COVID-19 vaccination status and its effect on outcome and disease severity

INTRODUCTION

WHO declared COVID-19 a public health emergency of international concern on 30 January 2020, and later a pandemic on 11 March 2020. Vaccination against COVID-19 is one of the critical tools to fight the ongoing pandemic. Globally, it began on 31^st December 2020, when WHO issued an emergency use listing (EUL) for the Pfizer vaccine. In India, the central drugs standard control organization (CDSCO), a regulatory body, has provided emergency use authorization to Covishield (AstraZeneca’s/ serum institute of India) and Covaxin (Bharat biotech limited) on 3^rd January 2021 and the first phase of vaccination started in January 2021 included health care professionals and frontline workers.¹ ChAdOx1 (Covishield) and BBV152 (Covaxin) were given free of cost in various government vaccination centres throughout India. The second phase of vaccination which was started in March 2021 enabled individuals above 60 and individuals between 45 and 59 with comorbidities. As of October 9, 2021, more than 946 million doses of vaccine have been administered and aims to vaccinate the entire eligible population of India in the near future.²

In an interim analysis of four randomized controlled trials, the efficacy of two doses of the ChAdOx nCoV-19 vaccine for preventing symptomatic COVID-19 was 70.4%.³ The BBV152 was found to have an overall efficacy of 77.8% against symptomatic COVID-19. The efficacy of ChAdOx nCoV-19 against the delta variant was found to be 67.0%, while that of BBV152 was 65.2%.⁴

According to a multicentre case control study in the US, Vaccination with an mRNA COVID-19 vaccine has significantly reduce COVID-19 hospitalization as well as the disease progression to death or mechanical ventilation.⁵

However not much studies have been undertaken in Kerala so far on the vaccination status among COVID-19 patients and the effectiveness of the vaccines. Hence the study had been conducted to assess the vaccination status and its role in mitigating the symptoms, severity and determining the outcomes of COVID-19 patients.

METHODS

This cross-sectional study was conducted in Arpoorkara panchayat, a rural area in central Kerala during the months of September and October 2021. The study samples were selected by simple random sampling from the list of COVID-19 patients of Arpookara Panchayat who were laboratory-confirmed cases of COVID-19 based on semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or rapid antigen test (RAT), each of them was interviewed and data was collected with a semi structured questionnaire.

Data related to demographic details, vaccination status, clinical manifestations, and disease outcomes were collected. Ethical approval was obtained from the institutional review board (IRB), govt. medical college, Kottayam. IRB No: 92/2021.

Inclusion criteria

Laboratory-confirmed cases of COVID-19 based on semiquantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or rapid antigen test (RAT).

Exclusion criteria

People who were unable to contact even after 3 attempts to contact them at their place of residence.

Sample size estimation

Sample Size was calculated using the formula:

N=Zα² p q/ d²

Where Zα= 1.96, p=21.1% as per the data obtained from district control cell of COVID-19.

The sample size calculated was 380. The inclusion criteria were those individuals who are 18 years or above, without any cognitive impairment and became COVID-19 positive during the months of June, July and August 2021. The exclusion criteria used was people who were unable to contact even after 3 attempts to contact them at their place of residence.

Operational definitions

Fully vaccinated: Individuals are considered as fully vaccinated if it has been over 2 weeks since their second dose.

Partially vaccinated: Individuals are considered as partly vaccinated If it has been over 2 weeks since their first dose.

Unvaccinated: They are individuals who have not taken even a single dose of vaccine or they are individuals who took the first vaccine but got COVID-19 positive within 2 weeks after the shot

Severe COVID-19 infection: A COVID-19 infection that caused the patient to get admitted and required oxygen support or ICU admission.

Data management and analysis

Data was properly coded and entered in Microsoft excel and was analyzed using IBM SPSS software version 20. The proportion of vaccination status among COVID-19 positive patients was expressed as percentage. Association between various categorical variables were assessed using chi- square test, with level of significance at 0.05. Risk for unvaccinated was assessed by logistic regression, adjusting age and comorbidities.

RESULTS

A total of 386 individuals with age ranging from 18 to 92 years and a mean age of 44.63 (±15.95) years were included in the study. Of the total responders, 49.2% (190) were female and 50.8% (196) were male.

We observed that 46.1% (178) of the study population were unvaccinated, whereas 30.8% (119) of the population were partially vaccinated as well as 23.1% (89) were fully vaccinated at the time of the diagnosing COVID-19.

