COVID-19-associated lymphopenia: Difference between revisions
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==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
*[[Lymphopenia]] is the most common laboratory finding in COVID-19, and is found in as many as 83% of hospitalized patients.<ref name="urlManagement of Patients with Confirmed 2019-nCoV | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html |title=Management of Patients with Confirmed 2019-nCoV | CDC |format= |work= |accessdate=}}</ref> | *[[Lymphopenia]] is the most common laboratory finding in COVID-19, and is found in as many as 83% of hospitalized patients.<ref name="urlManagement of Patients with Confirmed 2019-nCoV | CDC">{{cite web |url=https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html |title=Management of Patients with Confirmed 2019-nCoV | CDC |format= |work= |accessdate=}}</ref> | ||
*Lymphopenia is [[lymphocyte]] count of less than 1.5 × 109/L. It is associated with a 3-fold increased risk of severe COVID-19 infection. | *Lymphopenia is [[lymphocyte]] count of less than 1.5 × 109/L. It is associated with a 3-fold increased risk of severe COVID-19 infection. | ||
*Patients with [[Lymphocytopenia|lymphopenia]] on admission have been associated with poor prognostic outcomes<ref name="HuangPranata2020">{{cite journal|last1=Huang|first1=Ian|last2=Pranata|first2=Raymond|title=Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis|journal=Journal of Intensive Care|volume=8|issue=1|year=2020|issn=2052-0492|doi=10.1186/s40560-020-00453-4}}</ref>. Recent studies have shown that 85% of severely ill patients have [[Lymphocytopenia|lymphopenia]]. Futhermore, patients who have died from [[COVID-19]] infection showed significantly lower [[lymphocyte]] level than survivors.<ref name="FathiRezaei2020">{{cite journal|last1=Fathi|first1=Nazanin|last2=Rezaei|first2=Nima|title=Lymphopenia in COVID‐19: Therapeutic opportunities|journal=Cell Biology International|year=2020|issn=1065-6995|doi=10.1002/cbin.11403}}</ref> | *Patients with [[Lymphocytopenia|lymphopenia]] on admission have been associated with poor prognostic outcomes<ref name="HuangPranata2020">{{cite journal|last1=Huang|first1=Ian|last2=Pranata|first2=Raymond|title=Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis|journal=Journal of Intensive Care|volume=8|issue=1|year=2020|issn=2052-0492|doi=10.1186/s40560-020-00453-4}}</ref>. Recent studies have shown that 85% of severely ill patients have [[Lymphocytopenia|lymphopenia]]. Futhermore, patients who have died from [[COVID-19]] infection showed significantly lower [[lymphocyte]] level than survivors.<ref name="FathiRezaei2020">{{cite journal|last1=Fathi|first1=Nazanin|last2=Rezaei|first2=Nima|title=Lymphopenia in COVID‐19: Therapeutic opportunities|journal=Cell Biology International|year=2020|issn=1065-6995|doi=10.1002/cbin.11403}}</ref> | ||
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===Other Diagnostic studies=== | ===Other Diagnostic studies=== | ||
*Bone marrow biopsy, although not recommended may be helpful if there is suspision of other disorders that can cause lymphopenia , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients. | *[[Bone marrow examination|Bone marrow biopsy]], although not recommended may be helpful if there is suspision of other disorders that can cause [[Lymphocytopenia|lymphopenia]] , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients. | ||
==Treatment== | ==Treatment== | ||
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The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial. This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of [[COVID-19]].<ref name="urlImmune-Based Therapy | Coronavirus Disease COVID-19">{{cite web |url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/ |title=Immune-Based Therapy | Coronavirus Disease COVID-19 |format= |work= |accessdate=}}</ref> | The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial. This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of [[COVID-19]].<ref name="urlImmune-Based Therapy | Coronavirus Disease COVID-19">{{cite web |url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/ |title=Immune-Based Therapy | Coronavirus Disease COVID-19 |format= |work= |accessdate=}}</ref> | ||
