CME INDIA Presentation by Dr. S. K. Gupta, MD (Med), FICP, CFM (France) Clinical Asst. Professor GS Medical College, CCSU, Uttar Pradesh India. Visiting Consultant, Max Super Specialty Hospital, New Delhi.

Post-Covid vaccination Infection.

What are breakthrough infections?

• Cases of vaccinated people, even those who have received both doses, testing positive for the virus are referred to as “breakthrough” infections, indicating that the virus has been able to breakthrough the defences created by the vaccine.

CDC definition of Breakthrough Infection:

• The US Center for Disease Control defines a breakthrough case 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 USFDA-approved vaccine.” (Two doses of Vaccine)

Why do breakthrough infections Occur?

1. No vaccine is 100% effective in all.
2. Some immunocompromised people may not develop any antibodies to vaccine.
3. Some may have been infected before the vaccination.
4. Virulent mutant strains of Virus may evade vaccine protection.

Why difference between results of vaccine trials and actual case scenario?

• During trials, various Covid-19 vaccines have been shown to be effective between 60% and 95%. In actual use scenarios, a vaccine may have different effectivity than what is reported in the trials. Because trials are done in controlled conditions on limited subjects with number of exclusion criteria.

Figure 1. ICMR data on post vaccination infection

Showed 0.03% to 0.04% (breakthrough infection) after about 125 million doses(first and second doses)

Govt. data of breakthrough infection is lower than actual because of

1. Asymptomatic/mild cases don’t get tested and hence get missed Grossly underreported.
2. Under reporting even by serious cases.

Some Recent Studies

1. Lately, ICMR estimates breakthrough infection in India to be around 4.5%. ICMR is to shortly come out with fresh data.

2. COVAT-2 Study

• From Jan 16, 2021 (Day 1 of vaccination) until May 15, 2021 (Day 21-36 after second dose, data-locking date), a total of 30 (30/492, 6.1%) HCW have reported to have COVID-19 among SARS-CoV-2 naïve cohorts (n=492) after the first dose of vaccination.
• Of the 30 participants 4 had suspected (symptomatic and positive HRCT signs but negative to either RT-PCR or RAT) and 26 had confirmed (RTPCR or RAT positive) COVID-19.
• Breakthrough infections (defined as SARS-CoV-2 infection >2 weeks after the second dose) were reported in 4.9% (24/492) of cases following both vaccines.
• Breakthrough infections were noted in 5.5% (22/399) cohorts in Covishield and 2.2% (2/93) of Covaxin recipients. Majority had mild (28/30) to moderate (2/30) COVID-19 infections and all recovered. None of the cohort who had COVID-19 following either vaccine had severe COVID requiring mechanical ventilation.

3. Fortis Hospital Study: Published May First week

113 HCW 28 (Covaxin) 85, (Covishield).

• ~17% 19 of 113 HCW.
• 34 days after the second dose.
• All mild.
• One hospitalisation. No deaths.

4. MAMC study

• 12% – 36 out of 297 HCW after two doses of Covaxin or Covishield.
• Mostly mild.
• Two hospitalisation and oxygen.
• No death.

5. AIIMS study (Total numbers not disclosed)

• 63 breakthrough case out of?
• 36 patients received two doses.
• 27 received at least one dose.
• Mean age of 37 (21-92)
• Fever etc. Symptoms same as in Non-Vaccinted.
• Not high in HCW with co morbidity.
• Viral load at the time of diagnosis was high in all the patients irrespective of vaccination status or type of vaccine received.

6. PGI Chandigarh Study, Largest study from India

• It followed 12,248 health care workers.
• 7170 had received the first dose of vaccine.
• 3650 subsequently receiving the second dose.
• A total of 5078 health care workers were unvaccinated while the rest had all received Covishield. 
• The researchers found that a total of 184 of the 7170 health care workers (2.6%) tested positive after receiving at least one dose of vaccine.
• Median time between receipt of the first dose and the positive test was 44 days.
• (16 Jan to April)
• 2.6% positive after single dose of Covishield (184 of the 7170 HCW).
• 1.6% After two doses of Covishield (48 of the 3000 HCW). Median time of infection 29.5 days after 2nd Dose..

7. Apollo Delhi study

16 Jan to 15 April (before Peak of second wave) Covishield

• 2.62% – 65 of 2,481 in two dose vaccinated.
• 2.65% – 20 of 745 after one dose.
• 0.06% Hospitalisation rate.
• No one died.
• Age did not influence the incidence of infection.
• Females were significantly more affected.

8. Max study

• 6% of ~14000 got after two doses
• 90% mild cases and only
• 10% required hospitalisation. All recovered well.
• One elderly Doctor died.

9. Medanta’s Study

  (March to May)

• 6% 250 out of 4,000 fully two dose vaccinated HCW, were infected.
• 97% mild recovered soon.
• 0.9% ICU 2out of 250 needed ICU.
• All recovered.

