Infectious diseases

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

It depends! You should consider ACs in immunocompetent patients with severe bacterial CAP in the absence of concurrent influenza, particularly in patients with a very high inflammatory response (eg, serum C-reactive protein [CRP] >150-200 mg/L). 1-13 In contrast, ACs is NOT recommended for patients with non-severe CAP.

Depending on the study, ACs in severe CAP has been associated with improvement in various patient outcomes, including reduced mortality, need for vasopressor or invasive mechanical ventilation, decrease in ICU stay and decrease in hospital length of stay.1-13 Significantly higher risk of hyperglycemia has been reported in the ACs group without demonstrable increase in the risk of upper GI bleed or hospital-acquired infections.2  

Which definition of severe CAP should we use when considering ACs? Unfortunately, it varies but a commonly cited definition is that proposed by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA).9  When determining which patients may benefit from ACs, I favor a broader definition of severe CAP through modification of the ATS/IDSA criteria to include several other criteria used in major trials such as the seminal Community-Acquired Pneumonia Evaluation Corticosteroids (CAPE COD) study criteria and the Pneumonia Severity Index. 1-4   According to this “modified ATS/IDSA criteria”, severe CAP is likely in the presence of either one major criterion OR ≥3 minor criteria as detailed below.

Major criteria (1 needed):1. Septic shock with need for vasopressor; 2. Respiratory failure requiring invasive, non-invasive mechanical ventilation or high-flow nasal cannula; OR 3. Pneumonia severity index class IV or V.  Note: high-flow nasal cannula and PSI IV or V have been added to ATS/IDSA criteria

Minor criteria (3 needed):1. Respiratory rate ≥30/min; 2. Pa02/Fi02 ratio ≤250; 3. Multilobar infiltrates; 4. Confusion/disorientation; 5. BUN≥20 mg/dL; 6. Leukopenia (WBC<4,000/uL); 7. Thrombocytopenia (platelet count < 100,000/uL; 8. Hypothermia (core temp <96.8 ⁰ F, 36 ⁰ C); 9. Hypotension requiring aggressive fluid resuscitation.

In addition, a high inflammatory response based on CRP greater than 150-200 mg/L significantly increases the odds of a favorable outcome (eg, reduced mortality) in CAP when ACs is used.2,3,8 In fact, in a meta-analysis involving data-driven analysis of randomized trials, a significant reduction in mortality with ACs was observed only in those with CRP>204 mg/dL (6.1% vs 13%).8  In a subgroup analysis of CAPE COD study, mortality was significantly reduced only in patients with CRP>150 mg/L (risk difference -7.3 %).2  A 2015 study involving only patients with CRP>150 mg/L and meeting ATS/IDSA criteria for severe CAP or PSI class V, treatment failure (composite deterioration/invasive mechanical ventilation and death within 72 h) was significantly lower in the ACs group (13% vs 31%).3   

Collectively, in the absence of any contraindication to corticosteroids or concurrent influenza, the weight of the evidence supports ACs in select patients with severe CAP, particularly when associated with CRP>150 mg/L.  In contrast, for patients with non-severe CAP and presumed lower level of inflammation, the benefit of ACs may not outweigh its risks and is not recommended, unless there are other indications for their use (eg, COPD exacerbation).  For all other patients, including those without severe CAP but with high CRP levels as above or severe CAP with lower CRP levels, ACs should be considered on a case-by-case basis.

When indicated for severe CAP, based on the inclusion criteria used by various clinical trials, ACs should be started as soon as severe CAP is diagnosed, preferably within 24 h.2,13 As for the choice of ACs regimen, no study has proven the superiority of one particular regime vs others.1  The CAPE COD study used IV hydrocortisone 200 mg/day continuous infusion for 4-8 days with taper over total of 8-14 days.2 Some have suggested methylprednisolone 0.5 mg/kg IV q 12 h or “typical doses” of 40-80 mg/day IV methylprednisolone equivalent for 5-7 days.1,3 Yet others have suggested that hydrocortisone 100 mg IV or methylprednisolone 40 mg IV be given in the emergency department as an initial dose when severe CAP is diagnosed. 11 If IV hydrocortisone is selected, a pragmatic approach using 50 mg every 6 hours, similar to that suggested in the management of septic shock by the 2026 Guidelines by the Surviving Sepsis Campaign14 may also be reasonable.

 

Bonus Pearls:

  1. Did you know that despite ready availability of antibiotics, mortality from CAP in hospitalized patients remains high with nearly 50,000 people dying each year in the U.S. alone? top-pneumonia-facts.pdf
  2. Did you know that in addition to their immune modulating action, experimental studies have shown that corticosteroids may decrease global bacterial burden in lung tissue and lead to less extensive pneumonia in piglets15 and significant reduction in intracellular bacterial survival in human monocytes?16 Who would have guessed?  

