What’s the effectiveness of Covid-19 vaccination in patients with multiple sclerosis (MS) treated with high-efficacy disease-modifying therapies?

The answer appears to be dependent on which high-efficacy disease-modifying agent is being used to treat MS.  Limited data suggest that cladribine treatment does not impair humoral response to Covid-19 vaccine in patients with MS, while ocrelizumab and fingolimod have a major negative impact on vaccine responsiveness based on humoral antibody measurements.1

A study involving 125 Covid-19 MS vaccine (mRNA, Pfizer BNT162b2) recipients  (58% females, 61% relapse-remitting, 19% primary-progressive, 14% secondary-progressive, 3% clinically isolated syndrome and 2% radiologically isolated syndrome), found high levels of SARS-CoV-2 anti-spike IgG in all subjects (n=23) receiving cladribine as early as 4.4 months from last treatment dose.1

In contrast only 4% of patients with MS treated with fingolimod had a post-vaccination humoral response (time-interval from last treatment dose to vaccination not reported).  Similarly, most patients under treatment with ocrelizumab failed to develop a post-vaccination humoral response, with only 23% demonstrating a protective antibody titer (time-interval from last treatment dose 3.1-8.9 months).

These results may not be totally surprising given the attenuated humoral response to several common vaccines in patients with MS treated with ocrelizumab or fingolimod.2,3

Given the potential suboptimal response to Covid-19 vaccine in patients with MS treated with fingolimod or ocrelizumab, until further data become available, it’s fair to state that patients treated with these agents should NOT depend on vaccination to protect them from Covid-19 and that they may need to still take extra precautions during the pandemic.   

 

Bonus Pearl: Did you know that fingolimod prevents lymphocyte egression from secondary lymphoid tissue and ocrelizumab is an anti-CD20 monoclonal antibody that depletes B lymphocytes?1

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Reference

  1. Achiron A, Mandel M, Dreyer-Alster S, et al. Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies. Therapeutic Adances in Neurological Disorders 2021;14:1-8. https://journals.sagepub.com/doi/full/10.1177/17562864211012835
  2. Bar-Or A, Calkwood JC, Chognot C, et al. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis. Neurology 2020; 95:e1999-22008. https://pubmed.ncbi.nlm.nih.gov/32727835/
  3. Kappos L, Mehling M, Arroyo R, et al. Randomized trial of vaccination in fingolimod-treated patients with multiple sclerosis. Neurology 2015;84:872-9. https://pubmed.ncbi.nlm.nih.gov/25636714/  

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!

What’s the effectiveness of Covid-19 vaccination in patients with multiple sclerosis (MS) treated with high-efficacy disease-modifying therapies?

Why is the Delta variant of SARS-CoV-2 increasingly becoming a “variant of concern” in the current Covid-19 pandemic?

The Delta variant (B.1.617.2, formerly India variant) has become an increasingly prevalent strain of SARS-Cov-2 causing Covid-19 in many countries outside of India, including the United States and United Kingdom, particularly affecting younger unvaccinated persons.  Several features of the Delta variant are of particular concern. 1-7

  1. Delta virus appears to be more transmissible when compared to previously emerged variant viruses. Data from new Public Health England (PHE) research suggests that the Delta variant is associated with a 64% increased risk of household transmission compared with the Alpha variant (B.,1.1.7, UK variant) and 40% more transmissibility in outdoors. 1,8  
  2. Delta virus is also associated with a higher rate of severe disease, doubling the risk of hospitalization based on preliminary data from Scotland. In vitro, it replicates more efficiently than the Alpha variant with higher respiratory viral loads.5
  3. Delta virus may also be associated with reduced vaccine effectiveness with increased vaccine breakthroughs. One study found that Delta variant is 6.8-fold more resistant to neutralization by sera from Covid-19 convalescent and mRNA vaccinated individuals.5 Fortunately, a pre-print study released by PHE in May 2021 found that 2 doses of the Pfizer vaccine were still 88% effective against symptomatic infection with Delta variant  (vs 93% for the Alpha variant) and 96% effective against hospitalization; 1 dose was only 33% effective against symptomatic disease (vs 50% for the Alpha variant).  Two doses of Astra Zeneca vaccine were 60% effective against symptomatic disease from the Delta variant.8 
  4. Aside from its somewhat unique epidemiologic features, Covid-19 caused by Delta variant seems to be behaving differently (starting out as a “bad cold” or “off feeling”), with top symptoms of headache, followed by runny nose and sore throat with less frequent fever and cough; loss of sense of smell was not common at all based on reported data to date.1

What the Delta variant reminds us is, again, the importance of vaccination, masks and social distancing. The pandemic is still with us!

