What’s the connection between Covid-19 and hypokalemia?

The association of hypokalemia with hospitalized Covid-19 patients has been recognized since the early days of the pandemic, with more severe cases associated with lower concentration of serum potassium.1-4

A study involving 175 hospitalized patients with Covid-19 found low serum potassium in 54% of patients with 18% having severe hypokalemia (<3.0 mmol/L) and 37% having serum potassium 3.-3.5 mmol/L.  Compared to patients with mild to moderate Covid-19, those with severe or critical disease were more likely to have low serum potassium (3.5 mmol/L or less) (85% vs 45%).1

Another study involving 306 hospitalized patients with Covid-19, nearly a third (31%) had hypokalemia (3.5 mmol/L or less). Hypokalemia was associated with invasive mechanical ventilation, longer hospital and ICU stays.2 In contrast, a non-peer-reviewed MedRxive study found no association between hypokalemia and ICU admission or in-hospital mortality, possibly related to milder hypokalemia in the patients studied.3

Although various mechanisms may be invoked to explain hypokalemia in hospitalized Covid-19 patients (eg, poor intake, diuretics, corticosteroids, diarrhea, etc…), the most fascinating explanation may revolve around the direct impact of SARS-CoV-2 on the renin-angiotensin system.5  Because this virus uses the enzymatic receptor of ACE2 to penetrate the host cell, it can lead to downregulation of ACE2. Since ACE2 serves as a counterbalance to ACE by transforming a part of angiotensin I and II before they attach to angiotensin II type 1 receptor (AT1R), aldosterone effect is enhanced with resultant hypokalemia. High urinary excretion of potassium in many patients with Covid-19 seem to support the latter hypothesis.1,3  

Who would have predicted the versatility of this virus in causing hypokalemia in addition to all the other physiologic derangements it causes?  

Bonus Pearl: Did you know that there may be an association between lower prevalence of dry cough in patients with Covid-19 and hypokalemia, possibly related to low ACE2—therefore bradykinin— activity mediated by SARS-CoV-2? 2

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References

  1. Chen D, Li X, Song Q, et al. Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China. JAMA Network Open 2020;3(6):e2011122. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767008
  2. Moreno-Perez O, Leon-Ramirez JM, Fuertes-Kenneally L, et al. Hypokalemia as a sensitive biomarker of disease severity and the requirement for invasive mechanical ventilation requirement in COVID-19 pneumonia: A case series of 306 Mediterranean patients. International J Infect Dis 2020;100:449-54. https://www.ijidonline.com/article/S1201-9712(20)30749-9/pdf
  3. Gaetano A, Annachiara F, Francesco F, et al. Hypokalemia in patients with COVID-19. MedRxive preprint. Doi:https://doi.org/10.1101/2020.0614.20131169. https://www.medrxiv.org/content/10.1101/2020.06.14.20131169v2.full.pdf
  4. Lippi G, South Am, Henry BM. Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19). Ann Clin Biochem 2020;57:262-65. https://pubmed.ncbi.nlm.nih.gov/32266828/
  5. Silhol F, Sarlon G, Deharo JC, et al. Downregulation of ACE2 induces overstimulation of renin-angiotensin system in COVID-19: Should we block the renin-angiotensin system? Hypertension Research 2020;43:854-856. https://www.nature.com/articles/s41440-020-0476-3

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. 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 Covid-19 and hypokalemia?

Can my patient with Covid-19 get reinfected?

Patients with prior history of Covid-19 have been shown to get reinfected, sometimes less severe and sometimes more severe than the first bout.1-3 What we don’t really know is how often reinfection actually occurs, either with or without symptoms.