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References

  1. Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 Focused update: Guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med 2024;52:e129-33. 2024 Focused Update: Guidelines on Use of… : Critical Care Medicine 
  2. Dequin P.-F, Meziani J.-P, Quenot T, et al. Hydrocortisone in severe community-acquire pneumonia. N Engl J Med 2023; 388: 1931-41. Hydrocortisone in Severe Community-Acquired Pneumonia | New England Journal of Medicine 
  3. Torres A, Sibila O, Ferrer M, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015;313:677-86 .Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial – PubMed
  4. Metlay JP, Waterer GW. Time to treat severe community-acquired pneumonia with steroids? N Engl J Med 2023; 388:2001-2. Time to Treat Severe Community-Acquired Pneumonia with Steroids? | New England Journal of Medicine
  5. Pitre Ty, Pauley E, Chaudhuri D, et al. Corticosteroids for adult patients hospitalized with non-viral community-acquired pneumonia: a systematic review and meta-analysis. Intensive Care Medicine 2025; 51:917-29. Corticosteroids for adult patients hospitalised with non-viral community-acquired pneumonia: a systematic review and meta-analysis | Intensive Care Medicine | Springer Nature Link
  6. Soumare A, Kapfer T, Botrel T, et al. Systemic corticosteroids, mortality, and infections in pneumonia and acute respiratory distress syndrome. Ann Intern Med 2026; 179L67-80. Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis – PubMed
  7. Keisham B, Duhan S, Bajaj D, et al. Steroid therapy in community-acquired pneumonia: an updated systematic review and meta-analysis. Heart & Lung 2026;79:102839. Steroid Therapy in Community-Acquired Pneumonia: An Updated Systematic Review and Meta-Analysis – PubMed
  8. Smit JM, Van Der Zee PA, Stoff SCM, et al. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomized trials. Lancet Resp Med 2025;13:221-33. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials – The Lancet Respiratory Medicine. 
  9. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. Jones BE, Ramirez JA, Oren E, et al. Diagnosis and management of community-acquired pneumonia. Am J Resp Crit Care 2026;212:24. – Search
  10. Reyes LF, Morris AC, Serrano-Mayorga C, et al. Community-acquired pneumonia. Lancet 2025;406:2371-88. Community-acquired pneumonia – The Lancet
  11. Long B, Gottlieb M. 2025 guideline updates for community-acquired pneumonia diagnosis and management. Am J Emerg Med 2026;107:16-20. 2025 guideline updates for community-acquired pneumonia diagnosis and management – EM consulte
  12. Confalonleri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: A preliminary randomized study. Am J Respir Crit Care Med 2005;171:242-8. Hydrocortisone Infusion for Severe Community-acquired Pneumonia | American Journal of Respiratory and Critical Care Medicine | Oxford Academic
  13. Pirracchio R, Venkatesh B, Legrand M. Low-dose corticosteroids for critically ill adults with severe pulmonary infections: A review. JAMA 2024;332:318-328.jama_pirracchio_2024_rv_240011_1721328820.09305 give steroids.pdf
  14. Prescott HC, Antonelli M, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock 2026. Crit Care Med 2026;54:725-812. Surviving Sepsis Campaign: International… : Critical Care Medicine
  15. Sibila O, Luna CM, Agusti C, et al. Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J 2008;32:1037-46. Effects of glucocorticoids in ventilated piglets with severe pneumonia | European Respiratory Society
  16. Meduri GU, Kananagat S, Bronze M, et al. Effects of methylprednisolone on intracellular bacterial growth. Clin Diag Lab Immunol 2001;8:1156-63.Effects of Methylprednisolone on Intracellular Bacterial Growth – PMC

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

Should I treat my patient with community-acquired pneumonia (CAP) with adjunctive corticosteroids?

Can an oral temperature of 37.4°C (99.4°F) in my 91-year-old patient be considered a fever?

FA Manian MD, MPH, , , , , , , , , , Leave a comment

Yes! The often-cited “normal body temperature” traces back to Carl Wunderlich’s seminal 1868 study, which measured axillary temperatures in thousands of hospitalized patients and reported an average temperature of 98.6°F (37°C), with an upper limit of 100.4°F (38°C).1 However, recent evidence suggests a decline in body temperature of about 0.05°F (0.03°C) per decade over the past 150 years2, prompting us to redefine “normal” temperature.

More specifically, a 2023 study of outpatients (mean age 52.7 years) found a mean oral temperature of 97.95°F (36.6°C) (95% range 96.7°F-99.2°F).3 The study also found that normal oral temperature declines with age, is lower in men than in women, and peaks in the late afternoon. 

Similarly, among non-infected hospitalized patients (mean age 61 years), a 2021 study reported a mean oral temperature of 98.0°F (36.7°C) (99% range 95.8°F-99.9°F),4 and a 2025 study in hospitalized adults concluded that the oral temperature threshold for fever should be 98.4°F (36.9°C) for those ≥85 years old.5

Additionally, the Infectious Diseases Society of America (IDSA) has recommended that for older adults in long-term care facilities, an oral temperature of 99°F (37.2°C) may indicate fever when observed across multiple measurements. 6 It also suggested that the most accurate method for establishing fever in older adults is a temperature elevation of >2°F (>1.1°C) above baseline, though this requires knowledge of the patient’s baseline temperature.6

Potential explanations for the decline in our body temperature—which reflects our basal metabolic rate— over the past 150 years include decreased prevalence of chronic infections (e.g., tuberculosis), improved sanitation, widespread use of anti-inflammatory medications, and even decreased physical activity! 3, 7

So, we should “personalize” the definition of fever and lower its threshold by 0.5°F, or as much as 2.0°F, depending on patient demographics and clinical settings. When repeated and confirmed, an oral temperature of 99.4°F (37.4°C) in our 91-year-old patient should not be automatically dismissed as “normal.” 

