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?

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)!