Symptomatic reinfection with genetically distinct SARS-CoV-2 following Covid-19 has been reported from several countries, including the USA. 1  A case series of 4 patients (age range of 33-51 y) found the severity of second infection ranging from asymptomatic to more severe disease requiring hospitalization.  First infection was mild in these cases with an intervening period of 48-142 days.1  BNO News, a Dutch website, lists many more “officially confirmed cases” as well as over a thousand “suspected reinfection cases”.4

Reinfection with Covid-19 in at least some people should not be too surprising. Some may have a suboptimal immune response to the first infection (eg with mild infection) that may be short-lasting, while others may have a better response.  Even in those with adequate response, SARS-CoV-2 antibodies may drop rapidly (half-life 36 days according to one study).3 Immunity to several other seasonal respiratory coronaviruses (cousins of SARS-CoV-2) also seems short lived (as short as 6 months).5 How much other arms of the immune system besides antibodies (eg, T cell immunity) play a role in conferring longer lasting immunity remains unclear.

These findings suggest that we cannot rely on natural infection to provide us individual or herd immunity.  Immunization is likely a better answer!

Bonus Pearl: Did you know that preliminary reports suggest that antibody loss with Covid-19 is more rapid than that found for SARS-CoV-1, the agent of SARS pandemic of 2003?3

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References

  1. Iwasaki A. What reinfections mean for COVID-19. Lancet Infect Dis 2020. Published online October 12, 2020. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30783-0/fulltext
  2. Tillett RL, Sevinsky JR, Hartley PD, et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis 2020. Published online October 12, 2020. https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(20)30764-7.pdf
  3. Ibarrondo J, Fulcher JA, Goodman-Meza D, et al. Rapid decay of anti-SARS-CoV-2 antibodies in persons with mild Covid-19. N Engl J Med 2020; September 10. https://www.nejm.org/doi/full/10.1056/nejmc2025179
  4. Kunzman K. Contagion Live. October 12, 2020. https://www.contagionlive.com/view/us-reports-first-confirmed-covid-19-reinfection-patient. Accessed Dec 23, 2020.
  5. Edridge AWD, Kaczorowska J, Hoste ACR, et al. Seasonal coronavirus protective immunity is short-lasting. Nature Medicine 2020;26:1691-93. https://pubmed.ncbi.nlm.nih.gov/32929268/

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. 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 my patient with Covid-19 get reinfected?

How effective are face masks in reducing transmission of Covid-19?

Overall, review of data to date suggests that face masks are quite effective in reducing the transmission of coronaviruses, including SARS-CoV-2, the cause of Covid-19. A Lancet 2020 meta-analysis involving over 12,000 subjects, found that transmission of coronaviruses (SARS-CoV-2, SARS and MERS) was reduced with face masks by 85% (adjusted O.R. 0.15, 95%CI 0.07-0.34).1

More specific to Covid-19, a study from Mass General Brigham hospitals found a significant drop in healthcare worker (HCW) SARS-CoV-2 PCR positivity rate from 21.3% to 11.5% following adoption of universal masking of HCWs and patients.2

An U.S. epidemiologic survey of 2,930 unique counties plus New York City found mandating face mask use in public was associated with a significant decline in the daily Covid-19 growth rate. 3 It was estimated that more than 200,000 Covid-19 cases were averted by May 22, 2020 as a result of the implementation of these mandates.

Another 2020 meta-analysis involving 21 studies reported an overall efficacy of masks (including surgical and N-95 masks) of 80% in healthcare workers and 47% in non-healthcare workers for respiratory virus transmission (including SARS, SARS-CoV-2 and influenza).4

A criticism of above reports has been their primarily retrospective nature. A randomized-controlled Danish study found a statistically insignificant 20% reduction in incident SARS-CoV-2 infection among mask wearers (5,6).    Despite its randomized-controlled design, this study had several limitations, including relatively low transmission rate in the community and lack of universal mask wearing in public during the study period. In addition, less than one-half of participants in the mask group reported adherence to wearing masks, and there was no assurance that masks were worn correctly when they did wear them. 

At most, this study suggests that it’s not enough for the uninfected to wear masks; the infected—often with little or no symptoms— should also wear them to help curb the pandemic.

