ABSTRACT
Background:
Healthcare workers (HCWs) were the most vulnerable group during COVID-19 pandemic and had faced many challenges including high rate of breakthrough infections.
Aims:
To study the incidence of reported breakthrough infections among HCWs in Government Medical College, Kozhikode and to compare profile of COVID-19 infection between fully vaccinated and unvaccinated COVID-19 positive HCWs.
Settings and Design:
The research was conducted as a prospective study for a duration of 78 weeks from 1st of March 2020 through 31st of August 2021 in Government Medical College, Kozhikode.
Methods and Material:
The study was conducted among HCWs in a COVID-19 tertiary care institute. Real-time data were collected from 401 breakthrough cases and 390 unvaccinated COVID-19 positive HCWs through telephonic interviews.
Statistical Analysis Used:
Univariate analysis was done using frequency for categorical variables and mean and standard deviation for quantitative variables. Chi-square test was used to find out statistical significance.
Results:
Incidence of breakthrough infection was found to be 5.62% with 43.3% being asymptomatic. Fever was the most predominant symptom (62.5%). None of the breakthrough cases developed complication requiring intensive care (ICU). There was a reduction in incidence of acute post-COVID-19 syndrome in vaccinated group (17.45%) compared to unvaccinated group (57.2%).
Conclusions:
COVID-19 vaccination plays a key role in preventing severity, complication, and ICU admissions in COVID-19 infection. Incidence of post-COVID-19 syndrome is also less among fully vaccinated compared to unvaccinated individuals.
Keywords: Breakthrough cases, COVID 19 vaccination, healthcare workers, post COVID 19 syndrome
Introduction
The novel coronavirus disease-2019 (“COVID-19”) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which started at the end of 2019 in Wuhan, experienced an outbreak that killed more than eighteen hundred and infected over seventy thousand individuals within the first 50 days of the epidemic.
The SARS-CoV-2 virus is genetically related to SARS-CoV which in late 2002 had caused the first pandemic threat of a novel and deadly coronavirus leading to an outbreak of SARS.[1] The SARS 2003 outbreak stopped in June 2003 resulting in 8098 reported cases globally with 774 deaths and a case fatality rate of 9·7%[2] whereas the novel SARS-CoV-2 that emerged in December 2019 rapidly spread as a global pandemic. This pandemic is a challenge to both developed and developing countries causing huge stress on the healthcare system. India stands second in global burden in COVID-19 cases with around 33.3 million cases and 444 thousand deaths by the middle of September 2021.[3]
In all the pandemics so far, the most affected were the healthcare system and healthcare workers (HCWs). They were standing in the frontlines of this global crisis with the substantial task of diagnosing and treating a growing number of acutely ill patients. WHO defines HCWs as “all people engaged in actions whose primary intent is to enhance health”.[4] This includes doctors, nurses, midwives, paramedical staff, hospital administrators and support staff, and community workers, all of whom face the occupational risk of becoming infected with COVID-19, and at worst even death. During the 2002 SARS outbreak, as per the WHO report out of 8098 confirmed cases, 1707 (21%) were HCWs.[5]
Vaccination against SARS-CoV-2 is a leading strategy to change the course of the COVID-19 pandemic worldwide. The rapidly growing infection rate of COVID-19 worldwide during 2020 stimulated international alliances and government efforts to urgently organise resources to make multiple vaccines on shortened timelines.[6] On 2nd December 2020, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) gave temporary regulatory approval for the Pfizer–BioNTech vaccine, becoming the first country to approve the vaccine and the first country in the Western world to approve the use of any COVID-19 vaccine.[7,8,9] Following the emergency use authorisation of the COVID-19 vaccinations at the international level, the Ministry of Health and Family Welfare in India launched a vaccination campaign to immunise Indian population with two types of COVID-19 vaccines approved in India which are Covishield manufactured by Serum Institute of India and Covaxin manufactured by Bharat Biotech in India. On January 16th 2021, Government of India started its first vaccination programme for HCWs on a priority basis. As of August 31st 2021, 6.512 million doses have been administered across the country.[10] Despite the high level of vaccine efficacy, a small percentage of fully vaccinated persons will develop symptomatic or asymptomatic infections with SARS-CoV-2 virus.[11,12,13,14] Trials have shown that Covishield has an efficacy of around 70% while Covaxin reportedly has shown an interim efficacy of around 81% in its Phase 3 trials.[15,16] That means none of these vaccines give 100% protection against COVID-19 disease and breakthrough COVID-19 infections are expected in a small number of people after vaccination which is defined by CDC as “A person who has SARS-CoV-2 RNA or antigen detected on a respiratory specimen collected ≥14 days after completing the primary series of a U.S. Food and Drug Administration (FDA)-authorized COVID-19 vaccine”.[17]
