Are women at higher risk of Covid-19 vaccine-related adverse events?

Data to date shows a preponderance of Covid-19 vaccine-related adverse events (AEs) among women compared to men. This finding may be due to the generally more robust immunological response to infections and vaccines among women, increased reporting of AEs by women, genetic factors, microbiome differences as well as other factors.1-3

A CDC study involving mRNA vaccines (Pfizer and Moderna) during the 1st month of vaccination roll out in the US, found that nearly 80% of adverse events were reported by women.  The great majority (>90%) of these AEs were not serious and included symptoms such as headache, dizziness and fatigue.1

A JAMA study involving individuals receiving one of the mRNA vaccines found that 94% (Pfizer) and 100% (Moderna) of anaphylaxis events occurred among women. Of note, the median age was ~40 years  with the majority of anaphylaxis events were reported after the first dose. 2

Higher incidence of AEs following Covid-19 vaccination is not surprising and may be explained biologically. Women typically have a more robust immune response to infections and vaccination, both at the level of innate and adaptive immunity with higher antibody responses.  

These findings may be in part due to hormones such as estrogen which is known to enhance differentiation of dendritic cells and proinflammatory cytokine production. Other proposed mechanisms include differences in microbiome between sexes and sex-based genetic influences on humoral immune profile with the X chromosome expressing 10 times more genes than the Y chromosome, including genes that influence immunity.3

Bonus Pearl: Did you know that anaphylactic reaction to the mRNA Covid-19 vaccines is extremely rare, occurring in only 2-5 cases/ million!2

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References

  1. Gee J, Marquez P, Su J, et al. First month of Covid-19 vaccine safety monitoring—United States, December 14, 2020—January 13, 2021. MMWR 2021;70:283-88. https://www.cdc.gov/mmwr/volumes/70/wr/mm7008e3.htm
  2. Shimabukuro TT, Cole M, Su JR. Reports of anaphylaxis after receipt of mRNA Covid-19 vaccines in the US—December 14, 2020-January 18, 2021. JAMA 20201;325:1101-1102. https://jamanetwork.com/journals/jama/fullarticle/2776557
  3. Fischinger S, Boudreau CM, Butler AL, et al. Sex differences in vaccine-induced humoral immunity. Semin Immunopath 2019;41:239-49. https://pubmed.ncbi.nlm.nih.gov/30547182/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Are women at higher risk of Covid-19 vaccine-related adverse events?

Is there an association between infections and falls?

Although the list of factors that lead to falls is long and varied, increasing number of reports have identified falls as a manifestation of infections, including Covid-19.1-4

A retrospective study involving over 1400 patients (mean age 72 years) admitted to the hospital for a fall or its complications found coexisting systemic infections (CSIs) in 21% of patients; 26% in those ≥75 years. Urinary tract infection accounted for 55% of CSIs, followed by pneumonia (36%), skin and soft tissue infections (7%), influenza/influenza-like illness (5%), bacteremia (5%), gastrointestinal infections (2%), and others. 1

Risk factors for CSI include preexisting symptoms (eg, weakness, dizziness), inability to get up on own, confusion, age ≥ 50 years and meeting the systemic inflammatory response syndrome (SIRS) criteria on presentation.1 Of note, CSI may not initially be suspected by providers in about one-third or more of the cases, with 15% of patients presenting with “mechanical fall” having a CSI.1,2  Fever or SIRS criteria (≥2) are absent in the majority of patients with CSI.1,2

More recently, reports of falls as a presenting feature of Covid-19 have also appeared in the lay press as well as the literature, with 1 study finding 24% of patients with Covid-19 seek care primarily because of syncope, near syncope, or a nonmechanical fall.3,4

Several factors may explain the association of infections with falls, including impairment of skeletal muscle function (eg, through cytokines, hypophosphatemia), poor oral intake and dehydration. 1 Perhaps that’s why inability to get up by one’s self from a fall in the absence of an obvious reason (eg, fracture) may be a clue to a CSI in patient presenting with a fall.