 Bonus pearl: Did you know that for his study, Carl Wunderlich measured axillary temperatures— a method now known to be less accurate than oral or rectal measurements— by utilizing a foot-long thermometer that required 20 minutes to register? 8

 

Contributed by Khaled Said, 4th year Medical Student, Ponce Health Sciences University School of Medicine, St. Louis, Missouri 

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References

  1. Mackowiak PA. Concepts of Fever. Arch Intern Med.1998;158(17):1870–1881.
  2. Myroslava P, Catherine L, Joanna L, Trevor H, Julie P. Decreasing human body temperature in the United States since the Industrial Revolution. ELife. 2020; 9:e49555
  3. Ley C, Heath F, Hastie T, Gao Z, Protsiv M, Parsonnet J. Defining Usual Oral Temperature Ranges in Outpatients Using an Unsupervised Learning Algorithm. JAMA Intern Med. 2023;183(10):1128–1135.
  4. Speaker SL, Pfoh ER, Pappas MA, Hu B, Rothberg MB. Oral Temperature of Noninfected Hospitalized Patients. 2021;325(18):1899–1901.
  5. Émond JP, Cheung VW, Brial A, Nguyen QD. Age-Adjusted Oral Temperature Thresholds for Rectal Fever Diagnosis in Hospitalized Older Adults. J Am Med Dir Assoc. 2026;27(2):106044.
  6. Rowe TA, Jump RLP, Andersen BM, et al. Reliability of nonlocalizing signs and symptoms as indicators of the presence of infection in nursing-home residents. Infection Control & Hospital Epidemiology. 2022;43(4):417-426.
  7. Yegian AK, Heymsfield SB, Lieberman DE. Historical body temperature records as a population-level ‘thermometer’ of physical activity in the United States. Curr Biol. 2021;31(20):R1375-R1376.
  8. Haidar G, Singh N. Fever of unknown origin. N Engl J Med. 2022;386(5):463-477.

 

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

Can an oral temperature of 37.4°C (99.4°F) in my 91-year-old patient be considered a fever?

Is it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

FA Manian MD, MPH, , , , , , , , Leave a comment

No, you are not imagining! Although during respiratory tract infection (RTI) season several viruses such as rhinovirus, respiratory syncytial virus (RSV) and coronavirus may cocirculate, influenza virus frequently outcompetes many RTI viruses, likely through a phenomenon called “viral interference.” 1-4

A negative viral interference is observed when a virus that has already infected a host makes that host resistant to infection by the second virus (isn’t that fascinating?). Although there a lot of virus, host and environmental variables that affect infection risk, potential mechanisms for this interference include a rapid and robust innate immune response to the first virus such as through upregulation of interferon (IFN) production which can protect against unrelated viruses, thereby creating a temporary “antiviral state.” 1-4

A negative viral interference has been shown between influenza-A virus (IAV) and SARS-CoV-2 by a cool 2024 study using the air-liquid interface culture model of the differentiated human airway epithelium. 4 Replicating IAV induced a robust interferon response and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections. In contrast, SARS-CoV-2 did not demonstrate significant viral interference with IAV.  The researchers took their experiment a step further and found that oseltamivir (Tamiflu), an anti-IAV agent, restored SARS-CoV-2 replication with IAV coinfection by reducing induction of IFN!

One explanation for the inability of SARS-CoV-2 to interfere with the production of influenza virus is its slower induction of IFN stimulating genes likely due to its more effective mechanisms of antagonizing the IFN response with infected cells.4 Another explanation is that SARS-CoV-2 has a slower growth rate than IAV, making it more susceptible to being “outgunned” by faster growing viruses. Some strains of IAV may also cause more damage to the epithelial cells than SARS-CoV-2 thus reducing the number of host cells available for SARs-CoV-2 infection.2 Last, secreted IFNs (eg, IFN λ) can also bind to receptors present at the surface of infected and neighboring state blocking the second virus from infecting the host.1

So, it looks like competition among living forms in this world also applies to the world of viruses!

Bonus Pearl: Did you know that the concept of viral interference was first described in the 1960s following observation that oral administration of live enterovirus vaccines decreased detection of several unrelated respiratory viruses such as influenza virus, RSV and human adenovirus?1

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References

  1. Piret J, Bolvin G. Viral interference between respiratory viruses. Emerg Infect Dis 2022;28:273-280. Viral Interference between Respiratory Viruses – PubMed
  2. Gilbert-Girard S, Piret J, Carbonneau J, et al. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses. PLOS Pathogens 2024;20(7):e1012017. Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses – PubMed
  3. Kaaijk P, Swaans N, Nicolaie AM, et al. Contribution of influenza viruses, other respiratory viruses and viral co-infections to influenza-like illness in older adults. Viruses 2022;14, 797. Contribution of Influenza Viruses, Other Respiratory Viruses and Viral Co-Infections to Influenza-like Illness in Older Adults – PubMed
  4. Cheemarla NR, Watkins TA, Mihaylova VT, et al. Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir. J Infect Dis 2024;229:1430-4. Viral Interference During Influenza A-SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir – PubMed

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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 it just my imagination or are Covid-19 cases going down as influenza cases are surging out of control during this flu season?