Indian Council of Medical Research studies showed that among 100.3 million people who had taken only the first dose of Covishield, 17,145 had got infected, which translates into a 0.02% prevalence.[18] Among the 15.7 million people who received the second dose of Covishield as well, 5,014 or about 0.03% had got infected later. Nearly 0.04% of people who had taken the second dose of Covaxin have tested positive for COVID-19.[18]
HCWs in the state of Kerala were immunised with either of the vaccines namely, Covishield or Covaxin. Surveillance data had shown few cases of breakthrough infection among HCWs all over the state. Therefore, the present study aimed to look into the incidence and profile of reported breakthrough infections among HCWs in Government Medical College, Kozhikode which is the largest public tertiary care centre in North Kerala. The study also did a comparison between COVID positive HCWs before and after the introduction of COVID vaccination. Knowledge regarding factors associated with breakthrough infections will help to identify high risk health workers, which is necessary for the effective functioning of health system.
Subjects and Methods
The study was conducted in Government Medical College, Kozhikode, in North Kerala catering more than 8500 HCWs including employees and students. The institution had made arrangements to make free vaccination accessible to every HCWs within the hospital. The institution also offered free SARS-CoV-2 reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing and antigen-detecting rapid diagnostic testing (Ag-RDT) to symptomatic as well as asymptomatic HCWs.
Study design
The research was conducted as a prospective study for a duration of 78 weeks from 1st of March 2020 through 31st of August 2021 in Government Medical College, Kozhikode. Study participants included HCWs who had turned COVID positive during the study period. COVID-19 vaccines were introduced in India from 16th January 2020, and the vaccine coverage for 2 doses among healthcare personnel in the institution reached around 98% during the study period. All staff and students who had received COVID vaccination were kept under surveillance for COVID-19 infection from the date of starting vaccination program.
Testing for the presence of SARS-CoV-2 by means of RT-PCR assay and/or Ag-RDT was available for fully vaccinated staff members and students who were symptomatic or had been exposed to an infected person, regardless of symptoms.
Ethics
The study protocol was reviewed by the institutional review board and institutional ethics committee at Government Medical College, Kozhikode, and research was initiated only after getting approval from both. All procedures followed were in accordance with the ethical standards of the responsible committee and with the Helsinki Declaration. Written informed consent was obtained from study participants prior to the study. The protection of the privacy of research participants was ensured. The authors vouch for the accuracy and completeness of the data reported and for the fidelity of the study to the protocol.
Outcome
The primary objective of this study was to find out the incidence and profile of breakthrough infections among HCWs in Government Medical College, Kozhikode. All HCWs who had become RT-PCR or Ag-RDT positive for COVID 19 after 14 days following 2nd dose of COVID vaccination were considered as a case of breakthrough infection. The secondary objective was to make a comparison between fully vaccinated HCWs who had received two doses of COVID vaccination and unvaccinated HCWs in the institution.
The data regarding sociodemographic details, potential source of infection, vaccination details, duration between vaccination date and postvaccination COVID-19 infection, symptomatology, persistence of COVID 19 symptoms, and potential primary contacts were collected as variables in this study through a telephonic interview. A pretested semi-structured questionnaire was utilised for collecting data.
Statistical analysis
Data collected using a semi structured questionnaire were entered in an Excel sheet and checked for data completeness. No missing data have been found. Univariate analysis was done using frequency and proportions for categorical variables and means and standard deviation in case of quantitative variables. The significance of the difference between proportions was assessed using the Chi-square test. A P value < 0.05 was considered statistically significant. The statistical analysis was conducted using the statistical package SPSS for Windows version 16 (SPSS Inc, Chicago, IL).
Results
Overall, 8665 HCWs in Government Medical College, Kozhikode had received at least one dose of COVID-19 vaccine by the end of 6 months following introduction of COVID vaccination in India on 16th January 2021. Among them only 7125 were fully vaccinated with 2 doses, whereas 1508 were partially vaccinated with the first dose of COVID vaccine. The rest remained unvaccinated as they were ineligible for COVID vaccination due to various contraindications as per the national guidelines existed during that time.