Among the vaccinated group 75.6% (182) had taken ChAdOx1 (nCOV-19 vaccine (recombinant) (Covishield) while 10.6% (26) had taken BBV152 (Covaxin).

*APL: Above poverty level, *BPL: Below poverty level.

Severity assessment

As per our study, 88.3% (341) of the study sample was symptomatic. Most of them experienced fever as the chief complaint. Other complaints include cough, sore throat, difficulty in breathing, loss of smell and taste, myalgia, headache, tiredness and rhinitis.

The admission rate was found to be 12.4% (43). They were admitted in various facilities like covid first line treatment centres (CFLTC), private hospitals, secondary or tertiary care centres at government sector. However, 87.6% (343) of patients were in home isolation or domiciliary care centres (DCC).

As per our study, the 4.1% (16) of the study population required oxygen support during their course of the illness.

Among the study population 2.1% (8) of patients required ICU admission. Out of 8 people admitted in ICU, six of the them died. Proportion of mortality in patients with coronavirus disease in ICU was 75%.

In study, 57.8% (223) of study population fully recovered after illness and 40.7% (157) suffer from post COVID-19 complications, which includes shortness of breath, myalgia, loss of smell, loss of taste/ rashes on skin.

Association between vaccination status and severity of the disease

As per our study, 90.4% (161) of unvaccinated and 86.5% (180) of the vaccinated population was found to be symptomatic. However, the symptomatic presentation was not significantly associated with the vaccination status.

The risk for hospital admission, ICU stay, and Oxygen requirement were significantly less among those who had taken at least one dose of vaccine compared with the unvaccinated people. The model was adjusted for age and comorbidities.

It was noted that 3.4% (6) of unvaccinated individuals died, and 41% (73) had some kind of post COVID-19 illnesses. While in the vaccinated category there were no deaths and 40.3% (84) suffered from post COVID-19 illnesses. The difference was found to be statistically significant (p=0.026).

DISCUSSION

Primary vaccination of two doses and booster doses against COVID-19 are recommended for all eligible persons and was available easily and for free. But many had not taken the vaccines. In this analysis of COVID-19 patients, nearly 46.1% (178) individuals were not vaccinated at the time of COVID infection. In an online survey on COVID-19 vaccination hesitancy in India by Chandani et al it is found that about 20.63% were not aware of the vaccine, 27% were not sure if they would get the vaccine, and 10% refused to obtain the vaccine.⁶ So, the high proportion of unvaccinated in our study during the study period in 2021, could be lack of awareness and fear of side-effects. Initially the policy of administration of vaccines was to those belonging to the high-risk category, this could have also affected the vaccine coverage among common population. It was found that the vaccination status among the study group at the time of interview was better as majority of them had been vaccinated even after the infection, 85% of the population reported to have taken at least one dose of the vaccine.

About 88.3% (340) of study population were symptomatic as per our study and the common symptoms were fever, cough, myalgia and throat pain. It was in accordance with study done by Larsen et al in university of Southern California. The order of symptoms occurrence could help the health care providers distinguish COVID-19 from other respiratory diseases thus leading to early diagnosis, isolation and better treatment of the disease.⁷ Vaccination status had no significant role on the symptomatic spectrum of the disease.

The hospital admission of patients in Kerala were based on the five tier COVID-19 care pyramid.⁸ According to our study, the hospital admission rates were significantly higher among the unvaccinated groups with nearly three times risk for them.

In an interim analysis of four randomized controlled trials, the efficacy of two doses of the ChAdOx nCoV-19 vaccine for preventing symptomatic COVID-19 was 70.4%.³ The BBV152 was found to have an overall efficacy of 77.8% against symptomatic COVID-19. The efficacy of ChAdOx nCoV-19 against the delta variant was found to be 67.0%, while that of BBV152 it was 65.2%.⁹

According to a multicentre case control study in the US, Vaccination with an mRNA COVID-19 vaccine has significantly reduce COVID-19 hospitalization and disease progression to death or mechanical ventilation.⁵

According to Tenforde et al 21-site case-control analysis at USA, the overall vaccine effectiveness is 85% for mRNA vaccines to prevent COVID-19 hospitalizations. The findings also correspond to an estimated vaccine effectiveness of 86% for COVID-19 hospitalizations caused by the Delta variant.⁵ In another study by Bajema et al, COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations.¹⁰ In a multicentre case control study in the US, vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation was highly unlikely.⁵ Several other studies done on COVID-19 vaccines also shows that vaccinated individuals were either asymptomatic or showed milder disease without requiring hospitalization.^11-15