So please do your part and tell your friends and family members to do the same by masking up while we are at war with Covid-19!

Bonus Pearl: Did you know that universal wearing of masks in the public in response to a respiratory virus pandemic is nothing new?  It was adopted as far back as 100 years ago during the 1918 Spanish influenza pandemic!

References

  1. Chu DK, Akl EA, Duda S, et al. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet 2020;395: 1973-87. https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31142-9.pdf
  2. Wang X, Ferro EG, Zhou G, et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA 2020;324:703-4. https://jamanetwork.com/journals/jama/fullarticle/2768533
  3. Lyu W, Wehby GL. Community use of face masks and COVID-19: evidence from a natural experiment of state mandates in the US. Health Affairs 2020;39: July 16. https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2020.00818
  4. Liang M, Gao L, Cheng Ce, et al. Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis. Travel Med Infect Dis 2020;36:1-8. https://pubmed.ncbi.nlm.nih.gov/32473312/ 
  5. Bundgaard H, Bundgaard JS, Tadeusz DE, et al. Effectiveness of adding a mask recommendation to other public health measures to prevent SARS-CoV-2 infection in Danish mask wearers. Ann Intern Med 2020; November 18. https://pubmed.ncbi.nlm.nih.gov/33205991/
  6. Frieden TR Cash-Goldwasser S. Of masks and methods. Ann Intern Med 2020; November 18. https://www.acpjournals.org/doi/10.7326/m20-7499

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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. 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 face masks in reducing transmission of Covid-19?

What’s the connection between break rooms and transmission of Covid-19 in health care settings?

Emerging data suggest that healthcare workers (HCWs) may be at increased risk of Covid-19 in break rooms when consuming food or when in the presence of others without a mask.1-4

In a study of over 700 HCWs screened for SARS-CoV-2 by PCR at a university hospital, staying in the same personnel break room as an HCW without a medical mask for more than 15 min and consuming food within 1 meter of an HCW were significantly associated with SARS-CoV-2 infection.1 Consumption of food in break rooms by personnel was thereafter “forbidden” in this facility. Interestingly, 28% of infected personnel in this study lacked symptoms at the time of testing.

A recent outbreak at a Boston hospital involving both patients and HCWs months after institution of strict infection control measures (including universal masking of visitors and HCWs and PCR testing of all patients on admission) traced the outbreak to a variety of factors, including HCWs eating in crowded work rooms.2,3

A CDC study of risk factors among adults 18 years or older with Covid-19 in the community identified dining at a restaurant as significant risk factors for Covid-19.4

Transmission of SARS-CoV-2 during eating or drinking is not surprising because masks cannot be effectively worn during food consumption. Combine eating or drinking with talking, laughing and suboptimal ventilation system and we have all the elements of perfect storm for transmission of Covid-19 during food breaks.

Bonus Pearl: Did you know that, in addition to dining at a restaurant, patients with Covid-19 without known close contact with infected persons have reported higher likelihood of going to bar/coffee shop? 4

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References

 

  1. Celebi G, Piskin N, Beklevic AC, et al. Specific risk factors for SARS-CoV-2 transmission among health care workers in a university hospital. Am J Infect Control 2020;48:1225-30. https://pubmed.ncbi.nlm.nih.gov/32771498/
  2. Freyer FJ. Brigham and Women’s hospital completes investigation of coronavirus outbreak. Boston Globe, October 19, 2020. https://www.bostonglobe.com/2020/10/19/metro/brigham-womens-hospital-completes-investigation-coronavirus-outbreak/
  3. Freyer FJ. At the Brigham, “battle-weary” staff may have allowed virus to slip in. Boston Globe, September 24, 2020. https://www.bostonglobe.com/2020/09/24/metro/brigham-womens-hospital-reports-cluster-10-covid-19-cases/
  4. Fisher KA, Tenforde MW, Felstein LR, et al. Community and close contact exposures associated with COVID-19 among symptomatic adults ≥18 years in 11 outpatient health care facilities—United States, July 2020. MMWR 2020;69:1258-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499837/

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 affiliates. 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 break rooms and transmission of Covid-19 in health care settings?

