vaccinated. These findings also suggest that reduced severity and mortality in 5^th wave could be due to complete vaccination of all the patients admitted.

The average length of study during 4^th wave was longer (9.56 days) as compared to 5^th wave (6.43 days). The possible explanation for this fact is that majority of the patients (87.3%) had mild disease in Omicron wave thus less stay in hospital while 41.4% patients had moderate disease in 4^th wave. These findings were in accordance with findings of the study by Maslo, et al. which found a shorter length of hospital stay and reduced mortality during the Omicron wave.¹⁵

This study has one main limitation. The authors did not perform genomic analysis to confirm the variant (Omicron or Delta) on majority of the samples due to resource constraints. However, data on various samples across the country suggest 4^th wave and 5^th wave as the predominant Delta and Omicron variants, respectively.^9,12

CONCLUSION

The severity of disease, length of hospital stays, and mortality were higher in the Delta variant-dominated 4^th wave of COVID-19 as compared to the Omicron variant-dominated 5^th wave in Pakistan. The vaccination was effective against both the Delta and the Omicron variant of COVID 19, as the mortality rate among the vaccinated patients during the two waves was not significantly different.

ETHICAL APPROVAL:
The Ethical Review Committee approved the study vide letter No. ERC/2022/MEDICINE/04.

PATIENTS’ CONSENT:
Patients’ informed consent for inclusion in this study and using their data in publishing the study was obtained before commencing this study.

COMPETING INTEREST:
The  authors  declare  that  they  have  no  competing  interests.

AUTHORS’ CONTRIBUTION:
JAK:  Study  design  and  planning.
IK:  Data  collection  and  data  analysis.
LS:  PCR  (COVID)  and  microbiological  consultant.
MB:  Ward  incharge  and  primary  physician  of  COVID  cases.
NAA:  Literature  review  and  write-up.
RA:  Data  analysis  and  critical  revision.

REFERENCES

1. Afrin SZ, Islam MT, Paul SK, Kobayashi N, Parvin R. Dynamics of SARS-CoV-2 variants of concern (VOC) in Bangladesh during the first half of 2021. Virol 2022; 565: 29-37. doi:10.1016/j.virol.2021.10.005.
2. Hasan M, Gupta S: Wave-wise comparison of COVID 19 based on SARS-CoV-2 variants of concern (VOCs) in Bangladesh, India, Sri Lanka, Pakistan, Nepal and the probable reasons behind the less devastating effects of Delta variant in Bangladesh: A review. Brac University; 2022.
3. Roser HR, Edouard M, Lucas RG. Coronavirus pandemic (COVID-19). Our world in data 2022.
4. Khan A, Bibi S, Kanwal H: Omicron: A new face of COVID‐19 pandemic. Health Sci Rep 2022; 5(2):e526. doi: 10.1002/ hsr2.526.
5. Rehman Z, Umair M, Ikram A, Fahim A, Salman M: Footprints of SARS-CoV-2 genome diversity in Pakistan, 2020-2021. Virologica Sinica 2022; 37:153-5. doi:10.1016/ j.virs.2022.01.009.
6. COVID-19 Health advisory platform by ministry of national health services regulations and coordination 2022.
7. Yousaf M, Hassan Raza S, Mahmood N, Core R, Zaman U, Malik A: Immunity debt or vaccination crisis? A multi-method evidence on vaccine acceptance and media framing for emerging COVID-19 variants. Vaccine 2022; 40:1855-63. doi:10.1016/j.vaccine.2022.01.055.
8. Poudel S, Ishak A, Perez-Fernandez J. Highly mutated SARS-CoV-2 Omicron variant sparks significant concern among global experts - What is known so far? Travel Med Infec Dis 2022; 45:102234. doi:10.1016/j.tmaid.2021.102234.
9. Anwar MZ, Lodhi MS, Khan MT, Khan MI, Sharif S. Coronavirus genomes and unique mutations in structural and non-structural proteins in Pakistani SARS-CoV-2 delta variants during the fourth wave of the pandemic. Genes 2022; 13(3):552. doi: 10.3390/genes13030552.
10. Classification of Omicron (B.1.1.529): SARS-CoV-2 variant of concern. (November 26, 2021). Accessed: 5 June, 2022: www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern.
11. Nyberg T, Ferguson NM, Nash SG. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B. 1.1. 529) and delta (B. 1.617. 2) variants in England: A cohort study. Lancet 2022; 399(10332): 1303-12. doi:10.1101/2021.12.21.21268116.
12. Bukhari MH. Is omicron a tsunami? What should be the strategy to prevent the loss? J Pak Med Assoc 2022; 72(5):798-9. doi: 10.47391/JPMA.22-60.
13. Bouzid D, Visseaux B, Kassasseya C, Daoud A, Fémy A, Hermand C, et al.Comparison of patients infected with Delta versus omicron COVID-19 variants presenting to Paris emergency departments: A retrospective cohort study. Ann Intern Med 2022; 175(6):831-7. doi: 10.7326/M22-0308.
14. Wolter N, Jassat W, Walaza S. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa. Medrxiv 2021; doi:10.1101/2021.12.21. 21268116.
15. Maslo C, Friedland R, Toubkin M, Laubscher A, Akaloo T, Kama B. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves. JAMA 2022; 327(6):583-4. doi:10.1001/jama.2021.24868.
16. Abdullah F, Myers J, Basu D, Tintinger G, Ueckermann V, Mathebula M, et al. Decreased severity of disease during the first global omicron variant COVID-19 outbreak in a large hospital in tshwane, south africa. Int J Infect Dis 2022; 116:38-42. doi:10.1016/j.ijid.2021.12.357.
17. Diamond M, Halfmann P, Maemura T. The SARS-CoV-2 B. 1.1. 529 Omicron virus causes attenuated infection and disease in mice and hamsters. Res Square 2021; doi: 10.21203/rs.3.rs-1211792/v1.