Mortality;

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

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

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?

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

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

Irrespective of in-vitro susceptibility results, cefepime should be avoided in the treatment of serious ESBL infections associated with bacteremia, pneumonia, intraabdominal infection, endocarditis, bone/joint infection or whenever a high bacterial inoculum is suspected. Cefepime should be considered only in non-severe infections (eg, uncomplicated urinary tract infection) when the minimum inhibitory concentration (MIC) is 2 mg/L or less (1).

 

To date, clinical studies comparing cefepime vs carbapenem have been small and/or retrospective, often with conflicting results (1). A 2016 propensity score-matched study of patients with ESBL bacteremia receiving cefepime therapy followed by carbapenem therapy vs carbapenem for the entire treatment duration found higher 14 day mortality in the cefepime group (41% vs 20% in the carbapenem group) (2).  Of note, 2 of the patients receiving cefepime who died were infected with an ESBL organism with MIC of 1 mcg/mL. 

 

Another study found cefepime to be inferior to carbapenem therapy in ESBL bacteremic patients with better outcome when cefepime MIC was 1 ug/m or less (3).

 

Two studies involving patients with ESBL UTIs found no significant difference between cefepime and carbapenem in clinical and microbiological response or in-hospital mortality, while another UTI study with a high rate of septic shock (33%) found that cefepime was inferior to carbapenem in clinical and microbiological response (2).

 

The diminished efficacy of cefepime for the treatment of ESBL infections may be related to its “inoculum effect” ie, marked increase in MIC with increased inoculum size compared to that used in standard laboratory susceptibility testing (1,4).   

 

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References

  1. Karaiskos I, Giamarellou H. Carbapenem-sparing strategies for ESBL producers: when and how. Antibiotics 2020;9,61. https://pubmed.ncbi.nlm.nih.gov/32033322/
  2. Wang R, Cosgrove S, Tschudin-Sutter S, et al. Cefepime therapy for cefepime-susceptible extended-spectrum beta-lactamase-producing Enerobacteriaceae bacteremia. Open Forum Infect Dis 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4942761/
  3. Lee NY, Lee CC, Huang WH, et al. Cefepime therapy for monomicrobial bacteremia caused by cefepime-susceptible extended-spectrum beta-lactamase-producing Enterobacteriaceae: MIC matters. Clin Infect Dis 203;56:488-95. https://academic.oup.com/cid/article/56/4/488/351224
  4. Smith KP, Kirby JE. The inoculum effect in the era of multidrug resistance:minor differences in inoculum have dramatic effect on MIC determination. Antimicrob Agents Chemother 2018;62:e00433-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105823/

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

Is cefepime an acceptable alternative to carbapenems in the treatment of cefepime susceptible extended spectrum beta-lactamase (ESBL) Gram-negatives?

When should I consider systemic corticosteroids in my patient with Covid-19?

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

As of July 30, 2020, The National Institute of Health (NIH) Coronavirus Disease 2019 (COVID-19) Guidelines Panel recommends using dexamethasone 6 mg per day for up to 10 days for the treatment of Covid-19 in patients who are mechanically ventilated (“Strong” recommendation based on 1 or more randomized trials) with a a less strong recommendation (“Moderate”) in those who require supplemental oxygen but who are not mechanically ventilated.1

These recommendations appear to primarily stem from a multicenter, open label randomized controlled trial of dexamethasone vs standard of care in hospitalized patients in United Kingdom, 2 with treated group receiving dexamethasone 6 mg IV or orally daily for 10 days or until hospital discharge (whichever came first).  Mortality at 28 days was significantly lower among patients on mechanical ventilation who received dexamethasone (29.3% vs 41.4%, rate ratio 0.64, 95% CI, 0.51-0.81) and in those receiving supplemental oxygen without mechanical ventilation (23.3% vs 26.2%). The risk of progression to invasive mechanical ventilation was also lower in the dexamethasone group. No significant difference in mortality was found in patients who did not require supplemental oxygen. 

Retrospective and case series studies have reported conflicting results on the efficacy of corticosteroid for the treatment of covid-19. 3-10 That’s why despite its limitations (open label, wide range of 02 supplementation, few patients receiving remdesvir), the randomized controlled trial discussed above should guide our decision making on the use of corticosteroids in patients with Covid-19.