Bonus Pearl: Did you know that falls are a leading cause of injury and death, afflicting one-third of adults aged greater than 65 years each year?1

Disclosure: The author of this blog also was a coinvestigator in 2 cited studies (ref. 1 and 2)

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References

  1. Manian FA, Hsu F, Huang D, et al. Coexisting systemic infections in patients hospitalized because of a fall: prevalence and risk factors. J Emerg Med 2020;58:733-40. https://www.sciencedirect.com/science/article/abs/pii/S0736467920300214
  2. Blair A, Manian FA. Coexisting systemic infections in patients who present with a fall. Am J Med Sci 2017;353:22-26. https://pubmed.ncbi.nlm.nih.gov/28104099/
  3. Chen T, Hanna J, Walsh EE, et al. Syncope, near syncope, or nonmechanical falls as a presenting feature of COVID-19. Ann Emerg Med 2020 July;76:115-117. https://pubmed.ncbi.nlm.nih.gov/32591120/
  4. Norman RE, Stall NM, Sinha SK. Typically atypical: COVID-19 presenting as a fall in an older adult. J Am Geriatr Soc 2020 July;68:E36-37. DOI:10.1111/gs.16526 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267373/pdf/JGS-9999-na.pdf

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is there an association between infections and falls?

Can my patient develop “anemia of chronic disease” acutely while hospitalized?

“Anemia of chronic disease” is better termed anemia of inflammation (AI) which may occur in acute as well as chronic inflammatory states. 1 As such, the view that anemia in the critically ill patients is simply caused by excess phlebotomy is inaccurate. 2 The CRIT study demonstrated that AI in critically ill patients develops even within 30 days, often despite blood transfusions. 3

In addition to the usual causes of AI (eg autoimmune disorders), AI can occur during bacterial, viral or yeast infections and sepsis 4,5.

Recent studies implicate both iron sequestration and impaired erythropoiesis as causes of AI. 1 Inflammation stimulates hepatic production of iron-regulatory peptide, hepcidin, which decreases delivery of iron from macrophages to developing erythrocytes.  Inflammation also causes production of pro-inflammatory cytokine, IL-6, which suppresses erythropoiesis.

Couple of cool studies using injection of heat-killed Brucella abortus in mice as a model of AI, showed dramatic hemoglobin drop by 7 days.6,7. In addition, not only were iron restriction from increase in hepcidin and transient erythropoiesis demonstrated, erythrocyte lifespan was also shortened in these experiments. AI is truly a multifactorial process.

 

References 

  1. Frankel PG. Anemia of inflammation: A review. Med Clin N Ame 2017;101:285-96. https://www.ncbi.nlm.nih.gov/pubmed/28189171
  2. Corwin HL, Krantz SB. Anemia of the critically ill: “Acute” anemia of chronic disease. Crit Care Med 2000;28:3098-99. https://www.ncbi.nlm.nih.gov/pubmed/10966311
  3. Corwin HL, Gettinger A, Pearl RG, et al. The CRIT study: anemia and blood transfusion in the critically ill-current clinical practice in the United states. Crit Care Med 2004;32:39-52. https://www.ncbi.nlm.nih.gov/pubmed/14707558
  4. Gabriel A, Kozek S, Chiari A, et al. High-dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome. J Trauma:Injury, Infection, and Critical Care 1998;44:361-67. https://www.ncbi.nlm.nih.gov/pubmed/9498512
  5. Roy CN. Anemia of inflammation. Hematology Am Soc Hematol Educ Program. 2010;2010:276-80. doi: 10.1182/asheducation-2010.1.276. https://www.ncbi.nlm.nih.gov/pubmed/21239806
  6. Kim A, Fung E, Parikh SG, et al. A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin. Blood 2014;123:1129-36. https://www.ncbi.nlm.nih.gov/pubmed/24357728
  7. Gardenghi S, Renaud TM, Meloni A, et al. Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus. Blood 2014;123:1137-45. https://www.ncbi.nlm.nih.gov/pubmed/24357729

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Can my patient develop “anemia of chronic disease” acutely while hospitalized?