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , Leave a comment

Hyponatremia has been reported between 20% and 35% of patients hospitalized for Covid-19, 1-5 with low serum sodium levels on admission often associated with progression to severe illness, mechanical ventilation, increased length of stay and death.1,2,4,5

A 2023 retrospective multicenter study involving over 2,600 hospitalized Covid-19 patients (between February 2020 and August 2022) found hyponatremia in 34.2%: Mild (Na 131-134 mmol/L) 25.1%, moderate (Na 126-130 mmol/L) 7.5% and severe (<126 mmol/L) 1.8%.3 There was a significant association between male sex at birth, hypertension, chronic kidney disease, immunosuppressives, thiazide diuretics and hyponatremia.3

Similarly, another retrospective study of hospitalized Covid-19 patients found an association between hyponatremia and several common chronic diseases, such as diabetes, hypertension, ischemic heart disease, chronic liver disease and chronic kidney disease.4 It’s important to note that since older age has also been found to be a risk factor for hyponatremia in Covid-19, the independent contribution of these conditions to hyponatremia is unclear.3

As with many other infectious diseases, the mechanism of hyponatremia in patients with Covid-19 likely has multiple causes, including hypovolemia, syndrome of inappropriate anti-diuretic hormone secretion (SIADH), diuretic use and corticosteroid deficiency, particularly in the critically ill. 1-4  

Interestingly, a study performed early in the pandemic (March 2020) found that the majority (57%)  of hospitalized Covid-19 patients with hyponatremic were euvolemic and that the administration of isotonic saline to such patients was independently associated with increased hospital mortality (cause unclear).2 The authors suggested closer attention to the volume status of Covid-19 patients with hyponatremia (eg, through closer attention to the jugular venous pressure on physical exam) before considering treatment with isotonic saline.

Last, Covid-19 may be associated with hyponatremia during the post-discharge period as well.  An intriguing 2024 study found nearly 25% of patients with Covid-19 developed hyponatremia (<135 mmol/L) during the 1-year follow-up period after discharge with most not reported to have hyponatremia during their index hospitalization.5 In the same study, hyponatremia was associated with older age, male sex, diabetes, hypertension, heart failure, previous invasive ventilatory support and increased rate of readmission.5

Bonus Pearl: Did you know that there is an inverse relationship between interleukin-6, a key pro-inflammatory cytokine, and plasma sodium levels in Covid-19 and that this association may be stronger than that of other viral or bacterial respiratory infections?2  

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References

  1. Ayus JC, Klantar-Zadeh K, Tantisattamo E, et al. Is hyponatremia a novel marker of inflammation in patients with Covid-19? Nephrol Dial Transplant 2023;38:1921-24. Is hyponatremia a novel marker of inflammation in patients with COVID-19? – PubMed (nih.gov)
  2. Pazos-Guerra M, Ruiz-Sanchez JG, Perez-Candel X, et al. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients. Front Endocrinol 2023; 14:1227058. Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients – PubMed (nih.gov)
  3. De Haan L, ten Wolde, Beudel M, et al. What is the aetiology of dynatreaemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, restrospective observational study in 11 Dutch hospitals. BMJ Open 2023;13:e075232. Original research: What is the aetiology of dysnatraemia in COVID-19 and how is this related to outcomes in patients admitted during earlier and later COVID-19 waves? A multicentre, retrospective observational study in 11 Dutch hospitals – PMC (nih.gov)
  4. Rehman F, Rehan ST, Rind BJ, et al. Hyponatremia causing factors and its association with disease severity and length of stay in Covid-19 patients: A retrospective study from tertiary care hospital. Medicine 2023; 102:45(e35920) Hyponatremia causing factors and its association with disease severity and length of stay in COVID-19 patients: A retrospective study from tertiary care hospital – PubMed (nih.gov)
  5. Biagetti B, Sanchez-Montalva A, Puig-Perez A, et al. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions. Scientific Reports 2024:14:595. Hyponatremia after COVID-19 is frequent in the first year and increases re-admissions – PubMed (nih.gov)

 

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

How common is hyponatremia in patients with Covid-19 and what’s its significance?  

My patient with Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , Leave a comment

Covid-19-associated rhabdomyolysis has been reported since the early years of the pandemic with an overall prevalence ranging from 4%-20% among hospitalized patients and nearly 50% in ICU patients.1-5

In a 2023 scoping review of Covid-19-associated rhabdomyolysis involving 117 cases (January 2020-July 2022),1 68.4% had at least one reported non-Covid-19 risk factor (excluding hypoxemia), including age 65 years or older, metabolic syndrome features, hypothyroidism, previous rhabdomyolysis, hemoglobinopathy, trauma/compression or selected rhabdomyolysis-associated medications.  Presenting symptoms did not always include myalgias or weakness with some patients only presenting with fever, back pain, respiratory symptoms, or fatigue. Mortality was high (32% and 21% in those with or without other risk factors, respectively).  Routine creatine kinase (CK) testing was suggested for hospitalized patients with a low threshold for testing outpatients with Covid-19.

A 2024 cross-sectional study involving hospitalized Covid-19-patients (March 2020-March 2021) reported the following independent factors for concurrent rhabdomyolysis: male gender, dyspnea, hyponatremia, myalgia, elevated D-dimer, aspartate transaminase-AST (3x higher than normal) and platelet count >450,000 (cells/L).2 In the same study, myalgia was reported in only 30% of patients with rhabdomyolysis.   

