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

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

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

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

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

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References

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

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

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

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?

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?

What’s the role of small droplets or aerosolized particles in the transmission of Covid-19?

Although transmission of SARS-CoV-2 is often considered to occur through large respiratory droplets by coughing or sneezing, emerging data suggests that smaller respiratory particles (5 microns or less) generated by breathing, speaking or singing also account for a sizeable number of infections. Several lines of evidence make a cogent argument for aerosols serving as an important mode of transmission for SARS-CoV-2. 1-9

 First, there are ample accounts of SARS-CoV-2 spreading by being near an infected individual without symptoms.  Since by definition, those without symptoms do not cough or sneeze transmission must have occurred through other means, including breathing, talking or touching surfaces that might have become secondarily contaminated through aerosol.1,2,5  To make matters worse, the peak of contagion in infected individuals occurs on or before symptoms occur.1

Second, aerosolized SARS-CoV-2 has been shown to remain viable in the air for at least 3 hours and viral RNA (not necessarily viable virus) has been found in the air outside patient rooms and inside patient rooms in the absence of cough.2,9 One study found SARS-CoV-2 in outdoor air at a hospital entrance and in front of a department store.7

Third, contaminated air samples and long-range aerosol transport and transmission have been reported by several studies involving a related coronavirus, SARS-CoV-1, the agent of SARS.2

What’s the ramifications of aerosol transmission of Covid-19? The most obvious is the requirement for universal wearing of masks or face covers in public spaces even when 6 feet apart. This practice is particularly important indoors where the amount of ventilation, number of people, duration of stay in the facility, and airflow direction may impact the risk of exposure to SARS-CoV-2.1

The other potential ramification of aerosolized SARS-CoV-2 is that due to their smaller size, these virus-laden particles may bypass the upper respiratory tract and be inhaled directly into the lungs resulting in more severe disease.4  So it really makes sense to routinely wear a mask when out in public places.

Bonus Pearl: Did you know that 1 minute of loud speaking could generate over 1000 virus-containing aerosols in the air with a “super-emitter” generating over 100,000 virus particles in their droplets during the same time?1

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 References

  1. Prather KA, Wang CC, Schooley RT. Reducing transmission of SARS-CoV-2. Science. May 27, 2020.
  2. Anderson EL, Turnham P, Griffin JR, et al. Consideration of the aerosol transmission for COVID-19 and public health. Risk Analysis 2020;40:902-7.
  3. Hamner L, Dubbel P, Capron I, et al. High SARS-CoV-2 attack rate following exposure at a choir practice-Skagit County, Washington, March 2020. MMWR 2020; 69: 606-10.
  4. Gralton J, Tovey E, McLaws ML, et al. The role of particle size in aerosolized pathogen transmission: a review. J Infect 2011;62:1-13.
  5. Asadi S, Bouvier N, Wexler AS et al. The coronavirus pandemic and aerosols: does COVID-19 transmit via expiratory particles. Aerosol Sci Technol 2020;54:635-38.
  6. Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Env International 2020;139:105730.
  7. Liu Y, Ning Z, Chen Y, e al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature 2020;582:557-60. https://www.nature.com/articles/s41586-020-2271-3.pdf
  8. Somsen GA, van Rijn C, Kooij S, et al. Small droplet aerosols in poorly ventilated spaces and SARS-CoV-2 transmission. Lancet Respir Med 2020; May 27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255254/pdf/main.pdf

9. Santarpia JL, Rivera DN, Herrera V, et al. Transmission potential of SARS-CoV-2 in viral shedding observed at the University of Nebraska Medical Center. 2020 (Preprint) https://www.ehs.ucsb.edu/files/docs/bs/Transmission_potential_of_SARS-CoV-2.pdf

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

What’s the role of small droplets or aerosolized particles in the transmission of Covid-19?

How can people with a respiratory virus such as Covid-19 be contagious even when they don’t cough or sneeze?

Couple of factors likely play a role in the transmission of respiratory viruses such as Covid-19 even in the absence of respiratory symptoms: 1. Generation of small droplets through everyday activities such as talking and breathing; 2. Presence of infectious virus in the respiratory tract before onset of symptoms.1-4

Small droplet generation during every day activity: Normal human speech and breathing can yield small particles or droplets that are too small to see by naked eye but are perfectly capable of serving as vehicles for aerial transport (more like hot air balloons than 737’s!) of a variety of communicable respiratory pathogens. 1  These small particles are believed to originate from the mucosal layers coating the respiratory tract as well as from vocal cord adduction and vibration within the larynx.1

In some cool experiments involving normal volunteers,1 the rate of particle emission during normal human speech positively correlated with the loudness of voice, ranging from 1-50 particles/second, irrespective of the language spoken (English, Spanish, Mandarin, or Arabic).  Perhaps, equally intriguing was identification of “speech superemitters”, consistently releasing an order of magnitude more particles than other participants.

