Portal de Periódicos da CAPES

Assessing the effectiveness of COVID-19 vaccines in Pakistan: A test-negative case-control study

2023; Elsevier BV; Volume: 86; Issue: 5 Linguagem: Inglês

10.1016/j.jinf.2023.01.016

1532-2742

Muhammad Imran Nisar, Nadia Ansari, Amyn A. Malik, Shahira Shahid, Kiran Ramzan Ali Lalani, Maaheen Ahmed Chandna, Ayesha Mansoor Younus, Zahra Hasan, Unab I. Khan, Farah Khalid, Marvi Mahesar, Muhammad Farrukh Qazi, İnci Yıldırım, Fyezah Jehan, Saad B. Omer,

COVID-19 Clinical Research Studies

A recent publication in this journal by Hannawi et al. assessed a novel SARS-CoV-2 bivalent recombinant vaccine, SCTV01C, given as a booster to those who had previously received the primary series of an inactivated vaccine.1Hannawi S. Saifeldin L. Abuquta A. Alamadi A. Mahmoud S.A. Li J. et al.Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C in adults previously vaccinated with inactivated vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial.J Infect. 2022; Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar The data showed that SCTV01C was well tolerated with a reactogenicity profile comparable to inactivated vaccines and induced substantial immune responses against Delta and Omicron variants.1Hannawi S. Saifeldin L. Abuquta A. Alamadi A. Mahmoud S.A. Li J. et al.Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C in adults previously vaccinated with inactivated vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial.J Infect. 2022; Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Inactivated vaccines are widely used in low-and middle-income countries.2Jara A. Undurraga E.A. González C. Paredes F. Fontecilla T. Jara G. et al.Effectiveness of an Inactivated SARS-CoV-2 vaccine in Chile.N Engl J Med. 2021; 385: 875-884Crossref PubMed Scopus (543) Google Scholar In Pakistan, Sinopharm (inactivated vaccine) was the first vaccine against COVID-19 to be introduced in February 2021. However, there is a paucity of vaccine effectiveness data from this region which undermines evidence-based decision-making. In addition, the protective effect of inactivated vaccines is considerably lower against emergent SARS-CoV-2 variants, signifying a need for booster doses.3Lopez 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: 585-594Crossref PubMed Scopus (1729) Google Scholar In Pakistan, eight different COVID-19 vaccines have been used since the launch of the government vaccination program against COVID-19, this provides an ideal setting for assessing the relative impact against symptomatic infection.4WH. OEvaluation of COVID-19 Vaccine effectiveness: Interim Guidance. World Health Organization, 17 March 2021: 2021Google Scholar We conducted a test-negative case-control study to assess the effectiveness of various COVID-19 vaccines, including mRNA, inactivated, and viral vector vaccines, that were deployed in Pakistan. Adult residents of Karachi, Pakistan, who tested for COVID-19 with RT-PCR at the Aga Khan University Hospital testing facility in June-September 2021 were contacted via phone calls. Participants who were symptomatic within a week prior to the test and provided verbal consent were enrolled in the study. Detailed information was collected on exposure, symptomatic history, and vaccination status using a structured questionnaire. Individuals who were positive on PCR were classified as cases and those who tested negative were classified as controls.The effectivenesss of different vaccines was calculated by comparing vaccination rates between cases and controls after adjusting for known confounders. In total, 1597 cases and 1590 controls were enrolled, of which 38·1% of the cases and 53·3%of controls were fully vaccinated respectively. The mean duration of the interval between last dose of vaccination and RT-PCR test among those who received a two-dose regimen was 27·3 days. Sinopharm was the most used vaccine (61·6%) followed by Sinovac (25·6%) and CanSinoBIO (8·9%). Only 33 individuals (2·3%) had received Sputnik-V, while the mRNA vaccines, Pfizer and Moderna, were each received by eight participants (0·5% each); Oxford/AstraZeneca was received by six (0·4%) and only two participants (0·1%) had received Janssen (Table 1).Table 