Potential mechanisms explaining the association between Covid-19 and rhabdomyolysis include hypoxemia, viral myositis (either directly or immune-mediated), viral-induced mitochondrial dysfunction, cytokine storm, hypovolemia and Covid-related coagulopathies.1,2,4

Bonus Pearl: Did you know that although the 3 most common symptoms of patients with rhabdomyolysis are myalgias, muscle weakness and dark urine, the triad is present in only 10% of patients? 6

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References

  1. Preger A, Wei R, Berg B, et al. Covid-19-associated rhabomyolysis: A scoping review. Intern J Infect Dis 2023:136:115-126. COVID-19-associated rhabdomyolysis: A scoping review – PubMed (nih.gov)
  2. Hashemi B, Farhangi N, Toloul A, et al. Prevalence and predictive factors of rhabydomyolysis in Covid-19 patients: A cross-sectional study. Indian J of Nephrol 2024;34:144-48. Prevalence and Predictive Factors of Rhabdomyolysis in COVID-19 Patients: A Cross-sectional Study – PubMed (nih.gov)
  3. Samardzic T, Muradashvill T, Guirguis S, et al. Relationship between rhabdomyolysis and SARS-CoV-2 disease severity. Cureus 16:e53029 (January 27, 2024). Relationship Between Rhabdomyolysis and SARS-CoV-2 Disease Severity – PubMed (nih.gov)
  4. Haroun MW, Dielev V, Kang J, et al. Rhabdomyolysis in Covid-19 patients: A retrospective observational study. Cureus 13:e12552. Rhabdomyolysis in COVID-19 Patients: A Retrospective Observational Study – PubMed (nih.gov)
  5. Albaba I, Chopra A, Al-Tarbsheh AH, et al. Incidence, risk factors, and outcomes of rhabdomyolysis in hospitalized patients with Covid-19 infection. Cureus 13:e19802. Incidence, Risk Factors, and Outcomes of Rhabdomyolysis in Hospitalized Patients With COVID-19 Infection – PubMed (nih.gov)
  6. Lu W, Li X, You W, et al. Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report. Medicine 2023;102:48(e36360). Rhabdomyolysis in a patient with end-stage renal disease and SARS-CoV-2 infection: A case report – PMC (nih.gov)

 

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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 Covid-19-related generalized weakness has rhabdomyolysis. How common is rhabdomyolysis in Covid-19?

How should I generally go about treating my non-ICU hospitalized patient with newly diagnosed Covid-19 and who doesn’t require more than conventional O2?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Much of the management of Covid-19 hospitalized patients who don’t require ICU care and need no more than conventional 02 (ie, high-flow or mechanical/non-mechanical ventilatory support) depends on the severity of their disease: “mild/moderate” (eg, SpO2≥94% on room air) vs “severe” (eg, Sp02<94% on room air) disease; respiration rate ≥30/min and lung infiltrates on chest radiograph>50% may also be considered, but I personally find these parameters less reliable.  Generally, patients hospitalized with Covid-19-related symptoms (respiratory or otherwise) require specific treatment to keep them from progressing or succumbing to their disease (see Figure below). 1-5

In patients with mild/moderate Covid-19, the first step is to determine whether they are at low risk (ie, NO risk factors) or high risk (ie, ≥1 risk factors) of progression to severe disease.  Recall that there are numerous risk factors for progression, including age (eg, ≥50 y) and many comorbidities, such as diabetes, chronic kidney disease, obesity, smoking (current or former), disability (eg, wheelchair dependence), and mental health disorders (eg, depression), just to name a few.1 If your patient with mild/moderate Covid-19 has ANY Covid-related symptoms and ANY risk factors for progression, you should strongly consider IV remdesivir. If your patient’s admission has nothing to do with Covid-19 but qualify for anti-Covid treatment, an oral anti-viral regimen (eg, nirmatrelvir-ritonavir [Paxlovid]) used for ambulatory patients may also be considered (see related pearl on P4P). If your patient has NO risk factors for progression to severe disease, symptomatic treatment is all that’s needed.

If your patient has severe disease but no need for 02 supplementation, IV remdesivir and prophylactic heparin (either fractionated [eg, enoxaparin] or unfractionated) should be considered; no need for dexamethasone or systemic steroids in this situation.

If your patient has severe Covid-19 and needs supplemental 02, you should consider initiation of remdesivir, dexamethasone and, at the minimum, prophylactic anticoagulation with either a fractionated or unfractionated heparin product as soon as possible.  Use of therapeutic anticoagulation in this setting (ie, outside of ICU) is controversial with NIH guidelines recommending therapeutic heparin for those with elevated D-dimer without increased bleeding risk (CIIa, “weak” with moderate supportive evidence).2,6,7  You may also be able to forgo systemic steroids in your patient with minimal 02 requirement (ie, 1-2 L) per NIH, particularly if immunocompromised, as hypoxia in such patients may be more related to viral infection itself and not significant inflammatory reaction.

If your patient with severe Covid-19 gets progressively worse requiring high-flow oxygen or non-invasive ventilation outside of ICU, you should consider adding baricitinib as a first line immunomodulator (tocilizumab or others in NIH guidelines as an alternative)2 in patients who are not already immunocompromised or do not already have and are not at high risk of secondary infections.

The duration of remdesivir treatment in hospitalized patients is usually 5 days (or until discharge) for severe Covid-19, and 3 days for those with mild/moderate disease. The ultimate duration should be individualized in patients at risk of ongoing viral replication.  One retrospective study in immunocompromised patients hospitalized for Covid-19 found remdesivir to be effective in reducing hospitalization and mortality when initiated within 2 days of hospitalization and given for a median of 5 days, even among those not requiring 02 supplementation or requiring only low flow 02.

Couple more things to keep in mind when managing severe Covid-19. When indicated, remdesivir should be given ideally as early as possible and no later than 10 days after onset of symptoms and dexamethasone should be given for up to 10 days or until discharge.  Anticoagulation, prophylactic or therapeutic, should only be prescribed in the absence of any contraindications for bleeding (see Figure footnote) and continued until discharge for no more than 14 days total.

As with all drugs, please make sure you are thoroughly familiar with the dosing, adverse effects and contraindications to above-referenced medications before prescribing them.