*There are insufficient data to recommend either for or against the use of the following agents for the treatment of [[COVID-19]]: | *There are insufficient data to recommend either for or against the use of the following agents for the treatment of [[COVID-19]]: | ||
**Interleukin-1 inhibitors (e.g., anakinra) | **Interleukin-1 inhibitors (e.g., [[anakinra]]) | ||
**Interleukin-6 inhibitors (e.g., sarilumab, siltuximab, tocilizumab) | **Interleukin-6 inhibitors (e.g., [[sarilumab]], [[siltuximab]], [[tocilizumab]]) | ||
Except in the context of a clinical trial, the Panel recommends against the use of other immunomodulators, such as: | |||
Interferons, because of the lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity. | Except in the context of a clinical trial, the Panel recommends against the use of other [[immunomodulators]], such as: | ||
Janus kinase inhibitors (e.g., baricitinib), because of their broad immunosuppressive effect.<ref name="urlImmune-Based Therapy | Coronavirus Disease COVID-19">{{cite web |url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/ |title=Immune-Based Therapy | Coronavirus Disease COVID-19 |format= |work= |accessdate=}}</ref> | |||
* [[Interferon|Interferons]], because of the lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity. | |||
* [[Janus kinase]] inhibitors (e.g., [[baricitinib]]), because of their broad [[immunosuppressive]] effect.<ref name="urlImmune-Based Therapy | Coronavirus Disease COVID-19">{{cite web |url=https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/ |title=Immune-Based Therapy | Coronavirus Disease COVID-19 |format= |work= |accessdate=}}</ref> | |||
==References== | ==References== | ||
Revision as of 12:32, 16 July 2020
For COVID-19 frequently asked inpatient questions, click here
For COVID-19 frequently asked outpatient questions, click here
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COVID-19-associated lymphopenia On the Web |
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American Roentgen Ray Society Images of COVID-19-associated lymphopenia |
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Risk calculators and risk factors for COVID-19-associated lymphopenia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Oluwabusola Fausat Adogba, MD[2]
Synonyms and keywords:
Overview
Coronavirus disease 2019 (COVID-19) has been considered as a global pandemic since its first emergence in Wuhan, China. On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. There is no established system for the classification regarding COVID-19 related lymphopenia. four hypothetical mechanisms regarding lymphopenia are Direct infection of Lymphocyte, direct destroying of lymphocytic organs, inflammatory cytokines such as TNFɑ, IL-6, Lymphocyte inhibition,
Historical Perspective
- Coronavirus disease 2019 (COVID-19) has been considered as a global pandemic since its first emergence in Wuhan,China.[1]
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
- Since the first descriptive study lymphocyte count has been a marker of interest.[2]
Classification
There is no established system for the classification regarding COVID-19 related lymphopenia.
Pathophysiology
- There are four hypothetical mechanisms regarding lymphopenia[3][4]
- Direct infection of Lymphocytes
- Direct destroying lymphatic organs
- Inflammatory cytokines such as TNF ɑ, IL-6 , etc inducing lymphopenia
- Inhibition of lymphocytes by metabolic molecules such as hyperlactic acidemia
Causes
The SARS-CoV-2 (COVID-19) viral infection is the known cause of lymphopenia in COVID-19 patients. To read more click here
COVID-19 related Lymphocytopenia starts acutely in the course of the disease, with other manifestations of the disease. Lymphocytopenia, is associated with corticosteroid use, infections with HIV and other viral, bacterial, and fungal agents, Hodgkin's disease, leukemia, malnutrition, systemic lupus erythematosus,[5] high stress levels, whole body radiation, rheumatoid arthritis, and iatrogenic conditions.