Profile of COVID positive HCWs till August 2021
By the end of August 2021, a total of 1070 HCWs in the institution were confirmed to be COVID-19 positive either using RT-PCR assay or Ag-RDT. Out of total COVID-19 positive HCWs, 35.42% (n = 379) became positive before the COVID vaccination programme was introduced in the institution on January 16th 2021 and 47.9% (n = 513) became positive after receiving at least one dose of vaccine [Table 1].
Table 1.
Profile of total COVID-19 positive HCWs in the institution
| Frequency | Percentage | |
|---|---|---|
| Number of unvaccinated HCWs turned COVID positive (n=557) | ||
| Before starting COVID | ||
| Vaccination | 379 | 35.4% |
| After starting COVID | ||
| Vaccination | 178 | 16.6% |
| HCWs turned COVID positive after receiving COVID vaccination (n=513) | ||
| Single dose alone | 94 | 8.7% |
| Within 2 weeks of 2nd dose | 18 | 1.6% |
| 2 weeks after 2nd dose | 401 | 37.5% |
| Total | 1070 | 100% |
*HCWs, health care workers
Breakthrough infection among HCWs
Four hundred and one HCWs turned positive for SARS-CoV-2 virus on RT-PCR assay or Ag-RDT after 14 or more days following receipt of a second dose of COVID vaccine making the incidence of breakthrough infection among HCWs in Government Medical College, Kozhikode as 5.62%.
Majority of breakthrough cases were between the age of 20–29 years (60.8%) with a mean age of 27.18 years (SD 8.87) and median of 24 years [Table 2]. Minimum age was 18 years and maximum age was 59 years. Breakthrough cases were predominant in female health workers (63%) than male health workers. First case of breakthrough infection was in a Physician on March 25th 2021 following which a general trend of monthly increase in cases was observed with maximum cases reported in August 2021 [Figures 1 and 2]. Minimum duration between second dose and COVID test positivity was found to be 19 days and maximum was 179 days with a mean duration of 97 days (SD = 40 days) and median 98 days (inter quartile range [IQR] = 57–124). Mean duration between first and second dose of COVID vaccination was 36 days with minimum duration being 28 days and maximum being 122 days. Majority of HCWs were diagnosed using rapid antigen test (86.3%, n = 346) followed by RT-PCR (12.5%, n = 50). Only 1.2% (n = 5) had undergone TruNAAT for diagnosing COVID. Most affected category in this study was physicians (37.4%).
Table 2.
Sociodemographic characteristics of COVID-19 positive HCWs
| n=401, n (%) | |
|---|---|
| Age group (years) | |
| <20 | 69 (17.2) |
| 20-29 | 244 (60.8) |
| 30-39 | 42 (10.5) |
| 40-49 | 30 (7.5) |
| 50-60 | 16 (4) |
| Gender | |
| Females | 252 (62.8) |
| Males | 149 (37.2) |
| Designation of HCWs | |
| Physicians | 150 (37.4) |
| Nurses | 56 (13.9) |
| Nursing Attenders/Cleaning staff | 26 (6.5) |
| Laboratory technicians | 13 (3.24) |
| Office staff | 4 (0.9) |
| Students | 141 (35.1) |
| Others | 11 (2.7) |
Figure 1.
Sources of infection of breakthrough cases
Figure 2.
Month wise trend in breakthrough cases
Clinical features of COVID-19 and post COVID-19 among breakthrough cases
43.3% (n = 174) of breakthrough cases were asymptomatic [Table 3]. Among symptomatics, majority presented with multiple symptoms (87%). The most common symptom was fever in 62.5%. Category B patients with moderate symptoms constituted 53.6% (n = 215), and 46.4% (n = 196) were Category A patients having mild symptoms alone or even asymptomatic. None of the breakthrough cases developed severe symptoms of Category C having complications which required intensive care (ICU) admission. Out of all breakthrough cases 30.9% were in home isolation whereas 60.1% had to get admitted in hospital at some point during their course of illness.
Table 3.