Figure. Management of SARS-CoV-2 positive hospitalized patients requiring no or only conventional 02 due to Covid-19

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References

  1. CDC. Interim Clinical Considerations for COVID-19 Treatment in Outpatients | CDC. Accessed Feb 1, 2024
  2. NIH. Clinical Spectrum | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024
  3. Uptodate. Coived-19 management in hospitalized patients. https://www.uptodate.com/contents/covid-19-management-in-hospitalized-adults. Accessed Feb 5, 2024.
  4. Bash K, Sacha G, Latifi M. Covid-19: A management update. Clev Clin J Med 2023;90:677-683. https://www.ccjm.org/content/90/11/677
  5. Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir reduced mortality in immunocompromised patients hospitalized for Covid-19 across variant waves: Findings from routine clinical practice. Clin Infect Dis 2023; 77;1626-34. https://pubmed.ncbi.nlm.nih.gov/37556727/
  6. Merz LE, Fogerty AE. The conundrum of anticoagulation for hospitalized patient with Covid-19. NEJM Evidence 2023;2 (2).  https://evidence.nejm.org/doi/full/10.1056/EVIDe2200329
  7. ATTACC, CTIV-4a, REMAP-CAP Investigators. Therapeutic anticoagulation with heparin in noncritically patients with Covid-19. N Engl J Med 2021; 385:790-802. https://pubmed.ncbi.nlm.nih.gov/34351721/

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

How should I generally go about treating my non-ICU hospitalized patient with newly diagnosed Covid-19 and who doesn’t require more than conventional O2?

When should I consider treating my adult ambulatory patient with newly diagnosed Covid-19 with an antiviral drug?

FA Manian MD, MPH, , , , , , , , , , , , , , , 1 Comment

You should seriously consider prescribing an antiviral agent either oral nirmatrelvir-ritonavir (Paxlovid) (within 5 days of onset of symptoms) or IV remdesivir (within 7 days of onset of symptoms) in all your ambulatory patients with mild/moderate Covid-19 at high risk of progression (ie, ≥1 risk factors) to severe disease (Figure). 1-3 Both of these drugs reduce hospitalization and mortality from Covid-19 by over 85%!1 Oral molnupiravir may be prescribed as a second-line agent (within 5 days of onset of symptoms), if neither Paxlovid or remdesivir is an option and the patient is not pregnant. There is no indication for the use of  dexamethasone or systemic steroids in the treatment of Covid-19 in ambulatory settings. As with all drugs, you should be familiar with adverse-effects and contraindications of these anti-viral agents before prescribing them. 

Couple of questions to ask when managing a patient with newly diagnosed Covid-19 in ambulatory setting:

  1. Does your patient truly have mild/moderate disease (eg, Sp02 on room air ≥94% on room air and not tachypneic) or severe disease (eg, Sp02 on room air <94%)?4 If severe disease is likely, you should refer your patient to a hospital for evaluation and treatment as soon as possible. If your patient is not symptomatic from Covid-19, no antiviral treatment is indicated. 
  2. Once you decide your patient has mild/moderate disease and doesn’t need to go to hospital, ask whether your patient has any risk factor associated with progression to severe Covid-19.2 Recall that there are numerous risk factors, including age over 50 and many physical disabilities, smoking (current or former) and mental health disorders, such as depression, ADHD, autism and depression that may be present even in the younger population.2
    • In the absence of any risk factor for progression, no antiviral therapy is indicated.

In the presence of 1 or more risk factors for progression or contraindications, you should consider initiation of Paxlovid x 5 days, if within 5 days of onset of Covid-19 symptoms or IV remdesivir x 3 days, if within 7 days of onset of Covid-19 symptoms.  

  • Remember that although Paxlovid may potentially interact with numerous drugs, fewer such drugs are absolutely contraindicated. Convenient online resources are available to help you decide if your patient can still receive Paxlovid safely.
  • Also don’t forget that remdesivir can now be given without dosage adjustment in renal insufficiency, including those on dialysis. 

If for some reason neither Paxlovid nor remdesivir is an option, oral molnupiravir can be considered with some caveats, including recommendations against its use during pregnancy and use of effective contraception during and following treatment in people who engage in sexual activity that may result in conception. 

Irrespective of treatment, it is prudent to monitor for any deterioration of sp02 at home when managing patients with mild/moderate Covid-19.  

Bonus pearl: Did you know that despite its high efficacy (89% reduction in hospitalization and death) against Covid-19,1,5 Paxlovid is severely underutilized in the outpatient setting with fewer than 25% of eligible patients with Covid-19 receiving it?6

Figure: Covid-19 management in ambulatory adult patients

 

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References

  1. Rubin R. Paxlovid Is Effective but Underused—Here’s What the Latest Research Says About Rebound and More | Infectious Diseases | JAMA | JAMA Network Published online January 31, 2024. doi:10.1001/jama.2023.28254
  2. Interim Clinical Considerations for COVID-19 Treatment in Outpatients | CDC. Accessed Feb 1, 2024
  3. Molnupiravir | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024.
  4. Clinical Spectrum | COVID-19 Treatment Guidelines (nih.gov). Accessed Feb 1, 2024
  5. Appaneal HJ, LaPlante KL, Lopes VV, et al. Nirmatrelvir/ritonavir utilization for the treatment of non-hospitalized adults with Covid-10 in the National Veterans Affairs (VA) Healthcare System. Infectious Diseases and Therapy 204;13:155-172. Nirmatrelvir/Ritonavir Utilization for the Treatment of Non-hospitalized Adults with COVID-19 in the National Veterans Affairs (VA) Healthcare System | Infectious Diseases and Therapy (springer.com)
  6. Hammond J, Leister-Tebbe H, Gardner A, et al. Oral Nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022; 386:397-408. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19 – PubMed (nih.gov)

 

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

 

 

When should I consider treating my adult ambulatory patient with newly diagnosed Covid-19 with an antiviral drug?