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References

  1. NIH. The Coronavirus Disease 2019 (COVID-19) Guidelines. https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/ Accessed August 6, 2020.
  2. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19—Preliminary report. N Engl J Med 2020; July 17, 2020. https://www.nejm.org/doi/full/10.1056/NEJMoa2021436
  3. Keller MJ, Kitsis EA, Arora S, et al. Effect of systemic glucocorticoids on mortality or mechanical ventilation in patients with COVID-19. J Hosp Med 2020;15(8):489-493. https://www.journalofhospitalmedicine.com/jhospmed/article/225402/hospital-medicine/effect-systemic-glucocorticoidsmortalityor-mechanical
  4. Wang Y, Jiang W, He Q, et al. A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia. Signal Transduct Target Ther. 2020;5(1):57. https://www.ncbi.nlm.nih.gov/pubmed/32341331
  5. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32167524
  6. Corral L, Bahamonde A, Arnaiz delas Revillas F, et al. GLUCOCOVID: A controlled trial of methylprednisolone in adults hospitalized with COVID-19 pneumonia. medRxiv. 2020. https://www.medrxiv.org/content/10.1101/2020.06.17.20133579v1
  7. Fadel R, Morrison AR, Vahia A, et al. Early short course corticosteroids in hospitalized patients with COVID-19. Clin Infect Dis. 2020. https://www.ncbi.nlm.nih.gov/pubmed/32427279
  8. Fernandez Cruz A, Ruiz-Antoran B, Munoz Gomez A, et al. Impact of glucocorticoid treatment in SARS-CoV-2 infection mortality: a retrospective controlled cohort study. Antimicrob Agents Chemother 2020. https://www.ncbi.nlm.nih.gov/pubmed/32571831
  9. Yang Z, Liu J, Zhou Y, Zhao X, Zhao Q, Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis. J Infect. 2020;81(1):e13-e20. https://www.ncbi.nlm.nih.gov/pubmed/32283144

 10. Lu X, Chen T, Wang Y, Wang J, Yan F. Adjuvant corticosteroid therapy for critically ill patients with COVID-19. Crit Care. 2020;24(1):241. https://www.ncbi.nlm.nih.gov/pubmed/32430057

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!

 

When should I consider systemic corticosteroids in my patient with Covid-19?

What’s the connection between elevated troponins and Covid-19?

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

Elevated cardiac troponins or myocardial injury (defined as troponin levels above the 99th percentile upper reference range) are not uncommon in Covid-19, having been reported in ~10-30% of hospitalized patient and usually observed in the absence of acute coronary syndrome (ACS) (1-4).

 
Elevated troponins have been associated with increased risk of in-hospital mortality in Covid-19. The prevalence of elevated troponins among patients who died was 76% compared to 10% among survivors in 1 Chinese study (3). Another study from China found increasing troponin levels over a 22 day period among those who died while troponin levels remained low in those who survived (5).

 
Risk factors for elevated troponins in Covid-19 include older age, cardiovascular comorbidities (eg, hypertension, coronary heart disease, heart failure), diabetes, chronic obstructive pulmonary disease, chronic renal failure, and the presence of a high inflammatory state, as indicated by elevated inflammatory markers such as C-reactive protein (CRP) (3).

 
Several mechanisms have been proposed to explain elevated troponins in Covid-19, including cytokine-induced myocardial injury, microangiopathy due to prothrombotic state, myocardial infarction (type I due to plaque rupture or type II due to oxygen supply/demand imbalance), and myocarditis either due to direct viral invasion or indirectly through immune-mediated mechanisms (1,2).

 
Patients with Covid-19 and modest troponin elevation with rapid fall in the absence of signs or symptoms of ACS, may have type II myocardial infarction due to demand ischemia, particularly in the setting of coronary disease. In contrast, more protracted elevation of troponins associated with high inflammatory markers such as CRP is suggestive of hyperinflammatory myocardial injury (1).

 

It will be interesting to see if trials of anti-inflammatory agents, such as colchicine and anti-interleukin-I, will have an impact on the troponin levels in Covid-19 patients (1).

