Breakthrough COVID-19 Infection among Health Care Workers after Booster Dose during Third Wave, in a Teaching Hospital, India

DISCUSSION

The effectiveness of a booster or third dose is established [14,15]. The present study is probably the first in India to measure the incidence of breakthrough COVID-19 infection after a booster dose. Within one week of taking the booster, we recorded 18 symptomatic and positive health care workers, which implied that they might be in the incubation period at the time of taking the booster. We had to stop the study as the number of positive persons in our institution daily almost reduced to zero after one month. The third wave in the country was almost over by 15th February 2022; the number of cases decreased to only 30,615 (91.83% reduction against 20th January number of 3,47,256). It indicated that the peak transmission period was only one month. It is known that adequate antibodies develop within a week after booster dose administration [10]. Breakthrough infection after booster is confirmed if infection occurs > 7 days after receiving the booster [12]. The study adopted this criterion to confirm the breakthrough infection. After one week, the odds ratio of getting positive results among received boosters drastically reduces compared to receiving two doses [16]. In the present study, the mean period between booster and positivity was 14 days. The occurrence of breakthrough infection during the peak transmission was 194.51/per 100,000 person-days followed. The most probable reason for contracting the disease perceived by the health care workers was a history of contact with a positive person (apart from ward duties). The reasons for breakthrough infection can be grouped into four categories: vaccine parameters, viral properties, host determinants, and immunity characteristics [17]. In the present study, the last two are more relevant. We had an intermediate risk of breakthrough infection compared to other studies among health care workers.

One of the reasons for the comparatively small number of breakthrough cases or intermediate risk in our study could be strict compliance to the optimal interval of 39 weeks between the second and booster doses, concordant with a small study that observed the best effect after a 35-week gap between the second and booster doses [6]. Many studies have calculated breakthrough infection after two doses. Breakthrough infections are certainly less after booster than receipt of two doses [7]. The booster dose offers protection even for very senior citizens [18]. After the booster, the vaccine efficacy may be as high as 97% for two months; then, it may decline [19]. The best protective property lies between half to one month. [6] In the present study, the mean follow-up period was only 15 days, implying that a longer follow-up could have detected a few more cases. In another small study, the breakthrough infections occurred 22 to 59 days after the booster [11]. However, a more extended follow-up period of about two months may not have added any additional cases: or the increase in the actual number of patients may have been minimal. The number of positive patients drastically declined across the city, state, and country when the present study was on. India reported the maximum number of cases on 20 January 2022, then the number reduced drastically [20]. There might be some asymptomatic cases among health care workers who could have gone undiagnosed. However, it has minimal clinical significance.

The breakthrough infection rate in the present study is higher than in a similar study among health care workers in Israel, which recorded an incidence of 12.8/100,000 person-days [12]. A smaller study in Italy among healthcare workers observed a higher incidence of 2.5 cases per 1000 person-days [21]. Therefore, we feel that our breakthrough infection rate was intermediate. The breakthrough incidence also depends on the previous infection, as hybrid immunity gives better protection [21]. In contrast to no hospitalization in the present study, data analysis from the United Kingdom recorded a low incidence of severe/hospitalization of 7·6 events per 1000 person-years [22]. But that study followed the persons for a more extended period. Theoretically, a longer follow-up in the present study may have resulted in a slight increase in the absolute number but decreased the rate of occurrence because of a substantial increase in the number of person-day follow-ups, i.e., the denominator. That might have been closer to the Israel study [12]. In the community, the incidence may be as low as 1.90 in the USA to 8.81/per 100,000 person-days in Israel [10,23]. The apparent reason for the higher incidence among health care workers than in the community is the greater exposure to the virus. In particular, the current study’s comparatively high incidence may be due to a short follow-up period and a large proportion [about one-fourth] having some comorbidity. Proportionate to the coverage of booster dose vaccination, the proportion of having received booster dose among positives decreases. Among those testing positive, the proportion of individuals receiving the booster dose has been reported at around 7% [19]. In concordance with the present study, it has been universally observed that the illness is usually mild among those who received booster doses, and usually hospitalization is not required [21]. Only about one to three percent may require hospitalization [6,10]. There may be different views about booster doses for infection prevention [24], but prevention of severe disease is sure] 25[.

One study reported seven cases after a booster dose. The isolates confirmed during the third wave were omicron (PANGO lineage B.1.1.529, Nextstrain clade 21K) [11]. We believe that most of our cases were omicron infections [26] .

There is some hesitancy in accepting the booster dose of the COVID-19 vaccine. India has covered only about 25% of the eligible population for the booster dose [27]. The usual reasons for hesitancy include fear of side effects, efficacy [particularly with changing strains] of vaccination, and the need. The need for increasing booster dose coverage continues as few cases are still being reported, indicating very low endemicity. A novel pictorial way of convincing people about the impact of a booster dose may be helpful [28]. The results of this study may help in promoting the booster dose.

CONCLUSION

The findings reiterate that a booster dose offers protection from the disease even to high-risk professionals like health care workers and prevents hospitalization during peak transmission. Naturally, the incidence of breakthrough infection in the community will be far less than observed in this study. Dissemination of these results should serve to encourage individuals to take booster doses.‎

Limitations: We did not study the genomic sequence of the isolated viruses, neutralizing antibody titer, or cell-mediated immunity. It was not a microbiological study; the only objective was to estimate the breakthrough infection rate after booster dose. We did not test asymptomatic individuals and did not ask for a history of COVID-19 infection. The follow-up period was short.

Acknowledgement: The authors are thankful to Dr. Sanjay Lalwani, Medical Director, Dr. Jitendra Oswal, Deputy Medical Director, Dr. Meera Modak, Professor and Head of the Department of Microbiology, and Dr. Anuradha Tolpadi, Professor, Department of Microbiology and In-charge of Hospital Infection Control Committee. We also thank to all health care workers for providing the desired information.

Statement of Ethics: The Institutional Ethics Committee (DCGI Reg. No. ECR518/Inst/MH/2014/RR-17) approved this research proposal. The authors obtained verbal consent from all the participants.

Conflict of Interest Statement: All the authors declare that they have no conflicts of interests regarding publication of this article.

Funding Sources:  The study did not receive any funding.

Author Contributions: We declare that all listed authors have made substantial contributions to all of the following three parts of the manuscript:

- Research design, or acquisition, analysis or interpretation of data;

- drafting the paper or revising it critically;

- approving the submitted version.

We also declare that no-one who qualifies for authorship has been excluded from the list of authors.