In alphabetical order. [6] [7]
- After influenza
- After snakebite
- Anesthesia
- Antibody deficiency syndrome
- Aplastic Anemia
- Banti's Syndrome
- Burns
- Congenital immune deficiency
- Cushing's Disease
- Dermatomyositis
- Drugs, toxins
- Exudative enteropathy
- Felty's Syndrome
- Heavy exercise
- HIV
- Hodgkin's Lymphoma
- Inflammatory Bowel Disease
- Lymphocyte tuberculosis
- Measles
- Paroxysmal nocturnal hemoglobinuria
- Polycythemia
- Postoperative
- Pregnancy
- Sarcoidosis
- Scarlet Fever
- Secondary hypersplenism
- Single non-Hodgkin's lymphomas
- Surgery
- Systemic Lupus Erythematosus
- Trauma
- Tuberculosis
- Uremia
- Whipple's Disease
- Zinc deficiency
Epidemiology and Demographics
- The incidence of the Coronavirus Disease 2019 (COVID-19) as of June 28, 2020 is approximately 9,843,073 cases worldwide with 495,760 deaths.[8]
- Patients of all age groups may develop COVID-19. However, the elderly population and immunocompromised individuals are more likely to develop severe cases of COVID-19.
Risk Factors
People of any age with certain underlying medical conditions are at increased risk for severe illness from COVID-19. These medical conditions include:[9]
- Chronic kidney disease
- Chronic obstructive pulmonary disease
- Immunocompromised state (weakened immune system) from solid organ transplant
- Obesity (body mass index [BMI] of 30 or higher)
- Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
- Sickle cell disease
- Type 2 diabetes mellitus
Screening
- Lymphopenia on admission has been associated with predicting the severity of clinical outcomes. Approximately, a three-fold increase in severity has been associated with lymphopenia on admission.[10]
- A routine CBC with differential can be used for monitoring and predicting disease progression and severity in patients.
Natural History, Complications, and Prognosis
- Lymphopenia is the most common laboratory finding in COVID-19, and is found in as many as 83% of hospitalized patients.[11]
- Lymphopenia is lymphocyte count of less than 1.5 × 109/L. It is associated with a 3-fold increased risk of severe COVID-19 infection.
- Patients with lymphopenia on admission have been associated with poor prognostic outcomes[12]. Recent studies have shown that 85% of severely ill patients have lymphopenia. Futhermore, patients who have died from COVID-19 infection showed significantly lower lymphocyte level than survivors.[13]
- Common hematologic complications of coronavirus also include neutrophilia and thrombocytosis.
Diagnosis
Diagnostic Choice of Study
Lymphopenia refers to a count of less than 1,000 lymphocytes per microliter of blood in adults, or less than 3,000 lymphocytes per microliter of blood in children.[14] The following tests are used to diagnose lymphopenia:
- Complete Blood test
- Flow cytometry
History and Symptoms
Lymphopenia as a result of COVID-19 can present with different symptoms. People with COVID-19 have had a wide range of symptoms reported – ranging from mild symptoms to severe illness. Symptoms may appear 2-14 days after exposure to the virus. People with these symptoms may have COVID-19:[15]
- Fever or chills
- Cough
- Shortness of breath or difficulty breathing
- Fatigue
- Muscle or body aches
- Headache
- New loss of taste or smell
- Sore throat
- Congestion or runny nose
- Nausea or vomiting
- Diarrhea
Physical Examination
- There are no physical findings associated with lymphopenia.
- However patients with significant lymphopenia can show signs of the associated disorder, in this case COVID-19 symptoms.
Laboratory findings
- Lymphocyte count on CBC with differential is less than 1.5x109/L is potentially associated with severe outcomes.[10]
- Peripheral blood smear- This maybe helpful, however there is insufficient evidence recommending routine peripheral blood smear in COVID-19 patients.
Electrocardiogram
There are no ECG findings associated with COVID-19 associated lymphopenia.
X-ray
There are no X-ray findings associated with COVID-19 associated lymphopenia.
Echocardiography or Ultrasound
There are no echocardiography or ultrasound findings associated with COVID-19 associated lymphopenia.
CT Scan
There are no CT scan findings associated with COVID-19 associated lymphopenia.
MRI
There are no MRI findings associated with COVID-19 associated lymphopenia.
Other imaging findings
There are no other imaging findings associated with COVID-19 associated lymphopenia.
Other Diagnostic studies
- Bone marrow biopsy, although not recommended may be helpful if there is suspision of other disorders that can cause lymphopenia , but there is not enough evidence to support bone marrow biopsy in COVID-19 patients.