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References
1. Cremer PC. SARS-CoV-2 and myocardial injury: few answers, many questions. Clev Clin J Med. Posted April 8, 2020. Doi:10.3949/ccjm.87a.ccc001 https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc001
2. Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019:possible mechanisms. J Card Failure 2020; https://pubmed.ncbi.nlm.nih.gov/32315733/
3. Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J 2020. https://pubmed.ncbi.nlm.nih.gov/32391877/
4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-59. https://jamanetwork.com/journals/jama/fullarticle/2765184
5. Zhou F, YU T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

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!

 

What’s the connection between elevated troponins and Covid-19?

What is the role of prone ventilation in patients with Covid-19 and ARDS?

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

A 2017 guideline strongly recommends the use of prone ventilation for 12+ hours daily in individuals with severe ARDS (1). A JAMA article gave similar recommendations for critically ill patients with COVID-19 (2).

The recommendations are often based on a NEJM 2013 randomized-controlled study involving 466 patients with severe ARDS (3). While previous research had demonstrated improved oxygenation in the prone position (4), this study demonstrated a significant survival benefit (3).  Mortality at 28 days was 16.0% in prone patients versus 32.8% in supine patients (p<0.001; HR 0.39 with 95% CI, 0.29 – 0.67) (3). Mortality was also lower in prone patients at 90 days (3).  A meta-analysis of 4 additional randomized-controlled trials confirmed the survival benefits (1). 

In patients with Covid-19 and ARDS, a small retrospective study involving 12 patients showed a significant association between prone positioning and lung recruitability (ie, lung tissue in which aeration can be restored) (p = 0.020) (5).

Physiologically, numerous mechanisms have been proposed for these findings, including the possbility that while blood flow consistently favors the dorsal alveoli regardless of position, the prone position allows dorsal alveoli to reopen, improving ventilation/perfusion matching (6). 

Of note, some institutions find difficulties with prone positioning, including higher rates of pressure sores and endotracheal tube obstruction (1).

 

Contributed by Grant Steele, Harvard Medical Student, Boston, MA.

 

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References:

1. Fan E, Del Sorbo L, Goligher E, et al. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome.” Am J Respir Crit Care Med 2017;195:1253-1263. https://www.atsjournals.org/doi/abs/10.1164/rccm.201703-0548ST 
2. Murthy S, Gomersall C, & Fowler R. Care for critically ill patients with COVID-19. JAMA – Published online March 11, 2020. doi:10.1001/jama.2020.3633 https://jamanetwork.com/journals/jama/fullarticle/2762996
3. Guérin C, Reignier J, Richard J-C, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159-2168. https://www.nejm.org/doi/full/10.1056/nejmoa1214103
4. Abroug F, Ouanes-Besbes L, Elatrous S, et al. The effect of prone positioning in acute respiratory distress syndrome or acute lung injury: a meta-analysis. Areas of uncertainty and recommendations for research. Intensive Care Medicine – Published online March 19, 2008. doi: 10.1007/s00134-008-1062-3 https://link.springer.com/article/10.1007/s00134-008-1062-3
5. Pan C, Chen L, Lu C, et al. Lung Recruitability in SARS-CoV-2 Associated Acute Respiratory Distress Syndrome: A Single-center, Observational Study. Am J Respir Crit Care Med – Published online March 23, 2020. doi: 10.1164/rccm.202003-0527LE. https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0527LE 
6. Nyrén S, Mure M, Jacobsson H, et al. Pulmonary perfusion is more uniform in the prone than in the supine position: scintigraphy in healthy humans. J Appl Physiol 1999;86:1135-1141. https://www.physiology.org/doi/abs/10.1152/jappl.1999.86.4.1135

 

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!

What is the role of prone ventilation in patients with Covid-19 and ARDS?

Do statins have a role in treating novel Coronavirus infection, COVID-19?

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

There is currently no firm clinical evidence that statins improve the outcome of COVID-19. However, there are some theoretical reasons for believing that statins may have a role in the treatment of COVID-19.  That’s because beyond their cholesterol lowering action, statins may also have clinically relevant anti-inflammatory and antiviral (pleotropic) properties.  