Bonus Pearl: Did you know that, on average, a Delta variant-infected person may transmit it to 6 other contacts (Ro~6.0) compared to 3 others (Ro~3) for the original SARS-CoV-2 strains found during the early part of the pandemic?1

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References

  1. https://www.bbc.com/news/health-57467051
  2. Knodell R. Health Advisory: Emergence of Delta variant of coronavirus causing Covid-19 in USA. Missouri Department of Health & Senior Services. 23 June, 2021. https://health.mo.gov/emergencies/ert/alertsadvisories/pdf/update62321.pdf
  3. Kupferschmidt K, Wadman M. Delta variant triggers new phase in the pandemic. Science 25 June 2021; 372:1375-76. https://science.sciencemag.org/content/sci/372/6549/1375.full.pdf
  4. Sheikh A, McMenamin J, Taylor B, et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021; 397:2461-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201647/
  5. Mlcochova P, Kemp S, Dhar MS, et al. Sars-Cov-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. In Review Nature portfolio, posted 22 June, 2021. https://www.researchsquare.com/article/rs-637724/v1
  6. Bernal JL, Andrews N, Gower C, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 variant. MedRxiv, posted May 24, 2021. https://www.medrxiv.org/content/10.1101/2021.05.22.21257658v1 vaccine efficacy
  7. Allen H, Vusirikala A, Flannagan J, et al. Increased household transmission of Covid-19 cases associatd with SARS-Cov-2 variant of concern B.1.617.2: a national case control study. Public Health England. 2021. https://khub.net/documents/135939561/405676950/Increased+Household+Transmission+of+COVID-19+Cases+-+national+case+study.pdf/7f7764fb-ecb0-da31-77b3-b1a8ef7be9aa  Accessed June 27, 2021.
  8. Callaway E. Delta coronavirus variant: scientists brace for impact. Nature. 22 June 2021. https://www.nature.com/articles/d41586-021-01696-3 

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.

Why is the Delta variant of SARS-CoV-2 increasingly becoming a “variant of concern” in the current Covid-19 pandemic?

My patient with Covid-19 and abdominal pain has an elevated lipase. Is there a connection between Covid-19 and acute pancreatitis?

Acute pancreatitis as a complication of Covid-19 is infrequent.1 Despite reports of elevated amylase/lipase and/or acute pancreatitis in some patients with Covid-19,2 the exact role that SARS-CoV-2 plays in causing acute pancreatitis is unclear at this time.

A retrospective study of over 11,000 hospitalized patients with Covid-19 in the U.S. found a point prevalence of acute pancreatitis of only 0.27%,3 while another retrospective study of Covid-19 patients seen in Spanish emergency rooms reported acute pancreatitis in only 0.07% of cases.4 Of interest, in the latter study, Covid-19 was associated with lower frequency of acute pancreatitis. Further adding to the controversy on the causative role of Covid-19 is lack of an observed increase in the incidence of acute pancreatitis during Covid-19 pandemic. 1

An earlier study from China reported mild elevation (<3x upper limits of normal) of amylase and/or lipase in 17% of patients with Covid-19 pneumonia, none of whom had abdominal pain. 5

The temporal relationship between Covid-19 and acute pancreatitis has varied from abdominal symptoms at the onset of Covid-19 symptoms to days after diagnosis of Covid-19? 1

Despite these disparate findings, Covid-19 related acute pancreatitis or pancreatic injury is plausible. Pancreatic ductal, acinar and islet cells express ACE2, an important receptor for SARS-CoV-2.1 Infection in the GI tract (virus can easily be found in the stool) may potentially spread from the duodenal epithelium to the pancreatic duct and the pancreatic parenchyma itself. Immune-mediated inflammatory response or endotheliitis caused by SARS-CoV-2 may also potentially explain reports of pancreatic injury in Covid-19. 1,2

Bonus Pearl: Did you know that SARS-CoV-2 has been found in pancreatic tissue of some patients who succumbed to Covid-19 and has been shown to infect human pancreatic beta cells in-vitro.6  Perhaps we should be on the lookout for diabetes as a consequence of Covid-19 as well!

