Who Benefits the Least from the COVID-19 Vaccines

Factors associated with inadequate vaccine responses in patients with breakthrough infections are still not fully understood. Studies show that genes, environment (such as air pollution), and gene-environmental interactions all influence Coronavirus disease. Less research has been done for the vaccines. 

An earlier study [Boyarsky et al, 2021]  found that 46% of transplant patients had no antibody response after two doses of messenger RNA (mRNA) vaccines. Several medical case reports about fatal breakthrough  infections listed chronic migraine, obesity, autoimmune conditions,  diabetes, atrial fibrillation, myeloma (with anti-BCMA CAR-T therapy), arterial hypertension and old age among pre-existing conditions.  Some fatal breakthroughs, however, had no apparent underlying causes. 

A new study used real-world data to evaluate risk factors of impaired antibody response to SARS-CoV-2 mRNA vaccines in individuals with chronic medical conditions evaluated in a respiratory specialty clinic. The percentage of patients without antibodies detected was as follows:

- 14% in asthma 

- 15% in COPD

- 19% in Sarcoidosis

- 36% in Interstitial lung diseases

- 37% in Rheumatic diseases

- 48% in Congestive Heart Failure (CHF). 

More than a fifth of patients with chronic medical conditions may still have insufficient levels of antibodies to fight COVID-19 even after a second mRNA vaccine dose. Interstitial lung disease and congestive heart failure are two independent risk factors for low antibody response to COVID vaccination. These patients tended to be older — between 65 and 95 years old with a median age of 80.5 — and had preexisting comorbidities, such as cardiovascular disease and Type 2 diabetes. A subset of patients was also on immunosuppressive drugs that may affect vaccine efficacy. 

Anther study that analyzed fatal breakthrough cases came with the following risk order: Overweight/Obesity; Chronic cardiac disease; Diabetes mellitus, Chronic neurologic disease; Chronic kidney disease; Chronic liver disease; Chronic pulmonary disease; Immunosupression.  Pregnancy was shown to double the risk of breakthrough infection. 

Note that the mean age of study population was 62 years and the individuals received two doses of mRNA vaccines. Newer study shows that advanced age is one of major risk factors of fatal breakthrough COVID-19 even after an additional booster dose. 

CDC data, sourced from more than two dozen states, shows that between April and June, a total of 77,000 breakthrough cases and 1,500 breakthrough deaths were recorded, compared to more than 1.74 million breakthrough cases and 15,000 deaths recorded between July and the first week of November. It is unclear exactly how many of these people had also been boosted. As of October 12, 2021, there have been at least 31,895 individuals with SARS-CoV-2 breakthrough infections who were hospitalized or died in the United States. 

REFERENCES

Boyarsky BJ, Werbel WA, Avery RK, Tobian AA, Massie AB, Segev DL, Garonzik-Wang JM. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. Jama. 2021 Jun 1;325(21):2204-6.

Juthani PV, Gupta A, Borges KA, Price CC, Lee AI, Won CH, Chun HJ. Hospitalisation among vaccine breakthrough COVID-19 infections. The Lancet Infectious Diseases. 2021 Nov 1;21(11):1485-6.

Shu-Yi Liao et al, Impaired SARS-CoV-2 mRNA vaccine antibody response in chronic medical conditions: a real-world analysis, Chest (2022). DOI: 10.1016/j.chest.2021.12.654

Anaphylaxis to COVID-19 vaccinies

Anaphylaxis  - severe, potentially life-threatening allergic reaction - can occur within seconds or minutes of exposure to allergens. Multiple cases of anaphylaxis have been described for COVID-19 vaccines. 

For the Pfizer/BioNTech vaccine, twenty-one anaphylaxis cases (a rate of 11.1 per million doses administered, later updated as 4.7/million from 28-million-datapoints), were documented in the US after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine during December 14–23, 2020. 17 of those had a documented history of allergies or allergic reactions, seven of whom had a history of anaphylaxis. 71% of them occurred within 15 min following the first dose of BioNTech vaccine. 