Clinical features of COVID and post-COVID symptoms in breakthrough cases
| COVID-19 symptoms | n (%) total=227 | Post-COVID-19 symptoms | n (%) total=70 |
|---|---|---|---|
| Fever | 142 (62.5) | Fatigue | 21 (30) |
| Headache | 104 (45.8) | Dyspnoea on exertion | 15 (21.4) |
| Sore throat | 62 (27.3) | Headache | 12 (17.1) |
| Cough | 61 (26.8) | Myalgia | 6 (8.5) |
| Myalgia | 50 (22) | Cough | 5 (7.1) |
| Rhinitis | 48 (21.1) | Giddiness | 4 (5.7) |
| Fatigue | 21 (9.3) | Chest discomfort | 2 (2.8) |
| Anosmia | 26 (11.5) | Hair fall | 2 (2.8) |
| Ageusia | 12 (5.3) | Sleep disturbances | 2 (2.8) |
| Vomiting/loose stools | 9 (3.9) |
*Multiple responses were counted in this table
Post COVID-19 symptoms in breakthrough cases
The guideline published by the National Institute for Health and Care Excellence (NICE), the Scottish Intercollegiate Guidelines Network, and the Royal College of General Practitioners has defined post-COVID as “signs and symptoms developed during or following a disease consistent with COVID-19 and which continue for more than four weeks but they are not explained by alternative diagnoses”.[19]
Incidence of post-COVID symptoms among breakthrough cases was 17.45% (n = 70) with fatigue being the predominant symptom.
Comparison between fully vaccinated and unvaccinated COVID-19 cases among HCWs in the institution
The most commonly affected age group in both vaccinated and unvaccinated was 20–29 years which corresponded to the vast majority of interns and post-graduates who were caring for COVID positive patients. Before vaccination was started, HCWs of age <20 years were spared but once vaccination was in place, fully vaccinated undergraduate students were allowed to see patients which resulted in 17.2% of breakthrough cases in age group less than 20 years which was statistically significant [Table 4]. Students were significantly affected around three times more in post-vaccination than in pre-vaccination phase [Table 4]. As students were accommodated in hostels, it became the major source of infection after the vaccination (45.3%) [Table 5] whereas community acquired COVID-19 cases reduced in the post-vaccination phase (7.2%) [Table 6]. There was a reduction in incidence of post-COVID-19 syndrome in vaccinated group (17.45%) compared to unvaccinated group of HCWs (57.2%). The most common symptom was fatigue in both groups [Tables 7 and 8].
Table 4.
Comparison between various age groups of COVID-19 positive HCWs
| Age Category | Unvaccinated n (%) | Fully vaccinated with 2 doses n (%) | P |
|---|---|---|---|
| <20 years | 0 | 69 (17.2%) | 0.001 |
| 20-29 years | 196 (50.3) | 244 (60.8) | |
| 30-39 years | 102 (26.2) | 42 (10.5) | |
| 40-49 years | 45 (11.5) | 30 (7.5) | |
| 50-59 years | 41 (10.5) | 16 (4) | |
| 60-69 years | 6 (1.5) | 0 | |
| Total | 390 | 401 |
Table 5.
Comparison of sources of infection between vaccinated and unvaccinated HCWs
| Sources of infection | Unvaccinated n (%) | Fully vaccinated n (%) | P |
|---|---|---|---|
| Hospital | 113 (28.9) | 112 (30.5) | 0.0001 |
| Hostel/household | 59 (15.1) | 182 (45.3) | |
| Friends/colleagues | 63 (16.1) | 61 (15.2) | |
| Community | 107 (27.5) | 29 (7.2) | |
| Unknown | 48 (12.3) | 7 (1.4) | |
| Total | 390 | 401 |
Table 6.
Comparison of various categories of COVID-19 positive cases between vaccinated and unvaccinated HCWs
| Category of HCWs | Unvaccinated n (%) | Fully vaccinated n (%) | P |
|---|---|---|---|
| Doctors | 129 (33) | 150 (37.4) | 0.012 |
| Nurses | 76 (19.5) | 56 (13.9) | |
| Nursing attenders | 54 (13.8) | 26 (6.5) | |
| Technicians | 30 (7.7) | 13 (3.24) | |
| Office staff | 20 (5.1) | 4 (0.9) | |
| Students | 51 (13.1) | 141 (35.1) | |
| Pharmacists | 6 (1.5) | 0 | |
| Security personnel | 11 (2.8) | 0 | |
| Others | 13 (3.3) | 11 (2.7) | |
| Total | 390 | 401 |
Table 7.