In the current study, there is statistically significant risk of ICU admission among unvaccinated patients. It is in accordance with another study done in Turkey, it is identified that 37.7% of the study population were admitted to hospital ICUs and nearly half of the patients (47.8%) were unvaccinated. In a study at Italy done by Lorenzoni et al among COVID-19 patients admitted at ICU, 18% were vaccinated, 8% were partially vaccinated, and 74% were not vaccinated.¹⁶ Several other studies by Rosenberg et al, Danza et al, Busic et al, Papagoras et al done on COVID-19 vaccines also showed that hospitalization rates were lower for the vaccinated people when compared to the unvaccinated group.^10,17-24

In the current study, there was significant reduction in oxygen requirement among those who had taken at least one dose of vaccination. According to a Busic et al on the role of vaccines in providing protection against respiratory deterioration among COVID-19 patients, vaccinated patients experienced significantly less requirement of high flow oxygen therapy (17% vs. 34%; HR: 0.45 [0.26-0.76]; p=0.005), and mechanical ventilation (8% vs. 18%; HR: 0.41 [0.20-0.88]; p=0.027) in comparison to the matched cohort of unvaccinated patients. Similar findings were obtained in a study on COVID-19 positive patients with systemic rheumatic diseases by Papagoras et al and another study conducted among healthcare workers from a hospital in Tamil Nadu.^25,26

According to our study, more than half of the unvaccinated and vaccinated population had recovered without any complications, 41% of unvaccinated population and 40.3% of vaccinated population suffered from some kind of post COVID-19 illnesses, and six unvaccinated individuals died due to COVID-19 while no one in the vaccinated population died of COVID-19. It is found that, there is statistically significant difference in outcome of disease between vaccinated and unvaccinated patients. It is in line with study done in England by Lopez Bernard et al to study the effectiveness of COVID vaccines, which found vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic COVID-19 in older adults, and prevented the disease from getting too severe.²⁷ Similar to findings in our study, several other studies also showed that COVID-19 vaccines may effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world.^28,29

Limitation

We haven’t taken in to account vaccinated uninfected controls for comparison and have not included the analysis of different platform vaccines.

CONCLUSION

Increasing the vaccination coverage of at least single dose of vaccine can reduce rate of hospital admission, ICU stay, Oxygen requirement and can improve the outcome of disease. The priority should be in focusing those unvaccinated individuals than increasing the coverage of second dose of vaccination.

ACKNOWLEDGEMENTS

Author would like to thanks Anakha O, Anand KP, Anantha Krishnan VP, Ananthakrishnan H, Anatta Chacko, Anchana T Shaji, Anitha Augustine, Anna Paul, Anna Sabu, Annie Ouseph, Anu Varsha M and Anugraha JS for their contribution in data collection.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee by Govt Medical College, Kottayam. IRB No: 92/2021.