Simply counting out loud has been associated with around 2-10 times as many total particles emitted as a single cough, 2 and the percentage of airborne droplet nuclei generated by singing is several times more than that emitted during normal talking and more like that of coughing! 3 Given, these observations, perhaps, the unfortunate outbreak of Covid-19 among members of a church choir in state of Washington 5 is not totally unexpected.

Presence of infectious virus in persons without symptoms:  An estimated 18% to 75% of patients testing positive for Covid-19 have no symptoms. This of course means that irrespective of whether symptoms ever develop, persons with Covid-19 may serve as a source of infection, by just breathing, talking, or singing when around susceptible people.

For these reasons, social distancing and wearing of masks during a pandemic makes sense!

Bonus Pearl: Did you know that infectious viral particles can be recovered from 40% of breath samples of patients with influenza? 6

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 References

  1. Asadi S, Wexler AS, Cappa CD, et al. Aerosol emission and superemission during human speech increase with voice loudness. Scientific Reports 2019;9:2348. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382806/
  2. Loudon RG, Roberts RM. Droplet expulsion from the respiratory tract. Am Rev Resp Dis 1967;435-42. https://doi.org/10.1164/arrd.1967.95.3.435
  3. Loudon RG, Roberts MR. Singing and the dissemination of tuberculosis. Am Rev Resp Dis 1968;98:297-300. DOI: 10.1164/arrd.1968.98.2.297 https://www.atsjournals.org/doi/abs/10.1164/arrd.1968.98.2.297?journalCode=arrd
  4. Lai KM, Bottomley C, McNerney. Propagation of respiratory aerosols by the Vuvuzela. PLoS One 2011;6:e20086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100331/
  5. Read R. A choir decided to go ahead with rehearsal. Now dozens of members have COVID-19 and two are dead. Los Angeles Times March 29, 2020. https://www.latimes.com/world-nation/story/2020-03-29/coronavirus-choir-outbreak
  6. Yan J, Grantham M, Pantelic J, et al. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. PNAS 2018;115:1081-1086 https://www.pnas.org/content/115/5/1081

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 can people with a respiratory virus such as Covid-19 be contagious even when they don’t cough or sneeze?

Key clinical pearls on the management of patients suspected of or diagnosed with Covid-19 in the outpatient setting

Here are some key points to remember when managing patients with Covid-19 symptoms in the outpatient setting.  These points are primarily based on the CDC guidelines and the current literature. They may be particularly useful to primary care providers (PCP) who do not have ready access to Covid-19 test kits or radiographic imaging in the diagnosis of patients suspected of or diagnosed with Covid-19.

  • Isolation precautions. 1,6-7 Minimize chances of exposure by placing a facemask on the patient and placing them in an examination room with the door closed. Use standard and transmission-based precautions including contact and airborne protocols when caring for the patient. Put on an isolation gown and N95 filtering facepiece respirator or higher. Use a facemask if a respirator is not available. Put on face shield or goggles if available. Adhere to strict hand hygiene practices with the use of alcohol-based hand rub with greater than 60% ethanol or 70% isopropanol before and after all patient contact. If there is no access to alcohol-based hand sanitizers, the CDC recommends hand washing with soap and water as the next best practice.

 

  • Risk Factors.2-3 Older patients and patients with severe underlying medical conditions seem to be at higher risk for developing more serious complications from Covid-19 illness. Known risk factors for severe Covid-19 include age over 60 years, hypertension, diabetes, cardiovascular disease, chronic respiratory disease, and immunosuppression.