1Socio-demographic characteristics and vaccination status among cases and controls.CharacteristicsTotalCasesControlsN = 3187(%)N = 1597(%)N = 1590(%)p-valueAge, years (mean ± SD)38.5 ± 13.340.6 ± 14.236.4 ± 12.018 – 29 years928 (29.1)382 (23.9)546 (34.3)<0.00130 – 39 years1045 (32.8)513 (32.1)532 (33.5)40 – 49 years544 (17.1)283 (17.7)261 (16.4)50 – 59 years358 (11.2)207 (13.0)151 (9.5)60 – 69 years230 (7.2)149 (9.3)81 (5.1)70+ years82 (2.6)63 (3.9)19 (1.2)GenderFemale1400 (43.9)703 (44.0)697 (43.8)0.97Male1787 (56.1)894 (56.0)893 (56.2)Healthcare workers626 (19.6)211 (13.2)415 (26.1)<0.001Ethnicityn = 3183n = 1595n = 1588Sindhi352 (11)156 (9.8)196 (12.3)0.06Punjabi244 (7.7)123 (7.7)121 (7.6)Pushto79 (2.5)39 (2.5)40 (2.5)Balochi50 (1.6)30 (1.9)20 (1.3)Urdu speaking2089 (65.5)1075 (67.4)1014 (63.9)Others*Ethnic groups from other parts of Pakistan.369 (11.7)172 (10.8)197 (12.4)Education status14.1 ± 3.513.9 ± 3.714.3 ± 3.2No formal education60 (1.9)41 (2.6)19 (1.2)<0.001Elementary (1 to 8 years)107 (3.4)57 (3.7)50 (3.2)Secondary (9 to 12 years)635 (20.3)352 (22.5)283 (18.1)Graduation (12 to 16 years)1901 (60.8)910 (58.3)991 (63.2)Higher Education (17+ years)426 (13.6)202 (12.9)224 (14.3)Previous COVID-19 infection297 (9.3)59 (3.7)238 (15)<0.001Use of facemask2899 (91.0)1442 (90.3)1457 (91.6)0.22Type of facemask⁎⁎Use of more than one type of facemask.Surgical mask2824 (88.6)1407 (88.1)1417 (89.1)0.22Cloth Mask66 (2.1)35 (2.2)312Jara A. Undurraga E.A. González C. Paredes F. Fontecilla T. Jara G. et al.Effectiveness of an Inactivated SARS-CoV-2 vaccine in Chile.N Engl J Med. 2021; 385: 875-884Crossref PubMed Scopus (543) Google ScholarRespirator84 (2.6)34 (2.1)50 (3.1)Social Distancing2261 (70.9)1175 (73.6)1086 (68.3)<0.001Exposure to person with similar illness684 (21.5)414 (25.9)270 (17.0)<0.001Nature of contactFamily member (lives with you)326 (47.7)215 (51.9)111 (41.1)<0.001Social contact86 (12.6)49 (11.8)37 (13.7)Workplace198 (29)90 (21.7)108 (40)Other74 (10.8)60 (14.5)14 (5.2)Health status of participants at the time of Index testIsolating at home3059 (96.0)1565 (98.0)1494 (94.1)<0.001Hospitalized41 (1.3)32 (2.0)9 (0.6)N/A87 (2.7)0 (0)85 (5.4)Pregnant60 (4.6)27 (3.8)33 (4.7)Concurrent medical conditions659 (20.7)395 (24.7)264 (16.6)<0.001Cancer26 (3.9)18 (4.6)8 (3.0)0.003Diabetes261 (39.6)171 (43.3)90 (34.1)Immunosuppression17 (2.6)11 (2.8)6 (2.3)Cardiovascular334 (50.7)221 (55.9)116 (43.9)Respiratory disorders75 (11.4)37 (9.4)39 (14.8)Others⁎⁎⁎Includes: high cholesterol, thyroid problems, allergies, renal disorders, etc.177 (26.9)100 (25.3)76 (28.8)Vaccination status ᵻVaccinated: one dose of any vaccine received before the index test.Non-vaccinated1732 (54.3)989 (61.9)743 (46.7)<0.001Vaccinated1455 (45.7)608 (38.1)847 (53.3)Vaccination category Non-vaccinated: never received a vaccine dose or duration between first dose of two-dose vaccine, or one dose of a single-dose regimen and index test was less than 14 days. Partially vaccinated: received one dose of a two-dose vaccine at least 14 days before the index test and had either not received the second dose or less than 14 days had elapsed between the second dose and time of index test. Fully vaccinated: received second dose of a two-dose vaccine or one dose of a single-dose regimen 14 or more days before the index test.Non-vaccinated1164 (36.5)670 (42.0)494 (31.1)<0.001Partially vaccinated568 (17.8)319 (20.0)249 (15.7)Fully vaccinated1455 (45.7)608 (38.1)847 (53.3)Type of vaccine administered ᵻmRNA vaccines: Pfizer-BioNTech, Moderna; Inactivated vaccines: Sinopharm, Sinovac; Viral-vector vaccines: Oxford/AstraZeneca, Sputnik-V, CanSinoBIO, Janssen.n = 1455n = 608n = 847RNA16 (1.1)5 (0.8)11 (1.3)0.18Inactivated1269 (87.2)537 (88.3)732 (86.4)Vector170 (11.7)66 (10.9)104 (12.3)Brand of vaccine administeredn = 1455n = 608n = 847Pfizer-BioNTech8 (0.5)4 (0.7)4 (0.5)0.05Moderna8 (0.5)1 (0.2)7 (0.8)Sinopharm896 (61.6)387 (63.7)509 (60.1)Sinovac373 (25.6)150 (24.7)223 (26.3)Oxford/AstraZeneca6 (0.4)3 (0.5)3 (0.4)Sputnik-V33 (2.3)12 (2.0)21 (2.5)CanSinoBIO129 (8.9)51 (8.4)78 (9.2)Janssen2 (0.1)0 (0)2 (0.1) Ethnic groups from other parts of Pakistan. Use of more than one type of facemask. Includes: high cholesterol, thyroid problems, allergies, renal disorders, etc.