REFERENCES

1. 1. COVID-19 Vaccine Introduction in India. Your Say. 2021. Available at: https://yoursay.plos.org/2021/09/covid-19-vaccine-introduction-in-india/. Accessed 05 August 2022.
2. 2. CoWIN Dashboard. Available at: https://dashboard.cowin.gov.in/?utm_medium=email&utm_source=transaction. Accessed 22 Jun, 2022.
3. 3. Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet Lond Engl. 2021;397(10269):99-111.
4. 4. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. The Lancet. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02000-6/fulltext. Accessed 5 August 2022.
5. 5. Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, et al. Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA. 2021;326(20):2043-54.
6. 6. Chandani S, Jani D, Sahu PK, Kataria U, Suryawanshi S, Khubchandani J, et al. COVID-19 vaccination hesitancy in India: State of the nation and priorities for research. Brain Behav Immun-Health. 2021;18:100375.
7. 7. Larsen JR, Martin MR, Martin JD, Kuhn P, Hicks JB. Modeling the Onset of Symptoms of COVID-19. Front Pub Heal. 2020;8:473.
8. 8. Guidelines and Advisory–dhs. Available at: https://dhs.kerala.gov.in/. Accessed on 28 Jun, 2022.
9. 9. Ella R, Reddy S, Blackwelder W, Potdar V, Yadav P, Sarangi V, et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. The Lancet. 2021;398(10317):2173-84.
10. 10. Bajema KL, Dahl RM, Prill MM, Meites E, Rodriguez-Barradas MC, Marconi VC, et al. Effectiveness of COVID-19 mRNA Vaccines Against COVID-19-Associated Hospitalization-Five Veterans Affairs Medical Centers, United States. MMWR Morb Mortal Wkly Rep. 2021;70(37):1294-9.
11. 11. Tenforde MW, Patel MM, Ginde AA, Douin DJ, Talbot HK, Casey JD, et al. Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States. MedRxiv Prepr Serv Health Sci. 2021;2021.07.08.21259776.
12. 12. Niyas VKM, Arjun R. Breakthrough COVID-19 infections among health care workers after two doses of ChAdOx1 nCoV-19 vaccine. QJM Mon J Assoc Physicians. 2021;114(10):757-8.
13. 13. Chau NVV, Ngoc NM, Nguyet LA, Quang VM, Ny NTH, Khoa DB, et al. An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam. E Clin Med. 2021;41:101143.
14. 14. Nasreen S, Chung H, He S, Brown KA, Gubbay JB, Buchan SA, et al. Effectiveness of COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario. Nat Microbiol. 2022;7(3):379-85.
15. 15. Lopez Bernal J, Andrews N, Gower C, Gallagher E, Simmons R, Thelwall S, et al. Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant. N Engl J Med. 2021;385(7):585-94.
16. 16. Lorenzoni G, Rosi P, De Rosa S, Ranieri VM, Navalesi P, Gregori D. COVID-19 Vaccination Status Among Adults Admitted to Intensive Care Units in Veneto, Italy. JAMA Netw Open. 2022;5(5):e2213553.
17. 17. Tenforde MW, Patel MM, Ginde AA, Douin DJ, Talbot HK, Casey JD, et al. Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing COVID-19 Hospitalizations in the United States. MedRxiv Prepr Serv Health Sci. 2021;2021.07.08.21259776.
18. 18. Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz MA, et al. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021;384(15):1412-23.
19. 19. León TM. COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis-California and New York. MMWR Morb Mortal Wkly Rep. 2022;71.
20. 20. Rosenberg ES, Holtgrave DR, Dorabawila V, Conroy M, Greene D, Lutterloh E, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status-New York. MMWR Morb Mortal Wkly Rep. 2021;70(34):1150-5.
21. 21. Rosenberg ES, Dorabawila V, Easton D, Bauer UE, Kumar J, Hoen R, et al. COVID-19 Vaccine Effectiveness in New York State. N Engl J Med. 2022;386(2):116–27.
22. 22. Danza P, Koo TH, Haddix M, Fisher R, Traub E, OYong K, et al. SARS-CoV-2 Infection and Hospitalization Among Adults Aged ≥18 Years, by Vaccination Status, Before and During SARS-CoV-2 B.1.1.529 (Omicron) Variant Predominance-Los Angeles County, California. MMWR Morb Mortal Wkly Rep. 2022;71(5):177-81.
23. 23. Tenforde MW, Self WH, Naioti EA, Ginde AA, Douin DJ, Olson SM, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults- United States, March-July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(34):1156-62.
24. 24. Busic N, Lucijanic T, Barsic B, Luksic I, Busic I, Kurdija G, et al. Vaccination provides protection from respiratory deterioration and death among hospitalized COVID-19 patients: Differences between vector and mRNA vaccines. J Med Virol. 2022;94(6):2849-54.
25. 25. Papagoras C, Fragoulis GE, Zioga N, Simopoulou T, Deftereou K, Kalavri E, et al. Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases. Ann Rheum Dis. 2022;81(7):1013-6.
26. 26. Victor PJ, Mathews KP, Paul H, Mammen JJ, Murugesan M. Protective Effect of COVID-19 Vaccine Among Health Care Workers During the Second Wave of the Pandemic in India. Mayo Clin Proc. 2021;96(9):2493-4.
27. 27. Lopez Bernal J, Andrews N, Gower C, Robertson C, Stowe J, Tessier E, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ. 2021;373:n1088.
28. 28. Liu Q, Qin C, Liu M, Liu J. Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: a systematic review and meta-analysis. Infect Dis Poverty. 2021;10:132.
29. 29. Watson OJ, Barnsley G, Toor J, Hogan AB, Winskill P, Ghani AC. Global impact of the first year of COVID-19 vaccination: a mathematical modelling study. Lancet Infect Dis. 2022;22(9):1293-302.