Treatment
Medical therapy
Immune-Based Therapy:
- There are insufficient data to recommend either for or against the use of COVID-19 convalescent plasma or SARS-CoV-2 immune globulins for the treatment of COVID-19.
The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of non-SARS-CoV-2-specific intravenous immune globulin (IVIG) for the treatment of COVID-19, except in the context of a clinical trial. This should not preclude the use of IVIG when it is otherwise indicated for the treatment of complications that arise during the course of COVID-19.[16]
- There are insufficient data to recommend either for or against the use of the following agents for the treatment of COVID-19:
- Interleukin-1 inhibitors (e.g., anakinra)
- Interleukin-6 inhibitors (e.g., sarilumab, siltuximab, tocilizumab)
Except in the context of a clinical trial, the Panel recommends against the use of other immunomodulators, such as:
- Interferons, because of the lack of efficacy in treatment of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and toxicity.
- Janus kinase inhibitors (e.g., baricitinib), because of their broad immunosuppressive effect.[16]
References
- ↑ "WHO Western Pacific | World Health Organization".
- ↑ Ruan, Qiurong; Yang, Kun; Wang, Wenxia; Jiang, Lingyu; Song, Jianxin (2020). "Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China". Intensive Care Medicine. 46 (5): 846–848. doi:10.1007/s00134-020-05991-x. ISSN 0342-4642.
- ↑ Fischer, Karin; Hoffmann, Petra; Voelkl, Simon; Meidenbauer, Norbert; Ammer, Julia; Edinger, Matthias; Gottfried, Eva; Schwarz, Sabine; Rothe, Gregor; Hoves, Sabine; Renner, Kathrin; Timischl, Birgit; Mackensen, Andreas; Kunz-Schughart, Leoni; Andreesen, Reinhard; Krause, Stefan W.; Kreutz, Marina (2007). "Inhibitory effect of tumor cell–derived lactic acid on human T cells". Blood. 109 (9): 3812–3819. doi:10.1182/blood-2006-07-035972. ISSN 0006-4971.
- ↑ Liao, Yuan-Chun; Liang, Wei-Guang; Chen, Feng-Wei; Hsu, Ju-Hui; Yang, Jiann-Jou; Chang, Ming-Shi (2002). "IL-19 Induces Production of IL-6 and TNF-α and Results in Cell Apoptosis Through TNF-α". The Journal of Immunology. 169 (8): 4288–4297. doi:10.4049/jimmunol.169.8.4288. ISSN 0022-1767.
- ↑ W L Ng, C M Chu, A K L Wu, V C C Cheng, K Y Yuen. "Lymphopenia at presentation is associated with increased risk of infections in patients with systemic lupus erythematosus". Quarterly Journal of Medicine. 99 (1): 37–47. doi:10.1093/qjmed/hci155.
- ↑ Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:77 ISBN 1591032016
- ↑ Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:68 ISBN 140510368X
- ↑ 10.0 10.1 Zhao, Qianwen; Meng, Meng; Kumar, Rahul; Wu, Yinlian; Huang, Jiaofeng; Deng, Yunlei; Weng, Zhiyuan; Yang, Li (2020). "Lymphopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A systemic review and meta-analysis". International Journal of Infectious Diseases. 96: 131–135. doi:10.1016/j.ijid.2020.04.086. ISSN 1201-9712.
- ↑ "Management of Patients with Confirmed 2019-nCoV | CDC".
- ↑ Huang, Ian; Pranata, Raymond (2020). "Lymphopenia in severe coronavirus disease-2019 (COVID-19): systematic review and meta-analysis". Journal of Intensive Care. 8 (1). doi:10.1186/s40560-020-00453-4. ISSN 2052-0492.
- ↑ Fathi, Nazanin; Rezaei, Nima (2020). "Lymphopenia in COVID‐19: Therapeutic opportunities". Cell Biology International. doi:10.1002/cbin.11403. ISSN 1065-6995.
- ↑ "Lymphocytopenia | National Heart, Lung, and Blood Institute (NHLBI)".