Anti-inflammatory: Anti-inflammatory effect of statins is well known and is thought to occur through a variety of molecular pathways of the innate and adaptive immune systems as well as attenuation of several circulating proinflammatory cytokines.1 Although observational studies have suggested that statins lower hospitalization and mortality among outpatients hospitalized with infection, pneumonia or sepsis, several randomized controlled trials (RCTs) have failed to show any mortality benefit among ICU patients with sepsis and ARDS treated with statins.2

In contrast, an RCT involving patients with sepsis (majority with pneumonia, mean CRP 195 mg/dL) reported significant reduction in progression to severe sepsis among statin-naïve patients  placed on atorvastatin 40 mg/day at the time of hospitalization.3 So, perhaps timing of statin therapy before florid sepsis and ARDS is an important factor.  

Some have suggested that statins may decrease the fatality rate of a related Coronavirus, Middle East Respiratory Syndrome (MERS) virus, by blunting exuberant inflammatory response that may result in a fatal outcome. 4

Antiviral: Statins may also have antiviral properties, including activity against influenza, hepatitis C virus, Zika and dengue viruses.2,5 Whether statins have activity against coronaviruses such as the agent of COVID-19 is unclear at this time.

It’s interesting to note that cholesterol may have an important role in the membrane attachment, fusion and replication of many enveloped viruses, including influenza.5 Covid-19 is also an enveloped virus.

So what do we do? Based on the current data, it makes sense to continue statins in patients who have known clinical indications for their use and no obvious contraindications because of COVID-19 (eg. rhabdomyolysis).6 As for statin-naïve patients, particularly those in early stages of sepsis and increased risk of cardiovascular events, benefit may outweigh the risk.  Only proper clinical studies will give us more definitive answers.

Bonus Pearl: Did you know that lipids make up a major component of the envelope in enveloped viruses and that cholesterol makes up nearly one-half of total lipid and over 10% the total mass of influenza viruses?

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References

  1. Tousoulis D, Psarros C, Demosthenous M, et al. Innate and adaptive inflammation as a therapeutic target in vascular diseae: The emerging role of statins. J Am Coll Cardiol 2014;63:2491-2502. https://www.sciencedirect.com/science/article/pii/S0735109714011553?via%3Dihub
  2. Fedson DS. Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola. Ann Transl Med 2016;4:421. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5124618/pdf/atm-04-21-421.pdf
  3. Patel JM, Snaith C, Thickette DR. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial) Critical Care 2012;16:R231. https://ccforum.biomedcentral.com/track/pdf/10.1186/cc11895
  4. Espano E, Nam JH, Song EJ, et al. Lipophilic statins inhibit Zika virus production in Vero cells. Scientific Reports 2019;9:11461. https://www.nature.com/articles/s41598-019-47956-1
  5. Sun X, Whittaker GR. Role for influenza virus envelope cholesterol in virus entry and infection. J Virol 2003;77:12543-12551. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC262566/
  6. Virani SS. Is there a role for statin therapy in acute viral infections. Am Coll Cardiol March 18, 2020. https://www.acc.org/latest-in-cardiology/articles/2020/03/18/15/09/is-there-a-role-for-statin-therapy-in-acute-viral-infections-covid-19

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!

Do statins have a role in treating novel Coronavirus infection, COVID-19?

Catch these selected key clinical pearls on coronavirus disease (Covid-19)!

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

Although the Covid-19 pandemic is continuing to evolve and our knowledge of its epidemiology and pathophysiology is still far from complete, you may find the following pearls based on published literature to date useful when discussing this disease with your colleagues or the public. 1-11