How might measuring viral load in respiratory specimens be helpful clinically in patients with Covid-19?

Although far from being perfect, there are emerging scientific data that suggest measuring viral load in respiratory specimens of patients with Covid-19 could be helpful in at least 2 ways: 1. Help determine who may be infectious (therefore isolated or undergo contact tracing); and 2. Identify patients at high risk for severe disease and death (1-4).

In a study involving 3,790 nasopharyngeal samples testing positive for SARS-CoV-2 by PCR, a significant correlation was found between isolation of the virus by culture—therefore potential contagiousness—and viral load determined by cycle threshold (CT) (ie, the number of cycles needed to detect the virus with higher numbers thought to be associated with lower risk of contagion) (2). Some have suggested that patients with CT above 33-34 are no longer contagious (3).

In another study involving 978 patients with Covid-19, high viral load in nasopharyngeal specimens was associated with higher risk of intubation (O.R. 2.7, 1.7-4.4), and mortality (6.1, 2.9-12.5) (4).

In addition, simultaneous presence of high viral loads in the respiratory specimens in the population suggests an expanding outbreak, while low viral loads may imply that the outbreak is waning (1).

Some have cautioned against over-reliance on viral loads in Covid-19 due to factors such as variation in the technique of obtaining specimens and testing instruments (5).

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References
1. Service RF. Covid-19. A call for diagnostic tests to report viral load. Science 2020, October 2;370:22. https://www.sciencemag.org/news/2020/09/one-number-could-help-reveal-how-infectious-covid-19-patient-should-test-results
2. Jaafar R, Aherfi S, Wurtz N, et al. Correlation between 3790 qPCR positives samples and positive cell cultures including 1941 SARS-CoV-2 isolates. Clin Infect Dis 2020, September. https://pubmed.ncbi.nlm.nih.gov/32986798/
3. La Scola B, Le Bideau M, Andreani J, et al. Viral RNA as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards. Eur J Clin Microbiol Infect Dis 2020;39:1059-1061. https://pubmed.ncbi.nlm.nih.gov/32342252/
4. Magleby R, Westblade LF, Trzebucki A, et al. Impact of severe acute respiratory syndrome coronavirus 2 viral load on risk of intubation and mortality among hospitalized patients with coronavirus disease 2019. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa851/5865363
5. Rhoads D, Peaper DR, She RC, et al. College of American Pathologists (CAP) Microbiology Committee perspective: caution must be used in interpreting the cycle threshold (Ct) value. Clin Infect Dis 12 August, 2020. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1199/5891762

 

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!

How might measuring viral load in respiratory specimens be helpful clinically in patients with Covid-19?

Why would my patient with Covid-19 infection test negative by PCR?

There are several potential reasons why someone who is infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of Covid-19, may test negative by PCR. These including the threshold for detection of virus (which can vary among different manufacturers from as low as 100 viral copies/ml to >6,000 copies/ml),1 timing of the sample collection with respect to infection stage (lowest false-negative rate [~20%] on day 3 of symptoms or 8 days post-infection),specimen storage and transport and, particularly in the case of nasopharyngeal specimens, the adequacy of the sample obtained. 3

Suboptimal specimen collection from nasopharynx has long been suspected as an explanation for false-negative PCR tests in patients who subsequently have a positive test or are highly suspected of having Covid-19, but without any good support data. Until now…

A clever study looked at the presence of human DNA recovered from nasopharyngeal swabs as a marker for adequate specimen collection quality and found that human DNA levels were significantly lower in samples from patients with confirmed or suspected Covid-19 that yielded negative results compared to those of representative pool of samples submitted for Covid-19 testing.3

Interestingly, major commercial assays do not include any internal controls that ensure adequate sampling before testing for SARS-CoV2.