ᵻ Vaccinated: one dose of any vaccine received before the index test.ᵻᵻ Non-vaccinated: never received a vaccine dose or duration between first dose of two-dose vaccine, or one dose of a single-dose regimen and index test was less than 14 days.Partially vaccinated: received one dose of a two-dose vaccine at least 14 days before the index test and had either not received the second dose or less than 14 days had elapsed between the second dose and time of index test.Fully vaccinated: received second dose of a two-dose vaccine or one dose of a single-dose regimen 14 or more days before the index test.ᵻᵻᵻ mRNA vaccines: Pfizer-BioNTech, Moderna; Inactivated vaccines: Sinopharm, Sinovac; Viral-vector vaccines: Oxford/AstraZeneca, Sputnik-V, CanSinoBIO, Janssen. Open table in a new tab After adjusting for age, gender, healthcare worker status, past COVID-19 infection, use of non-pharmaceutical interventions, diabetes, and hypertension, it was found that two doses of mRNA vaccines conferred the greatest protection (VE: 67·4%; 95% CI: 1·8–89·2%), followed by Sputnik-V (VE: 58·5%; 95% CI: 12·8–80·2%), Sinovac (49·3%; 95% CI: 34·8–60·6%) and Sinopharm (VE: 33·8%; 95% CI: 18·6, 46·1%) (Fig. 1), while a single shot of CanSinoBIO was 47·9% effective in preventing symptomatic COVID-19. Among the partially vaccinated participants, VE estimates were lower, 29·8% for the mRNA vaccines, and 31·8% for Oxford/AstraZeneca. One dose of inactivated vaccines was ineffective in providing protection against symptomatic COVID-19 infection (Fig. 1). We found that two doses of inactivated vaccines had lower effectiveness against symptomatic disease (between 34% and 48%) compared with 2 doses of the mRNA vaccine (67%) during the period when the delta variant was in circulation. Overall, these estimates are lower than previous clinical trials.5Han B. Song Y. Li C. Yang W. Ma Q. Jiang Z. et al.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy children and adolescents: a double-blind, randomised, controlled, phase 1/2 clinical trial.Lancet Infect Dis. 2021; 21: 1645-1653Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar This could be because the vaccines may have become less effective as a result of emerging variants. We report a widespread use of two inactivated vaccines, Sinopharm and Sinovac, among the study population. We found that a two-dose schedule of Sinovac was around 47% effective at preventing symptomatic infection due to the Delta variant. This is consistent with previous estimates, including a recently published study from Jiangsu, China, which showed the vaccine to be 51% effective against symptomatic infection by the Delta variant.6Hu Z. Tao B. Li Z. Song Y. Yi C. Li J. et al.Effectiveness of inactivated COVID-19 vaccines against severe illness in B.1.617.2 (Delta) variant-infected patients in Jiangsu, China.Int J Infect Dis. 2022; 116: 204-209Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar A similar estimate (46.8%) was reported for the Sinovac vaccine against the earlier variants in a test-negative case control study from Brazil 24,7Ranzani O.T. Hitchings M.D.T. Dorion M. D'Agostini T.L. de Paula R.C. de Paula O.F.P. et al.Effectiveness of the CoronaVac vaccine in older adults during a gamma variant associated epidemic of COVID-19 in Brazil: test negative case-control study.BMJ. 2021; 374: n2015Crossref PubMed Scopus (180) Google Scholar while VE for Sinovac was estimated to be of 67% against symptomatic infection from a cohort study in Chile.2Jara A. Undurraga E.A. González C. Paredes F. Fontecilla T. Jara G. et al.Effectiveness of an Inactivated SARS-CoV-2 vaccine in Chile.N Engl J Med. 2021; 385: 875-884Crossref PubMed Scopus (543) Google Scholar Decline in the effectiveness of different COVID-19 vaccines against later variants has been reported from other studies as well.8Zheng C. Shao W. Chen X. Zhang B. Wang G. Zhang W. Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis.Int J Infect Dis. 2022; 114: 252-260Abstract Full Text Full Text PDF PubMed Scopus (265) Google Scholar Bernal et al. reported effectiveness of two doses of Pfizer-BioNTech vaccine to be 93·7% and 88% against the alpha and Delta variants respectively, while Oxford-AstraZeneca vaccine was 74·5% against the alpha variant but 67% against the Delta variant.9Lopez 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: n1088Crossref PubMed Scopus (692) Google Scholar Nasreen et al. reported a similar decline of the effectiveness of the mRNA vaccines against the Delta variant in Ontario.10Chung H. He S. Nasreen S. Sundaram M.E. Buchan S.A. Wilson S.E. et al.Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada: test negative design study.BMJ. 2021; 374: n1943Crossref PubMed Scopus (180) Google Scholar Our study had a few limitations. Documentary verification of the vaccine status was not available as data were collected through phone calls which could have led to misclassification. We tried minimizing this bias by scheduling follow-up calls so that participants could verify their vaccination date using their vaccine card or certificate. The study participants may not be an ideal representative of the target population as certain groups were excluded based on the presence of risk factors. We had access to one of the largest testing facilities in the city and were able to assess the effectiveness across a range of vaccines against the Delta variant. The test negative study design controlled for differences in health-seeking behaviors and validity of the diagnostic tests, as all participants were tested at the same place. In addition, investigator bias was minimized as the lab personnel were blinded to both clinical presentation and vaccination status of the participants. In conclusion, inactivated COVID-19 vaccines were moderately effective against symptomatic infection in the adult Pakistani population. The mRNA vaccines had higher effectiveness comparable to that observed in other parts of the world. Our findings support a universal evaluation of all vaccines and consideration of additional doses for those who received inactivated vaccines. As countries implement or consider additional vaccine doses in various risk groups, there may be a need for additional booster doses among those who initially received the inactivated vaccines. Muhammad Imran Nisar: Conceptualization, Visualization, Supervision, Writing – review & editing, Data curation. Nadia Ansari: Conceptualization, Visualization, Methodology, Project administration, Investigation, Data curation, Formal analysis, Writing – original draft. Amyn Abdul Malik: Conceptualization, Visualization, Formal analysis. Shahira Shahid: Methodology, Writing – review & editing. Kiran Ramzan Ali Lalani: Methodology, Project administration, Investigation, Data curation. Maaheen Ahmed Chandna: Investigation, Data curation, Formal analysis. Ayesha Mansoor Younus: Investigation, Data curation, Formal analysis, Writing – review & editing, Data curation. Zahra Hasan: Project administration, Resources. Unab Khan: Project administration, Resources. Farah Khalid: Formal analysis. Marvi Mahesar: Methodology. Muhammad Farrukh Qazi: Formal analysis. Inci Yildirim: Conceptualization, Visualization, Writing – review & editing. Fyezah Jehan: Conceptualization, Visualization, Supervision, Writing – review & editing. Saad Bin Omer: Conceptualization, Visualization, Supervision, Writing – review & editing. The authors declare no competing interests. Written consent was obtained from the study participants before their enrollment. Deidentified data and data dictionary will be made available by the corresponding author upon request. The authors are grateful for the diligent efforts of the data collection team: Mr. Aziz Ali, Ms. Hasrat Naz, Ms. Kiran Jabeen, Mr. Majid Hussain, Ms. Poonam Ali Shah, and Ms. Rudaba Rais. The authors acknowledge the Aga Khan University Clinical Laboratory, the Department of Family Medicine (AKUH), Mr. Mir Asghar Ali, Mr. Navroz Wasanjee and the research administration team of the Department of Pediatrics and Child Health (AKUH), for their invaluable support and contributions in making this study possible. This study was funded by the Infectious Diseases Research Laboratory (IDRL) at the Aga Khan University), Pakistan. The funder of the study had no role in study design, data collection, data analysis, data interpretation, manuscript prepared and reviewed.