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 References

  1. De-Madaria E, Capurso G. Covid-19 and acute pancreatitis: examining the causality. Nature Reviews Gastroenterol Hepatol 2021;18: 3-4. https://www.nature.com/articles/s41575-020-00389-y
  2. Kandasamy S. An unusual presentation of Covid-19: acute pancreatitis. Ann Hepatobiliary Pancreat Surg 2020;24:539-41. https://synapse.koreamed.org/upload/SynapseXML/2110ahbps/pdf/AHBPS-24-539.pdf
  3. Inamdar S, Benias PC, Liu Y, et al. Prevalence, risk factors, and outcomes of hospitalized patients with coronavirus disease 2019 presenting as acute pancreatitis. Gastroenterol 2020;159:2226-28. https://www.gastrojournal.org/article/S0016-5085(20)35115-5/pdf
  4. Miro O, Llorens P, Jimenez S, et al. Frequency of five unusual presentations in patients with Covid-19: results of the UMC-19-S. Epidemiol Infect 2020;148:e189. https://pubmed.ncbi.nlm.nih.gov/32843127/
  5. Wang F, Wang H, Fan J, et al. Pancreatic injury patterns in patients with coronavirus disease 19 pneumonia. Gastroenterology 2020;159:367-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118654/
  6. Wu C-T, Lidsky PV, Xiao Y, et al. SARS-CoV-2 infects human pancreatic beta cells and elicits beta cell impairment. Cell Metab 2021 May 18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130512/

 

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!

My patient with Covid-19 and abdominal pain has an elevated lipase. Is there a connection between Covid-19 and acute pancreatitis?

The urine culture of my female patient with urgency is growing Lactobacillus spp.  Should I treat it?

Lactobacillus spp. isolated from urine generally do not require treatment because these organisms are often part of the normal bacterial flora of the genitourinary (GU) and gastrointestinal tracts, are generally of low virulence, are rarely associated with urinary tract infections (UTIs) and may in fact have potential benefits in preventing UTIs. 1-4

In a study involving female urinary microbiome, subjects with urgency urinary incontinence were less likely to have Lactobacillus spp. based on 16S rRNA gene sequencing of transurethral catheter urine than those without symptoms, suggestive of possible protective role of this organism in female GU tract.1

Reports of Lactobacillus UTI are rare but one particular species, Lactobacillus delbrueckii, has been implicated in several case reports involving primarily elderly women.3,4

Vaginal colonization with lactobacilli provides a natural, nonspecific defense mechanism against infection in part by production of lactic acid and lowering of the regional pH which, when combined with hydrogen peroxide production by commensal anaerobes, interferes with colonization of the vaginal mucosal surfaces by potential pathogens. Lactobacilli also interfere with the adherence of pathogens by production of biosurfactants.3

It’s no surprise that lactobacilli are often considered “friendly bugs” and used in many probiotic preparations as well.5

Bonus Pearl: Did you know that contrary to the current dogma, urine is not sterile when tested by more sensitive enhanced urine culture or gene sequencing techniques?  Even in asymptomatic people, it may contain several organisms, including Lactobacillus, Gardnerella, Streptococcus, Staphylococcus (not aureus) and Corynebacterium? 2

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References

  1. Pearce MM, Hilt EE, Rosenfeld AM, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio 2014;5:e01283-14. https://pubmed.ncbi.nlm.nih.gov/25006228/
  2. Thomas-White K, Forster SC, Kumar N, et al. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nature Communications 2018;9:1557. https://www.nature.com/articles/s41467-018-03968-5.pdf (urine not sterile, bladder with lactobacillus prevention, normal asymptomatic
  3. Darbro BW, Petroelje BK, Doern GV. Lactobacillus delbureckii as the cause of urinary tract infection. J Clin Microbiol 2009;47:275-277. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2620876/#:~:text=Urinary%20tract%20infections%20caused%20by,a%20setting%20of%20ureteral%20obstruction.
  4. Maillet F, Passeron A, Podglajen I, et al. Lactobacillus delbrueckii urinary tract infection in a male patient. Med Mal Infect 2019;49:225-230. https://www.sciencedirect.com/science/article/pii/S0399077X1830787X?via%3Dihub
  5. Reid G. The scientific basis for probiotic strains of Lactobacillus. App Env Microbiol 1999;65:3763-3766. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99697/ 

 

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!