A typical microbiology lab can reject a sputum culture if gram-stain suggests poor quality specimen (eg, saliva only) but it looks like no similar rule exists for nasopharyngeal PCR tests for SARS-CoV-2 through commercial labs. Apparently, the US-CDC diagnostic panel does include a human RNAseP RNA-specific primer/probe set but the interpretation criteria for this control may also be too liberal.3

For these reasons, in patients highly suspected of having Covid-19 but with a negative initial PCR test, a repeat test on the same day or next 2 days is recommended.4

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References

  1. Prinzi A. False negatives and refinfections: the challenges of SARS-CoV-2 RT-PCR testing. Available at https://asm.org/Articles/2020/April/False-Negatives-and-Reinfections-the-Challenges-of     Accessed October 5, 2020.
  2. Kucirka LM, Lauer SA, Laeyendecker O, et al. Variation in false-negative rate of reverse transcriptase polymerase chain reaction-based SARS-CoV-2 tests by time since exposure. Ann Intern Med 2020 May 13:M20-1495. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240870/
  3. Kinloch NN, Ritchie G, Brumme CJ, et al. Suboptimal biological sampling as a probable cause of false-negative COVID-19 diagnostic test results. J Infect Dis 2020;222:899-902. https://academic.oup.com/jid/article/222/6/899/5864227
  4. Green DA, Zucker J, Westbade LF, et al. Clinical performance of SARS-CoV-2 molecular testing. J Clin Microbiol 2020. DOI:10.1128/JCM.00995-20. https://jcm.asm.org/content/58/8/e00995-20

 

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!

Why would my patient with Covid-19 infection test negative by PCR?

How often is Covid-19 in hospitalized patients complicated by bacterial infection?

Despite frequent use of empiric antibiotics in hospitalized patients with Covid-19,current data suggests a low rate of documented bacterial co-infection (BCI) in such patients. In fact, the overall reported rate of BCI in hospitalized patients with Covid-19 is generally no greater than 10%.1-3   It’s quite likely that most patients with Covid-19 and chest radiograph changes solely have a coronavirus (SARS-CoV-2) lung infection,4 particularly early in the course of the disease.  

A meta-analysis involving 30 studies (primarily retrospective) found that overall 7% of hospitalized Covid-19 patients had a laboratory-confirmed BCI with higher proportion among ICU patients (14%).Mycoplasma pneumoniae was the most common (42% of BCIs), followed by Pseudomonas aeruginosa and H. influenzae.  Notably, diagnosis of M. pneumoniae infection was based on antibody testing for IgM, which has been associated with false-positive results. Other caveats include lack of a uniform definition of respiratory tract infection among studies and potential impact of concurrent or prior antibiotic therapy on the yield of bacteriologic cultures. 5,6

A low prevalence of BCI was also found in a UK study involving 836 hospitalized Covid-19 patients: 3.2% for early BCI (0-5 days after admission) and 6.1% throughout hospitalization, including hospital-acquired infections.Staphylococcus aureus was the most common respiratory isolate among community-acquired cases, while Pseudomonas spp. was the predominant healthcare associated respiratory isolate.  Similarly, S. aureus. and Streptococcus pneumoniae were the most commonly isolated organisms from blind bronchoalveolar lavage of critically ill patients with Covid-19 during their first 5 days of admission, while gram-negative bacilli became dominant later during the hospitalization.8

The discordance between high rates of antibiotic treatment and confirmed bacterial co-infection in Covid-19 patients is likely a reflection of the difficulty in distinguishing Covid-19 pneumonia from bacterial pneumonia based on clinical or radiographic findings alone.

We need better tests to help distinguish bacterial vs Covid-19 pneumonia. Some have suggested using a low serum procalcitonin to help guide the withholding of or early discontinuation of antibiotics, especially in less severe Covid-19 cases. Formal studies of the accuracy of procalcitonin in Covid-19 are needed to test this hypothesis, given its suboptimal sensitivity in bacterial community-acquired pneumonia. 