Comparison of major clinical features between vaccinated and unvaccinated HCWs
| Symptoms | Unvaccinated (n=261) n (%) | Fully vaccinated (n=227) n (%) | P |
|---|---|---|---|
| Fever | 123 (32.8) | 142 (29.7) | 0.0001 |
| Myalgia | 61 (16.3) | 50 (10.5) | |
| Sore throat | 40 (10.7) | 62 (13) | |
| Cough | 24 (6.4) | 61 (12.8) | |
| Fatigue | 25 (6.7) | 21 (43.9) | |
| Headache | 54 (14.3) | 104 (21.7) | |
| Anosmia | 24 (6.4) | 26 (54.3) | |
| Ageusia | 23 (6.2) | 12 (2.5) |
Table 8.
Comparison of major post-COVID symptoms between vaccinated and unvaccinated HCWs
| Symptoms | Unvaccinated (n=194) n (%) | Fully vaccinated (n=70) n (%) | P |
|---|---|---|---|
| Fatigue | 103 (53.4) | 21 (30) | 0.18 |
| Myalgia | 34 (17.6) | 6 (8.5) | |
| DOE | 93 (48.1) | 15 (21.4) | |
| Cough | 21 (10.7) | 5 (7.1) | |
| Headache | 24 (12.2) | 12 (17.1) | |
| Chest discomfort | 17 (9) | 2 (2.8) | |
| Sleep disturbances | 8 (3.9) | 2 (2.8) |
Discussion
This study was done to describe the characteristics of breakthrough cases among HCWs during the first 6 months after COVID-19 vaccination was introduced in Government Medical College, Kozhikode, and also to compare the profile of breakthrough cases with that of unvaccinated COVID-19 positive HCWs. Our study found a breakthrough infection incidence of 5.62% which was consistent with other studies[20,21] but high in comparison to findings by Moriah Bergwerk et al.[22] A study done in Delhi reported 6.1% non-breakthrough infections in the HCWs who were vaccinated with at least a single dose of a COVID-19 vaccine, or both doses, but prior to 14 days since the administration of the second dose.[21] But it was only 1.57% in the present study. The median interval between the receipt of the second dose of vaccine and diagnosis was 37 days in a study[22] against a median of 98 days in the present study. Physicians constituted the majority of breakthrough cases in our study and same was found by Pragya Sharma et al.[21] Moza Alishaq et al.[23] revealed that nursing and midwifery job family were the largest group with breakthrough infection (41.5%), followed by allied health professionals and physicians, the main source of infection being house hold contacts followed by hospital contact. Asymptomatic were more in breakthrough cases in our study than that of unvaccinated HCWs. Similar was the scenario in a randomised trial of the mRNA-1273 vaccine (Moderna) vs. placebo where vaccinated participants were two-thirds less likely to be asymptomatic carriers than unvaccinated participants.[11] Most common symptom in our study among breakthrough cases was fever. But in many studies fever as a symptom was less in breakthrough cases.[22,24]
Hospitalisation among breakthrough cases was more in this study the reason being the hospital institutional policy of admitting junior doctors who were staying in campus hostels to avoid further spread of infection. But symptoms were less severe among breakthrough cases in line with other studies.[24,25,26] The study by Tenforde et al.[27] demonstrates that vaccines are associated with a lower likelihood of hospitalisation along with attenuation of the seriousness of illness during hospitalisation. This is also supported by Sun et al.[28] whose study established a decrease in disease severity and hospitalisations in vaccinated immunocompromised persons who had a breakthrough infection compared with immunocompromised persons who had a COVID-19 infection before vaccination. In contrary, Juthani et al.[29] found that 26% of breakthrough cases had severe or critical illness, the median age for severity being 80·5 years (IQR 76·5–85·0). A recent systematic review by Stephen Y Wang et al.[30] also found that 37% of severe or critically ill COVID-19 breakthrough cases had a mean age of 71.5 years. But our cohort included working age groups, the highest age being 60 years.
Rate of post-COVID-19 syndrome in our study was 17.45% among breakthrough cases and 57.2% among unvaccinated HCWs. Almost similar figures were arrived by Moriah Berghwerg.[22] A cohort study by Reaz Mahmud et al.[31] in Bangladesh found that 46% of unvaccinated COVID cases had developed post-COVID-19 syndrome with post-viral fatigue being the most predominant symptom. Female gender was found to a significant risk factor.