The urine culture of my female patient with urgency is growing Lactobacillus spp.  Should I treat it?

Can Covid-19 exacerbate seizures in patients with epilepsy?

There have been several reports of seizure exacerbation in epileptic patients after Covid-19 infection. Seizure exacerbations have been observed in epileptic patients with uncontrolled epilepsy, as well as patients who were previously controlled with antiepileptic drugs (AEDs).1,2

In a survey of 362 epileptic patients in Wuhan, China, the site of the initial outbreak, 31 (8.6%) patients reported an increased number of seizures in the month after the public lockdown began; 16 (51.6%) of the 31 patients with seizure exacerbation had prior exposure to Covid-19.1

In a study of 439 patients with Covid-19 infection in Egypt, 19 (4.3%) patients presented with acute seizures.2  Two of the 19 seizure patients had a previous diagnosis of epilepsy, which had been controlled for up to 2 years. Interestingly, the other 17 patients had new onset seizures without a previous epilepsy diagnosis.

Covid-19 has been proposed to induce seizures by eliciting inflammatory cytokines in the central nervous system, leading to neuronal necrosis and increased glutamate levels in the cerebral cortex and hippocampus.3

Covid-19 infection may have also indirectly caused seizure exacerbations in a number of epileptic patients. Interestingly, stress related to worrying about the effect of the outbreak on a patient’s seizure activity was associated with seizure exacerbations (odds ratio: 2.5, 95% CI: 1.1-6.1)2. It is also possible that some seizure exacerbations may have been due to fear of visiting the hospital and AED withdrawal, as was demonstrated during the 2003 SARS outbreak.4

Bonus Pearl: Did you know that Guillain–Barré Syndrome has also been observed in patients with Covid-19 infection?5

Contributed by Luke Vest, Medical Student, St. Louis University Medical School

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References:

  1. Huang, S., Wu, C., Jia, Y., et al. (2020). COVID-19 outbreak: The impact of stress on seizures in patients with epilepsy. Epilepsia, 61(9), 1884-1893. https://doi.org/10.1111/epi.16635  
  2. Khedr, E. M., Shoyb, A., Mohammaden, M., & Saber, M. (2021). Acute symptomatic seizures and COVID-19: Hospital-based study. Epilepsy Res, 174, 106650. https://doi.org/10.1016/j.eplepsyres.2021.106650
  1. Nikbakht, F., Mohammadkhanizadeh, A., & Mohammadi, E. (2020). How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms. Multiple sclerosis and related disorders, 46, 102535. https://doi.org/10.1016/j.msard.2020.102535
  2. Lai, S. L., Hsu, M. T., & Chen, S. S. (2005). The impact of SARS on epilepsy: the experience of drug withdrawal in epileptic patients. Seizure, 14(8), 557–561. https://doi.org/10.1016/j.seizure.2005.08.010
  3.  Abu-Rumeileh, S., Abdelhak, A., Foschi, M., Tumani, H., & Otto, M. (2021). Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. Journal of neurology, 268(4), 1133–1170. https://doi.org/10.1007/s00415-020-10124-x   

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, or St. Louis University Medical School. 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!

Can Covid-19 exacerbate seizures in patients with epilepsy?

What’s the connection between severe hypoglycemia and hypothermia?

The association of severe hypoglycemia and low body temperatures has been well documented at least since 1960s.  Hypothermia is thought to be caused by low blood glucose in the brain (neuroglucopenia) which may serve as a protective mechanism for decreasing energy demand during glucose deprivation.1-2

A 2012 retrospective study involving mostly patients with diabetes mellitus with severe hypoglycemia (majority with serum glucose 18-54 mg/dl) found that 23% of patients had hypothermia (defined as body temperature < 95◦F or 35◦C). The incidence of hypothermia was not affected by age, diabetes, season or time of day.  Two patients had extremely low temperatures (<90◦F).  There was an association between hypothermia and severity of hypoglycemia.1

An older experimental study (1974) involving 36 recumbent nude men in thermoneutral environment found that that insulin-induced hypoglycemia was associated with rectal temperatures below 96.2◦F (36◦C) in 33%.  Cooling was attributed to reduction in heat production and to secretion of sweat, peripheral vasodilatation and hyperventilation.2