Anaphylactic shock to Pfizer vaccine happened in those with history of anaphylaxis to other vaccines (rabies and influenza A(H1N1) vaccine), drugs (prochlorperazine, antibiotics, sulfa drugs), venom (jellyfish sting) or nuts. Out of 21, 4 were allergic to sulfa drugs, 2 were allergic to nuts.

Moderna COVID-19 vaccine caused much fewer anaphylactic episodes (2.5 anaphylaxis cases per million doses administered for 27 million datapoints), but there were similarities with Pfizer cases. Out of 10 cases described in MMWR, 4 had Penicillin allergy (like 1 Pfizer case). Also, in common were allergies to sulfa drugs and azithromycin.   A Kansas woman who died 2nd day after experiencing anaphylactic reaction to her first Moderna shot, previously had an allergic reaction to Albuterol, a drug used to treat wheezing and shortness of breath.

The Pfizer-BioNTech vaccine contains lipid nanoparticles one of which is “pegylated” (Polyethylene glycol, molecular weight 2000 Da, abbreviated to PEG2000). The Moderna mRNA vaccine also includes a different pegylated lipid (also a PEG2000). Polyethylene glycols, also known as macrogols, could be causing serious allergic reactions ins some people.

One of the culprits of anaphylaxis in Astrazeneca could be polysorbate 80, used in the formulation of protein-based biopharmaceuticals, cosmetics, skin-care products, chewing gum and foods (ice creams and puddings). 41 reports of possible anaphylaxis were seen among around 5 million vaccinations in the United Kingdom. Four cases of people potentially experiencing anaphylactic reactions within 30 minutes of receiving the AstraZeneca vaccine have been reported in Queensland and one case with fatal outcome happened in Georgia. 

Polysorbate 80 is also an ingredient in Johnson and Johnson vaccine. For this vaccine, no cases of anaphylaxis were reported in ~22,000 participants of phase 3 clinical trial who received it. Five patients reported developing hives within a week. There was one case of what was considered severe “a hypersensitivity reaction,” but it was reportedly not related to anaphylaxis. Last month, however, one individual in South Africa developed anaphylaxis. No details have been published yet. 

According to the CDC, polysorbate 80 is an inactive ingredient in many viral vector vaccines for influenza (Fluarid, Fluax, etc), rotavirus, shingles, Hepatitis A, Hepatitis B, HPV, and meningococcus. Polysorbate 80 is also an ingredient in COVID-19 Sputnik V vaccine from Gamaleya Research Institute.

REFERENCES

Turner PJ, Ansotegui IJ, Campbell DE, Cardona V, Ebisawa M, Yehia EG, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Leung AS. COVID-19 vaccine-associated anaphylaxis: A statement of the World Allergy Organization Anaphylaxis Committee. World Allergy Organization Journal. 2021 Feb 3:100517.

Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020. MMWR Morb Mortal Wkly Rep 2021;70:46–51. DOI: http://dx.doi.org/10.15585/mmwr.mm7002e1external icon.

CDC COVID-19 Response Team; Food and Drug Administration. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID-19 Vaccine - United States, December 21, 2020-January 10, 2021. MMWR Morb Mortal Wkly Rep. 2021 Jan 29;70(4):125-129. doi: 10.15585/mmwr.mm7004e1. PMID: 33507892; PMCID: PMC7842812.

Kounis NG, Koniari I, de Gregorio C, Velissaris D, Petalas K, Brinia A, Assimakopoulos SF, Gogos C, Kouni SN, Kounis GN, Calogiuri G. Allergic Reactions to Current Available COVID-19 Vaccinations: Pathophysiology, Causality, and Therapeutic Considerations. Vaccines. 2021 Mar;9(3):221.

Public Health England. COVID-19: the green book, chapter 14a.

Moghimi SM. Allergic Reactions and Anaphylaxis to LNP-Based COVID-19 Vaccines. Molecular Therapy. 2021 Mar 3;29(3):898-900.