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Reference

  1. Stevens RW, Jensen K, O’Horo JC, et al. Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care. Infect Control Hosp Epidemiology 2020. https://reference.medscape.com/medline/abstract/32703323
  2. Lansbury L, Lim B, Baskaran V, et al. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect 2020;81:266-75. https://pubmed.ncbi.nlm.nih.gov/32473235/
  3. Rawson TM, Moore LSP, Zhu N. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis 2020 (Manuscrpit published online ahead of print 2 June ). Doi:10.1093/cid/ciaa530.https://pubmed.ncbi.nlm.nih.gov/32358954/
  4. Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus 2019 (COVID-19) pandemic. Ann Intern Med 2020; 173:304-305. https://pubmed.ncbi.nlm.nih.gov/32379883/
  5. Chang CY, Chan KG. Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics. J Infect 2020;81:e29-30. https://pubmed.ncbi.nlm.nih.gov/32628960/
  6. Rawson TM, Moore LSP, Zhu N, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Reply letter. Clin Infect Dis 2020. https://academic.oup.com/cid/advance-
  7. Hughes S, Troise O, Donaldson H, et al. Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting. Clin Microbiol Infect 2020. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30369-4/fulltext
  8. Dudoignon E, Camelena F, Deniau B, et al. Bacterial pneumonia in COVID-19 critically ill patients: A case series. Clin Infect Dis 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337703/

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!

How often is Covid-19 in hospitalized patients complicated by bacterial infection?

How might categorizing severity of illness help in the management of my patient with Covid-19?

Although the criteria for Covid-19 severity of illness categories may overlap at times or vary across guidelines and clinical trials, I have found those published in the National Institute of Health (USA) Covid-19 Treatment Guidelines most useful and uptodate.1  Keep in mind that the primary basis for severity categories in Covid-19 is the degree by which it alters pulmonary anatomy and physiology and respiratory function (see my table below).

The first question to ask when dealing with Covid-19 patients is whether they have any signs or symptoms that can be attributed to the disease (eg, fever, cough, sore throat, malaise, headache, muscle pain, lack of sense of smell). In the absence of any attributable symptoms, your patient falls into “Asymptomatic” or “Presymptomatic” category.  These patients should be monitored for any new signs or symptoms of Covid-19 and should not require additional laboratory testing or treatment.

If symptoms of Covid-19 are present (see above), the next question to ask is whether the patient has any shortness of breath or abnormal chest imaging. If neither is present, the illness can be classified as “Mild” with no specific laboratory tests or treatment indicated in otherwise healthy patients. These patients may be safely managed in ambulatory settings or at home through telemedicine or remote visits. Those with risk factors for severe disease (eg, older age, obesity, cancer, immunocompromised state), 2 however, should be closely monitored as rapid clinical deterioration may occur.

Once lower respiratory tract disease based on clinical assessment or imaging develops, the illness is no longer considered mild. This is a good time to check a spot 02 on room air and if it’s 94% or greater at sea level, the illness qualifies for “Moderate” severity. In addition to close monitoring for signs of progression, treatment for possible bacterial pneumonia or sepsis should be considered when suspected. Corticosteroids are not recommended here and there are insufficient data to recommend either for or against the use of remdesivir in patients with mild/moderate Covid-19.