 

  • Symptoms.2,4,8,9 Reported illnesses have ranged from mild symptoms to severe illness and death. These symptoms may appear after a 2- to 14-day incubation period.
    • Fever at any time 88-99%
    • Cough 59-79%
    • Dyspnea 19-55%
    • Fatigue 23-70%
    • Myalgias 15%-44%
    • Sputum production 23-34%
    • Nausea or vomiting 4%-10%
    • Diarrhea 3%-10%
    • Headache 6%-14%
    • Sore throat 14%
    • Rhinorrhea/nasal congestion (4.8%)
    • Anosmia (undocumented percentage)

 

  • Treatment for mild illness.5 Most patients have mild illness and are able to recover at home. Counsel patients suspected to have Covid-19 to begin a home quarantine staying in one room away from other people as much as possible. Patients should drink lots of fluids to stay hydrated and rest. Over the counter medicines may help with symptoms. There is controversy regarding the safety of NSAIDs in Covid-19 (See related P4P pearl). Generally, symptoms last a few days and  patients get better after a week. There is no official guidance from the CDC or other reliable sources on how often a PCP should check in with a patient confirmed with Covid-19 and in quarantine. Please use good judgement and utilize telehealth capabilities via phone call, video call, etc… if possible.

 

  • Treatment for severe illness.3 Patients should be transferred immediately to the nearest hospital. If there is no transfer service available, a family member with appropriate personal protective equipment (PPE) precautions, should drive patient to nearest hospital for critical care services.

 

  • Ending home isolation. 5
    • Without testing: Patients can stop isolation without access to a test result after 3 things have happened. 1) No fever for at least 72 hours. This is 3 full days of no fever and without the use of medication that reduces fever; 2) Respiratory symptoms have improved.; and 3) At least 7 days have passed since symptoms first appeared.
    • With testing. 5 Home isolation may be ended after all of the following 3 criteria have been met: 1) No fever for at least 72 hours. This is 3 full days of no fever and without the use of medication that reduces fever; 2) Respiratory symptoms have improved; and 3) Negative results from at least 2 consecutive nasopharyngeal swab specimens collected more than 24 hours apart.

To all the healthcare providers out there, please be safe and stay healthy!

 

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Contributed by Erica Barnett, Harvard Medical Student, Boston, MA.

 

References:

  1. CDC. Evaluating and Testing Persons for Coronavirus Disease 2019 (COVID-19). https://www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html
  2. CDC. Symptoms and Testing. https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/index.html
  3. World Health Organization. Operational Considerations for case management for COVID-19 in health facility and community. https://apps.who.int/iris/bitstream/handle/10665/331492/WHO-2019-nCoV-HCF_operations-2020.1-eng.pdf
  4. Partners in Health. Resource Guide 1: Testing, Tracing, community management. https://www.pih.org/sites/default/files/2020-03/PIH_Guide_COVID_Part_I_Testing_Tracing_Community_Managment_3_28.pdf
  5. CDC. Caring for someone at home. https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/care-for-someone.html
  6. CDC. Using PPE. https://www.cdc.gov/coronavirus/2019-ncov/hcp/using-ppe.html
  7. CDC. Hand Washing. https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene.html
  8. Harvard Health Publishing. COVID-19 Basics. https://www.health.harvard.edu/diseases-and-conditions/covid-19-basics
  9. Guan W, Ni Z, Hu Y, et al. Clinical characteristics of Coronavirus disease 2019 in China. N Engl J Med 2020, March 6. DOI:10.1056/NEJM022002032 https://www.ncbi.nlm.nih.gov/pubmed/32109013

 

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!

Key clinical pearls on the management of patients suspected of or diagnosed with Covid-19 in the outpatient setting

How long are the symptoms of hospitalized patients with Covid-19 expected to last?

Although most patients with Covid-19 may have mild or no symptoms, those who are ill enough to be hospitalized often have fever, cough, or shortness of breath that lasts for 2 weeks or longer. 

Fever: A Chinese study 1 involving 137 successfully discharged hospitalized patients reported that fever (37.3° C or 99.1° F or higher) lasted a median of 12 days (range 8-13 days). It’s important to point out that nearly one-quarter of these patients were also placed on corticosteroids during their hospitalization which might have resulted in the resolution of fever sooner and therefore altered the “natural course” of Covid-19.  In a smaller study from Singapore2 involving generally less ill hospitalized patients, fever didn’t usually last as long (median 4 days, range 0-15 days). 

Cough/shortness of breath: Cough may last nearly 3 weeks (median 19 days) while shortness of breath can go on for about 2 weeks (median 13 days).1

All symptoms: Even among those who are less ill and do not require supplemental oxygen, it may take nearly 2 weeks (median 12 days, range 5-24 days) for all the Covid-19-related symptoms (defined as fever, cough, and shortness of breath, sore throat, diarrhea, and rhinorrhea) to resolve.2 

It goes without saying that recovery from Covid-19 among hospitalized patients may be slow. In a Seattle study3 involving hospitalized patients who were admitted to the ICU, the median duration on the ventilator was 10 days (IQR 7-12 days), and the median length of hospital stay was 17 days (IQR 16-23 days).