But before you attribute hypothermia to hypoglycemia, make sure other causes of hypothermia such as sepsis, hypoadrenalism, hypothyroidism, alcohol and stroke are ruled out.3  

Bonus Pearl: Did you know that heat production is accomplished by shivering, which can increase the normal basal metabolic rate by 2-5 times as well as via non-shivering thermogenesis through increased levels of thyroxine and epinephrine?3

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References

  1. Tran C, Gariani K, Hermann FR, et al. Hypothermia is a frequent sign of severe hypoglycaemia in patients with diabetes. Diab Metab 2012;38:370-72. https://www.sciencedirect.com/science/article/abs/pii/S1262363612000535?via%3Dihub
  2. Strauch BS, Felig P, Baxter JD, et al. Hypothermia in hypoglycemia. JAMA 1969;210:345-46. https://jamanetwork.com/journals/jama/article-abstract/349081
  3. McCullough L, Arora S. Diagnosis and treatment of hypothermia. Am Fam Physician 2004;70:2325-2332. https://www.aafp.org/afp/2004/1215/p2325.html

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!

What’s the connection between severe hypoglycemia and hypothermia?

Is my patient with varicose veins at higher risk of venous thromboembolism?

Although varicose veins are common and usually not associated with serious health complications, increasing scientific evidence suggests that they are associated with increased risk of subsequent incident deep venous thrombosis (DVT) and pulmonary embolism (PE). 1-3

A 2018 retrospective cohort study involving patients with the diagnosis of varicose veins and controls (>200,000 subjects each) based on claims data from Taiwan found a higher incidence rate of DVT among cases (hazard ratio [HR] 5.3, 95%C.I. 5.1-5.6). Increased risk of DVT with varicose veins was reported in all age groups but decreased with increasing age.  The HR was higher within the first year of the diagnosis of varicose veins. 1

In the same study, the incidence of PE was higher among participants with varicose veins (HR 1.7 95% C.I. 1.5-1.9).  Again, the association did not significantly differ by age.1  Other smaller studies have found similar association between DVT and varicose veins. 2,3

Although these studies at best demonstrate an association (not necessarily a cause and effect relationship) between varicose veins and venous thromboembolism, several possible explanations have been posited. Animal studies have demonstrated higher concentrations of macrophages, monocytes, neutrophils, lymphocytes, and matrix metalloproteinases in venous valves exposed to high pressure for prolonged periods.  The resultant inflammatory state in patients with varicose veins may in turn promote a prothrombotic state contributing to venous thromboembolism. 1,4

Bonus Pearl: Did you know that nearly 1 of 4  adults in the United States have been reported to have varicose veins?

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References

  1. Chang SL, Huang YL, Lee MC, et al. Association of varicose veins with incident venous thromboembolism and peripheral artery disease. JAMA 208;319:807-817. https://jamanetwork.com/journals/jama/fullarticle/2673551
  2. Muller-Buhl U, Leutgeb R, et al. Varicose veins are a risk factor for deep venous thrombosis in general practice patients. Vasa 2012;41:360-65. https://pubmed.ncbi.nlm.nih.gov/22915533/
  3. Engbers MJ, Karasu A, Blom JW, et al. Clinical features of venous insufficiency and the risk of venous thrombosis in older people. Br J Haematol 2015;171:417-23. https://pubmed.ncbi.nlm.nih.gov/26221838/
  4. Riva N, Donadini MP, Ageno W. Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation. Thromb Haemost 2015;113:1176-1183. https://pubmed.ncbi.nlm.nih.gov/25472800/

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!

Is my patient with varicose veins at higher risk of venous thromboembolism?

How effective are the mRNA Covid-19 vaccines in reducing the risk of hospitalization among adults 65 years of age or older?

The mRNA vaccines by Pfizer and Moderna seem very effective in not only reducing risk of symptomatic Covid-19 but also risk of hospitalization among adults 65 years of age or older.   A CDC study published on April 28, 2021, showed a vaccine efficacy of 94% among fully immunized and 64% among partially immunized adults ≥ 65 years of age  with approximately one-half of subjects  ≥75 years old.1

This study was carried out in 24 hospitals in 14 states in the U.S. during January 1, 2021-March 26, 2021, and involved 417 patients: 187 case-patients with Covid-19 and 230 controls with negative SARS-CoV-2 PCR test.  Among patients with Covid-19, 10% were partially immunized (vs 27% among controls) and 0.5% were fully immunized (vs. 8% among controls). 1