Once spot 02 on room air drops below 94%, Covid-19 illness is considered “Severe”; other parameters include respiratory rate >30, Pa02/Fi02 < 300 mmHg or lung infiltrates >50%. Here, patients require further evaluation, including pulmonary imaging, ECG, CBC with differential and a metabolic profile, including liver and renal function tests. C-reactive protein (CRP), D-dimer and ferritin are also often obtained for their prognostic value. These patients need close monitoring, preferably in a facility with airborne infection isolation rooms.  In addition to treatment of bacterial pneumonia or sepsis when suspected, consideration should also be given to treatment with corticosteroids. Remdesivir is recommended for patients who require supplemental oxygen but whether it’s effective in those with more severe hypoxemia (eg, those who require oxygen through a high-flow device, noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation-ECMO) is unclear. Prone ventilation may be helpful here in patients with refractory hypoxemia as long as it is not used to avoid intubation in those who otherwise require mechanical ventilation.

“Critical” illness category is the severest forms of Covid-19 and includes acute respiratory distress syndrome (ARDS), septic shock, cardiac dysfunction and cytokine storm. In addition to treatment for possible bacterial pneumonia or sepsis when suspected, corticosteroids and supportive treatment for hemodynamic instability and ARDS, including prone ventilation, are often required. The effectiveness of remdesivir in patients with severe hypoxemia (see above) is unclear at this time.

 

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 References

  1. NIH COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/. Accessed Aug 27, 2020.
  2. CDC. Covid-19.  https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html/. Accessed Aug 27, 2020.  

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!

 

How might categorizing severity of illness help in the management of my patient with Covid-19?

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

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 role does obesity play in severe Covid-19?

Obesity has been shown to be a strong independent predictor of not only Covid-19-related hospitalization but also critical illness requiring invasive mechanical ventilation (IMV) or ICU support (1-3).

 
A large New York City study involving over 4,000 Covid-19 patients found obesity ( BMI≥30 kg/m2) to be an independent risk factor for hospitalization; BMI 30-40 kg/m2 was associated with ~4-fold and >40 kg/m2 with ~6-fold increased risk. Obesity was also strongly associated with increased risk of critical illness, stronger than other common preexisting conditions such as heart disease, hypertension or diabetes (1, preprint).

 
Another New York City study found that among Covid-19 patients younger than 60 years of age, obese patients were twice as likely to be hospitalized or have critical illness (2). Similarly, a French study found severe obesity (BMI >35 kg/m2) to be strongly associated with IMV compared to those with BMI <25 kg/m2 (O.R. 7.4, 1.7-33) (3).

 
Many factors likely play a role in making obese patients particularly susceptive to severe Covid-19. Obesity is a well-recognized inflammatory state and is associated with abnormal secretion of cytokines and adipokines which may have an effect on lung parenchyma and bronchi (1,3,4). Somewhat paradoxically, obese patients may also have an impaired adaptive immune response to certain infections, including influenza (4). Abdominal obesity is also associated with impaired ventilation of the base of the lungs resulting in reduced oxygenation (1).

 

 

Bonus Pearl: Did you know among pre-existing conditions commonly found in the population (eg, hypertension, diabetes, COPD), obesity has been found to be the only condition independently associated with pulmonary embolism in Covid-19 (O.R. 2.7, 1.3-5.5) (5).

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References
1. Petrilli CM, Jones SA, Yang J, et al. Factors associated with hospitalization and critical illness among 4, 103 patients with Covid-19 disease in New York City. MedRxiv preprint doi: https://doi.org/10.1101/2020.04.0820057794
2. Lighter J, Phillips M, Hochman S, et al. Obesity in patients younger than 60 years is a risk factor for COVID-19 hospital admission. Clin Infect Dis 2020. https://pubmed.ncbi.nlm.nih.gov/32271368/
3. Simonnet A, Chetboun M, Poissy J, et al. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. https://pubmed.ncbi.nlm.nih.gov/32271993/
4. Sattar N, BcInnes IB, McMurray JJV. Obesity a risk factor for severe COVID-19 infection:multiple potential mechanisms. Circulation 2020. https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047659
5. Poyiadji N, Cormier P, Patel PY, et al. Acute pulmonary embolism and COVID-19. Radiology 2020; https://pubmed.ncbi.nlm.nih.gov/32407256/

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 role does obesity play in severe Covid-19?