  • Age group: Primarily an adult disease. Children (< 15-year-old) account for only a minority of symptomatic patients (<1%); ~50% of patients are between 15-49 years of age with 15% in the ≥ 65 year group. 1
  • Incubation period: A bit longer than seasonal flu. Median 4.0 days (IQR 2.0-7.0 days); an upper range up to 24 days has also been reported. In contrast, for seasonal flu the median incubation period is shorter (median 2.0 days, 1.0-7.0 days. 1,4,11
  • Transmission: Contact, droplet, and possibly airborne. On average each person may transmit Covid-19 virus to 2-3 other persons (vs <2 people for seasonal flu). Unlike SARS or MERS, but more akin to the seasonal flu, asymptomatic persons may also be able to transmit the disease. 4,5,11
  • Comorbid conditions (eg, diabetes, hypertension, COPD…): Present in about 1/3 of reported patients. 1
  • Symptoms 1,5
    • ~80% of patients may be either asymptomatic or have mild disease
    • Fever may be absent in ~50% of patients on presentation but will eventually develop in ~90% of hospitalized patients
    • Cough (2/3 dry) is present in majority (~80%) of cases
    • Rhinorrhea is uncommon (<10%), in contrast to the seasonal influenza
    • GI symptoms (nausea/vomiting/diarrhea) are uncommon by some reports(<10%), but not by others (>30.0%). 12
    • May take 9-12 days from onset of symptoms to severe disease
  • Labs 1
    • Lymphopenia is common (up to ~80%)
    • Abnormal liver function (AST and ALT) is found in about 1/3 of patients
    • C-reactive protein (CRP) is usually elevated (~80% of severe cases)
    • Procalcitonin is usually normal
  • Treatment: Supportive for now. Candidate drugs include remdesivir, lopinavir/ritonavir, chloroquine phosphate, ribavirin and several others.4
  • Mortality: Reported mortality among mostly symptomatic hospitalized cases is ~2.0% (0.9% without comorbidities, 5-10% in those with comorbidities, 50% among critically ill). Overall mortality rates will likely drop as more patients without symptoms or with mild disease are tested. In contrast, 2 other coronavirus diseases, SARS and MERS, have mortality rates of ~9.0% and 36.0%, respectively. 1,4,5

 

Bonus pearl: Did you know that, Covid-19-infected patients shed the virus in their nasopharyngeal secretions on the average for 12 days, some as long as 24 days?3

 

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References

  1. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med 2020. First published Feb 28, 220, last updated March 6, 2020. https://www.nejm.org/doi/10.1056/NEJMoa2002032
  2. Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel Coronavirus in the United States. N Engl J Med 2020; 382:929-36. https://www.nejm.org/doi/full/10.1056/NEJMoa2001191
  3. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA. Doi:10.1001/jama.2020.3204. Published online March 3, 2020. https://jamanetwork.com/journals/jama/fullarticle/2762688
  4. Wang Y, Wang Y, Chen Y, et al. Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol 2020. Doi: 10.1002/jmv.25748. https://www.ncbi.nlm.nih.gov/pubmed/32134116
  5. Fauci AS, Lane HC, Redfield RR. Covid-19—Navigating the uncharted. N Eng J Med 2020. DOI:10.1056/NEJMe2002387. https://www.nejm.org/doi/full/10.1056/NEJMe2002387
  6. Del Rio C, Malani PN. 2019 novel coronavirus—important information for clinicians. JAMA 2020, Feb 5. https://www.ncbi.nlm.nih.gov/pubmed/32022836
  7. Lipsitch M, Swerdlow DL, Finelli L. Defining the epidemiology of Covid-19—studies needed. N Engl J Med 2020. Feb 19. DOI:10.1056/NEJMp2002125. https://www.ncbi.nlm.nih.gov/pubmed/32074416/
  8. Morens DM, Daszak P, Taubenberger JK. Escaping Pandora’s box—another novel coronavirus. N Eng J Med 2020. Feb 26. DOI:10.1056/NEJMp2002106. https://www.nejm.org/doi/full/10.1056/NEJMp2002106
  9. She J, Jiang J, Ye L, et al. 2019 novel coronavirus of pneumonia in Wuhan, China: merging attack and management strategies. Clin Trans Med 2020;9:19. https://clintransmed.springeropen.com/articles/10.1186/s40169-020-00271-z
  10. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497-506. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30183-5/fulltext
  11. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020. Feb 21. https://jamanetwork.com/journals/jama/fullarticle/2762028
  12. Pan L, Mu M, Yang P, et al. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. Am j Gastroenterol 2020. https://journals.lww.com/ajg/Documents/COVID_Digestive_Symptoms_AJG_Preproof.pdf
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When should I consider a switch to oral antibiotics and discharge from hospital in my recently admitted elderly patient with community-acquired pneumonia (CAP)?