10. KIMS HEALTH – Kerala Study

• Breakthrough COVID-19 Infections among Health Care Workers after Two Doses of ChAdOx1 nCoV-19 Vaccine.
• None of the 108 breakthrough infections among 1322 fully vaccinated healthcare workers in a major Kerala hospital required Oxygen or ICU care. Overall 8.2% were infected @ mean 69 days. Mean age 31.9.
• Most of the patients did not have anything significant. Fever was the most common symptom (57.4% patients), followed by sore throat (51.8%) and myalgia (50.9%) (Figure 1). 7 (6.4%) patients were asymptomatic. 6 patients (5.5%) required hospital admission for mild to moderate symptoms. None of the patients required supplemental oxygen or ICU admission. There was no mortality.

11. Similar 6-7% breakthrough infection in combined data of 5383 Narayana Park and Civil Hospital

Breakthrough infection Genomics

• 63-76 % cases by B.1.617.2 Delta variant‼️
• 8 % B.617.1 lineage.

National Centre for Disease Control, Delhi, CSIR Institute of Genomics and Integrative Biology and the Academy for Scientific and Innovative Research.

Conclusions

What do we learn from above data on Break through infections?

1. Breakthrough infections occur in about 5-6% HCW despite two doses vaccination.
2. HCW are more prone to breakthrough infection by virtue of their job- Higher exposure, stress, work load.
3. Actually, Young HCW are more prone to Breakthrough infections probably because of preferential duties in high risk areas and higher mobility.
4. Health workers’ data of breakthrough infections may not be applicable to society as large because differential exposure conditions.
5. Co-morbidities may not remain a predisposing factor after vaccination as far as breakthrough infections are concerned.

Break the Myth

• Good protection may develop 3 to 4 weeks after two doses of vaccination rather than just 14 days as being propagated (because median time of breakthrough infection in most studies is 30 days after vaccination suggesting, up to 3 weeks post vaccination vulnerability followed by 7 to 10 days of Incubation period of Virus)
• Vaccines in India – Covishield and Covaxin are 99 -100% effective in preventing death and hospitalization even after heavy exposure in high stress conditions.
• Vaccines in India – Covishield and Covaxin are ~95 to 97.5% effective in preventing covid infection despite high exposure conditions.
• New variants remain a challenge calling for improvement and customization of vaccines (delta variant played a spoil sport in most cases).

CME INDIA Learning Points

• In spite of vaccination and the presence of a satisfactory antibody level, it has been observed that in some instances breakthrough infections occur.
• Defining a vaccine breakthrough infection.
• CDC: For the purpose of surveillance, a vaccine breakthrough infection is defined as the detection of SARS-CoV-2 RNA or antigen in a respiratory specimen collected from a person ≥14 days after they have completed all recommended doses of a U.S. Food and Drug Administration (FDA)-authorized COVID-19 vaccine.
• Many studies have now found reduced vaccine effectiveness against VOCs within particular time windows.
• We need to emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.
• From a biological point of view, the breakthrough cases might be due to immune evasion, mediated by particular alterations present in these strains.
• Majority of studies have not looked into importance of Cell-mediated Immunity, thus bypassing the importance of considering T-cell responses to Covid-19.
• Current vaccines do produce various T-cell responses. (i.e., Th1, Th2, Th17, and Treg). These may be of importance in careful monitoring after infection and after vaccination, particularly given concerns about autoimmunity in the context of Covid-19.
• Most important issue as per CDC: “Even though a small percentage of fully vaccinated people will get sick, vaccination will protect most people from getting sick. There also is some evidence that vaccination may make illness less severe in people who get vaccinated but still get sick. Despite this, some fully vaccinated people will still be hospitalized and die. However, the overall risk of hospitalization and death among fully vaccinated people will be much lower than among people with similar risk factors who are not vaccinated.”

CME INDIA Tail Piece

CDC Breakthrough Reporting Form

References

1. Antibody Response after Second-dose of ChAdOx1-nCOV (Covishield™®) and BBV-152 (Covaxin™®) among Health Care Workers in India: Final Results of Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) study Awadhesh Kumar Singh, Sanjeev Ratnakar Phatak, Ritu Singh, Kingshuk Bhattacharjee, Nagendra Kumar Singh, Arvind Gupta, Arvind Sharma medRxiv 2021.06.02.21258242; doi: https://doi.org/10.1101/2021.06.02.21258242
2. Kustin, T., Harel, N., Finkel, U. et al. Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals. Nat Med (2021). https://doi.org/10.1038/s41591-021-01413-7
3. Vettakkara Kandy Muhammed Niyas, Rajalakshmi Arjun, Correspondence: Breakthrough COVID-19 Infections among Health Care Workers after Two Doses of ChAdOx1 nCoV-19 Vaccine, QJM: An International Journal of Medicine, 2021;, hcab167, https://doi.org/10.1093/qjmed/hcab167

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