An Israeli study in a nationwide mass vaccination setting involving persons (28% ≥ 60 y) receiving Pfizer mRNA vaccine similarly found a vaccine efficacy of 74% for hospitalization for partially immunized and 87% for fully immunized persons.2

The high effectiveness of mRNA vaccines against more severe Covid-19 requiring hospitalization is great news, of course, as advanced age is by far the greatest risk factor for death from Covid-19, independent of underlying comorbidities.3   

Bonus Pearl: Did you know that prior to the availability of effective Covid-19 vaccination, adults over 65 years of age represented 80% of hospitalizations and had a 23-fold greater risk of death than those under 65?3

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References

  1. Tenforde MW, Olson SM, Self WH, et al. Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years-United States, January-March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w
  2. Dagan N, Barda N, Kepten E, et al. BNT162b2mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:1412-1423. https://www.nejm.org/doi/10.1056/NEJMoa2101765
  3. Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect older people. Aging (Albany NY) 2020;12:9959-9981. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288963/

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!

How effective are the mRNA Covid-19 vaccines in reducing the risk of hospitalization among adults 65 years of age or older?

My patient with renal insufficiency developed hyponatremia after an IV contrast study.  Is there a connection between hyponatremia and iodinated contrast media?

There are several reports in the literature of hyponatremia (sometimes severe) developing in patients undergoing coronary angiography or routine IV contrast CT studies. 1-3 Although generally asymptomatic, severe hyponatremia with symptoms may also occur, particularly in those at risk of hyponatremia due to other factors.  

In a case series of 5 patients with advanced renal disease who underwent cardiac catheterization and developed post-procedure hyponatremia, the mean plasma sodium concentration decreased from 138.6 mEq/L to 122.6 mEq/L within 2-22 hours post-procedure; no patient had any neurological symptoms associated with hyponatremia. There was a strong correlation between dose of contrast administered and change in sodium level. 2

Severe symptomatic hyponatremia (confusion, stupor) was also reported in an elderly woman with blood creatinine of 0.9 mg/dL following coronary angiography (baseline plasma sodium 142 mmo/L vs. 115 mmol/L >16 hours post-procedure).  The authors suggested that a diagnosis of hyponatremia be considered in any patient who develops behavioral or neurologic manifestations after coronary angiography.3

Aside from coronary angiography, a prospective study among 103 adults (mean serum creatinine 0.79 mg/dl) undergoing contrast-enhanced CT found a drop in serum sodium from a mean concentration of 136 mmol/L to 132 mmol/L 24 hours after the procedure without any associated symptoms.1

Potential mechanisms for the development of hyponatremia after IV contrast studies include hemodilution due to translocation of fluid from intracellular space caused by high osmolality of the contrast media.1  

Bonus Pearl

Did you know that even the newer “low osmolar contrast” agents are more than 3 times the osmolality of blood?4

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References

  1. Sankaran S, Saharia GK, Naik S, et al. Effect of iodinated contrast media on serum electrolyte concentrations in patients undergoing routine contrast computed tomography scan procedure. Int J Appl Basic Med Res 2019;9:217-220. https://www.ijabmr.org/article.asp?issn=2229-516X;year=2019;volume=9;issue=4;spage=217;epage=220;aulast=Sankaran
  2. Sirken G, Raja R, Garces J, et al. Contrast-induced translocational hyponatremia and hyperkalemia in advanced kidney disease. Am J Kidney Dis 2004;43:e9.1-e9.5. https://www.sciencedirect.com/science/article/abs/pii/S0272638603013854?via%3Dihub
  3. Jung ES, Kang WC, Jang YR, et al. Acute severe symptomatic hyponatremia following coronary angiography. Korean Circ J 2011;41:552-554. https://europepmc.org/article/pmc/pmc3193049
  4. Bucher AM, De Cecco CN, Schoefpf UJ, et al. Is contrast medium osmolality a causal factor for contrast-induced nephropathy? BioMed Res International 2014; Volume 2014, article ID 931413. https://www.hindawi.com/journals/bmri/2014/931413/

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!

My patient with renal insufficiency developed hyponatremia after an IV contrast study.  Is there a connection between hyponatremia and iodinated contrast media?

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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Enter your email address to subscribe to this blog and receive notifications of new posts by email.

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?