My newly-admitted patient has positive blood cultures for Staphylococcus aureus.  How long should his S. aureus bacteremia be treated?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Because of the tendency of S. aureus bacteremia (SAB) to disseminate (eg, endocarditis, spinal epidural abscess, other metastatic infections), it should be treated with a minimum of 2 weeks of IV antibiotics following first repeat negative blood cultures, irrespective of the source of infection or rate of clinical improvement. 1-6

Beyond 2 weeks, the ultimate duration of parenteral antibiotics for treatment of SAB depends on several factors, including whether it is considered an “uncomplicated” or “complicated”. 1,2

Generally, uncomplicated SAB is defined as:

  • Negative results of follow-up blood culture at 2-4 days after bacteremia and
  • Clinical defervescence within 72 h of IV therapy and removal of the presumed focus of infection (eg, debridement of soft tissue infection or IV catheter) and
  • No evidence of metastatic infection among patients with catheter-related bloodstream infection or with primary bacteremia without evidence of endocarditis on transthoracic (TTE) or transesophageal echocardiogram (TEE) and
  • No endovascular foreign material (eg, prosthetic devices)

Patients not meeting the above criteria should be considered to have complicated SAB. Some studies have also reported primary bacteremia without obvious source and community-acquired SAB as risk factors for complications.4,6  

Even uncomplicated SAB should still receive at least 2 weeks of IV anti-staphylococcal therapy.  In a prospective observational study involving 111 patients with uncomplicated SAB, shorter course (<2 weeks) of IV antibiotic therapy was associated with significantly higher rate of relapse with a trend toward primary bacteremia associated with increased treatment failure.4

All other patients not considered to have an uncomplicated SAB, should receive extended antibiotic therapy (eg, 4-6 weeks or longer) depending on several factors, including clinical course and suspicion for a diagnosis of established metastatic disease (eg, endocarditis, spinal epidural abscess, etc…).  Continued parenteral antibiotic therapy is standard practice as there is insufficient data to support use of oral antibiotics in the treatment of complicated SAB before 4-6 weeks of therapy is completed.2

Standard practice in the treatment of SAB should also include an infectious disease (ID) consultation which has been associated with significantly reduced rates of mortality and risk of relapse.7

 Bonus Pearl: Did you know that SAB is associated with a mortality of 20-30% in developed countries despite antibacterial therapies and source control strategies? 1

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References

  1. Lam JC, Stokes W. The golden grapes of wrath—Staphylococcus aureus bacteremia: A clinical review. Am J Med 2023, 136:19-26. https://pubmed.ncbi.nlm.nih.gov/36179908/
  2. Kimming A, Hagel St, Weis S, et al. Management of Staphylococcus aureus bloodstream infections. Frontiers in Medicine 2021; 7: Article 616524. https://www.frontiersin.org/articles/10.3389/fmed.2020.616524/full
  3. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18-e55. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/216060
  4. Chong YP, Moon SM, Bang KM, et al. Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: Analysis of a prospective observational cohort study. Antimicrob Agents Chemother 2013;57:1150-56. https://pubmed.ncbi.nlm.nih.gov/23254436/
  5. Kuehl R, Morata L, Boeing C, et al. Defining persistent Staphylococcus aureus bacteremia: secondary analysis of a prospective cohort study. Lancet 2020;20: 1409-17. https://pubmed.ncbi.nlm.nih.gov/32763194/
  6. Fowler VG, Olsen MK, Corey R, et al. Clinical identifiers of complicated Staphylococcus aureus Arch Intern Med 2003;163:2066-72. https://pubmed.ncbi.nlm.nih.gov/14504120/
  7. Vogel M, Schmitz RPH, Hagel S, et al. Infectious disease consultation for Staphylococcus aureus bacteremia—A systematic review and meta-analysis. J Infect 2016, 72:19-28. https://pubmed.ncbi.nlm.nih.gov/26453841/ 

Disclosures/Disclaimers: 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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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 newly-admitted patient has positive blood cultures for Staphylococcus aureus.  How long should his S. aureus bacteremia be treated?

Is loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

FA Manian MD, MPH, , , , , , , , , , , , Leave a comment

Absolutely! Although loss of smell was a cardinal symptom of Covid-19 with earlier strains of SARS-CoV-2 (eg, Wuhan, alpha, delta), on average omicron causes olfactory dysfunction in only 13% of patients, 3-4 times lower than the earlier strains.1

But why is omicron less likely to causes loss of smell or taste? There may be at least 2 explanations. First explanation revolves around the solubility of omicron in the olfactory mucus. Recall that to access the olfactory epithelium, viruses and other pathogens have to first dissolve in and penetrate the mucus layer that not only allows odorants to reach the olfactory receptors but also protects the olfactory epithelium from toxins and pathogens. Hydrophilic and acid proteins can penetrate the mucus barrier more easily because they are more soluble in the mucus layer.1

What does this have to do with omicron? Well, it turns out that omicron with all its mutations in the spike protein is actually more alkaline than the Wuhan and delta strains. This means that omicron may have lower solubility in mucus and have a harder time reaching and infecting the olfactory epithelium. 1 Since the composition of olfactory mucous differs significantly from other mucus layers in the respiratory tract, omicron may still cause disease.2

Another potential mechanism may be related to the inefficiency of omicron in other steps necessary to infect nonneuronal cells of the olfactory epithelium within the nasal cavity, such as the endosomal route. 1 It turns out that cells of the olfactory epithelium express less of the endosomal membrane fusion proteases (cathepsins) which omicron prefers for cell entry! Fascinating! 