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

A frequently used validated set of clinical stability criteria in patients with CAP and supported by the 2019 ATS/IDSA CAP guidelines consists of a temperature ≤37.8 ᵒC (100.0 ᵒF) AND no more than 1 CAP-related sign of clinical instability as listed below: 1-3

  • Heart rate >100/min
  • Systolic blood pressure <90 mm Hg
  • Respiration rate >24 breaths/min
  • Arterial oxygen saturation <90% or Pa02<60 mm Hg (room air)

Using these criteria, the risk of clinical deterioration serious enough to necessitate transfer to an intensive care unit may be 1% or less, 1 while failure to achieve clinical stability within 5 days is associated with higher mortality and worse clinical outcome. 2 The median time to clinical stability (as defined) for CAP treatment is 3 days.1  

A 2016 randomized-controlled trial involving patients hospitalized with CAP found that implementation of above clinical stability criteria was associated with safe discontinuation of antibiotics after a minimum of 5 days of appropriate therapy. 3 

Potential limitations of the above study include heavy use of quinolones (80%), underrepresentation of patients with severe CAP (Pneumonia Risk Index, PSI, V), and exclusion of nursing home residents, immunosuppressed patients, those with chest tube, or infection caused by less common organisms, such as Staphylococcus aureus or Pseudomonas aeruginosa.

Lack of clinical stability after 5 days of CAP treatment should prompt evaluation for complications of pneumonia (eg, empyema, lung abscess), infection due to  organisms resistant to selected antibiotics, or an alternative source of infection/inflammatory/poor response. 2

References

  1. Halm, EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA 1998;279:279:1452-57. https://reference.medscape.com/medline/abstract/9600479
  2. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. Am J Respir Crit Care Med 2019;200:e45-e67. https://www.ncbi.nlm.nih.gov/pubmed/31573350
  3. Uranga A, Espana PP, Bilbao A, et al. Duration of antibiotic treatment in community-acquired pneumonia. A multicenter randomized clinical trial. JAMA Intern Med 2016;176:1257-65. https://www.ncbi.nlm.nih.gov/pubmed/27455166/
When should I consider a switch to oral antibiotics and discharge from hospital in my recently admitted elderly patient with community-acquired pneumonia (CAP)?

My patient with diabetes mellitus is now admitted with pneumonia. Does diabetes increase the risk of pneumonia requiring hospitalization?

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

The weight of the evidence to date suggests that diabetes mellitus (DM) does increase the risk of pneumonia-related hospitalization.1-3

A large population-based study involving over 30,000 patients found an adjusted relative risk (RR) of hospitalization with pneumonia of 1.26 (95% C.I 1.2-1.3) among patients with DM compared to non-diabetics.  Of note, the risk of pneumonia-related hospitalization was significantly higher in type 1 as well as type 2 DM and among patients whose A1C level was ≥9.1  Another population-based study found a high prevalence of DM (25.6%) in patients hospitalized with CAP, more than double that in the population studied.2  A 2016 meta-analysis of observational studies also found increased incidence of respiratory tract infections among patients with diabetes (OR 1.35, 95% C.I. 1.3-1.4).

Not only does DM increase the risk of pneumonia-related hospitalization, but it also appears to adversely affect its outcome with increased in-hospital mortality.2 Among patients with type 2 DM,  excess mortality has also been reported at 30 days, 90 days and 1 year following hospitalization for pneumonia. 4,5 More specifically, compared to controls with CAP, 1 year mortality of patients with DM was 30% (vs 17%) in 1 study. 4

Potential reasons for the higher incidence of pneumonia among patients with DM include increased risk of aspiration (eg, in the setting of gastroparesis, decreased cough reflex), impaired immunity (eg, chemotaxis, intracellular killing), pulmonary microangiopathy and coexisting morbidity. 1,3,5,6

Bonus Pearl: Did you know that worldwide DM has reached epidemic levels, such that if DM were a nation, it would surpass the U.S. as the 3rd most populous country! 7