Hopefully, as we find effective anti-Covid-19 drugs, the duration of these symptoms and length of hospitalization can be significantly reduced. Stay tuned!

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References

  1. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COCID-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
  2. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. JAMA 2020; March 3, 2020 (corrected March 20). https://jamanetwork.com/journals/jama/fullarticle/2762688
  3. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. Covid-19 in critically ill patients in the seattle region—Case series. N Engl J Med 2020; March 30. https://www.nejm.org/doi/full/10.1056/NEJMoa2004500

 

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 long are the symptoms of hospitalized patients with Covid-19 expected to last?

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

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

Routine screening of my patient suspected of having tuberculosis (TB) shows that he is HIV seropositive. Does HIV affect the clinical manifestation of TB?

Patients with newly-diagnosed TB are ~20 times more likely to be coinfected with HIV than those without TB. Unfortunately, the diagnosis of TB in HIV-infected patients is often delayed in part related to its atypical presentation1.

In HIV-infected patients with high CD4 counts, clinical manifestations of TB are usually similar to those without HIV infection (eg, subacute fever, weight loss, cough) with CXR often showing upper lobe infiltrates and/or cavitations typically seen in reactivation TB.

Lower CD4 counts, however, are associated with atypical CXR findings, including pleural effusions, lower or middle lobe infiltrates, mediastinal adenopathy, and lack of cavitary lesions1,2.  A normal CXR has been reported in 21% of patients with CD4 <200 cells/μl (vs 5% in those with higher counts)2.

Advanced immune suppression in HIV infection is also associated with negative sputum smears for acid-fast bacilli, concurrent extra-pulmonary disease, and immune reconstitution symptoms after initiation of anti-TB therapy1.

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References

  1. Kwan CK, Ernst JD. HIV and tuberculosis: a deadly human syndemic. Clin Microbiol Rev 2011;24:351-376. https://cmr.asm.org/content/24/2/351
  2. Greenberg, SD, Frager D, Suster B, et al. Active pulmonary tuberculosis in patients with AIDS: spectrum of radiographic findings (including a normal appearance). Radiology 1994;193:115-9. https://pubs.rsna.org/doi/abs/10.1148/radiology.193.1.7916467
Routine screening of my patient suspected of having tuberculosis (TB) shows that he is HIV seropositive. Does HIV affect the clinical manifestation of TB?

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?

Active TB should be suspected based on a combination of epidemiological (eg, exposure, travel to, or residence in a high prevalence area, history of prior TB), clinical (eg, cough lasting 2-3 weeks or longer, fever, night sweats, weight loss, fatigue, less commonly, chest pain, dyspnea, and hemoptysis), chest radiograph abnormalities (eg, infiltrates, fibrosis, cavitation), and histopathologic (eg, caseating granuloma)1.

Among HIV-negative patients, the highest prevalence of TB is found those who have been incarcerated, use intravenous drugs, have alcohol use disorder, or are immunocompromised (including diabetes mellitus)2,3

Patients suspected of TB based on clinical criteria should undergo chest radiography.  Reactivation pulmonary TB (~90% of TB in adults) classically presents with upper lobe and/or the superior segment of the lower lobe disease.  Remember that up to 5% of patients with active pulmonary TB have normal chest radiograph, however4.  

All hospitalized patients suspected of having active TB should be placed on appropriate isolation precautions until TB is excluded.

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References

  1. Sia IG, Wieland ML. Current concepts in the management of tuberculosis. Mayo Clin Proc. 2011;86:348-361. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068897/
  2. Center for Disease Control. Tuberculosis: Data and Statistics. https://www.cdc.gov/tb/statistics/default.htm. Accessed October 3, 2016.
  3. World Health Organization. Tuberculosis. http://www.who.int/mediacentre/ factsheets/fs104/en/. Accessed October 3, 2016.
  4. Marciniuk, D, McNab, BD, Martin WT, Hoeppner, VH. Detection of pulmonary tuberculosis in patients with a normal chest radiograph. Chest 1999;115:445-452. https://journal.chestnet.org/article/S0012-3692(15)50590-4/abstract

 

 

Contributed by Charles C. Jain MD, Medical Resident, Massachusetts General Hospital

 

When should I seriously consider active tuberculosis (TB) in my newly-admitted HIV-negative patient with a cough?