Summary and Conclusion
Vaccination against COVID-19 still remains the most important strategy in preventing COVID-19 cases. Though breakthrough cases are possible, vaccination prevents severity and complication and reduces ICU admissions and incidence of post-COVID-19 syndrome. Protecting HCWs is key to ensuring a functioning health system and a functioning society. So it is advisable to make it mandatory to be part of hospital policy to vaccinate HCWs preferably free of cost with complete doses of COVID-19 vaccine.
Limitation: The details about vaccination status, date of vaccination, and symptomatology were collected through a telephonic interview which could have led to information bias.
Future aspects of the study: Further studies are needed to assess the long-term sequelae and duration of protection of COVID-19 vaccines.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
The authors would like to acknowledge the participants for their valuable time and support.
References
- 1.Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020;20:e238–44. doi: 10.1016/S1473-3099(20)30484-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.WHO issues consensus document on the epidemiology of SARS. Wkly Epidemiol Rec. 2003;78:373–5. [PubMed] [Google Scholar]
- 3.COVID Live-Coronavirus Statistics –Worldometer [Internet. [Last accessed on 2021 Oct 18]. Available from:https://www.worldometers.info/coronavirus/
- 4.The world health report:2006:Working together for health. Geneva: World Health Organization; 2006. [Last accessed on 2021 Oct 22]. Available from:https://apps.who.int/iris/handle/10665/43432 . [Google Scholar]
- 5.Hsu LY, Lee CC, Green JA, Ang B, Paton NI, Lee L, et al. Severe acute respiratory syndrome (SARS) in Singapore:Clinical features of index patient and initial contacts. Emerg Infect Dis. 2003;9:713–7. doi: 10.3201/eid0906.030264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Update on WHO Solidarity Trial –Accelerating a safe and effective COVID-19 vaccine. World Health Organization (WHO) [Updated 2021 Oct 26]. Available from:https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/accelerating-a-safe-and-effective-covid-19-vaccine .
- 7.Mahase E. Vaccinating the UK:How the covid vaccine was approved, and other questions answered. BMJ. 2020;371:m4759. doi: 10.1136/bmj.m4759. [DOI] [PubMed] [Google Scholar]
- 8.Forman R, Shah S, Jeurissen P, Jit M, Mossialos E. COVID-19 vaccine challenges:What have we learned so far and what remains to be done? Health Policy. 2021;125:553–67. doi: 10.1016/j.healthpol.2021.03.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.The mechanics of medicines regulation: Shining a spotlight on the MHRA vaccine approval decision. Brodies. 2020. Available from:https://brodies.com/insights/healthcare-and-life-sciences/the-mechanics-of-medicines-regulation-shining-a-spotlight-on-the-mhra-vaccine-approval-decision/
- 10.PIB's Bulletin on COVID-19. [Last accessed on 2021 Nov 02]. Available from:https://pib.gov.in/PressReleasePage.aspx/PRID=1750879 .
- 11.El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, et al. Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase. N Engl J Med. 2021;385:1774–85. doi: 10.1056/NEJMoa2113017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Sadoff J, Gray G, Vandebosch A, Cárdenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26. COV2. S vaccine against Covid-19. N Engl J Med. 2021;384:2187–201. doi: 10.1056/NEJMoa2101544. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Thompson MG, Burgess JL, Naleway AL, Tyner HL, Yoon SK, Meece J, et al. Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines in preventing SARS-CoV-2 infection among health care personnel, first responders, and other essential and frontline workers —Eight U. S. Locations, December 2020–March 2021. MMWR Morb Mortal Wkly Rep. 2021;70:495–500. doi: 10.15585/mmwr.mm7013e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Swift MD, Breeher LE, Tande AJ, Tommaso CP, Hainy CM, Chu H, et al. Effectiveness of messenger RNA coronavirus disease 2019 (COVID-19) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a cohort of healthcare personnel. Clin Infect Dis. 2021;73:e1376–9. doi: 10.1093/cid/ciab361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Sapkal GN, Yadav PD, Ella R, Deshpande GR, Sahay RR, Gupta N, et al. Inactivated COVID-19 vaccine BBV152/COVAXIN effectively neutralizes recently emerged B.1.1.7 variant of SARS-CoV-2. J Travel Med. 2021;28:taab051. doi: 10.1093/jtm/taab051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Emary KRW, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, et al. Efficacy of ChAdO×1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7):An exploratory analysis of a randomised controlled trial. Lancet. 2021;397:1351–62. doi: 10.1016/S0140-6736(21)00628-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.CDC COVID-19 Vaccine Breakthrough Case Investigations Team. COVID-19 vaccine breakthrough infections reported to CDC —United States, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep. 2021;70:792–3. doi: 10.15585/mmwr.mm7021e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.ICMR newsletter e- Samvaad April 2021. [Last accessed on 2021 Nov 10]. Available from:https://www.icmr.gov.in/pdf/press_realease_files/Newsletter_English_April_2021.pdf .