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References

  1. Kornum JB, Thomsen RW, RUS A, et al. Diabetes, glycemic control, and risk of hospitalization with pneumonia. A population-based case-control study. Diabetes Care 2008;31:1541-45. https://www.ncbi.nlm.nih.gov/pubmed/17595354
  2. Martins M, Boavida JM, Raposo JF, et al. Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients. BMJ Open Diabetes Research and Care 2016;4:e000181.doi:10.1136/bmjdrc-2015000181. https://drc.bmj.com/content/4/1/e000181
  3. Abu-Ahour W, Twells L, Valcour J, et al. The association between diabetes mellitus and incident infections: a systematic review and meta-analysis of observational studies. BMJ Open Diabetes Research and Care 2017;5:e000336. https://drc.bmj.com/content/5/1/e000336. 
  4. Falcone M, Tiseo G, Russo A, et al. Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes. Results from a prospective cohort study. Medicine 2016;95:e2531. https://www.ncbi.nlm.nih.gov/pubmed/26844461
  5. Kornum JB, Thomsen RW, Rus A, et al. Type 2 diabetes and pneumonia outcomes. A population-based cohort study. Diabetes Care 2007;30:2251-57. https://www.ncbi.nlm.nih.gov/pubmed/17595354
  6. Koziel H, Koziel MJ. Pulmonary complications of diabetes mellitus. Pneumonia. Infect Dis Clin North Am 1995;9:65-96. https://www.ncbi.nlm.nih.gov/pubmed/7769221
  7. Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clinical Diabetes and Endocrinology 2017;3:1 https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-016-0039-3  

 

My patient with diabetes mellitus is now admitted with pneumonia. Does diabetes increase the risk of pneumonia requiring hospitalization?

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?

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

The most consistent risk factor for isolation of P. aeruginosa from sputum of adults with COPD is the presence of more advanced pulmonary disease (eg, FEV-1 <35%-50% of predicted value) or functional impairment (1-5).

 

Chronic corticosteroid use is also frequently cited as an important predictor of respiratory tract colonization/infection due to P. aeruginosa in patients with COPD, while the data on antibiotic use during the previous months have been conflicting (2,4). Other risk factors may include prior isolation of P. aeruginosa and hospital admission during the previous year (1).
A prospective study of patients hospitalized for COPD exacerbation found P. aeruginosa to be the most frequently isolated organism, growing from 26% of validated sputum samples at initial admission, followed by Streptococcus pneumoniae and Hemophilus influenzae. In the same study, bronchiectasis (present in up to 50% of patients with COPD) was not shown to be independently associated with the isolation of P. aeruginosa (1).
Of interest, compared to the patients without P. aeruginosa, patients hospitalized for acute exacerbation of COPD and isolation of P. aeruginosa from sputum have significantly higher mortality: 33% at 1 year, 48% at 2 years and 59% at 3 years (5).

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References
1. Garcia-Vidal C, Almagro P, Romani V, et al. Pseudomonas aeruginosa in patients hospitalized for COPD exacerbation: a prospective study. Eur Respir J 2009;34:1072-78. https://www.ncbi.nlm.nih.gov/pubmed/19386694
2. Murphy TF. Pseudomonas aeruginosa in adults with chronic obstructive pulmonary disease. Curr Opin Pulm Med 2009;15:138-42. https://www.ncbi.nlm.nih.gov/pubmed/19532029
3. Miravitlles M, Espinosa C, Fernandez-Laso E, et al. Relationship between bacterial flora in sputum and functional impairment in patients with acute exacerbations of COPD. Chest 1999;116:40-6. https://www.ncbi.nlm.nih.gov/pubmed/10424501
4. Murphy TF, Brauer AL, Eschberger K, et al. Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2008;177:853-60. https://www.ncbi.nlm.nih.gov/pubmed/18202344
5. Almagro P, Silvado M, Garcia-Vidal C, et al. Pseudomonas aeruginosa and mortality after hospital admission for chronic obstructive pulmonary disease. Respiration 2012;84:36-43. https://www.karger.com/Article/FullText/331224

 

 

When should I consider Pseudomonas aeruginosa as a cause of respiratory tract infection in my hospitalized patient with COPD exacerbation?