Bonus Pearl: Did you know that only 5-10% of functional olfactory neurons are required for a relatively normal sense of smell? This means that SARS-CoV-2 needs to eliminate at least 90% of all support cells of the olfactory neurons within a 3-4 day period (before their regeneration) for the host to notice anosmia?

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References

  1. Butowt R, Bilinska K, von Bartheld C. Why does the omicron variant largely spare olfactory function? Implications for the pathogenesis of anosmia in coronavirus disease 2019. J Infect Dis 2022;226:1304-1308. Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019 – PubMed (nih.gov)
  2. Yoshikawa K, Wang H, Jaen C, et al. The human olfactory cleft mucus proteome and its age-related changes. Sci Rep 2018;8:17170. The human olfactory cleft mucus proteome and its age-related changes – PMC (nih.gov)
  3. Harding JW, Getchell TV, Margolis FL. Degeneration of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZNS04 irrigation on behavior, biochemistry and morphology. Brain Res 1978;140:271-85. Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology – PubMed (nih.gov)

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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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 loss of sense of smell or taste much less common in Omicron-related Covid-19 compared to earlier strains of SARS-CoV-2?

What’s the connection between flu vaccination and lower risk of Alzheimer’s Disease?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

As far fetched that it may sound, there is growing evidence that flu vaccination is associated with lower risk of being diagnosed with Alzheimer’s Disease (AD).1

The most compelling evidence to date comes from a 2022 retrospective, propensity-matched study involving a nationwide sample of over 2 million U.S. adults ≥ 65 years old.1  This study found a 40% reduction in the risk of incident AD during the 4-year follow-up period when individuals receiving at least 1 dose of flu vaccine were compared to those who did not receive flu vaccination during the study period (number needed to treat-NTT 29.4). 

Despite its limitations, the results of the above study were concordant with those of several smaller studies that found an association between flu vaccination and lower risk of dementia of any cause.1-3  A 2022 meta-analysis also concluded that flu vaccination was associated with significantly lower risk (33%) of dementia among older people. Interestingly, in a study involving veterans, receipt of ≥6 doses of flu vaccines (not fewer) was associated with lower risk of dementia.4

Several hypotheses have been posited to explain the potential beneficial impact of flu vaccination on the risk of dementia, including: 1. Influenza-specific mechanisms, such as mitigation of damage secondary to influenza infection and/or epitopic similarity between influenza proteins and AD pathology; 2. Non-influenza-specific training of the innate immune system; and 3. Non-influenza-specific changes in adaptive immunity via lymphocyte-mediated cross-reactivity.1

So, in addition to its protective effect against severe influenza,5 and its association with lower risk of hospitalization for cardiac disease and stroke and reduction in death due to combined cardiovascular disease events (eg, heart attacks/strokes),  flu vaccination may be protective against AD! Who would have thought that a simple vaccine may have far reaching health benefits?

Bonus Pearl: Did you know that mice infected with non-neurotropic influenza strains have been found to have excessive microglial activation and subsequent alteration of neuronal morphology, particularly in the hippocampus, and that in APP/PS1 transgenic mice, peripheral influenza infection induces persistent elevations of amyloid- (A) plaque burden?1  Intriguing indeed!!!

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References

  1. Bukhbinder AS, Ling Y, Hasan O, et al. Risk of Alzheimer’s disease following influenza vaccination: A claims-based cohort study using propensity score matching. Journal of Alzheimer’s Disease 2022; 88:1061-1074. https://pubmed.ncbi.nlm.nih.gov/26945371/  
  2. Liu JC, Hsu YP, Kao PF, et al. Influenza vaccination reduces dementia risk in chronic kidney disease patients: A population-based cohort study. Medicine (Baltimore) 2016 95 :32868. https://pubmed.ncbi.nlm.nih.gov/26945371/
  3. Wiemken TL, Salas J, Hoft DF, et al. Dementia risk following influenza vaccination in a large veteran cohort. Vaccine 2021;39:5524-5531. https://pubmed.ncbi.nlm.nih.gov/34420785/
  4. Veronese N, Demurtas J, Smith L, et al. Influenza vaccination reduces dementia risk: A systematic review and meta-analysis. Ageing Res Rev 2022;73:101534. https://pubmed.ncbi.nlm.nih.gov/34861456/
  5. Godoy P, Romero A, Soldevila N, et al. Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-cae analysis, Spain, 2010/11 to 2015/16.  Euro Surveill 2018;23:1700732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208006/
  6. Hosseini S, Michaelsen-Preusse K, Schughart K, et al. Long-term consequences of non-neurotropic H3N2 influenza A virus infection for the progression of Alzheimer’s Disease symptoms. Front. Cell. Neurosci 28 April 2021; https://doi.org/10.3389/fncel.2021.643650 https://www.frontiersin.org/articles/10.3389/fncel.2021.643650/full

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, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their 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!

 

What’s the connection between flu vaccination and lower risk of Alzheimer’s Disease?