- 19.National Institute for Health and Care Excellence (NICE) Royal College of General Practitioners Healthcare Improvement Scotland SIGN. COVID-19 Rapid Guideline:Managing the Long-Term Effects of COVID-19. National Institute for Health and Care Excellence; London, UK: 2020. [Google Scholar]
- 20.Maurya D, Kaur A, Faraz F, Tandon S, Rana A, Grover S. Assessment of breakthrough infections among post-vaccinated healthcare workers in a tertiary dental hospital in New Delhi, India. medRxiv. 2021 doi:https://doi.org/10.1101/2021.11.15.21266333. [Google Scholar]
- 21.Sharma P, Mishra S, Basu S, Kumar R, Tanwar N. Breakthrough infection with severe acute respiratory syndrome coronavirus 2 among healthcare workers in Delhi:A single-institution study. Cureus. 2021;13:e19070. doi: 10.7759/cureus.19070. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, et al. Covid–19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385:1474–84. doi: 10.1056/NEJMoa2109072. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Alishaq M, Nafady-Hego H, Jeremijenko A, Al Ajmi JA, Elgendy M, Vinoy S, et al. Risk factors for breakthrough SARS-CoV-2 infection in vaccinated healthcare workers. PLoS One. 2021;16:e0258820. doi: 10.1371/journal.pone.0258820. doi:10.1371/journal.pone. 0258820. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Meyer S, Saupe A, Bieringer A, Holtzman C, Magnuson L, Bye E, et al. Characteristics of COVID-19 vaccine breakthrough cases in Minnesota, Open Forum Infect Dis. 2021;2021;8((Suppl 1)):S113. [Google Scholar]
- 25.Chia PY, Ong SWX, Chiew CJ, Ang LW, Chavatte JM, Mak TM, et al. Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections:A multicentre cohort study. Clin Microbiol Infect. 2022;28:612. doi: 10.1016/j.cmi.2021.11.010. e1-7. doi:10.1016/j.cmi.2021.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Tartof SY, Slezak JM, Fischer H, Hong V, Ackerson BK, Ranasinghe ON, et al. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA:A retrospective cohort study. Lancet. 2021;398:1407–16. doi: 10.1016/S0140-6736(21)02183-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, et al. Influenza and other viruses in the acutely ill (IVY) Network. Association Between mRNA Vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326:2043–54. doi: 10.1001/jama.2021.19499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Sun J, Zheng Q, Madhira V, Olex AL, Anzalone AJ, Vinson A, et al. Association between immune dysfunction and COVID-19 breakthrough infection after SARS-CoV-2 vaccination in the US. JAMA Intern Med. 2022;182:153–62. doi: 10.1001/jamainternmed.2021.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Juthani PV, Gupta A, Borges KA, Price CC, Lee AI, Won CH, et al. Hospitalisation among vaccine breakthrough COVID-19 infections. Lancet Infect Dis. 2021;21:1485–6. doi: 10.1016/S1473-3099(21)00558-2. Erratum in: Lancet Infect Dis 2022;22:e1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Wang SY, Juthani PV, Borges KA, Shallow MK, Gupta A, Price C, et al. Severe breakthrough COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era. Lancet Microbe. 2022;3:e4–5. doi: 10.1016/S2666-5247(21)00306-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Mahmud R, Rahman MM, Rassel MA, Monayem FB, Sayeed SKJB, Islam MS, et al. Post-COVID-19 syndrome among symptomatic COVID-19 patients:A prospective cohort study in a tertiary care center of Bangladesh. PLoS One. 2021;16:e0249644. doi: 10.1371/journal.pone.0249644. [DOI] [PMC free article] [PubMed] [Google Scholar]